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Surgery_Schwartz_10902 | Surgery_Schwartz | in patients with metastatic disease and to evaluate the response to treatment in patients with metastatic or locally advanced disease.Additional Treatment Modalities Radiotherapy, Thermal Ablation, and Chemotherapy External-beam radiotherapy is occasionally required to control unresectable, locally invasive, or recurrent disease and to treat metastases in support bones to decrease the risk of fractures. It also is of value for the treatment and control of pain from bony metastases when there is minimal or no RAIU. Stereotac-tic brain radiotherapy and intensity-modulated radiation therapy have both been used successfully for metastatic lesions. Percuta-neous thermal ablation by increasing (radiofrequency ablation) or decreasing temperature (cryoablation) in the lesion to induce irreversible cellular damage has shown promise for lung, bone, and liver lesions.53,54 Single-drug and multidrug chemotherapy has been used with little success in disseminated thyroid can-cer, and there is no | Surgery_Schwartz. in patients with metastatic disease and to evaluate the response to treatment in patients with metastatic or locally advanced disease.Additional Treatment Modalities Radiotherapy, Thermal Ablation, and Chemotherapy External-beam radiotherapy is occasionally required to control unresectable, locally invasive, or recurrent disease and to treat metastases in support bones to decrease the risk of fractures. It also is of value for the treatment and control of pain from bony metastases when there is minimal or no RAIU. Stereotac-tic brain radiotherapy and intensity-modulated radiation therapy have both been used successfully for metastatic lesions. Percuta-neous thermal ablation by increasing (radiofrequency ablation) or decreasing temperature (cryoablation) in the lesion to induce irreversible cellular damage has shown promise for lung, bone, and liver lesions.53,54 Single-drug and multidrug chemotherapy has been used with little success in disseminated thyroid can-cer, and there is no |
Surgery_Schwartz_10903 | Surgery_Schwartz | cellular damage has shown promise for lung, bone, and liver lesions.53,54 Single-drug and multidrug chemotherapy has been used with little success in disseminated thyroid can-cer, and there is no role for routine chemotherapy. Doxorubicin (Adriamycin) and paclitaxel (Taxol) were previously the most frequently used agents. The former acts as a radiation sensitizer and should be considered in patients undergoing external-beam radiation.Novel Therapies These therapies are directed at the molecular pathways known to be involved in thyroid cancers. Sorafenib Table 38-7Complications of radioactive iodine therapy (131I) and doses at which they are observedACUTELONG-TERMNeck pain, swelling, and tendernessThyroiditis (if remnant present)Sialadenitis (50–450 mCi), taste dysfunctionHemorrhage (brain metastases)Cerebral edema (brain metastases, 200 mCi)Vocal cord paralysisNausea and vomiting (50–450 mCi)Bone marrow suppression (200 mCi)HematologicBone marrow suppression (>500 mCi)Leukemia (>1000 | Surgery_Schwartz. cellular damage has shown promise for lung, bone, and liver lesions.53,54 Single-drug and multidrug chemotherapy has been used with little success in disseminated thyroid can-cer, and there is no role for routine chemotherapy. Doxorubicin (Adriamycin) and paclitaxel (Taxol) were previously the most frequently used agents. The former acts as a radiation sensitizer and should be considered in patients undergoing external-beam radiation.Novel Therapies These therapies are directed at the molecular pathways known to be involved in thyroid cancers. Sorafenib Table 38-7Complications of radioactive iodine therapy (131I) and doses at which they are observedACUTELONG-TERMNeck pain, swelling, and tendernessThyroiditis (if remnant present)Sialadenitis (50–450 mCi), taste dysfunctionHemorrhage (brain metastases)Cerebral edema (brain metastases, 200 mCi)Vocal cord paralysisNausea and vomiting (50–450 mCi)Bone marrow suppression (200 mCi)HematologicBone marrow suppression (>500 mCi)Leukemia (>1000 |
Surgery_Schwartz_10904 | Surgery_Schwartz | metastases)Cerebral edema (brain metastases, 200 mCi)Vocal cord paralysisNausea and vomiting (50–450 mCi)Bone marrow suppression (200 mCi)HematologicBone marrow suppression (>500 mCi)Leukemia (>1000 mCi)FertilityOvarian/testicular damage, infertilityIncreased spontaneous abortion ratePulmonary fibrosisChronic sialadenitis, nodules, taste dysfunctionIncreased risk of cancerAnaplastic thyroid cancerGastric cancerHepatocellular cancerLung cancerBreast cancer (>1000 mCi)Bladder cancerHypoparathyroidismBrunicardi_Ch38_p1625-p1704.indd 165401/03/19 11:21 AM 1655THYROID, PARATHYROID, AND ADRENALCHAPTER 38and lenvatinib are U.S. Food and Drug Administration (FDA) and European Medical Agency (EMA)-approved for use in patients with advanced differentiated thyroid cancer that is non-responsive to RAI after evaluation in phase 3 placebo-controlled double blinded trials (the DECISION study and the SELECT study, respectively).55,56 Both drugs are multikinase inhibitors and target RET kinase | Surgery_Schwartz. metastases)Cerebral edema (brain metastases, 200 mCi)Vocal cord paralysisNausea and vomiting (50–450 mCi)Bone marrow suppression (200 mCi)HematologicBone marrow suppression (>500 mCi)Leukemia (>1000 mCi)FertilityOvarian/testicular damage, infertilityIncreased spontaneous abortion ratePulmonary fibrosisChronic sialadenitis, nodules, taste dysfunctionIncreased risk of cancerAnaplastic thyroid cancerGastric cancerHepatocellular cancerLung cancerBreast cancer (>1000 mCi)Bladder cancerHypoparathyroidismBrunicardi_Ch38_p1625-p1704.indd 165401/03/19 11:21 AM 1655THYROID, PARATHYROID, AND ADRENALCHAPTER 38and lenvatinib are U.S. Food and Drug Administration (FDA) and European Medical Agency (EMA)-approved for use in patients with advanced differentiated thyroid cancer that is non-responsive to RAI after evaluation in phase 3 placebo-controlled double blinded trials (the DECISION study and the SELECT study, respectively).55,56 Both drugs are multikinase inhibitors and target RET kinase |
Surgery_Schwartz_10905 | Surgery_Schwartz | to RAI after evaluation in phase 3 placebo-controlled double blinded trials (the DECISION study and the SELECT study, respectively).55,56 Both drugs are multikinase inhibitors and target RET kinase and the vascular endothelial growth factor (VEGF)-receptor; however, lenvatinib also inhib-its the fibroblast growth factor and the platelet-derived growth factor receptor. Sorafenib demonstrated progression-free sur-vival (PFS) improvement by 5 months with about 12% partial response rates, whereas lenvatinib prolonged median PFS by 15.7 months compared with placebo with response rates of 65%, including some complete responses. Vandetanib is mainly a RET-kinase inhibitor, but it also affects the VEGF-receptor and epidermal growth factor receptor. It has been evaluated in a phase 2 trial and also demonstrated an improved PFS.57 However, none of the agents show improvements in overall survival. Moreover, they are associated with significant side effects (diarrhea, fatigue hypertension, | Surgery_Schwartz. to RAI after evaluation in phase 3 placebo-controlled double blinded trials (the DECISION study and the SELECT study, respectively).55,56 Both drugs are multikinase inhibitors and target RET kinase and the vascular endothelial growth factor (VEGF)-receptor; however, lenvatinib also inhib-its the fibroblast growth factor and the platelet-derived growth factor receptor. Sorafenib demonstrated progression-free sur-vival (PFS) improvement by 5 months with about 12% partial response rates, whereas lenvatinib prolonged median PFS by 15.7 months compared with placebo with response rates of 65%, including some complete responses. Vandetanib is mainly a RET-kinase inhibitor, but it also affects the VEGF-receptor and epidermal growth factor receptor. It has been evaluated in a phase 2 trial and also demonstrated an improved PFS.57 However, none of the agents show improvements in overall survival. Moreover, they are associated with significant side effects (diarrhea, fatigue hypertension, |
Surgery_Schwartz_10906 | Surgery_Schwartz | also demonstrated an improved PFS.57 However, none of the agents show improvements in overall survival. Moreover, they are associated with significant side effects (diarrhea, fatigue hypertension, hepatotoxicity, bleed-ing, and thrombosis) that affect patient quality of life. As such, they are considered only in patients with metastatic, rapidly progressive, symptomatic disease that is unable to respond to other local treatment approaches and generally in the context of clinical trials. Oncogenic kinase inhibitors that selectively inhibit the mutant V600E BRAF kinase (dabrafenib) has also shown promise in treating a subset of patients with advanced differentiated thyroid cancer.58Medullary Carcinoma MTC accounts for about 5% of thyroid malignancies and arises from the parafollicular or C cells of the thyroid, which, in turn, are derived from the ultimobranchial bod-ies. These cells are concentrated superolaterally in the thyroid lobes, and this is where MTC usually develops. C cells | Surgery_Schwartz. also demonstrated an improved PFS.57 However, none of the agents show improvements in overall survival. Moreover, they are associated with significant side effects (diarrhea, fatigue hypertension, hepatotoxicity, bleed-ing, and thrombosis) that affect patient quality of life. As such, they are considered only in patients with metastatic, rapidly progressive, symptomatic disease that is unable to respond to other local treatment approaches and generally in the context of clinical trials. Oncogenic kinase inhibitors that selectively inhibit the mutant V600E BRAF kinase (dabrafenib) has also shown promise in treating a subset of patients with advanced differentiated thyroid cancer.58Medullary Carcinoma MTC accounts for about 5% of thyroid malignancies and arises from the parafollicular or C cells of the thyroid, which, in turn, are derived from the ultimobranchial bod-ies. These cells are concentrated superolaterally in the thyroid lobes, and this is where MTC usually develops. C cells |
Surgery_Schwartz_10907 | Surgery_Schwartz | cells of the thyroid, which, in turn, are derived from the ultimobranchial bod-ies. These cells are concentrated superolaterally in the thyroid lobes, and this is where MTC usually develops. C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower serum calcium levels, although its effects in humans are mini-mal. Most MTCs occur sporadically. However, approximately 25% occur within the spectrum of several inherited syndromes such as familial MTC, MEN2A, and MEN2B. All these variants are known to result secondary to germline mutations in the RET proto-oncogene. The syndromes also are characterized by geno-type-phenotype correlations, with specific mutations leading to particular clinical manifestations. The salient clinical and genetic features of these syndromes are outlined in Table 38-8. Some clinical features of MEN2B patients are shown in Fig. 38-20.Table 38-8Clinical and genetic features of medullary thyroid cancer syndromesSYNDROMEMANIFESTATIONSRET | Surgery_Schwartz. cells of the thyroid, which, in turn, are derived from the ultimobranchial bod-ies. These cells are concentrated superolaterally in the thyroid lobes, and this is where MTC usually develops. C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower serum calcium levels, although its effects in humans are mini-mal. Most MTCs occur sporadically. However, approximately 25% occur within the spectrum of several inherited syndromes such as familial MTC, MEN2A, and MEN2B. All these variants are known to result secondary to germline mutations in the RET proto-oncogene. The syndromes also are characterized by geno-type-phenotype correlations, with specific mutations leading to particular clinical manifestations. The salient clinical and genetic features of these syndromes are outlined in Table 38-8. Some clinical features of MEN2B patients are shown in Fig. 38-20.Table 38-8Clinical and genetic features of medullary thyroid cancer syndromesSYNDROMEMANIFESTATIONSRET |
Surgery_Schwartz_10908 | Surgery_Schwartz | are outlined in Table 38-8. Some clinical features of MEN2B patients are shown in Fig. 38-20.Table 38-8Clinical and genetic features of medullary thyroid cancer syndromesSYNDROMEMANIFESTATIONSRET MUTATIONSMEN2A MTC, pheochromocytoma, primary hyperparathyroidism, lichen planus amyloidosis Exon 10—codons 609, 611, 618, 620Exon 11—codon 634 (more commonly associated with pheochromocytoma and primary hyperparathyroidism)MEN2BMTC, pheochromocytoma, Marfanoid habitus, mucocutaneous ganglioneuromatosisExon 16—codon 918Familial MTCMTCCodons 609, 611, 618, 620, and 634 Codons 768, 790, 791, or 804 (rare)MEN2A and Hirschsprung’s diseaseMTC, pheochromocytoma, primary hyperparathyroidism, Hirschsprung’s diseaseCodons 609, 618, 620MEN2 = multiple endocrine neoplasia type 2; MTC = medullary thyroid cancer.BAFigure 38-20. Features of MEN2B: thickened lips (A) and mucosal neuromas (A and B).Brunicardi_Ch38_p1625-p1704.indd 165501/03/19 11:21 AM 1656SPECIFIC CONSIDERATIONSPART IIPatients with MTC | Surgery_Schwartz. are outlined in Table 38-8. Some clinical features of MEN2B patients are shown in Fig. 38-20.Table 38-8Clinical and genetic features of medullary thyroid cancer syndromesSYNDROMEMANIFESTATIONSRET MUTATIONSMEN2A MTC, pheochromocytoma, primary hyperparathyroidism, lichen planus amyloidosis Exon 10—codons 609, 611, 618, 620Exon 11—codon 634 (more commonly associated with pheochromocytoma and primary hyperparathyroidism)MEN2BMTC, pheochromocytoma, Marfanoid habitus, mucocutaneous ganglioneuromatosisExon 16—codon 918Familial MTCMTCCodons 609, 611, 618, 620, and 634 Codons 768, 790, 791, or 804 (rare)MEN2A and Hirschsprung’s diseaseMTC, pheochromocytoma, primary hyperparathyroidism, Hirschsprung’s diseaseCodons 609, 618, 620MEN2 = multiple endocrine neoplasia type 2; MTC = medullary thyroid cancer.BAFigure 38-20. Features of MEN2B: thickened lips (A) and mucosal neuromas (A and B).Brunicardi_Ch38_p1625-p1704.indd 165501/03/19 11:21 AM 1656SPECIFIC CONSIDERATIONSPART IIPatients with MTC |
Surgery_Schwartz_10909 | Surgery_Schwartz | 38-20. Features of MEN2B: thickened lips (A) and mucosal neuromas (A and B).Brunicardi_Ch38_p1625-p1704.indd 165501/03/19 11:21 AM 1656SPECIFIC CONSIDERATIONSPART IIPatients with MTC often present with a neck mass that may be associated with palpable cervical lymphadenopathy (15% to 20%). Pain or aching is more common in patients with these tumors, and local invasion may produce symptoms of dys-phagia, dyspnea, or dysphonia. Distant blood-borne metastases to the liver, bone (frequently osteoblastic), and lung occur later in the disease. The female-to-male ratio is 1.5:1. Most patients present between 50 and 60 years old, although patients with familial disease present at a younger age. Medullary thyroid tumors secrete not only calcitonin and carcinoembryonic anti-gen (CEA), but also other peptides such as calcitonin gene–related peptide, histaminadases, prostaglandins E2 and F2α, and serotonin. Patients with extensive metastatic disease frequently develop diarrhea, which may | Surgery_Schwartz. 38-20. Features of MEN2B: thickened lips (A) and mucosal neuromas (A and B).Brunicardi_Ch38_p1625-p1704.indd 165501/03/19 11:21 AM 1656SPECIFIC CONSIDERATIONSPART IIPatients with MTC often present with a neck mass that may be associated with palpable cervical lymphadenopathy (15% to 20%). Pain or aching is more common in patients with these tumors, and local invasion may produce symptoms of dys-phagia, dyspnea, or dysphonia. Distant blood-borne metastases to the liver, bone (frequently osteoblastic), and lung occur later in the disease. The female-to-male ratio is 1.5:1. Most patients present between 50 and 60 years old, although patients with familial disease present at a younger age. Medullary thyroid tumors secrete not only calcitonin and carcinoembryonic anti-gen (CEA), but also other peptides such as calcitonin gene–related peptide, histaminadases, prostaglandins E2 and F2α, and serotonin. Patients with extensive metastatic disease frequently develop diarrhea, which may |
Surgery_Schwartz_10910 | Surgery_Schwartz | other peptides such as calcitonin gene–related peptide, histaminadases, prostaglandins E2 and F2α, and serotonin. Patients with extensive metastatic disease frequently develop diarrhea, which may result from increased intestinal motility and impaired intestinal water and electrolyte flux. About 2% to 4% of patients develop Cushing’s syndrome as a result of ectopic production of adrenocorticotropic hormone (ACTH).Pathology. MTCs typically are unilateral (80%) in patients with sporadic disease and multicentric in familial cases, with bilateral tumors occurring in up to 90% of familial patients. Familial cases also are associated with C-cell hyperplasia, which is considered a premalignant lesion. Microscopically, tumors are composed of sheets of infiltrating neoplastic cells separated by collagen and amyloid. Marked heterogeneity is present; cells may be polygonal or spindle shaped. The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly | Surgery_Schwartz. other peptides such as calcitonin gene–related peptide, histaminadases, prostaglandins E2 and F2α, and serotonin. Patients with extensive metastatic disease frequently develop diarrhea, which may result from increased intestinal motility and impaired intestinal water and electrolyte flux. About 2% to 4% of patients develop Cushing’s syndrome as a result of ectopic production of adrenocorticotropic hormone (ACTH).Pathology. MTCs typically are unilateral (80%) in patients with sporadic disease and multicentric in familial cases, with bilateral tumors occurring in up to 90% of familial patients. Familial cases also are associated with C-cell hyperplasia, which is considered a premalignant lesion. Microscopically, tumors are composed of sheets of infiltrating neoplastic cells separated by collagen and amyloid. Marked heterogeneity is present; cells may be polygonal or spindle shaped. The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly |
Surgery_Schwartz_10911 | Surgery_Schwartz | and amyloid. Marked heterogeneity is present; cells may be polygonal or spindle shaped. The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly used as a diagnostic tumor marker. These tumors also stain positively for CEA and calcito-nin gene–related peptide.Diagnosis. The diagnosis of MTC is established by history, physical examination, raised serum calcitonin, or CEA levels, and FNAB cytology of the thyroid mass. Attention to family history is important because about 25% of patients with MTC have familial disease. Because it is not possible to distinguish sporadic from familial disease at initial presentation, all new patients with MTC should be screened for RET point mutations, pheochromocytoma, and HPT. Screening of patients with famil-ial MTC for RET point mutations has largely replaced using provocative testing with pentagastrin or calcium-stimulated calcitonin levels to make the diagnosis. Calcitonin and CEA are used to identify | Surgery_Schwartz. and amyloid. Marked heterogeneity is present; cells may be polygonal or spindle shaped. The presence of amyloid is a diagnostic finding, but immunohistochemistry for calcitonin is more commonly used as a diagnostic tumor marker. These tumors also stain positively for CEA and calcito-nin gene–related peptide.Diagnosis. The diagnosis of MTC is established by history, physical examination, raised serum calcitonin, or CEA levels, and FNAB cytology of the thyroid mass. Attention to family history is important because about 25% of patients with MTC have familial disease. Because it is not possible to distinguish sporadic from familial disease at initial presentation, all new patients with MTC should be screened for RET point mutations, pheochromocytoma, and HPT. Screening of patients with famil-ial MTC for RET point mutations has largely replaced using provocative testing with pentagastrin or calcium-stimulated calcitonin levels to make the diagnosis. Calcitonin and CEA are used to identify |
Surgery_Schwartz_10912 | Surgery_Schwartz | MTC for RET point mutations has largely replaced using provocative testing with pentagastrin or calcium-stimulated calcitonin levels to make the diagnosis. Calcitonin and CEA are used to identify patients with persistent or recurrent MTC. Calcitonin is a more sensitive tumor marker, but CEA is a better predictor of prognosis.Treatment. The ATA published revised guidelines for the man-agement of medullary cancers in 2015.59 A neck ultrasound is recommended to evaluate the central and lateral neck compart-ments and the superior mediastinum. Serum calcitonin, CEA, calcium levels should also be measured, and RET proto-onco-gene mutation testing should be performed. Pheochromocy-tomas need to be excluded. If patients are found to have a pheochromocytoma, this must be operated on first. Primary hyperparathyroidism, if present, is treated at the time of thyroidectomy. These tumors are generally (>50%) bilateral. Total thyroidectomy is the treatment of choice for patients with MTC because of | Surgery_Schwartz. MTC for RET point mutations has largely replaced using provocative testing with pentagastrin or calcium-stimulated calcitonin levels to make the diagnosis. Calcitonin and CEA are used to identify patients with persistent or recurrent MTC. Calcitonin is a more sensitive tumor marker, but CEA is a better predictor of prognosis.Treatment. The ATA published revised guidelines for the man-agement of medullary cancers in 2015.59 A neck ultrasound is recommended to evaluate the central and lateral neck compart-ments and the superior mediastinum. Serum calcitonin, CEA, calcium levels should also be measured, and RET proto-onco-gene mutation testing should be performed. Pheochromocy-tomas need to be excluded. If patients are found to have a pheochromocytoma, this must be operated on first. Primary hyperparathyroidism, if present, is treated at the time of thyroidectomy. These tumors are generally (>50%) bilateral. Total thyroidectomy is the treatment of choice for patients with MTC because of |
Surgery_Schwartz_10913 | Surgery_Schwartz | hyperparathyroidism, if present, is treated at the time of thyroidectomy. These tumors are generally (>50%) bilateral. Total thyroidectomy is the treatment of choice for patients with MTC because of the high incidence of multicentricity, the more aggressive course, and the fact that 131I therapy usually is not effective.Central compartment nodes frequently are involved early in the disease process, so that a bilateral prophylactic central neck node dissection should be routinely performed. In patients with palpable or imaging-detected cervical nodes, symptoms and signs of distant disease or calcitonin levels >500 pg/mL, additional imaging to include a neck and chest CT and a triple-phase liver CT or contrast-enhanced MRI and an axial MRI/bone scan is recommended to assess for metastatic disease. In patients with no distant disease but nodal involvement, an ipsilateral or bilateral lateral neck dissection (levels IIA, III, IV, and V) is performed. Less aggressive neck surgery should | Surgery_Schwartz. hyperparathyroidism, if present, is treated at the time of thyroidectomy. These tumors are generally (>50%) bilateral. Total thyroidectomy is the treatment of choice for patients with MTC because of the high incidence of multicentricity, the more aggressive course, and the fact that 131I therapy usually is not effective.Central compartment nodes frequently are involved early in the disease process, so that a bilateral prophylactic central neck node dissection should be routinely performed. In patients with palpable or imaging-detected cervical nodes, symptoms and signs of distant disease or calcitonin levels >500 pg/mL, additional imaging to include a neck and chest CT and a triple-phase liver CT or contrast-enhanced MRI and an axial MRI/bone scan is recommended to assess for metastatic disease. In patients with no distant disease but nodal involvement, an ipsilateral or bilateral lateral neck dissection (levels IIA, III, IV, and V) is performed. Less aggressive neck surgery should |
Surgery_Schwartz_10914 | Surgery_Schwartz | disease. In patients with no distant disease but nodal involvement, an ipsilateral or bilateral lateral neck dissection (levels IIA, III, IV, and V) is performed. Less aggressive neck surgery should be consid-ered to preserve speech and swallowing while maintaining locoregional control in patients with limited metastatic disease. The role of prophylactic lateral neck dissection is controversial and may be considered based on calcitonin levels. Some groups favor this procedure if central neck lymph nodes are involved or if the primary tumor is ≥1.5 cm.In the case of locally recurrent or widely metastatic dis-ease, tumor debulking is advised not only to ameliorate symp-toms of pain, flushing, and diarrhea, but also to decrease risk of death from recurrent central neck or mediastinal disease. External-beam radiotherapy is controversial but can be consid-ered for patients with resected T4 disease and for patients with unresectable residual or recurrent tumor and symptomatic bony | Surgery_Schwartz. disease. In patients with no distant disease but nodal involvement, an ipsilateral or bilateral lateral neck dissection (levels IIA, III, IV, and V) is performed. Less aggressive neck surgery should be consid-ered to preserve speech and swallowing while maintaining locoregional control in patients with limited metastatic disease. The role of prophylactic lateral neck dissection is controversial and may be considered based on calcitonin levels. Some groups favor this procedure if central neck lymph nodes are involved or if the primary tumor is ≥1.5 cm.In the case of locally recurrent or widely metastatic dis-ease, tumor debulking is advised not only to ameliorate symp-toms of pain, flushing, and diarrhea, but also to decrease risk of death from recurrent central neck or mediastinal disease. External-beam radiotherapy is controversial but can be consid-ered for patients with resected T4 disease and for patients with unresectable residual or recurrent tumor and symptomatic bony |
Surgery_Schwartz_10915 | Surgery_Schwartz | disease. External-beam radiotherapy is controversial but can be consid-ered for patients with resected T4 disease and for patients with unresectable residual or recurrent tumor and symptomatic bony metastases. Liver metastases tend to be multiple and are typi-cally not amenable to resection, percutaneous ethanol ablation, or radiofrequency ablation. However, chemoembolization may be helpful in this setting. There is no effective chemotherapy regimen.Various targeted therapies directed against the RET kinase have been investigated for the treatment of MTC.43 Many of these also inhibit VEGF receptor due to their close structural similarities. Sorafenib, sunitinib, lenvatinib, and cabozantinib are some such multikinase inhibitors, whereas axitinib and pazopanib act only on VEGFR. Vandetanib inhibits both targets and is also an EGF receptor inhibitor, and cabozantinib targets c-MET in addition to RET and VEGF receptor. Both drugs are currently approved by the FDA and EMA for the treatment | Surgery_Schwartz. disease. External-beam radiotherapy is controversial but can be consid-ered for patients with resected T4 disease and for patients with unresectable residual or recurrent tumor and symptomatic bony metastases. Liver metastases tend to be multiple and are typi-cally not amenable to resection, percutaneous ethanol ablation, or radiofrequency ablation. However, chemoembolization may be helpful in this setting. There is no effective chemotherapy regimen.Various targeted therapies directed against the RET kinase have been investigated for the treatment of MTC.43 Many of these also inhibit VEGF receptor due to their close structural similarities. Sorafenib, sunitinib, lenvatinib, and cabozantinib are some such multikinase inhibitors, whereas axitinib and pazopanib act only on VEGFR. Vandetanib inhibits both targets and is also an EGF receptor inhibitor, and cabozantinib targets c-MET in addition to RET and VEGF receptor. Both drugs are currently approved by the FDA and EMA for the treatment |
Surgery_Schwartz_10916 | Surgery_Schwartz | both targets and is also an EGF receptor inhibitor, and cabozantinib targets c-MET in addition to RET and VEGF receptor. Both drugs are currently approved by the FDA and EMA for the treatment of advanced and progressive MTC based on data that they prolong progression-free survival, in addition to reducing secretion of calcitonin and CEA.60,61 They are recommended as first-line sys-temic therapy in symptomatic patients with advanced MTC. An anti-CEA monoclonal antibody (labetuzumab) also has shown antitumor response in a small group of patients. Patients with recurrent/metastatic disease should be enrolled in well-designed clinical trials.In patients who have hypercalcemia and an increased PTH at the time of thyroidectomy, only obviously enlarged parathy-roid glands should be removed. The other parathyroid glands should be preserved and marked in patients with normocalce-mia, as only about 20% of patients with MEN2A develop HPT. When a normal parathyroid cannot be maintained on a | Surgery_Schwartz. both targets and is also an EGF receptor inhibitor, and cabozantinib targets c-MET in addition to RET and VEGF receptor. Both drugs are currently approved by the FDA and EMA for the treatment of advanced and progressive MTC based on data that they prolong progression-free survival, in addition to reducing secretion of calcitonin and CEA.60,61 They are recommended as first-line sys-temic therapy in symptomatic patients with advanced MTC. An anti-CEA monoclonal antibody (labetuzumab) also has shown antitumor response in a small group of patients. Patients with recurrent/metastatic disease should be enrolled in well-designed clinical trials.In patients who have hypercalcemia and an increased PTH at the time of thyroidectomy, only obviously enlarged parathy-roid glands should be removed. The other parathyroid glands should be preserved and marked in patients with normocalce-mia, as only about 20% of patients with MEN2A develop HPT. When a normal parathyroid cannot be maintained on a |
Surgery_Schwartz_10917 | Surgery_Schwartz | The other parathyroid glands should be preserved and marked in patients with normocalce-mia, as only about 20% of patients with MEN2A develop HPT. When a normal parathyroid cannot be maintained on a vascu-lar pedicle, it should be removed, biopsied to confirm that it is a parathyroid, and then autotransplanted to the forearm of the nondominant arm, particularly in patients with MEN2A. Reim-plantation into the sternocleidomastoid muscle is also accept-able for patients with known MEN2B and familial MTC.Prophylactic total thyroidectomy is indicated in RET mutation carriers once the mutation is confirmed. The ATA guidelines stratify mutation into various risk levels to offer recommendations regarding age at which a prophylactic Brunicardi_Ch38_p1625-p1704.indd 165601/03/19 11:21 AM 1657THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-21. Magnetic resonance imaging scan of a patient with anaplastic thyroid cancer. Note heterogeneity consistent with necrosis.thyroidectomy should be | Surgery_Schwartz. The other parathyroid glands should be preserved and marked in patients with normocalce-mia, as only about 20% of patients with MEN2A develop HPT. When a normal parathyroid cannot be maintained on a vascu-lar pedicle, it should be removed, biopsied to confirm that it is a parathyroid, and then autotransplanted to the forearm of the nondominant arm, particularly in patients with MEN2A. Reim-plantation into the sternocleidomastoid muscle is also accept-able for patients with known MEN2B and familial MTC.Prophylactic total thyroidectomy is indicated in RET mutation carriers once the mutation is confirmed. The ATA guidelines stratify mutation into various risk levels to offer recommendations regarding age at which a prophylactic Brunicardi_Ch38_p1625-p1704.indd 165601/03/19 11:21 AM 1657THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-21. Magnetic resonance imaging scan of a patient with anaplastic thyroid cancer. Note heterogeneity consistent with necrosis.thyroidectomy should be |
Surgery_Schwartz_10918 | Surgery_Schwartz | PARATHYROID, AND ADRENALCHAPTER 38Figure 38-21. Magnetic resonance imaging scan of a patient with anaplastic thyroid cancer. Note heterogeneity consistent with necrosis.thyroidectomy should be performed and to predict phenotypes, including pheochromocytomas.59 In general, in patients with less aggressive mutations (designated ATA moderate-risk), thy-roidectomy may be delayed >5 years, especially if there is a nor-mal annual serum calcitonin, neck ultrasound, less aggressive family history, or family preference. Children with MEN2A and mutations at codon 634 (designated high-risk) are advised to undergo thyroidectomy at <5 years of age, and those with MEN2B-related mutations (designated highest-risk) should undergo the procedure before age 1. Central neck dissection can be avoided in children who are RET-positive and calcitonin-negative with a normal ultrasound examination. When the cal-citonin is increased or the ultrasound suggests a thyroid cancer, a prophylactic central neck | Surgery_Schwartz. PARATHYROID, AND ADRENALCHAPTER 38Figure 38-21. Magnetic resonance imaging scan of a patient with anaplastic thyroid cancer. Note heterogeneity consistent with necrosis.thyroidectomy should be performed and to predict phenotypes, including pheochromocytomas.59 In general, in patients with less aggressive mutations (designated ATA moderate-risk), thy-roidectomy may be delayed >5 years, especially if there is a nor-mal annual serum calcitonin, neck ultrasound, less aggressive family history, or family preference. Children with MEN2A and mutations at codon 634 (designated high-risk) are advised to undergo thyroidectomy at <5 years of age, and those with MEN2B-related mutations (designated highest-risk) should undergo the procedure before age 1. Central neck dissection can be avoided in children who are RET-positive and calcitonin-negative with a normal ultrasound examination. When the cal-citonin is increased or the ultrasound suggests a thyroid cancer, a prophylactic central neck |
Surgery_Schwartz_10919 | Surgery_Schwartz | children who are RET-positive and calcitonin-negative with a normal ultrasound examination. When the cal-citonin is increased or the ultrasound suggests a thyroid cancer, a prophylactic central neck dissection is indicated.Postoperative Follow-Up and Prognosis. Patients are fol-lowed by annual measurements of calcitonin and CEA levels, in addition to history and physical examination. Other modalities used to localize recurrent disease include ultrasound, CT, MRI, and more recently, FDG-PET/CT scans. Prognosis is related to disease stage. The 10-year survival rate is approximately 80% but decreases to 45% in patients with lymph node involvement. Survival also is significantly influenced by disease type. It is best in patients with non-MEN familial MTC, followed by those with MEN2A, and then those with sporadic disease. Progno-sis is the worst (survival of 35% at 10 years) in patients with MEN2B. Performing prophylactic surgery in RET oncogene mutation carriers not only improves | Surgery_Schwartz. children who are RET-positive and calcitonin-negative with a normal ultrasound examination. When the cal-citonin is increased or the ultrasound suggests a thyroid cancer, a prophylactic central neck dissection is indicated.Postoperative Follow-Up and Prognosis. Patients are fol-lowed by annual measurements of calcitonin and CEA levels, in addition to history and physical examination. Other modalities used to localize recurrent disease include ultrasound, CT, MRI, and more recently, FDG-PET/CT scans. Prognosis is related to disease stage. The 10-year survival rate is approximately 80% but decreases to 45% in patients with lymph node involvement. Survival also is significantly influenced by disease type. It is best in patients with non-MEN familial MTC, followed by those with MEN2A, and then those with sporadic disease. Progno-sis is the worst (survival of 35% at 10 years) in patients with MEN2B. Performing prophylactic surgery in RET oncogene mutation carriers not only improves |
Surgery_Schwartz_10920 | Surgery_Schwartz | and then those with sporadic disease. Progno-sis is the worst (survival of 35% at 10 years) in patients with MEN2B. Performing prophylactic surgery in RET oncogene mutation carriers not only improves survival rates but also ren-ders most patients calcitonin free.Anaplastic Carcinoma Anaplastic carcinoma accounts for approximately 1% of all thyroid malignancies in the United States. Women are more commonly affected, and the majority of tumors present in the seventh and eighth decade of life. The typical patient has a long-standing neck mass, which rapidly enlarges and may be painful. Associated symptoms such as dys-phonia, dysphagia, and dyspnea are common. The tumor is large and may be fixed to surrounding structures or may be ulcerated with areas of necrosis (Fig. 38-21). Lymph nodes usually are palpable at presentation. Evidence of metastatic spread also may be present. Diagnosis is confirmed by FNAB revealing char-acteristic giant and multinucleated cells. Differential diagnoses on | Surgery_Schwartz. and then those with sporadic disease. Progno-sis is the worst (survival of 35% at 10 years) in patients with MEN2B. Performing prophylactic surgery in RET oncogene mutation carriers not only improves survival rates but also ren-ders most patients calcitonin free.Anaplastic Carcinoma Anaplastic carcinoma accounts for approximately 1% of all thyroid malignancies in the United States. Women are more commonly affected, and the majority of tumors present in the seventh and eighth decade of life. The typical patient has a long-standing neck mass, which rapidly enlarges and may be painful. Associated symptoms such as dys-phonia, dysphagia, and dyspnea are common. The tumor is large and may be fixed to surrounding structures or may be ulcerated with areas of necrosis (Fig. 38-21). Lymph nodes usually are palpable at presentation. Evidence of metastatic spread also may be present. Diagnosis is confirmed by FNAB revealing char-acteristic giant and multinucleated cells. Differential diagnoses on |
Surgery_Schwartz_10921 | Surgery_Schwartz | are palpable at presentation. Evidence of metastatic spread also may be present. Diagnosis is confirmed by FNAB revealing char-acteristic giant and multinucleated cells. Differential diagnoses on FNA can include lymphomas, medullary carcinomas, direct extension from a laryngeal carcinoma, or other metastatic car-cinomas or melanoma. When spindle cell elements are present, primary and metastatic sarcomas need to be considered as well. Immunohistochemical markers can aid with excluding other diagnoses. Core or incisional biopsy occasionally is needed to confirm the diagnosis, especially when there is necrotic material on the FNA.Pathology. On gross inspection, anaplastic tumors are firm and whitish in appearance. Microscopically, sheets of cells with marked heterogeneity are seen. The three main histologic growth patterns are spindle cell, squamoid, and pleomorphic giant cell. Tumors may show a predominance of one pattern or a mixture of various patterns. Foci of more differentiated | Surgery_Schwartz. are palpable at presentation. Evidence of metastatic spread also may be present. Diagnosis is confirmed by FNAB revealing char-acteristic giant and multinucleated cells. Differential diagnoses on FNA can include lymphomas, medullary carcinomas, direct extension from a laryngeal carcinoma, or other metastatic car-cinomas or melanoma. When spindle cell elements are present, primary and metastatic sarcomas need to be considered as well. Immunohistochemical markers can aid with excluding other diagnoses. Core or incisional biopsy occasionally is needed to confirm the diagnosis, especially when there is necrotic material on the FNA.Pathology. On gross inspection, anaplastic tumors are firm and whitish in appearance. Microscopically, sheets of cells with marked heterogeneity are seen. The three main histologic growth patterns are spindle cell, squamoid, and pleomorphic giant cell. Tumors may show a predominance of one pattern or a mixture of various patterns. Foci of more differentiated |
Surgery_Schwartz_10922 | Surgery_Schwartz | main histologic growth patterns are spindle cell, squamoid, and pleomorphic giant cell. Tumors may show a predominance of one pattern or a mixture of various patterns. Foci of more differentiated thy-roid tumors, either follicular or papillary, may be seen, suggest-ing that anaplastic tumors arise from more well-differentiated tumors.Treatment and Prognosis. This tumor is one of the most aggressive thyroid malignancies, with few patients surviving 6 months beyond diagnosis. All forms of treatment have been disappointing. The ATA has published guidelines for the man-agement of patients with anaplastic cancer.62 Imaging (ultra-sound, CT, MRI, or PET-CT) should be obtained to assess resectability. All patients should have preoperative laryngos-copy to assess the status of the vocal cords. A total or near-total thyroidectomy with therapeutic lymph node dissection is rec-ommended for patients with an intrathyroidal mass (although lobectomy may also be appropriate, particularly if there is | Surgery_Schwartz. main histologic growth patterns are spindle cell, squamoid, and pleomorphic giant cell. Tumors may show a predominance of one pattern or a mixture of various patterns. Foci of more differentiated thy-roid tumors, either follicular or papillary, may be seen, suggest-ing that anaplastic tumors arise from more well-differentiated tumors.Treatment and Prognosis. This tumor is one of the most aggressive thyroid malignancies, with few patients surviving 6 months beyond diagnosis. All forms of treatment have been disappointing. The ATA has published guidelines for the man-agement of patients with anaplastic cancer.62 Imaging (ultra-sound, CT, MRI, or PET-CT) should be obtained to assess resectability. All patients should have preoperative laryngos-copy to assess the status of the vocal cords. A total or near-total thyroidectomy with therapeutic lymph node dissection is rec-ommended for patients with an intrathyroidal mass (although lobectomy may also be appropriate, particularly if there is |
Surgery_Schwartz_10923 | Surgery_Schwartz | total or near-total thyroidectomy with therapeutic lymph node dissection is rec-ommended for patients with an intrathyroidal mass (although lobectomy may also be appropriate, particularly if there is concern for vocal cord paralysis). If extrathyroidal extension is present, an en bloc resection should be considered if all gross disease can be removed (R1). Tracheostomy should be avoided as long as possible unless there is impending airway loss. Adjuvant radiation which should be offered to patients with a good performance status and no metastatic disease who desire aggressive management. Cytotoxic chemotherapy (with some combination of a taxane, anthracycline, and platinum) is typi-cally given concurrently and has been associated with prolonged survival, although these agents are also being used in a neoadju-vant fashion, particularly in patients with unresectable disease.Lymphoma Lymphomas account for <1% of thyroid malignan-cies, and most are of the non-Hodgkin’s B-cell type. | Surgery_Schwartz. total or near-total thyroidectomy with therapeutic lymph node dissection is rec-ommended for patients with an intrathyroidal mass (although lobectomy may also be appropriate, particularly if there is concern for vocal cord paralysis). If extrathyroidal extension is present, an en bloc resection should be considered if all gross disease can be removed (R1). Tracheostomy should be avoided as long as possible unless there is impending airway loss. Adjuvant radiation which should be offered to patients with a good performance status and no metastatic disease who desire aggressive management. Cytotoxic chemotherapy (with some combination of a taxane, anthracycline, and platinum) is typi-cally given concurrently and has been associated with prolonged survival, although these agents are also being used in a neoadju-vant fashion, particularly in patients with unresectable disease.Lymphoma Lymphomas account for <1% of thyroid malignan-cies, and most are of the non-Hodgkin’s B-cell type. |
Surgery_Schwartz_10924 | Surgery_Schwartz | being used in a neoadju-vant fashion, particularly in patients with unresectable disease.Lymphoma Lymphomas account for <1% of thyroid malignan-cies, and most are of the non-Hodgkin’s B-cell type. Although the disease can arise as part of a generalized lymphomatous con-dition, most thyroid lymphomas develop in patients with chronic lymphocytic thyroiditis. Chronic antigenic lymphocyte stimu-lation has been suggested to result in lymphocyte transforma-tion. Patients usually present with symptoms similar to those of patients with anaplastic carcinoma, although the rapidly enlarg-ing neck mass often is painless. Patients may present with acute respiratory distress. Ultrasound can be useful for early diagno-sis, and lymphoma appears as a well-defined hypoechoic mass. The diagnosis usually is suggested by FNAB, but FNAB can be nondiagnostic, particularly in the setting of low-grade lym-phomas. Therefore, needle core or open biopsy may be neces-sary for definitive diagnosis. Staging studies | Surgery_Schwartz. being used in a neoadju-vant fashion, particularly in patients with unresectable disease.Lymphoma Lymphomas account for <1% of thyroid malignan-cies, and most are of the non-Hodgkin’s B-cell type. Although the disease can arise as part of a generalized lymphomatous con-dition, most thyroid lymphomas develop in patients with chronic lymphocytic thyroiditis. Chronic antigenic lymphocyte stimu-lation has been suggested to result in lymphocyte transforma-tion. Patients usually present with symptoms similar to those of patients with anaplastic carcinoma, although the rapidly enlarg-ing neck mass often is painless. Patients may present with acute respiratory distress. Ultrasound can be useful for early diagno-sis, and lymphoma appears as a well-defined hypoechoic mass. The diagnosis usually is suggested by FNAB, but FNAB can be nondiagnostic, particularly in the setting of low-grade lym-phomas. Therefore, needle core or open biopsy may be neces-sary for definitive diagnosis. Staging studies |
Surgery_Schwartz_10925 | Surgery_Schwartz | by FNAB, but FNAB can be nondiagnostic, particularly in the setting of low-grade lym-phomas. Therefore, needle core or open biopsy may be neces-sary for definitive diagnosis. Staging studies should be obtained expeditiously to assess the extent of extrathyroidal spread.Brunicardi_Ch38_p1625-p1704.indd 165701/03/19 11:21 AM 1658SPECIFIC CONSIDERATIONSPART IITreatment and Prognosis. Patients with thyroid lymphoma respond rapidly to chemotherapy (CHOP—cyclophosphamide, doxorubicin, vincristine, and prednisone), which also has been associated with improved survival. Combined treatment with radiotherapy and chemotherapy often is recommended. Thy-roidectomy and nodal resection are used to alleviate symptoms of airway obstruction in patients who do not respond quickly to the above regimens or who have completed the regimen before diagnosis. Prognosis depends on the histologic grade of the tumor and whether the lymphoma is confined to the thy-roid gland or is disseminated. The overall | Surgery_Schwartz. by FNAB, but FNAB can be nondiagnostic, particularly in the setting of low-grade lym-phomas. Therefore, needle core or open biopsy may be neces-sary for definitive diagnosis. Staging studies should be obtained expeditiously to assess the extent of extrathyroidal spread.Brunicardi_Ch38_p1625-p1704.indd 165701/03/19 11:21 AM 1658SPECIFIC CONSIDERATIONSPART IITreatment and Prognosis. Patients with thyroid lymphoma respond rapidly to chemotherapy (CHOP—cyclophosphamide, doxorubicin, vincristine, and prednisone), which also has been associated with improved survival. Combined treatment with radiotherapy and chemotherapy often is recommended. Thy-roidectomy and nodal resection are used to alleviate symptoms of airway obstruction in patients who do not respond quickly to the above regimens or who have completed the regimen before diagnosis. Prognosis depends on the histologic grade of the tumor and whether the lymphoma is confined to the thy-roid gland or is disseminated. The overall |
Surgery_Schwartz_10926 | Surgery_Schwartz | or who have completed the regimen before diagnosis. Prognosis depends on the histologic grade of the tumor and whether the lymphoma is confined to the thy-roid gland or is disseminated. The overall 5-year survival rate is about 50%; patients with extrathyroidal disease have markedly lower survival rates.Metastatic Carcinoma The thyroid gland is a rare site of metastases from other cancers, including kidney, breast, lung, and melanoma. Clinical examination and a review of the patient’s history often suggest the source of the metastatic dis-ease, and FNAB usually provides definitive diagnosis. Resec-tion of the thyroid, usually lobectomy, may be helpful in many patients, depending on the status of their primary tumor.Thyroid Surgery Conduct of Thyroidectomy Patients with any recent or remote history of altered phonation or prior neck or upper chest surgery that places the recurrent laryngeal or vagus nerves at risk should undergo vocal cord assessment by direct or indirect laryngos-copy | Surgery_Schwartz. or who have completed the regimen before diagnosis. Prognosis depends on the histologic grade of the tumor and whether the lymphoma is confined to the thy-roid gland or is disseminated. The overall 5-year survival rate is about 50%; patients with extrathyroidal disease have markedly lower survival rates.Metastatic Carcinoma The thyroid gland is a rare site of metastases from other cancers, including kidney, breast, lung, and melanoma. Clinical examination and a review of the patient’s history often suggest the source of the metastatic dis-ease, and FNAB usually provides definitive diagnosis. Resec-tion of the thyroid, usually lobectomy, may be helpful in many patients, depending on the status of their primary tumor.Thyroid Surgery Conduct of Thyroidectomy Patients with any recent or remote history of altered phonation or prior neck or upper chest surgery that places the recurrent laryngeal or vagus nerves at risk should undergo vocal cord assessment by direct or indirect laryngos-copy |
Surgery_Schwartz_10927 | Surgery_Schwartz | history of altered phonation or prior neck or upper chest surgery that places the recurrent laryngeal or vagus nerves at risk should undergo vocal cord assessment by direct or indirect laryngos-copy before thyroidectomy. Laryngeal examination is also advised in patients with known posterior extension of thyroid cancer and extensive central nodal metastases.40 The patient is positioned supine, with a sandbag between the scapulae. The head is placed on a donut cushion, and the neck is extended to provide maximal exposure. A Kocher transverse collar incision, typically 3 to 5 cm in length, is placed in or parallel to a natu-ral skin crease 1 cm below the cricoid cartilage (Fig. 38-22A), although longer incisions may be needed. The subcutaneous tis-sues and platysma are incised sharply, and subplatysmal flaps are raised superiorly to the level of the thyroid cartilage and inferiorly to the suprasternal notch (Fig. 38-22B). The strap muscles are divided in the midline along the entire | Surgery_Schwartz. history of altered phonation or prior neck or upper chest surgery that places the recurrent laryngeal or vagus nerves at risk should undergo vocal cord assessment by direct or indirect laryngos-copy before thyroidectomy. Laryngeal examination is also advised in patients with known posterior extension of thyroid cancer and extensive central nodal metastases.40 The patient is positioned supine, with a sandbag between the scapulae. The head is placed on a donut cushion, and the neck is extended to provide maximal exposure. A Kocher transverse collar incision, typically 3 to 5 cm in length, is placed in or parallel to a natu-ral skin crease 1 cm below the cricoid cartilage (Fig. 38-22A), although longer incisions may be needed. The subcutaneous tis-sues and platysma are incised sharply, and subplatysmal flaps are raised superiorly to the level of the thyroid cartilage and inferiorly to the suprasternal notch (Fig. 38-22B). The strap muscles are divided in the midline along the entire |
Surgery_Schwartz_10928 | Surgery_Schwartz | subplatysmal flaps are raised superiorly to the level of the thyroid cartilage and inferiorly to the suprasternal notch (Fig. 38-22B). The strap muscles are divided in the midline along the entire length of the mobilized flaps, and the thyroid gland is exposed. On the side to be approached first, the sternohyoid muscles are sepa-rated from the underlying sternothyroid muscle by blunt dissec-tion until the internal jugular vein and ansa cervicalis nerve are identified. The strap muscles rarely need to be divided to gain exposure to the thyroid gland. If this maneuver is necessary, the muscles should be divided high to preserve their innervation by branches of the ansa cervicalis. If there is evidence of direct tumor invasion into the strap muscles, the portion of involved muscle should be resected en bloc with the thyroid gland. The sternothyroid muscle is then dissected off the underlying thyroid by a combination of sharp and blunt dissection, thus exposing the middle thyroid veins. | Surgery_Schwartz. subplatysmal flaps are raised superiorly to the level of the thyroid cartilage and inferiorly to the suprasternal notch (Fig. 38-22B). The strap muscles are divided in the midline along the entire length of the mobilized flaps, and the thyroid gland is exposed. On the side to be approached first, the sternohyoid muscles are sepa-rated from the underlying sternothyroid muscle by blunt dissec-tion until the internal jugular vein and ansa cervicalis nerve are identified. The strap muscles rarely need to be divided to gain exposure to the thyroid gland. If this maneuver is necessary, the muscles should be divided high to preserve their innervation by branches of the ansa cervicalis. If there is evidence of direct tumor invasion into the strap muscles, the portion of involved muscle should be resected en bloc with the thyroid gland. The sternothyroid muscle is then dissected off the underlying thyroid by a combination of sharp and blunt dissection, thus exposing the middle thyroid veins. |
Surgery_Schwartz_10929 | Surgery_Schwartz | resected en bloc with the thyroid gland. The sternothyroid muscle is then dissected off the underlying thyroid by a combination of sharp and blunt dissection, thus exposing the middle thyroid veins. The thyroid lobe is retracted medially and anteriorly, and the lateral tissues are swept posterolaterally using a peanut sponge. The middle thyroid veins are ligated and divided (Fig. 38-22C). Attention is then turned to the midline where Delphian nodes and the pyramidal lobe are identified. The fascia just cephalad and caudad to the isthmus is divided. The superior thyroid pole is identified by retracting the thyroid first inferiorly and medially, and then the upper pole of the thy-roid is mobilized caudally and laterally. The dissection plane is kept as close to the thyroid as possible, and the superior pole vessels are individually identified, skeletonized, ligated, and divided low on the thyroid gland to avoid injury to the exter-nal branch of the superior laryngeal nerve (Fig. | Surgery_Schwartz. resected en bloc with the thyroid gland. The sternothyroid muscle is then dissected off the underlying thyroid by a combination of sharp and blunt dissection, thus exposing the middle thyroid veins. The thyroid lobe is retracted medially and anteriorly, and the lateral tissues are swept posterolaterally using a peanut sponge. The middle thyroid veins are ligated and divided (Fig. 38-22C). Attention is then turned to the midline where Delphian nodes and the pyramidal lobe are identified. The fascia just cephalad and caudad to the isthmus is divided. The superior thyroid pole is identified by retracting the thyroid first inferiorly and medially, and then the upper pole of the thy-roid is mobilized caudally and laterally. The dissection plane is kept as close to the thyroid as possible, and the superior pole vessels are individually identified, skeletonized, ligated, and divided low on the thyroid gland to avoid injury to the exter-nal branch of the superior laryngeal nerve (Fig. |
Surgery_Schwartz_10930 | Surgery_Schwartz | and the superior pole vessels are individually identified, skeletonized, ligated, and divided low on the thyroid gland to avoid injury to the exter-nal branch of the superior laryngeal nerve (Fig. 38-22D). Once these vessels are divided, the tissues posterior and lateral to the superior pole can be swept from the gland in a posteromedial direction, to reduce the risk of damaging vessels supplying the upper parathyroid.The RLNs should then be identified, and the ATA 2015 guidelines strongly recommend visual identification in all cases.40 The course of the right RLN is more oblique than the left RLN. The nerves can be most consistently identified at the level of the cricoid cartilage. The parathyroids usually can be identified within 1 cm of the crossing of the inferior thyroid artery and the RLN, although they also may be ectopic in loca-tion. The lower pole of the thyroid gland should be mobilized by gently sweeping all tissues dorsally. The inferior thyroid vessels are dissected, | Surgery_Schwartz. and the superior pole vessels are individually identified, skeletonized, ligated, and divided low on the thyroid gland to avoid injury to the exter-nal branch of the superior laryngeal nerve (Fig. 38-22D). Once these vessels are divided, the tissues posterior and lateral to the superior pole can be swept from the gland in a posteromedial direction, to reduce the risk of damaging vessels supplying the upper parathyroid.The RLNs should then be identified, and the ATA 2015 guidelines strongly recommend visual identification in all cases.40 The course of the right RLN is more oblique than the left RLN. The nerves can be most consistently identified at the level of the cricoid cartilage. The parathyroids usually can be identified within 1 cm of the crossing of the inferior thyroid artery and the RLN, although they also may be ectopic in loca-tion. The lower pole of the thyroid gland should be mobilized by gently sweeping all tissues dorsally. The inferior thyroid vessels are dissected, |
Surgery_Schwartz_10931 | Surgery_Schwartz | the RLN, although they also may be ectopic in loca-tion. The lower pole of the thyroid gland should be mobilized by gently sweeping all tissues dorsally. The inferior thyroid vessels are dissected, skeletonized, ligated, and divided as close to the surface of the thyroid gland as possible to minimize devascular-ization of the parathyroids (extracapsular dissection) or injury to the RLN. The RLN is most vulnerable to injury in the vicinity of the ligament of Berry. The nerve often passes through this structure along with small crossing arterial and venous branches (Fig. 38-22E). Any bleeding in this area should be controlled with gentle pressure before carefully identifying the vessel and ligating it. Use of the electrocautery should be avoided in prox-imity to the RLN. Once the ligament is divided, the thyroid can be separated from the underlying trachea by sharp dissection. The pyramidal lobe, if present, must be dissected in a cephalad direction to above the level of the notch in | Surgery_Schwartz. the RLN, although they also may be ectopic in loca-tion. The lower pole of the thyroid gland should be mobilized by gently sweeping all tissues dorsally. The inferior thyroid vessels are dissected, skeletonized, ligated, and divided as close to the surface of the thyroid gland as possible to minimize devascular-ization of the parathyroids (extracapsular dissection) or injury to the RLN. The RLN is most vulnerable to injury in the vicinity of the ligament of Berry. The nerve often passes through this structure along with small crossing arterial and venous branches (Fig. 38-22E). Any bleeding in this area should be controlled with gentle pressure before carefully identifying the vessel and ligating it. Use of the electrocautery should be avoided in prox-imity to the RLN. Once the ligament is divided, the thyroid can be separated from the underlying trachea by sharp dissection. The pyramidal lobe, if present, must be dissected in a cephalad direction to above the level of the notch in |
Surgery_Schwartz_10932 | Surgery_Schwartz | is divided, the thyroid can be separated from the underlying trachea by sharp dissection. The pyramidal lobe, if present, must be dissected in a cephalad direction to above the level of the notch in the thyroid cartilage or higher in continuity with the thyroid gland. If a lobectomy is to be performed, the isthmus is divided flush with the trachea on the contralateral side and suture ligated. The procedure is repeated on the opposite side for a total thyroidectomy.Parathyroid glands located anteriorly on the surface of the thyroid that cannot be dissected from the thyroid with a good blood supply or that have been inadvertently removed during the thyroidectomy should be resected, confirmed as parathy-roid tissue by frozen section, divided into 1-mm fragments, and reimplanted into individual pockets in the sternocleido-mastoid muscle. The sites should be marked with silk sutures and a clip. Various novel techniques using indocyanine fluo-rescence angiography and near-infrared | Surgery_Schwartz. is divided, the thyroid can be separated from the underlying trachea by sharp dissection. The pyramidal lobe, if present, must be dissected in a cephalad direction to above the level of the notch in the thyroid cartilage or higher in continuity with the thyroid gland. If a lobectomy is to be performed, the isthmus is divided flush with the trachea on the contralateral side and suture ligated. The procedure is repeated on the opposite side for a total thyroidectomy.Parathyroid glands located anteriorly on the surface of the thyroid that cannot be dissected from the thyroid with a good blood supply or that have been inadvertently removed during the thyroidectomy should be resected, confirmed as parathy-roid tissue by frozen section, divided into 1-mm fragments, and reimplanted into individual pockets in the sternocleido-mastoid muscle. The sites should be marked with silk sutures and a clip. Various novel techniques using indocyanine fluo-rescence angiography and near-infrared |
Surgery_Schwartz_10933 | Surgery_Schwartz | individual pockets in the sternocleido-mastoid muscle. The sites should be marked with silk sutures and a clip. Various novel techniques using indocyanine fluo-rescence angiography and near-infrared autofluorescence have shown utility in the identification and viability assessment of parathyroid glands; however, they are not routinely used at the present time.63,64 If a subtotal thyroidectomy is to be performed, once the superior pole vessels are divided and the thyroid lobe mobilized anteriorly, the thyroid lobe is cross-clamped with a Mayo clamp, leaving approximately 4 g of the posterior por-tion of the thyroid. The thyroid remnant is suture ligated, taking care to avoid injury to the RLN. Routine drain placement rarely is necessary. After adequate hemostasis is obtained, the strap muscles are reapproximated in the midline. The platysma is approximated in a similar fashion. The skin can be closed with subcuticular sutures or clips.Nerve Monitoring Intraoperative RLN and external | Surgery_Schwartz. individual pockets in the sternocleido-mastoid muscle. The sites should be marked with silk sutures and a clip. Various novel techniques using indocyanine fluo-rescence angiography and near-infrared autofluorescence have shown utility in the identification and viability assessment of parathyroid glands; however, they are not routinely used at the present time.63,64 If a subtotal thyroidectomy is to be performed, once the superior pole vessels are divided and the thyroid lobe mobilized anteriorly, the thyroid lobe is cross-clamped with a Mayo clamp, leaving approximately 4 g of the posterior por-tion of the thyroid. The thyroid remnant is suture ligated, taking care to avoid injury to the RLN. Routine drain placement rarely is necessary. After adequate hemostasis is obtained, the strap muscles are reapproximated in the midline. The platysma is approximated in a similar fashion. The skin can be closed with subcuticular sutures or clips.Nerve Monitoring Intraoperative RLN and external |
Surgery_Schwartz_10934 | Surgery_Schwartz | are reapproximated in the midline. The platysma is approximated in a similar fashion. The skin can be closed with subcuticular sutures or clips.Nerve Monitoring Intraoperative RLN and external laryngeal nerve monitoring techniques are being increasingly used during thyroid and parathyroid surgery. Both continuous monitoring using endotracheal tube electrodes and intermittent monitor-ing by periodic stimulation and laryngeal palpation are used. Many published studies have established the feasibility of nerve monitoring; however, none were able to show that the technique equivocally reduces nerve injury (particularly by experienced Brunicardi_Ch38_p1625-p1704.indd 165801/03/19 11:21 AM 1659THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-22. Conduct of thyroidectomy. A. Correct placement of thyroidectomy incision. B. Raising subplatysmal flaps. C. Dissection of middle thyroid vein. D. Dissection of the superior pole vessels, which should be individually ligated. E. Dissection at | Surgery_Schwartz. are reapproximated in the midline. The platysma is approximated in a similar fashion. The skin can be closed with subcuticular sutures or clips.Nerve Monitoring Intraoperative RLN and external laryngeal nerve monitoring techniques are being increasingly used during thyroid and parathyroid surgery. Both continuous monitoring using endotracheal tube electrodes and intermittent monitor-ing by periodic stimulation and laryngeal palpation are used. Many published studies have established the feasibility of nerve monitoring; however, none were able to show that the technique equivocally reduces nerve injury (particularly by experienced Brunicardi_Ch38_p1625-p1704.indd 165801/03/19 11:21 AM 1659THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-22. Conduct of thyroidectomy. A. Correct placement of thyroidectomy incision. B. Raising subplatysmal flaps. C. Dissection of middle thyroid vein. D. Dissection of the superior pole vessels, which should be individually ligated. E. Dissection at |
Surgery_Schwartz_10935 | Surgery_Schwartz | of thyroidectomy incision. B. Raising subplatysmal flaps. C. Dissection of middle thyroid vein. D. Dissection of the superior pole vessels, which should be individually ligated. E. Dissection at the ligament of Berry. Note small artery and vein within the ligament and the recurrent laryngeal nerve coursing laterally. F. Endoscopic thyroidectomy via axillary incisions. m. = muscle; n. = nerve; v. = vein.IncorrectCricoid cartilageCorrectAPlatysmaCauteryFive straight clamps on dermisBMiddle thyroid v.CCricothyroid m.External branch ofsuperior laryngeal n.Superior thyroid vesselsDBrunicardi_Ch38_p1625-p1704.indd 165901/03/19 11:21 AM 1660SPECIFIC CONSIDERATIONSPART IISmall artery & veinin ligament of BerryRecurrent laryngeal n.ThyroidEFFigure 38-22. (Continued)surgeons and especially when the RLN is routinely visually identified) until recently. In 2009, Barczynski and colleagues65 were the first to demonstrate in their prospective randomized trial with 2000 nerves at risk that | Surgery_Schwartz. of thyroidectomy incision. B. Raising subplatysmal flaps. C. Dissection of middle thyroid vein. D. Dissection of the superior pole vessels, which should be individually ligated. E. Dissection at the ligament of Berry. Note small artery and vein within the ligament and the recurrent laryngeal nerve coursing laterally. F. Endoscopic thyroidectomy via axillary incisions. m. = muscle; n. = nerve; v. = vein.IncorrectCricoid cartilageCorrectAPlatysmaCauteryFive straight clamps on dermisBMiddle thyroid v.CCricothyroid m.External branch ofsuperior laryngeal n.Superior thyroid vesselsDBrunicardi_Ch38_p1625-p1704.indd 165901/03/19 11:21 AM 1660SPECIFIC CONSIDERATIONSPART IISmall artery & veinin ligament of BerryRecurrent laryngeal n.ThyroidEFFigure 38-22. (Continued)surgeons and especially when the RLN is routinely visually identified) until recently. In 2009, Barczynski and colleagues65 were the first to demonstrate in their prospective randomized trial with 2000 nerves at risk that |
Surgery_Schwartz_10936 | Surgery_Schwartz | when the RLN is routinely visually identified) until recently. In 2009, Barczynski and colleagues65 were the first to demonstrate in their prospective randomized trial with 2000 nerves at risk that neuromonitoring was asso-ciated with a statistically significant improvement in transient RLN injury rates when compared to the practice of visualiza-tion of the nerve alone and particularly in patients at higher risk of nerve injury. Of note, there was no difference in permanent RLN injury rates, and a later meta-analysis of all the published studies also failed to show a protective effect of neuromonitor-ing. Despite conflicting data, the technology has become widely adopted. The current ATA guidelines recommend that intraop-erative neural stimulation may be used to facilitate nerve iden-tification of the RLN and confirm its function, especially prior to proceeding with contralateral thyroidectomy.Minimally Invasive Approaches Several approaches to minimally invasive thyroidectomy have | Surgery_Schwartz. when the RLN is routinely visually identified) until recently. In 2009, Barczynski and colleagues65 were the first to demonstrate in their prospective randomized trial with 2000 nerves at risk that neuromonitoring was asso-ciated with a statistically significant improvement in transient RLN injury rates when compared to the practice of visualiza-tion of the nerve alone and particularly in patients at higher risk of nerve injury. Of note, there was no difference in permanent RLN injury rates, and a later meta-analysis of all the published studies also failed to show a protective effect of neuromonitor-ing. Despite conflicting data, the technology has become widely adopted. The current ATA guidelines recommend that intraop-erative neural stimulation may be used to facilitate nerve iden-tification of the RLN and confirm its function, especially prior to proceeding with contralateral thyroidectomy.Minimally Invasive Approaches Several approaches to minimally invasive thyroidectomy have |
Surgery_Schwartz_10937 | Surgery_Schwartz | of the RLN and confirm its function, especially prior to proceeding with contralateral thyroidectomy.Minimally Invasive Approaches Several approaches to minimally invasive thyroidectomy have been described. Miniincision procedures use a small, 3-cm incision with no flap creation and minimal dissection to deliver the thyroid into the wound and then perform the pretracheal and paratracheal dissec-tion. Video assistance can be used to improve the visualization Brunicardi_Ch38_p1625-p1704.indd 166001/03/19 11:21 AM 1661THYROID, PARATHYROID, AND ADRENALCHAPTER 38via the small incision. Totally endoscopic approaches also have been described, via the supraclavicular, anterior chest, axillary, and breast approach. The axillary, anterior chest, and breast approaches eliminate the skin incision in the neck but are more invasive. The endoscopic approaches can also be performed with the assistance of robotic techniques. More recently, there have been studies of transoral robotic-assisted | Surgery_Schwartz. of the RLN and confirm its function, especially prior to proceeding with contralateral thyroidectomy.Minimally Invasive Approaches Several approaches to minimally invasive thyroidectomy have been described. Miniincision procedures use a small, 3-cm incision with no flap creation and minimal dissection to deliver the thyroid into the wound and then perform the pretracheal and paratracheal dissec-tion. Video assistance can be used to improve the visualization Brunicardi_Ch38_p1625-p1704.indd 166001/03/19 11:21 AM 1661THYROID, PARATHYROID, AND ADRENALCHAPTER 38via the small incision. Totally endoscopic approaches also have been described, via the supraclavicular, anterior chest, axillary, and breast approach. The axillary, anterior chest, and breast approaches eliminate the skin incision in the neck but are more invasive. The endoscopic approaches can also be performed with the assistance of robotic techniques. More recently, there have been studies of transoral robotic-assisted |
Surgery_Schwartz_10938 | Surgery_Schwartz | in the neck but are more invasive. The endoscopic approaches can also be performed with the assistance of robotic techniques. More recently, there have been studies of transoral robotic-assisted thyroidectomy in which the thyroid is approached through the oral cavity.66 These methods are feasible, but clear benefits over the “tradi-tional” open approach via small neck incisions have not been established.4Typically, endoscopic thyroidectomies are performed under general anesthesia. For the axillary approach, a 30-mm skin incision is made in the axilla, and 12-mm and 5-mm trocars are inserted through this incision (Fig. 38-22F). An additional 5-mm trocar is inserted adjacent to the incision. For the anterior chest approach, a 12-mm skin incision is made in the skin of the anterior chest approximately 3 to 5 cm below the border of the ipsilateral clavicle. Two additional 5-mm trocars are inserted by endoscopic guidance below the ipsilateral clavicle, and carbon dioxide (CO2) is then | Surgery_Schwartz. in the neck but are more invasive. The endoscopic approaches can also be performed with the assistance of robotic techniques. More recently, there have been studies of transoral robotic-assisted thyroidectomy in which the thyroid is approached through the oral cavity.66 These methods are feasible, but clear benefits over the “tradi-tional” open approach via small neck incisions have not been established.4Typically, endoscopic thyroidectomies are performed under general anesthesia. For the axillary approach, a 30-mm skin incision is made in the axilla, and 12-mm and 5-mm trocars are inserted through this incision (Fig. 38-22F). An additional 5-mm trocar is inserted adjacent to the incision. For the anterior chest approach, a 12-mm skin incision is made in the skin of the anterior chest approximately 3 to 5 cm below the border of the ipsilateral clavicle. Two additional 5-mm trocars are inserted by endoscopic guidance below the ipsilateral clavicle, and carbon dioxide (CO2) is then |
Surgery_Schwartz_10939 | Surgery_Schwartz | approximately 3 to 5 cm below the border of the ipsilateral clavicle. Two additional 5-mm trocars are inserted by endoscopic guidance below the ipsilateral clavicle, and carbon dioxide (CO2) is then insufflated up to a pressure of 4 mmHg to facilitate creation of a working space. The anterior border of the sternocleidomastoid muscle is then separated from the ster-nohyoid muscle to expose the sternothyroid muscle. The thy-roid gland is exposed by splitting the sternothyroid muscle. The lower pole is retracted upward and dissected from the adipose tissue to identify the RLN. As the RLN is exposed, Berry’s liga-ment is exposed and incised with a 5-mm clip or laparoscopic coagulating shears. The upper pole of the thyroid gland is sepa-rated from the cricothyroid muscle, and the external branch of the superior laryngeal nerve can be identified during this maneu-ver. The upper pole of the thyroid gland then is dissected free.Surgical Removal of Intrathoracic Goiter A goiter is consid-ered | Surgery_Schwartz. approximately 3 to 5 cm below the border of the ipsilateral clavicle. Two additional 5-mm trocars are inserted by endoscopic guidance below the ipsilateral clavicle, and carbon dioxide (CO2) is then insufflated up to a pressure of 4 mmHg to facilitate creation of a working space. The anterior border of the sternocleidomastoid muscle is then separated from the ster-nohyoid muscle to expose the sternothyroid muscle. The thy-roid gland is exposed by splitting the sternothyroid muscle. The lower pole is retracted upward and dissected from the adipose tissue to identify the RLN. As the RLN is exposed, Berry’s liga-ment is exposed and incised with a 5-mm clip or laparoscopic coagulating shears. The upper pole of the thyroid gland is sepa-rated from the cricothyroid muscle, and the external branch of the superior laryngeal nerve can be identified during this maneu-ver. The upper pole of the thyroid gland then is dissected free.Surgical Removal of Intrathoracic Goiter A goiter is consid-ered |
Surgery_Schwartz_10940 | Surgery_Schwartz | of the superior laryngeal nerve can be identified during this maneu-ver. The upper pole of the thyroid gland then is dissected free.Surgical Removal of Intrathoracic Goiter A goiter is consid-ered mediastinal if at least 50% of the thyroid tissue is located intrathoracically. Mediastinal goiters can be primary or second-ary. Primary mediastinal goiters constitute approximately 1% of all mediastinal goiters and arise from accessory (ectopic) thy-roid tissue located in the chest. These goiters are supplied by intrathoracic blood vessels and do not have any connection to thyroid tissue in the neck. The vast majority of mediastinal goi-ters are, however, secondary mediastinal goiters that arise from downward extension of cervical thyroid tissue along the fascial planes of the neck and derive their blood supply from the supe-rior and inferior thyroid arteries. Virtually all intrathoracic goi-ters can be removed via a cervical incision. Patients who have (a) invasive thyroid cancers, (b) | Surgery_Schwartz. of the superior laryngeal nerve can be identified during this maneu-ver. The upper pole of the thyroid gland then is dissected free.Surgical Removal of Intrathoracic Goiter A goiter is consid-ered mediastinal if at least 50% of the thyroid tissue is located intrathoracically. Mediastinal goiters can be primary or second-ary. Primary mediastinal goiters constitute approximately 1% of all mediastinal goiters and arise from accessory (ectopic) thy-roid tissue located in the chest. These goiters are supplied by intrathoracic blood vessels and do not have any connection to thyroid tissue in the neck. The vast majority of mediastinal goi-ters are, however, secondary mediastinal goiters that arise from downward extension of cervical thyroid tissue along the fascial planes of the neck and derive their blood supply from the supe-rior and inferior thyroid arteries. Virtually all intrathoracic goi-ters can be removed via a cervical incision. Patients who have (a) invasive thyroid cancers, (b) |
Surgery_Schwartz_10941 | Surgery_Schwartz | their blood supply from the supe-rior and inferior thyroid arteries. Virtually all intrathoracic goi-ters can be removed via a cervical incision. Patients who have (a) invasive thyroid cancers, (b) had previous thyroid operations and may have developed parasitic mediastinal vessels, or (c) pri-mary mediastinal goiters with no thyroid tissue in the neck may require a median sternotomy for removal.49 The chest, however, should be prepared in most cases in the event it is necessary to perform a median sternotomy to control mediastinal bleeding or completely remove an unsuspected invasive cancer. The goiter is approached via a neck incision. The superior pole vessels and the middle thyroid veins are identified and ligated first. Early division of the isthmus helps with subsequent mobilization of the substernal goiter from beneath the sternum. Placement of large 1-0 or 2-0 sutures deep into the goiter, when necessary, helps deliver it. For patients in whom thyroid cancer is suspected or | Surgery_Schwartz. their blood supply from the supe-rior and inferior thyroid arteries. Virtually all intrathoracic goi-ters can be removed via a cervical incision. Patients who have (a) invasive thyroid cancers, (b) had previous thyroid operations and may have developed parasitic mediastinal vessels, or (c) pri-mary mediastinal goiters with no thyroid tissue in the neck may require a median sternotomy for removal.49 The chest, however, should be prepared in most cases in the event it is necessary to perform a median sternotomy to control mediastinal bleeding or completely remove an unsuspected invasive cancer. The goiter is approached via a neck incision. The superior pole vessels and the middle thyroid veins are identified and ligated first. Early division of the isthmus helps with subsequent mobilization of the substernal goiter from beneath the sternum. Placement of large 1-0 or 2-0 sutures deep into the goiter, when necessary, helps deliver it. For patients in whom thyroid cancer is suspected or |
Surgery_Schwartz_10942 | Surgery_Schwartz | of the substernal goiter from beneath the sternum. Placement of large 1-0 or 2-0 sutures deep into the goiter, when necessary, helps deliver it. For patients in whom thyroid cancer is suspected or demonstrated in an intrathoracic gland, attempts should be made to avoid rupture of the thyroid capsule. When sternotomy is indicated, the sternum usually should be divided to the level of the third intercostal space and then laterally on one side at the space between the third and fourth ribs (Fig. 38-23).Central and Lateral Neck Dissection for Nodal Metastases Central compartment (medial to the carotid sheath) lymph nodes frequently are involved in patients with papillary, medullary, and Hürthle cell carcinomas and should be removed at the time of thyroidectomy, preserving the RLNs and parathyroid glands. Central neck dissection is particularly important in patients with medullary and Hürthle cell carcinoma because of the high fre-quency of microscopic tumor spread and because these | Surgery_Schwartz. of the substernal goiter from beneath the sternum. Placement of large 1-0 or 2-0 sutures deep into the goiter, when necessary, helps deliver it. For patients in whom thyroid cancer is suspected or demonstrated in an intrathoracic gland, attempts should be made to avoid rupture of the thyroid capsule. When sternotomy is indicated, the sternum usually should be divided to the level of the third intercostal space and then laterally on one side at the space between the third and fourth ribs (Fig. 38-23).Central and Lateral Neck Dissection for Nodal Metastases Central compartment (medial to the carotid sheath) lymph nodes frequently are involved in patients with papillary, medullary, and Hürthle cell carcinomas and should be removed at the time of thyroidectomy, preserving the RLNs and parathyroid glands. Central neck dissection is particularly important in patients with medullary and Hürthle cell carcinoma because of the high fre-quency of microscopic tumor spread and because these |
Surgery_Schwartz_10943 | Surgery_Schwartz | glands. Central neck dissection is particularly important in patients with medullary and Hürthle cell carcinoma because of the high fre-quency of microscopic tumor spread and because these tumors cannot be ablated with 131I. An ipsilateral modified radical neck dissection is indicated in the presence of palpable cervical lymph nodes or prophylactically in some patients with medul-lary carcinoma.A modified radical (functional) neck dissection can be per-formed via the cervical incision used for thyroidectomy, which can be extended laterally (Fig. 38-24A) to the anterior margin of the trapezius muscle. The procedure involves removal of all fibro-fatty tissue along the internal jugular vein (levels II, III, and IV) and the posterior triangle (level V). In contrast to a radical neck dissection, the internal jugular vein, the spinal accessory nerve, the cervical sensory nerves, and the sternoclei-domastoid muscle are preserved unless they are adherent to or invaded by tumor. The procedure | Surgery_Schwartz. glands. Central neck dissection is particularly important in patients with medullary and Hürthle cell carcinoma because of the high fre-quency of microscopic tumor spread and because these tumors cannot be ablated with 131I. An ipsilateral modified radical neck dissection is indicated in the presence of palpable cervical lymph nodes or prophylactically in some patients with medul-lary carcinoma.A modified radical (functional) neck dissection can be per-formed via the cervical incision used for thyroidectomy, which can be extended laterally (Fig. 38-24A) to the anterior margin of the trapezius muscle. The procedure involves removal of all fibro-fatty tissue along the internal jugular vein (levels II, III, and IV) and the posterior triangle (level V). In contrast to a radical neck dissection, the internal jugular vein, the spinal accessory nerve, the cervical sensory nerves, and the sternoclei-domastoid muscle are preserved unless they are adherent to or invaded by tumor. The procedure |
Surgery_Schwartz_10944 | Surgery_Schwartz | the internal jugular vein, the spinal accessory nerve, the cervical sensory nerves, and the sternoclei-domastoid muscle are preserved unless they are adherent to or invaded by tumor. The procedure begins by opening the plane between the strap muscles medially and the sternocleidomas-toid muscle laterally. The anterior belly of the omohyoid muscle is retracted laterally, and the dissection is carried posteriorly until the carotid sheath is reached. The internal jugular vein is retracted medially with a vein retractor and the fibro-fatty tissue and lymph nodes are dissected away from it by a combination of sharp and blunt dissection. The lateral dissection is carried along the posterior border of the sternocleidomastoid muscle, remov-ing the tissue from the posterior triangle. The deep dissection plane is the anterior scalenus muscle, the phrenic nerve, the bra-chial plexus, and the medial scalenus muscle. The phrenic nerve is preserved on the scalenus anterior muscle, as are the | Surgery_Schwartz. the internal jugular vein, the spinal accessory nerve, the cervical sensory nerves, and the sternoclei-domastoid muscle are preserved unless they are adherent to or invaded by tumor. The procedure begins by opening the plane between the strap muscles medially and the sternocleidomas-toid muscle laterally. The anterior belly of the omohyoid muscle is retracted laterally, and the dissection is carried posteriorly until the carotid sheath is reached. The internal jugular vein is retracted medially with a vein retractor and the fibro-fatty tissue and lymph nodes are dissected away from it by a combination of sharp and blunt dissection. The lateral dissection is carried along the posterior border of the sternocleidomastoid muscle, remov-ing the tissue from the posterior triangle. The deep dissection plane is the anterior scalenus muscle, the phrenic nerve, the bra-chial plexus, and the medial scalenus muscle. The phrenic nerve is preserved on the scalenus anterior muscle, as are the |
Surgery_Schwartz_10945 | Surgery_Schwartz | dissection plane is the anterior scalenus muscle, the phrenic nerve, the bra-chial plexus, and the medial scalenus muscle. The phrenic nerve is preserved on the scalenus anterior muscle, as are the cervical sensory nerves in most patients (Fig. 38-24B). Dissection along the spinal accessory nerve superiorly is most important because this is a frequent site of metastatic disease.123Figure 38-23. Conduct of thyroidectomy. Incisions for a partial sternotomy.Brunicardi_Ch38_p1625-p1704.indd 166101/03/19 11:21 AM 1662SPECIFIC CONSIDERATIONSPART IIComplications of Thyroid Surgery Nerves, parathyroids, and surrounding structures are all at risk of injury during thyroidec-tomy. Injury to the RLN may occur by severance, ligation, or traction, but should occur in <1% of patients undergoing thy-roidectomy by experienced surgeons. The RLN is most vulner-able to injury during the last 2 to 3 cm of its course, but also can be damaged if the surgeon is not alert to the possibility of nerve | Surgery_Schwartz. dissection plane is the anterior scalenus muscle, the phrenic nerve, the bra-chial plexus, and the medial scalenus muscle. The phrenic nerve is preserved on the scalenus anterior muscle, as are the cervical sensory nerves in most patients (Fig. 38-24B). Dissection along the spinal accessory nerve superiorly is most important because this is a frequent site of metastatic disease.123Figure 38-23. Conduct of thyroidectomy. Incisions for a partial sternotomy.Brunicardi_Ch38_p1625-p1704.indd 166101/03/19 11:21 AM 1662SPECIFIC CONSIDERATIONSPART IIComplications of Thyroid Surgery Nerves, parathyroids, and surrounding structures are all at risk of injury during thyroidec-tomy. Injury to the RLN may occur by severance, ligation, or traction, but should occur in <1% of patients undergoing thy-roidectomy by experienced surgeons. The RLN is most vulner-able to injury during the last 2 to 3 cm of its course, but also can be damaged if the surgeon is not alert to the possibility of nerve |
Surgery_Schwartz_10946 | Surgery_Schwartz | thy-roidectomy by experienced surgeons. The RLN is most vulner-able to injury during the last 2 to 3 cm of its course, but also can be damaged if the surgeon is not alert to the possibility of nerve branches and the presence of a nonrecurrent nerve, par-ticularly on the right side. If the injury is recognized intraopera-tively, most surgeons advocate primary reapproximation of the perineurium using nonabsorbable sutures. Approximately 20% of patients are at risk of injury to the external branches of the 123McFee incisionABSpinal accessory n.Phrenic n.Vagus n.Scalenusanticus m.LymphnodesCarotid a. Internaljugular v.Figure 38-24. Conduct of neck dissection. A. Incisions for modified radical neck dissection. B. Anatomic relations of structures identified during a modified radical neck dissection. a. = artery; m. = muscle; n. = nerve.Brunicardi_Ch38_p1625-p1704.indd 166201/03/19 11:21 AM 1663THYROID, PARATHYROID, AND ADRENALCHAPTER 38superior laryngeal nerve, especially if superior | Surgery_Schwartz. thy-roidectomy by experienced surgeons. The RLN is most vulner-able to injury during the last 2 to 3 cm of its course, but also can be damaged if the surgeon is not alert to the possibility of nerve branches and the presence of a nonrecurrent nerve, par-ticularly on the right side. If the injury is recognized intraopera-tively, most surgeons advocate primary reapproximation of the perineurium using nonabsorbable sutures. Approximately 20% of patients are at risk of injury to the external branches of the 123McFee incisionABSpinal accessory n.Phrenic n.Vagus n.Scalenusanticus m.LymphnodesCarotid a. Internaljugular v.Figure 38-24. Conduct of neck dissection. A. Incisions for modified radical neck dissection. B. Anatomic relations of structures identified during a modified radical neck dissection. a. = artery; m. = muscle; n. = nerve.Brunicardi_Ch38_p1625-p1704.indd 166201/03/19 11:21 AM 1663THYROID, PARATHYROID, AND ADRENALCHAPTER 38superior laryngeal nerve, especially if superior |
Surgery_Schwartz_10947 | Surgery_Schwartz | a. = artery; m. = muscle; n. = nerve.Brunicardi_Ch38_p1625-p1704.indd 166201/03/19 11:21 AM 1663THYROID, PARATHYROID, AND ADRENALCHAPTER 38superior laryngeal nerve, especially if superior pole vessels are ligated en masse. The cervical sympathetic trunk is at risk of injury in invasive thyroid cancers and retroesophageal goiters and may result in Horner’s syndrome. Transient hypocalcemia (from surgical injury or inadvertent removal of parathyroid tis-sue) has been reported in up to 50% of cases, but permanent hypoparathyroidism occurs <2% of the time. Postoperative hypocalcemia is more likely in patients who undergo concomi-tant thyroidectomy and central and lateral neck dissection and in patients with Graves’ disease. Postoperative hematomas or bleeding may also complicate thyroidectomies and rarely neces-sitate emergency reoperation to evacuate the hematoma. Bilat-eral vocal cord dysfunction with airway compromises requires immediate reintubation and tracheostomy. Seromas may | Surgery_Schwartz. a. = artery; m. = muscle; n. = nerve.Brunicardi_Ch38_p1625-p1704.indd 166201/03/19 11:21 AM 1663THYROID, PARATHYROID, AND ADRENALCHAPTER 38superior laryngeal nerve, especially if superior pole vessels are ligated en masse. The cervical sympathetic trunk is at risk of injury in invasive thyroid cancers and retroesophageal goiters and may result in Horner’s syndrome. Transient hypocalcemia (from surgical injury or inadvertent removal of parathyroid tis-sue) has been reported in up to 50% of cases, but permanent hypoparathyroidism occurs <2% of the time. Postoperative hypocalcemia is more likely in patients who undergo concomi-tant thyroidectomy and central and lateral neck dissection and in patients with Graves’ disease. Postoperative hematomas or bleeding may also complicate thyroidectomies and rarely neces-sitate emergency reoperation to evacuate the hematoma. Bilat-eral vocal cord dysfunction with airway compromises requires immediate reintubation and tracheostomy. Seromas may |
Surgery_Schwartz_10948 | Surgery_Schwartz | and rarely neces-sitate emergency reoperation to evacuate the hematoma. Bilat-eral vocal cord dysfunction with airway compromises requires immediate reintubation and tracheostomy. Seromas may need aspiration to relieve patient discomfort. Wound cellulitis and infection and injury to surrounding structures, such as the carotid artery, jugular vein, and esophagus, are infrequent.PARATHYROIDHistorical BackgroundIn 1849, the curator of the London Zoological Gardens, Sir Richard Owen, provided the first accurate description of the normal parathyroid gland after autopsy examination of an Indian rhinoceros. However, human parathyroids were not grossly and microscopically described until 1879 by Ivar Sandström, a med-ical student in Uppsala, Sweden. He suggested that these glands be named the glandulae parathyroideae, although their function was not known.The association of HPT and the bone disease osteitis fibrosa cystica (described by von Recklinghausen) was recog-nized in 1903. Calcium | Surgery_Schwartz. and rarely neces-sitate emergency reoperation to evacuate the hematoma. Bilat-eral vocal cord dysfunction with airway compromises requires immediate reintubation and tracheostomy. Seromas may need aspiration to relieve patient discomfort. Wound cellulitis and infection and injury to surrounding structures, such as the carotid artery, jugular vein, and esophagus, are infrequent.PARATHYROIDHistorical BackgroundIn 1849, the curator of the London Zoological Gardens, Sir Richard Owen, provided the first accurate description of the normal parathyroid gland after autopsy examination of an Indian rhinoceros. However, human parathyroids were not grossly and microscopically described until 1879 by Ivar Sandström, a med-ical student in Uppsala, Sweden. He suggested that these glands be named the glandulae parathyroideae, although their function was not known.The association of HPT and the bone disease osteitis fibrosa cystica (described by von Recklinghausen) was recog-nized in 1903. Calcium |
Surgery_Schwartz_10949 | Surgery_Schwartz | glandulae parathyroideae, although their function was not known.The association of HPT and the bone disease osteitis fibrosa cystica (described by von Recklinghausen) was recog-nized in 1903. Calcium measurement became possible in 1909, and the association between serum calcium levels and the para-thyroid glands was established. The first successful parathyroid-ectomy was performed in 1925 by Felix Mandl on a 38-year-old man who had severe bone pain secondary to advanced osteitis fibrosa cystica. The patient’s condition dramatically improved after the operation, and he lived for another 7 years before dying of recurrent HPT or renal failure. In 1926, the first parathyroid operation was performed at Massachusetts General Hospital. Edward Churchill, assisted by an intern named Oliver Cope, operated on the famous sea captain Charles Martell for severe primary HPT (PHPT). It was not until his seventh operation, which included total thyroidectomy, that an ectopic adenoma was found | Surgery_Schwartz. glandulae parathyroideae, although their function was not known.The association of HPT and the bone disease osteitis fibrosa cystica (described by von Recklinghausen) was recog-nized in 1903. Calcium measurement became possible in 1909, and the association between serum calcium levels and the para-thyroid glands was established. The first successful parathyroid-ectomy was performed in 1925 by Felix Mandl on a 38-year-old man who had severe bone pain secondary to advanced osteitis fibrosa cystica. The patient’s condition dramatically improved after the operation, and he lived for another 7 years before dying of recurrent HPT or renal failure. In 1926, the first parathyroid operation was performed at Massachusetts General Hospital. Edward Churchill, assisted by an intern named Oliver Cope, operated on the famous sea captain Charles Martell for severe primary HPT (PHPT). It was not until his seventh operation, which included total thyroidectomy, that an ectopic adenoma was found |
Surgery_Schwartz_10950 | Surgery_Schwartz | Cope, operated on the famous sea captain Charles Martell for severe primary HPT (PHPT). It was not until his seventh operation, which included total thyroidectomy, that an ectopic adenoma was found substernally. Unfortunately, Captain Martell died 6 weeks later, likely due to laryngeal spasm and complications of renal stones and ureteral obstruction. The first successful para-thyroidectomy for HPT in the United States was performed on a 56-year-old woman in 1928 by Isaac Y. Olch at the Barnes Hospital in St. Louis, Missouri. At operation, a parathyroid ade-noma was found attached to the left lower lobe of the thyroid gland. Postoperatively, the patient developed tetany, requiring lifelong supplemental calcium.EmbryologyIn humans, the superior parathyroid glands are derived from the fourth branchial pouch, which also gives rise to the thyroid gland. The third branchial pouches give rise to the inferior para-thyroid glands and the thymus (Fig. 38-25). The parathyroids remain closely | Surgery_Schwartz. Cope, operated on the famous sea captain Charles Martell for severe primary HPT (PHPT). It was not until his seventh operation, which included total thyroidectomy, that an ectopic adenoma was found substernally. Unfortunately, Captain Martell died 6 weeks later, likely due to laryngeal spasm and complications of renal stones and ureteral obstruction. The first successful para-thyroidectomy for HPT in the United States was performed on a 56-year-old woman in 1928 by Isaac Y. Olch at the Barnes Hospital in St. Louis, Missouri. At operation, a parathyroid ade-noma was found attached to the left lower lobe of the thyroid gland. Postoperatively, the patient developed tetany, requiring lifelong supplemental calcium.EmbryologyIn humans, the superior parathyroid glands are derived from the fourth branchial pouch, which also gives rise to the thyroid gland. The third branchial pouches give rise to the inferior para-thyroid glands and the thymus (Fig. 38-25). The parathyroids remain closely |
Surgery_Schwartz_10951 | Surgery_Schwartz | branchial pouch, which also gives rise to the thyroid gland. The third branchial pouches give rise to the inferior para-thyroid glands and the thymus (Fig. 38-25). The parathyroids remain closely associated with their respective branchial pouch derivatives. The position of normal superior parathyroid glands is more consistent, with 80% of these glands being found near the posterior aspect of the upper and middle thyroid lobes, at the level of the cricoid cartilage. Approximately 1% of normal upper glands may be found in the paraesophageal or retro-esophageal space. Enlarged superior glands may descend in the tracheoesophageal groove and come to lie caudal to the inferior glands. Truly ectopic superior parathyroid glands are rare, but they may be found in the middle or posterior mediastinum or in the aortopulmonary window.51 As the embryo matures, the thy-mus and inferior parathyroids migrate together caudally in the neck. The most common location for inferior glands is within a | Surgery_Schwartz. branchial pouch, which also gives rise to the thyroid gland. The third branchial pouches give rise to the inferior para-thyroid glands and the thymus (Fig. 38-25). The parathyroids remain closely associated with their respective branchial pouch derivatives. The position of normal superior parathyroid glands is more consistent, with 80% of these glands being found near the posterior aspect of the upper and middle thyroid lobes, at the level of the cricoid cartilage. Approximately 1% of normal upper glands may be found in the paraesophageal or retro-esophageal space. Enlarged superior glands may descend in the tracheoesophageal groove and come to lie caudal to the inferior glands. Truly ectopic superior parathyroid glands are rare, but they may be found in the middle or posterior mediastinum or in the aortopulmonary window.51 As the embryo matures, the thy-mus and inferior parathyroids migrate together caudally in the neck. The most common location for inferior glands is within a |
Surgery_Schwartz_10952 | Surgery_Schwartz | or in the aortopulmonary window.51 As the embryo matures, the thy-mus and inferior parathyroids migrate together caudally in the neck. The most common location for inferior glands is within a distance of 1 cm from a point centered where the inferior thyroid artery and RLN cross. Approximately 15% of inferior glands Parathyroid IIIForamen caecumThyroglossal ductMedian thyroidThymusTracheaEsophagusFifth branchialpouchFourthbranchialpouchThirdbranchialpouchParathyroid IVUltimobranchialbodyMedian thyroidLateralthyroid or ultimobranchial bodyEsophagusParathyroid IVParathyroid IIIThymusABFigure 38-25. Parathyroid embryology. Figure demonstrates a schematic view of the pharynx of an 8to 10-mm embryo (A) and locations of the thyroid, parathyroid, and thymic tissues in a 13to 14-mm embryo (B). The lower parathyroids are derived from the third branchial pouch and migrate with the thymus, whereas the upper parathyroids are derived from the fourth branchial pouch and lie in close proximity to the | Surgery_Schwartz. or in the aortopulmonary window.51 As the embryo matures, the thy-mus and inferior parathyroids migrate together caudally in the neck. The most common location for inferior glands is within a distance of 1 cm from a point centered where the inferior thyroid artery and RLN cross. Approximately 15% of inferior glands Parathyroid IIIForamen caecumThyroglossal ductMedian thyroidThymusTracheaEsophagusFifth branchialpouchFourthbranchialpouchThirdbranchialpouchParathyroid IVUltimobranchialbodyMedian thyroidLateralthyroid or ultimobranchial bodyEsophagusParathyroid IVParathyroid IIIThymusABFigure 38-25. Parathyroid embryology. Figure demonstrates a schematic view of the pharynx of an 8to 10-mm embryo (A) and locations of the thyroid, parathyroid, and thymic tissues in a 13to 14-mm embryo (B). The lower parathyroids are derived from the third branchial pouch and migrate with the thymus, whereas the upper parathyroids are derived from the fourth branchial pouch and lie in close proximity to the |
Surgery_Schwartz_10953 | Surgery_Schwartz | lower parathyroids are derived from the third branchial pouch and migrate with the thymus, whereas the upper parathyroids are derived from the fourth branchial pouch and lie in close proximity to the ultimobranchial bodies. (Reproduced with permission from Randolph G: Surgery of the Thyroid and Parathyroid Glands. Philadelphia, PA: Elsevier/Saunders; 2003.)Brunicardi_Ch38_p1625-p1704.indd 166301/03/19 11:21 AM 1664SPECIFIC CONSIDERATIONSPART IIare found in the thymus. The position of the inferior glands, however, tends to be more variable due to their longer migratory path. Undescended inferior glands may be found near the skull base, angle of the mandible, or superior to the upper parathyroid glands along with an undescended thymus. The frequency of intrathyroidal glands is about 2%.Anatomy and HistologyMost patients have four parathyroid glands. The superior glands usually are dorsal to the RLN at the level of the cricoid cartilage, whereas the inferior parathyroid glands are | Surgery_Schwartz. lower parathyroids are derived from the third branchial pouch and migrate with the thymus, whereas the upper parathyroids are derived from the fourth branchial pouch and lie in close proximity to the ultimobranchial bodies. (Reproduced with permission from Randolph G: Surgery of the Thyroid and Parathyroid Glands. Philadelphia, PA: Elsevier/Saunders; 2003.)Brunicardi_Ch38_p1625-p1704.indd 166301/03/19 11:21 AM 1664SPECIFIC CONSIDERATIONSPART IIare found in the thymus. The position of the inferior glands, however, tends to be more variable due to their longer migratory path. Undescended inferior glands may be found near the skull base, angle of the mandible, or superior to the upper parathyroid glands along with an undescended thymus. The frequency of intrathyroidal glands is about 2%.Anatomy and HistologyMost patients have four parathyroid glands. The superior glands usually are dorsal to the RLN at the level of the cricoid cartilage, whereas the inferior parathyroid glands are |
Surgery_Schwartz_10954 | Surgery_Schwartz | and HistologyMost patients have four parathyroid glands. The superior glands usually are dorsal to the RLN at the level of the cricoid cartilage, whereas the inferior parathyroid glands are located ventral to the nerve. Normal parathyroid glands are gray and semitransparent in newborns but appear golden yellow to light brown in adults. Parathyroid color depends on cellularity, fat content, and vas-cularity. Moreover, they often are embedded in and sometimes difficult to discern from surrounding fat. Normal parathyroid glands are located in loose tissue or fat and are ovoid. They measure up to 7 mm in size and weigh approximately 40 to 50 mg each. Parathyroid glands usually derive their blood supply from branches of the inferior thyroid artery, although branches from the superior thyroid artery supply at least 20% of upper glands. Branches from the thyroidea ima, and vessels to the trachea, esophagus, larynx, and mediastinum may also be found. The parathyroid glands drain | Surgery_Schwartz. and HistologyMost patients have four parathyroid glands. The superior glands usually are dorsal to the RLN at the level of the cricoid cartilage, whereas the inferior parathyroid glands are located ventral to the nerve. Normal parathyroid glands are gray and semitransparent in newborns but appear golden yellow to light brown in adults. Parathyroid color depends on cellularity, fat content, and vas-cularity. Moreover, they often are embedded in and sometimes difficult to discern from surrounding fat. Normal parathyroid glands are located in loose tissue or fat and are ovoid. They measure up to 7 mm in size and weigh approximately 40 to 50 mg each. Parathyroid glands usually derive their blood supply from branches of the inferior thyroid artery, although branches from the superior thyroid artery supply at least 20% of upper glands. Branches from the thyroidea ima, and vessels to the trachea, esophagus, larynx, and mediastinum may also be found. The parathyroid glands drain |
Surgery_Schwartz_10955 | Surgery_Schwartz | thyroid artery supply at least 20% of upper glands. Branches from the thyroidea ima, and vessels to the trachea, esophagus, larynx, and mediastinum may also be found. The parathyroid glands drain ipsilaterally by the superior, middle, and inferior thyroid veins.Akerström and colleagues,67 in an autopsy series of 503 cadavers, found four parathyroid glands in 84% of cases. Super-numerary glands were present in 13% of patients, most com-monly in the thymus. Only 3% of patients had less than four glands. Similar results were obtained in other dissection studies of 428 human subjects by Gilmour who reported a 6.7% inci-dence of supernumerary glands.68Histologically, parathyroid glands are composed of chief cells and oxyphil cells arranged in trabeculae, within a stroma composed primarily of adipose cells (Fig. 38-26). The parathy-roid glands of infants and children are composed mainly of chief cells, which produce parathyroid hormone (PTH). Acidophilic, mitochondria-rich oxyphil cells are | Surgery_Schwartz. thyroid artery supply at least 20% of upper glands. Branches from the thyroidea ima, and vessels to the trachea, esophagus, larynx, and mediastinum may also be found. The parathyroid glands drain ipsilaterally by the superior, middle, and inferior thyroid veins.Akerström and colleagues,67 in an autopsy series of 503 cadavers, found four parathyroid glands in 84% of cases. Super-numerary glands were present in 13% of patients, most com-monly in the thymus. Only 3% of patients had less than four glands. Similar results were obtained in other dissection studies of 428 human subjects by Gilmour who reported a 6.7% inci-dence of supernumerary glands.68Histologically, parathyroid glands are composed of chief cells and oxyphil cells arranged in trabeculae, within a stroma composed primarily of adipose cells (Fig. 38-26). The parathy-roid glands of infants and children are composed mainly of chief cells, which produce parathyroid hormone (PTH). Acidophilic, mitochondria-rich oxyphil cells are |
Surgery_Schwartz_10956 | Surgery_Schwartz | cells (Fig. 38-26). The parathy-roid glands of infants and children are composed mainly of chief cells, which produce parathyroid hormone (PTH). Acidophilic, mitochondria-rich oxyphil cells are derived from chief cells, can be seen around puberty, and increase in numbers in adult-hood. A third group of cells, known as water-clear cells, also are derived from chief cells, are present in small numbers, and are rich in glycogen. Although most oxyphil and water-clear Figure 38-26. Normal parathyroid histology showing chief cells interspersed with adipose cells.cells retain the ability to secrete PTH, their functional signifi-cance is not known.Parathyroid Physiology and Calcium HomeostasisCalcium is the most abundant cation in human beings and has several crucial functions. Extracellular calcium levels are 10,000-fold higher than intracellular levels, and both are tightly controlled. Extracellular calcium is important for excitationcontraction coupling in muscle tissues, synaptic | Surgery_Schwartz. cells (Fig. 38-26). The parathy-roid glands of infants and children are composed mainly of chief cells, which produce parathyroid hormone (PTH). Acidophilic, mitochondria-rich oxyphil cells are derived from chief cells, can be seen around puberty, and increase in numbers in adult-hood. A third group of cells, known as water-clear cells, also are derived from chief cells, are present in small numbers, and are rich in glycogen. Although most oxyphil and water-clear Figure 38-26. Normal parathyroid histology showing chief cells interspersed with adipose cells.cells retain the ability to secrete PTH, their functional signifi-cance is not known.Parathyroid Physiology and Calcium HomeostasisCalcium is the most abundant cation in human beings and has several crucial functions. Extracellular calcium levels are 10,000-fold higher than intracellular levels, and both are tightly controlled. Extracellular calcium is important for excitationcontraction coupling in muscle tissues, synaptic |
Surgery_Schwartz_10957 | Surgery_Schwartz | calcium levels are 10,000-fold higher than intracellular levels, and both are tightly controlled. Extracellular calcium is important for excitationcontraction coupling in muscle tissues, synaptic transmission in the nervous system, coagulation, and secretion of other hormones. Intracellular calcium is an important second messenger regulat-ing cell division, motility, membrane trafficking, and secretion. Calcium is absorbed from the small intestine in its inorganic form. Calcium fluxes in the steady state are depicted in Fig. 38-27.Extracellular calcium (900 mg) accounts for only 1% of the body’s calcium stores, the majority of which is sequestered in the skeletal system. Approximately 50% of the serum cal-cium is in the ionized form, which is the active component. The remainder is bound to albumin (40%) and organic anions such as phosphate and citrate (10%). The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized calcium levels range from 4.4 to | Surgery_Schwartz. calcium levels are 10,000-fold higher than intracellular levels, and both are tightly controlled. Extracellular calcium is important for excitationcontraction coupling in muscle tissues, synaptic transmission in the nervous system, coagulation, and secretion of other hormones. Intracellular calcium is an important second messenger regulat-ing cell division, motility, membrane trafficking, and secretion. Calcium is absorbed from the small intestine in its inorganic form. Calcium fluxes in the steady state are depicted in Fig. 38-27.Extracellular calcium (900 mg) accounts for only 1% of the body’s calcium stores, the majority of which is sequestered in the skeletal system. Approximately 50% of the serum cal-cium is in the ionized form, which is the active component. The remainder is bound to albumin (40%) and organic anions such as phosphate and citrate (10%). The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized calcium levels range from 4.4 to |
Surgery_Schwartz_10958 | Surgery_Schwartz | to albumin (40%) and organic anions such as phosphate and citrate (10%). The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized calcium levels range from 4.4 to 5.2 mg/dL (1.1 to 1.3 mmol/L). Both concentrations are tightly regulated. The total serum calcium level must always be considered in its rela-tionship to plasma protein levels, especially serum albumin. For each gram per deciliter of alteration of serum albumin above or below 4.0 mg/dL, there is a 0.8 mg/dL increase or decrease in protein-bound calcium and, thus, in total serum calcium levels. Total and, particularly, ionized calcium levels are influenced by various hormone systems.Parathyroid Hormone. The parathyroid cells rely on a G-protein–coupled membrane receptor, designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels69 (Fig. 38-28). PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, cat-echolamines, | Surgery_Schwartz. to albumin (40%) and organic anions such as phosphate and citrate (10%). The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized calcium levels range from 4.4 to 5.2 mg/dL (1.1 to 1.3 mmol/L). Both concentrations are tightly regulated. The total serum calcium level must always be considered in its rela-tionship to plasma protein levels, especially serum albumin. For each gram per deciliter of alteration of serum albumin above or below 4.0 mg/dL, there is a 0.8 mg/dL increase or decrease in protein-bound calcium and, thus, in total serum calcium levels. Total and, particularly, ionized calcium levels are influenced by various hormone systems.Parathyroid Hormone. The parathyroid cells rely on a G-protein–coupled membrane receptor, designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels69 (Fig. 38-28). PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, cat-echolamines, |
Surgery_Schwartz_10959 | Surgery_Schwartz | receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels69 (Fig. 38-28). PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, cat-echolamines, and hypomagnesemia. The PTH gene is located on chromosome 11. PTH is synthesized in the parathyroid gland as a precursor hormone preproPTH, which is cleaved first to pro-PTH and then to the final 84-amino-acid PTH. Secreted PTH has a half-life of 2 to 4 minutes. In the liver, PTH is metabolized into the active N-terminal component and the relatively inactive C-terminal fraction. The C-terminal component is excreted by the kidneys and accumulates in chronic renal failure.PTH functions to regulate calcium levels via its actions on three target organs, the bone, kidney, and gut. PTH increases the resorption of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation. At the kidney, calcium is primarily absorbed in concert with sodium in the proximal | Surgery_Schwartz. receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels69 (Fig. 38-28). PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, cat-echolamines, and hypomagnesemia. The PTH gene is located on chromosome 11. PTH is synthesized in the parathyroid gland as a precursor hormone preproPTH, which is cleaved first to pro-PTH and then to the final 84-amino-acid PTH. Secreted PTH has a half-life of 2 to 4 minutes. In the liver, PTH is metabolized into the active N-terminal component and the relatively inactive C-terminal fraction. The C-terminal component is excreted by the kidneys and accumulates in chronic renal failure.PTH functions to regulate calcium levels via its actions on three target organs, the bone, kidney, and gut. PTH increases the resorption of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation. At the kidney, calcium is primarily absorbed in concert with sodium in the proximal |
Surgery_Schwartz_10960 | Surgery_Schwartz | of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation. At the kidney, calcium is primarily absorbed in concert with sodium in the proximal convoluted tubule, but fine adjustments occur more distally. PTH acts to limit calcium excretion at the dis-tal convoluted tubule via an active transport mechanism. PTH also inhibits phosphate reabsorption (at the proximal convoluted tubule) and bicarbonate reabsorption. It also inhibits the Na+/H+ antiporter, which results in a mild metabolic acidosis in hyper-parathyroid states. PTH and hypophosphatemia also enhance 1-hydroxylation of 25-hydroxyvitamin D, which is responsible for its indirect effect of increasing intestinal calcium absorption.Calcitonin. Calcitonin is produced by thyroid C cells and func-tions as an antihypercalcemic hormone by inhibiting osteoclast-mediated bone resorption. Calcitonin production is stimulated Brunicardi_Ch38_p1625-p1704.indd 166401/03/19 11:21 AM | Surgery_Schwartz. of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation. At the kidney, calcium is primarily absorbed in concert with sodium in the proximal convoluted tubule, but fine adjustments occur more distally. PTH acts to limit calcium excretion at the dis-tal convoluted tubule via an active transport mechanism. PTH also inhibits phosphate reabsorption (at the proximal convoluted tubule) and bicarbonate reabsorption. It also inhibits the Na+/H+ antiporter, which results in a mild metabolic acidosis in hyper-parathyroid states. PTH and hypophosphatemia also enhance 1-hydroxylation of 25-hydroxyvitamin D, which is responsible for its indirect effect of increasing intestinal calcium absorption.Calcitonin. Calcitonin is produced by thyroid C cells and func-tions as an antihypercalcemic hormone by inhibiting osteoclast-mediated bone resorption. Calcitonin production is stimulated Brunicardi_Ch38_p1625-p1704.indd 166401/03/19 11:21 AM |
Surgery_Schwartz_10961 | Surgery_Schwartz | cells and func-tions as an antihypercalcemic hormone by inhibiting osteoclast-mediated bone resorption. Calcitonin production is stimulated Brunicardi_Ch38_p1625-p1704.indd 166401/03/19 11:21 AM 1665THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-27. Calcium balance and fluxes in a normal human. Solid arrows depict a direct effect, whereas dashed arrows depict an indirect effect. The thickness of the arrows is representative of the magnitude of the flux. ECF = extracellular fluid; PTH = parathyroid hormone; VIT. = vitamin. (Reproduced with permission from Felig P, Frohman L: Endocrinology and Metabolism. New York, NY: McGraw-Hill Education; 2001.)PTHPTHVIT. DECFCALCIUM900 mgKidneyUrine0.15 0.3 g900 1400 gBone0.25 0.5 g0.25 0.5 g0.25 0.5 g0.1 0.2 g0.4 1.5 g0.35 1.0 gVIT. DPTHby calcium and pentagastrin and also by catecholamines, chole-cystokinin, and glucagon. When administered intravenously to experimental animals, it produces hypocalcemia. At the kidney, calcitonin | Surgery_Schwartz. cells and func-tions as an antihypercalcemic hormone by inhibiting osteoclast-mediated bone resorption. Calcitonin production is stimulated Brunicardi_Ch38_p1625-p1704.indd 166401/03/19 11:21 AM 1665THYROID, PARATHYROID, AND ADRENALCHAPTER 38Figure 38-27. Calcium balance and fluxes in a normal human. Solid arrows depict a direct effect, whereas dashed arrows depict an indirect effect. The thickness of the arrows is representative of the magnitude of the flux. ECF = extracellular fluid; PTH = parathyroid hormone; VIT. = vitamin. (Reproduced with permission from Felig P, Frohman L: Endocrinology and Metabolism. New York, NY: McGraw-Hill Education; 2001.)PTHPTHVIT. DECFCALCIUM900 mgKidneyUrine0.15 0.3 g900 1400 gBone0.25 0.5 g0.25 0.5 g0.25 0.5 g0.1 0.2 g0.4 1.5 g0.35 1.0 gVIT. DPTHby calcium and pentagastrin and also by catecholamines, chole-cystokinin, and glucagon. When administered intravenously to experimental animals, it produces hypocalcemia. At the kidney, calcitonin |
Surgery_Schwartz_10962 | Surgery_Schwartz | calcium and pentagastrin and also by catecholamines, chole-cystokinin, and glucagon. When administered intravenously to experimental animals, it produces hypocalcemia. At the kidney, calcitonin increases phosphate excretion by inhibiting its reab-sorption. Calcitonin plays a minimal, if any, role in the regula-tion of calcium levels in humans. However, it is very useful as a marker of MTC and in treating acute hypercalcemic crisis.Vitamin D. Vitamin D refers to vitamin D2 and vitamin D3, both of which are produced by photolysis of naturally occurring ste-rol precursors. Vitamin D2 is available commercially in pharma-ceutical preparations, whereas vitamin D3 is the most important physiologic compound and is produced from 7-dehydrocholes-terol, which is found in the skin. Vitamin D is metabolized in the liver to its primary circulating form, 25-hydroxyvitamin D. Further hydroxylation in the kidney results in 1,25-dihydroxy vitamin D, which is the most metabolically active form of | Surgery_Schwartz. calcium and pentagastrin and also by catecholamines, chole-cystokinin, and glucagon. When administered intravenously to experimental animals, it produces hypocalcemia. At the kidney, calcitonin increases phosphate excretion by inhibiting its reab-sorption. Calcitonin plays a minimal, if any, role in the regula-tion of calcium levels in humans. However, it is very useful as a marker of MTC and in treating acute hypercalcemic crisis.Vitamin D. Vitamin D refers to vitamin D2 and vitamin D3, both of which are produced by photolysis of naturally occurring ste-rol precursors. Vitamin D2 is available commercially in pharma-ceutical preparations, whereas vitamin D3 is the most important physiologic compound and is produced from 7-dehydrocholes-terol, which is found in the skin. Vitamin D is metabolized in the liver to its primary circulating form, 25-hydroxyvitamin D. Further hydroxylation in the kidney results in 1,25-dihydroxy vitamin D, which is the most metabolically active form of |
Surgery_Schwartz_10963 | Surgery_Schwartz | in the liver to its primary circulating form, 25-hydroxyvitamin D. Further hydroxylation in the kidney results in 1,25-dihydroxy vitamin D, which is the most metabolically active form of vitamin D. Vitamin D stimulates the absorption of calcium and phosphate from the gut and the resorption of calcium from the bone.HyperparathyroidismHyperfunction of the parathyroid glands may be classified as primary, secondary, or tertiary. PHPT arises from increased PTH production from abnormal parathyroid glands and results from a disturbance of normal feedback control exerted by serum calcium. Elevated PTH levels may also occur as a compensa-tory response to hypocalcemic states resulting from chronic renal failure or GI malabsorption of calcium. This secondary HPT can be reversed by correction of the underlying problem (e.g., kidney transplantation for chronic renal failure). However, chronically stimulated glands may occasionally become autono-mous, resulting in persistence or recurrence of | Surgery_Schwartz. in the liver to its primary circulating form, 25-hydroxyvitamin D. Further hydroxylation in the kidney results in 1,25-dihydroxy vitamin D, which is the most metabolically active form of vitamin D. Vitamin D stimulates the absorption of calcium and phosphate from the gut and the resorption of calcium from the bone.HyperparathyroidismHyperfunction of the parathyroid glands may be classified as primary, secondary, or tertiary. PHPT arises from increased PTH production from abnormal parathyroid glands and results from a disturbance of normal feedback control exerted by serum calcium. Elevated PTH levels may also occur as a compensa-tory response to hypocalcemic states resulting from chronic renal failure or GI malabsorption of calcium. This secondary HPT can be reversed by correction of the underlying problem (e.g., kidney transplantation for chronic renal failure). However, chronically stimulated glands may occasionally become autono-mous, resulting in persistence or recurrence of |
Surgery_Schwartz_10964 | Surgery_Schwartz | the underlying problem (e.g., kidney transplantation for chronic renal failure). However, chronically stimulated glands may occasionally become autono-mous, resulting in persistence or recurrence of hypercalcemia after successful renal transplantation, resulting in tertiary HPT.Primary Hyperparathyroidism. PHPT is a common dis-order, affecting 100,000 individuals annually in the United States. PHPT occurs in 0.1% to 0.3% of the general population and is more common in women (1:500) than in men (1:2000). Increased PTH production leads to hypercalcemia via increased GI absorption of calcium, increased production of vitamin D3, and reduced renal calcium clearance. PHPT is characterized by increased parathyroid cell proliferation and PTH secretion that is independent of calcium levels.Etiology The exact cause of PHPT is unknown, although exposure to low-dose therapeutic ionizing radiation and familial predisposition account for some cases. Various diets and inter-mittent exposure to | Surgery_Schwartz. the underlying problem (e.g., kidney transplantation for chronic renal failure). However, chronically stimulated glands may occasionally become autono-mous, resulting in persistence or recurrence of hypercalcemia after successful renal transplantation, resulting in tertiary HPT.Primary Hyperparathyroidism. PHPT is a common dis-order, affecting 100,000 individuals annually in the United States. PHPT occurs in 0.1% to 0.3% of the general population and is more common in women (1:500) than in men (1:2000). Increased PTH production leads to hypercalcemia via increased GI absorption of calcium, increased production of vitamin D3, and reduced renal calcium clearance. PHPT is characterized by increased parathyroid cell proliferation and PTH secretion that is independent of calcium levels.Etiology The exact cause of PHPT is unknown, although exposure to low-dose therapeutic ionizing radiation and familial predisposition account for some cases. Various diets and inter-mittent exposure to |
Surgery_Schwartz_10965 | Surgery_Schwartz | exact cause of PHPT is unknown, although exposure to low-dose therapeutic ionizing radiation and familial predisposition account for some cases. Various diets and inter-mittent exposure to sunshine may also be related. Other causes include renal leak of calcium and declining renal function with age as well as alteration in the sensitivity of parathyroid glands to suppression by calcium. The latency period for development of PHPT after radiation exposure is longer than that for the development of thyroid tumors, with most cases occurring 30 to 40 years after exposure. Patients who have been exposed to radiation have similar clinical presentations and calcium levels when compared to patients without a history of radiation expo-sure. However, the former tends to have higher PTH levels and a higher incidence of concomitant thyroid neoplasms. Lithium therapy has been known to shift the set point for PTH secre-tion in parathyroid cells, thereby resulting in elevated PTH lev-els and mild | Surgery_Schwartz. exact cause of PHPT is unknown, although exposure to low-dose therapeutic ionizing radiation and familial predisposition account for some cases. Various diets and inter-mittent exposure to sunshine may also be related. Other causes include renal leak of calcium and declining renal function with age as well as alteration in the sensitivity of parathyroid glands to suppression by calcium. The latency period for development of PHPT after radiation exposure is longer than that for the development of thyroid tumors, with most cases occurring 30 to 40 years after exposure. Patients who have been exposed to radiation have similar clinical presentations and calcium levels when compared to patients without a history of radiation expo-sure. However, the former tends to have higher PTH levels and a higher incidence of concomitant thyroid neoplasms. Lithium therapy has been known to shift the set point for PTH secre-tion in parathyroid cells, thereby resulting in elevated PTH lev-els and mild |
Surgery_Schwartz_10966 | Surgery_Schwartz | a higher incidence of concomitant thyroid neoplasms. Lithium therapy has been known to shift the set point for PTH secre-tion in parathyroid cells, thereby resulting in elevated PTH lev-els and mild hypercalcemia. Lithium stimulates the growth of abnormal parathyroid glands in vitro and also in susceptible patients in vivo. PHPT results from the enlargement of a single gland or parathyroid adenoma in approximately 80% of cases, multiple adenomas or hyperplasia in 15% to 20% of patients, and parathyroid carcinoma in 1% of patients. Existence of two enlarged glands or double adenomas is supported by bio-chemical (calcium and PTH), intraoperative PTH (IOPTH), molecular, and histologic data. This entity is less common in younger patients but accounts for up to 10% of older patients with PHPT. It should be emphasized that when more than one abnormal parathyroid gland is identified preoperatively or intra-operatively, the patient has hyperplasia (all glands abnormal) until proven | Surgery_Schwartz. a higher incidence of concomitant thyroid neoplasms. Lithium therapy has been known to shift the set point for PTH secre-tion in parathyroid cells, thereby resulting in elevated PTH lev-els and mild hypercalcemia. Lithium stimulates the growth of abnormal parathyroid glands in vitro and also in susceptible patients in vivo. PHPT results from the enlargement of a single gland or parathyroid adenoma in approximately 80% of cases, multiple adenomas or hyperplasia in 15% to 20% of patients, and parathyroid carcinoma in 1% of patients. Existence of two enlarged glands or double adenomas is supported by bio-chemical (calcium and PTH), intraoperative PTH (IOPTH), molecular, and histologic data. This entity is less common in younger patients but accounts for up to 10% of older patients with PHPT. It should be emphasized that when more than one abnormal parathyroid gland is identified preoperatively or intra-operatively, the patient has hyperplasia (all glands abnormal) until proven |
Surgery_Schwartz_10967 | Surgery_Schwartz | with PHPT. It should be emphasized that when more than one abnormal parathyroid gland is identified preoperatively or intra-operatively, the patient has hyperplasia (all glands abnormal) until proven otherwise.Genetics Most cases of PHPT are sporadic. However, PHPT also occurs within the spectrum of a number of inherited Brunicardi_Ch38_p1625-p1704.indd 166501/03/19 11:21 AM 1666SPECIFIC CONSIDERATIONSPART IIdisorders such as MEN1, MEN2A, isolated familial HPT, and familial HPT with jaw-tumor syndrome. All of these syndromes are inherited in an autosomal dominant fashion. PHPT is the earliest and most common manifestation of MEN1 and develops in 80% to 100% of patients by age 40 years old. These patients also are prone to pancreatic neuroendocrine tumors and pitu-itary adenomas and, less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrino-mas, which often are multiple and | Surgery_Schwartz. with PHPT. It should be emphasized that when more than one abnormal parathyroid gland is identified preoperatively or intra-operatively, the patient has hyperplasia (all glands abnormal) until proven otherwise.Genetics Most cases of PHPT are sporadic. However, PHPT also occurs within the spectrum of a number of inherited Brunicardi_Ch38_p1625-p1704.indd 166501/03/19 11:21 AM 1666SPECIFIC CONSIDERATIONSPART IIdisorders such as MEN1, MEN2A, isolated familial HPT, and familial HPT with jaw-tumor syndrome. All of these syndromes are inherited in an autosomal dominant fashion. PHPT is the earliest and most common manifestation of MEN1 and develops in 80% to 100% of patients by age 40 years old. These patients also are prone to pancreatic neuroendocrine tumors and pitu-itary adenomas and, less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrino-mas, which often are multiple and |
Surgery_Schwartz_10968 | Surgery_Schwartz | less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrino-mas, which often are multiple and metastatic at diagnosis. Insu-linomas develop in 10% to 15% of cases, whereas many patients have nonfunctional pancreatic endocrine tumors. Prolactinomas occur in 10% to 50% of MEN1 patients and constitute the most common pituitary lesion. MEN1 has been shown to result from germline mutations in the MEN1 gene, a tumor suppressor gene located on chromosome 11q12-13 that encodes menin, a protein that is postulated to interact with the transcription factors JunD and nuclear factor-κB in the nucleus, in addition to replication protein A and other proteins.70 Most MEN1 mutations result in a nonfunctional protein and are scattered throughout the translated nine exons of the gene. This makes presymptomatic screening for mutation carriers difficult. MEN1 mutations also have been found in kindreds | Surgery_Schwartz. less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrino-mas, which often are multiple and metastatic at diagnosis. Insu-linomas develop in 10% to 15% of cases, whereas many patients have nonfunctional pancreatic endocrine tumors. Prolactinomas occur in 10% to 50% of MEN1 patients and constitute the most common pituitary lesion. MEN1 has been shown to result from germline mutations in the MEN1 gene, a tumor suppressor gene located on chromosome 11q12-13 that encodes menin, a protein that is postulated to interact with the transcription factors JunD and nuclear factor-κB in the nucleus, in addition to replication protein A and other proteins.70 Most MEN1 mutations result in a nonfunctional protein and are scattered throughout the translated nine exons of the gene. This makes presymptomatic screening for mutation carriers difficult. MEN1 mutations also have been found in kindreds |
Surgery_Schwartz_10969 | Surgery_Schwartz | protein and are scattered throughout the translated nine exons of the gene. This makes presymptomatic screening for mutation carriers difficult. MEN1 mutations also have been found in kindreds initially suspected to represent isolated famil-ial HPT. HPT develops in about 20% of patients with MEN2A and generally is less severe. MEN2A is caused by germline mutations of the RET proto-oncogene located on chromosome 10. In contrast to MEN1, genotype-phenotype correlations have been noted in this syndrome in that individuals with mutations at codon 634 are more likely to develop HPT. Patients with the familial HPT with jaw-tumor syndrome have an increased predisposition to parathyroid carcinoma. This syndrome maps to a tumor suppressor locus HRPT2 (CDC73 or parafibromin) on chromosome 1. Patients belonging to isolated HPT kindreds also appear to demonstrate linkage to HRPT2. More recently, a subset of patients with MEN-1 phenotype in the absence of MENIN mutations were found to harbor | Surgery_Schwartz. protein and are scattered throughout the translated nine exons of the gene. This makes presymptomatic screening for mutation carriers difficult. MEN1 mutations also have been found in kindreds initially suspected to represent isolated famil-ial HPT. HPT develops in about 20% of patients with MEN2A and generally is less severe. MEN2A is caused by germline mutations of the RET proto-oncogene located on chromosome 10. In contrast to MEN1, genotype-phenotype correlations have been noted in this syndrome in that individuals with mutations at codon 634 are more likely to develop HPT. Patients with the familial HPT with jaw-tumor syndrome have an increased predisposition to parathyroid carcinoma. This syndrome maps to a tumor suppressor locus HRPT2 (CDC73 or parafibromin) on chromosome 1. Patients belonging to isolated HPT kindreds also appear to demonstrate linkage to HRPT2. More recently, a subset of patients with MEN-1 phenotype in the absence of MENIN mutations were found to harbor |
Surgery_Schwartz_10970 | Surgery_Schwartz | belonging to isolated HPT kindreds also appear to demonstrate linkage to HRPT2. More recently, a subset of patients with MEN-1 phenotype in the absence of MENIN mutations were found to harbor inactivating mutation NH2Ca2+Ca2+Ca2+[Ca2+]iCASRPKCCOOHG proteins PLCIns (1,4,5) P3Regulation of PTHParathyroid cellSystemic effectsKidney25(OH)D3LiverVitamin D1,25(OH)2D3BoneSmall intestineERCa2+Ca2+Ca2+Ca2+Ca2+Ca2+Figure 38-28. Regulation of calcium homeostasis. The calcium-sensing receptor (CASR) is expressed on the surface of the parathyroid cell and senses fluctuations in the concentration of extracellular calcium. Activation of the receptor is thought to increase intracellular cal-cium levels, which, in turn, inhibit parathyroid hormone (PTH) secretion via posttranslational mechanisms. Increased PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption. PTH also stimulates renal 1-α-hydroxylase activity, leading to an | Surgery_Schwartz. belonging to isolated HPT kindreds also appear to demonstrate linkage to HRPT2. More recently, a subset of patients with MEN-1 phenotype in the absence of MENIN mutations were found to harbor inactivating mutation NH2Ca2+Ca2+Ca2+[Ca2+]iCASRPKCCOOHG proteins PLCIns (1,4,5) P3Regulation of PTHParathyroid cellSystemic effectsKidney25(OH)D3LiverVitamin D1,25(OH)2D3BoneSmall intestineERCa2+Ca2+Ca2+Ca2+Ca2+Ca2+Figure 38-28. Regulation of calcium homeostasis. The calcium-sensing receptor (CASR) is expressed on the surface of the parathyroid cell and senses fluctuations in the concentration of extracellular calcium. Activation of the receptor is thought to increase intracellular cal-cium levels, which, in turn, inhibit parathyroid hormone (PTH) secretion via posttranslational mechanisms. Increased PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption. PTH also stimulates renal 1-α-hydroxylase activity, leading to an |
Surgery_Schwartz_10971 | Surgery_Schwartz | PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption. PTH also stimulates renal 1-α-hydroxylase activity, leading to an increase in 1,25-dihydroxy vitamin D, which also exerts a negative feedback on PTH secretion. PKC = protein kinase C; PLC = phospholipase C. (Reproduced with permission from Carling T: Molecular pathology of parathyroid tumors, Trends Endocrinol Metab. 2001 Mar;12(2):53-58.)Brunicardi_Ch38_p1625-p1704.indd 166601/03/19 11:21 AM 1667THYROID, PARATHYROID, AND ADRENALCHAPTER 38in the tumor suppressor gene CDKN1B on chromosome 12p13 and given the diagnosis of MEN4.71,72 CDKN1B encodes p27kip1, which is involved in cyclin D1 signaling.Approximately 25% to 40% of sporadic parathyroid ade-nomas and some hyperplastic parathyroid glands have loss of heterozygosity (LOH) at 11q13, the site of the MEN1 gene. The parathyroid adenoma 1 oncogene (PRAD1 or CCND1), which encodes cyclin D1, a cell cycle | Surgery_Schwartz. PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption. PTH also stimulates renal 1-α-hydroxylase activity, leading to an increase in 1,25-dihydroxy vitamin D, which also exerts a negative feedback on PTH secretion. PKC = protein kinase C; PLC = phospholipase C. (Reproduced with permission from Carling T: Molecular pathology of parathyroid tumors, Trends Endocrinol Metab. 2001 Mar;12(2):53-58.)Brunicardi_Ch38_p1625-p1704.indd 166601/03/19 11:21 AM 1667THYROID, PARATHYROID, AND ADRENALCHAPTER 38in the tumor suppressor gene CDKN1B on chromosome 12p13 and given the diagnosis of MEN4.71,72 CDKN1B encodes p27kip1, which is involved in cyclin D1 signaling.Approximately 25% to 40% of sporadic parathyroid ade-nomas and some hyperplastic parathyroid glands have loss of heterozygosity (LOH) at 11q13, the site of the MEN1 gene. The parathyroid adenoma 1 oncogene (PRAD1 or CCND1), which encodes cyclin D1, a cell cycle |
Surgery_Schwartz_10972 | Surgery_Schwartz | some hyperplastic parathyroid glands have loss of heterozygosity (LOH) at 11q13, the site of the MEN1 gene. The parathyroid adenoma 1 oncogene (PRAD1 or CCND1), which encodes cyclin D1, a cell cycle control protein, is overexpressed in about 18% of parathyroid adenomas. This was demonstrated to result from a rearrangement on chromosome 11 that places the PRAD1 gene under the control of the PTH promoter. Sporadic parathyroid tumors also appear to carry alterations in cyclin dependent kinase inhibitor encoding genes, in particular somatic inactivating mutations of CDKN1B. Other chromosomal regions deleted in parathyroid adenomas and possibly reflecting loss of tumor suppressor genes include 1p, 6q, and 15q, whereas ampli-fied regions suggesting oncogenes have been identified at 16p and 19p. RET mutations are rare in sporadic parathyroid tumors. Sporadic parathyroid cancers are characterized by uniform loss of the tumor suppressor gene RB, which is involved in cell cycle regulation, and | Surgery_Schwartz. some hyperplastic parathyroid glands have loss of heterozygosity (LOH) at 11q13, the site of the MEN1 gene. The parathyroid adenoma 1 oncogene (PRAD1 or CCND1), which encodes cyclin D1, a cell cycle control protein, is overexpressed in about 18% of parathyroid adenomas. This was demonstrated to result from a rearrangement on chromosome 11 that places the PRAD1 gene under the control of the PTH promoter. Sporadic parathyroid tumors also appear to carry alterations in cyclin dependent kinase inhibitor encoding genes, in particular somatic inactivating mutations of CDKN1B. Other chromosomal regions deleted in parathyroid adenomas and possibly reflecting loss of tumor suppressor genes include 1p, 6q, and 15q, whereas ampli-fied regions suggesting oncogenes have been identified at 16p and 19p. RET mutations are rare in sporadic parathyroid tumors. Sporadic parathyroid cancers are characterized by uniform loss of the tumor suppressor gene RB, which is involved in cell cycle regulation, and |
Surgery_Schwartz_10973 | Surgery_Schwartz | RET mutations are rare in sporadic parathyroid tumors. Sporadic parathyroid cancers are characterized by uniform loss of the tumor suppressor gene RB, which is involved in cell cycle regulation, and 60% have HRPT2 (CDC73) mutations. These alterations are rare in benign parathyroid tumors and may have implications for diagnosis. The p53 tumor suppressor gene is also inactivated in a subset (30%) of parathyroid carcinomas.73Clinical Manifestations Patients with PHPT formerly pre-sented with the “classic” pentad of symptoms (i.e., kidney stones, painful bones, abdominal groans, psychic moans, and fatigue overtones). With the advent and widespread use of auto-mated blood analyzers in the early 1970s, there has been an alteration in the “typical” patient with PHPT. They are more likely to be minimally symptomatic or asymptomatic. Currently, most patients present with weakness, fatigue, polydipsia, poly-uria, nocturia, bone and joint pain, constipation, decreased appe-tite, nausea, | Surgery_Schwartz. RET mutations are rare in sporadic parathyroid tumors. Sporadic parathyroid cancers are characterized by uniform loss of the tumor suppressor gene RB, which is involved in cell cycle regulation, and 60% have HRPT2 (CDC73) mutations. These alterations are rare in benign parathyroid tumors and may have implications for diagnosis. The p53 tumor suppressor gene is also inactivated in a subset (30%) of parathyroid carcinomas.73Clinical Manifestations Patients with PHPT formerly pre-sented with the “classic” pentad of symptoms (i.e., kidney stones, painful bones, abdominal groans, psychic moans, and fatigue overtones). With the advent and widespread use of auto-mated blood analyzers in the early 1970s, there has been an alteration in the “typical” patient with PHPT. They are more likely to be minimally symptomatic or asymptomatic. Currently, most patients present with weakness, fatigue, polydipsia, poly-uria, nocturia, bone and joint pain, constipation, decreased appe-tite, nausea, |
Surgery_Schwartz_10974 | Surgery_Schwartz | to be minimally symptomatic or asymptomatic. Currently, most patients present with weakness, fatigue, polydipsia, poly-uria, nocturia, bone and joint pain, constipation, decreased appe-tite, nausea, heartburn, pruritus, depression, and memory loss. Patients with PHPT also tend to score lower than healthy controls when assessed by general multidimensional health assessment tools such as the Medical Outcomes Study Short-Form Health Survey (SF-36) and other specific questionnaires. Furthermore, these symptoms and signs improve in most, but certainly not all, patients after parathyroidectomy. Truly “asymptomatic” PHPT appears to be rare, occurring in <5% of patients, as determined by prospectively administered questionnaires. Complications of PHPT are described in the following section.Renal Disease. Approximately 80% of patients with PHPT have some degree of renal dysfunction or symptoms. Kidney stones were previously reported in up to 80% of patients but now occur in about 20% to 25%. | Surgery_Schwartz. to be minimally symptomatic or asymptomatic. Currently, most patients present with weakness, fatigue, polydipsia, poly-uria, nocturia, bone and joint pain, constipation, decreased appe-tite, nausea, heartburn, pruritus, depression, and memory loss. Patients with PHPT also tend to score lower than healthy controls when assessed by general multidimensional health assessment tools such as the Medical Outcomes Study Short-Form Health Survey (SF-36) and other specific questionnaires. Furthermore, these symptoms and signs improve in most, but certainly not all, patients after parathyroidectomy. Truly “asymptomatic” PHPT appears to be rare, occurring in <5% of patients, as determined by prospectively administered questionnaires. Complications of PHPT are described in the following section.Renal Disease. Approximately 80% of patients with PHPT have some degree of renal dysfunction or symptoms. Kidney stones were previously reported in up to 80% of patients but now occur in about 20% to 25%. |
Surgery_Schwartz_10975 | Surgery_Schwartz | Disease. Approximately 80% of patients with PHPT have some degree of renal dysfunction or symptoms. Kidney stones were previously reported in up to 80% of patients but now occur in about 20% to 25%. The calculi are typically com-posed of calcium phosphate or oxalate. In contrast, PHPT is found to be the underlying disorder in only 3% of patients pre-senting with nephrolithiasis. Nephrocalcinosis, which refers to renal parenchymal calcification, is found in <5% of patients and is more likely to lead to renal dysfunction. Chronic hypercalce-mia also can impair concentrating ability, thereby resulting in polyuria, polydipsia, and nocturia. The incidence of hyperten-sion is variable but has been reported to occur in up to 50% of patients with PHPT. Hypertension appears to be more common in older patients and correlates with the magnitude of renal dys-function and, in contrast to other symptoms, is least likely to improve after parathyroidectomy.Bone Disease. Bone disease, including | Surgery_Schwartz. Disease. Approximately 80% of patients with PHPT have some degree of renal dysfunction or symptoms. Kidney stones were previously reported in up to 80% of patients but now occur in about 20% to 25%. The calculi are typically com-posed of calcium phosphate or oxalate. In contrast, PHPT is found to be the underlying disorder in only 3% of patients pre-senting with nephrolithiasis. Nephrocalcinosis, which refers to renal parenchymal calcification, is found in <5% of patients and is more likely to lead to renal dysfunction. Chronic hypercalce-mia also can impair concentrating ability, thereby resulting in polyuria, polydipsia, and nocturia. The incidence of hyperten-sion is variable but has been reported to occur in up to 50% of patients with PHPT. Hypertension appears to be more common in older patients and correlates with the magnitude of renal dys-function and, in contrast to other symptoms, is least likely to improve after parathyroidectomy.Bone Disease. Bone disease, including |
Surgery_Schwartz_10976 | Surgery_Schwartz | in older patients and correlates with the magnitude of renal dys-function and, in contrast to other symptoms, is least likely to improve after parathyroidectomy.Bone Disease. Bone disease, including osteopenia, osteoporo-sis, and osteitis fibrosa cystica, is found in about 15% of patients with PHPT. Increased bone turnover, as found in patients with osteitis fibrosa cystica, can be determined by documenting an elevated blood alkaline phosphatase level. Advanced PHPT with osteitis fibrosa cystica now occurs in <5% of patients. It has pathognomonic radiologic findings, which are best seen on X-rays of the hands and are characterized by subperiosteal resorption (most apparent on the radial aspect of the middle pha-lanx of the second and third fingers), bone cysts, and tufting of the distal phalanges (Fig. 38-29). The skull also may be affected and appears mottled with a loss of definition of the inner and outer cortices. Brown or osteoclastic tumors and bone cysts also may be present. | Surgery_Schwartz. in older patients and correlates with the magnitude of renal dys-function and, in contrast to other symptoms, is least likely to improve after parathyroidectomy.Bone Disease. Bone disease, including osteopenia, osteoporo-sis, and osteitis fibrosa cystica, is found in about 15% of patients with PHPT. Increased bone turnover, as found in patients with osteitis fibrosa cystica, can be determined by documenting an elevated blood alkaline phosphatase level. Advanced PHPT with osteitis fibrosa cystica now occurs in <5% of patients. It has pathognomonic radiologic findings, which are best seen on X-rays of the hands and are characterized by subperiosteal resorption (most apparent on the radial aspect of the middle pha-lanx of the second and third fingers), bone cysts, and tufting of the distal phalanges (Fig. 38-29). The skull also may be affected and appears mottled with a loss of definition of the inner and outer cortices. Brown or osteoclastic tumors and bone cysts also may be present. |
Surgery_Schwartz_10977 | Surgery_Schwartz | phalanges (Fig. 38-29). The skull also may be affected and appears mottled with a loss of definition of the inner and outer cortices. Brown or osteoclastic tumors and bone cysts also may be present. Severe bone disease, resulting in bone pain and tenderness and/or pathologic fractures, is rarely observed nowa-days. However, reductions of bone mineral density (BMD) with osteopenia and osteoporosis are more common. Patients with normal serum alkaline phosphatase levels almost never have clinically apparent osteitis fibrosa cystica. HPT typically results in a loss of bone mass at sites of cortical bone such as the radius and relative preservation of cancellous bone such as that located at the vertebral bodies. Patients with PHPT, however, also may Figure 38-29. X-ray of the hand showing subperiosteal bone resorption most apparent along the radial aspect of the middle pha-lanx, characteristic of osteitis fibrosa cystica.Brunicardi_Ch38_p1625-p1704.indd 166701/03/19 11:21 AM | Surgery_Schwartz. phalanges (Fig. 38-29). The skull also may be affected and appears mottled with a loss of definition of the inner and outer cortices. Brown or osteoclastic tumors and bone cysts also may be present. Severe bone disease, resulting in bone pain and tenderness and/or pathologic fractures, is rarely observed nowa-days. However, reductions of bone mineral density (BMD) with osteopenia and osteoporosis are more common. Patients with normal serum alkaline phosphatase levels almost never have clinically apparent osteitis fibrosa cystica. HPT typically results in a loss of bone mass at sites of cortical bone such as the radius and relative preservation of cancellous bone such as that located at the vertebral bodies. Patients with PHPT, however, also may Figure 38-29. X-ray of the hand showing subperiosteal bone resorption most apparent along the radial aspect of the middle pha-lanx, characteristic of osteitis fibrosa cystica.Brunicardi_Ch38_p1625-p1704.indd 166701/03/19 11:21 AM |
Surgery_Schwartz_10978 | Surgery_Schwartz | subperiosteal bone resorption most apparent along the radial aspect of the middle pha-lanx, characteristic of osteitis fibrosa cystica.Brunicardi_Ch38_p1625-p1704.indd 166701/03/19 11:21 AM 1668SPECIFIC CONSIDERATIONSPART IIhave osteoporosis of the lumbar spine that improves dramati-cally following parathyroidectomy. Fractures also occur more frequently in patients with PHPT, and the incidence of fractures also decreases after parathyroidectomy. Bone disease correlates with serum PTH and vitamin D levels.Gastrointestinal Complications. PHPT has been associated with peptic ulcer disease. In experimental animals, hypergastrin-emia has been shown to result from PTH infusion into blood ves-sels supplying the stomach, independent of its effects on serum calcium. An increased incidence of pancreatitis also has been reported in patients with PHPT, although this appears to occur only in patients with profound hypercalcemia (Ca2+ ≥12.5 mg/dL). Patients with PHPT also have an increased | Surgery_Schwartz. subperiosteal bone resorption most apparent along the radial aspect of the middle pha-lanx, characteristic of osteitis fibrosa cystica.Brunicardi_Ch38_p1625-p1704.indd 166701/03/19 11:21 AM 1668SPECIFIC CONSIDERATIONSPART IIhave osteoporosis of the lumbar spine that improves dramati-cally following parathyroidectomy. Fractures also occur more frequently in patients with PHPT, and the incidence of fractures also decreases after parathyroidectomy. Bone disease correlates with serum PTH and vitamin D levels.Gastrointestinal Complications. PHPT has been associated with peptic ulcer disease. In experimental animals, hypergastrin-emia has been shown to result from PTH infusion into blood ves-sels supplying the stomach, independent of its effects on serum calcium. An increased incidence of pancreatitis also has been reported in patients with PHPT, although this appears to occur only in patients with profound hypercalcemia (Ca2+ ≥12.5 mg/dL). Patients with PHPT also have an increased |
Surgery_Schwartz_10979 | Surgery_Schwartz | pancreatitis also has been reported in patients with PHPT, although this appears to occur only in patients with profound hypercalcemia (Ca2+ ≥12.5 mg/dL). Patients with PHPT also have an increased incidence of choleli-thiasis, presumably due to an increase in biliary calcium, which leads to the formation of calcium bilirubinate stones.Neuropsychiatric Complications. Severe hypercalcemia may lead to various neuropsychiatric manifestations such as florid psy-chosis, obtundation, or coma. Other findings such as depression, anxiety, and fatigue are more commonly observed in patients with only mild hypercalcemia. The etiology of these symptoms is not known. Studies demonstrate that levels of certain neu-rotransmitters (monoamine metabolites 5-hydroxyindoleacetic acid and homovanillic acid) are reduced in the cerebrospi-nal fluid of patients with PHPT when compared to controls. Electroencephalogram abnormalities also occur in patients with primary and secondary HPT and normalize following | Surgery_Schwartz. pancreatitis also has been reported in patients with PHPT, although this appears to occur only in patients with profound hypercalcemia (Ca2+ ≥12.5 mg/dL). Patients with PHPT also have an increased incidence of choleli-thiasis, presumably due to an increase in biliary calcium, which leads to the formation of calcium bilirubinate stones.Neuropsychiatric Complications. Severe hypercalcemia may lead to various neuropsychiatric manifestations such as florid psy-chosis, obtundation, or coma. Other findings such as depression, anxiety, and fatigue are more commonly observed in patients with only mild hypercalcemia. The etiology of these symptoms is not known. Studies demonstrate that levels of certain neu-rotransmitters (monoamine metabolites 5-hydroxyindoleacetic acid and homovanillic acid) are reduced in the cerebrospi-nal fluid of patients with PHPT when compared to controls. Electroencephalogram abnormalities also occur in patients with primary and secondary HPT and normalize following |
Surgery_Schwartz_10980 | Surgery_Schwartz | reduced in the cerebrospi-nal fluid of patients with PHPT when compared to controls. Electroencephalogram abnormalities also occur in patients with primary and secondary HPT and normalize following parathyroidectomy.Other Features. PHPT also can lead to fatigue and muscle weakness, which is prominent in the proximal muscle groups. Although the exact etiology of this finding is not known, muscle biopsy studies show that weakness results from a neuropathy, rather than a primary myopathic abnormality. Patients with HPT also have an increased incidence of chondrocalcinosis, gout, and pseudogout, with deposition of uric acid and calcium pyro-phosphate crystals in the joints. Calcification at ectopic sites such as blood vessels, cardiac valves, and skin also has been reported, as has hypertrophy of the left ventricle independent of the presence of hypertension. There is also evidence for subtle cardiovascular manifestations in mild disease, such as changes in endothelial function, increased | Surgery_Schwartz. reduced in the cerebrospi-nal fluid of patients with PHPT when compared to controls. Electroencephalogram abnormalities also occur in patients with primary and secondary HPT and normalize following parathyroidectomy.Other Features. PHPT also can lead to fatigue and muscle weakness, which is prominent in the proximal muscle groups. Although the exact etiology of this finding is not known, muscle biopsy studies show that weakness results from a neuropathy, rather than a primary myopathic abnormality. Patients with HPT also have an increased incidence of chondrocalcinosis, gout, and pseudogout, with deposition of uric acid and calcium pyro-phosphate crystals in the joints. Calcification at ectopic sites such as blood vessels, cardiac valves, and skin also has been reported, as has hypertrophy of the left ventricle independent of the presence of hypertension. There is also evidence for subtle cardiovascular manifestations in mild disease, such as changes in endothelial function, increased |
Surgery_Schwartz_10981 | Surgery_Schwartz | of the left ventricle independent of the presence of hypertension. There is also evidence for subtle cardiovascular manifestations in mild disease, such as changes in endothelial function, increased vascular stiffness, and perhaps subtle diastolic dysfunction. Several large studies from Europe also suggest that PHPT is associated with increased death rates from cardiovascular disease and cancer even in patients with mild HPT, although this finding was not substantiated in North American studies.Physical Findings Parathyroid tumors are seldom palpable, except in patients with profound hypercalcemia or parathyroid cancer. A palpable neck mass in a patient with PHPT is more likely to be thyroid in origin or a parathyroid cancer. Patients also may demonstrate evidence of band keratopathy, a depo-sition of calcium in Bowman’s membrane just inside the iris of the eye. This nonspecific condition generally is caused by chronic eye diseases such as uveitis, glaucoma, and trauma but also may | Surgery_Schwartz. of the left ventricle independent of the presence of hypertension. There is also evidence for subtle cardiovascular manifestations in mild disease, such as changes in endothelial function, increased vascular stiffness, and perhaps subtle diastolic dysfunction. Several large studies from Europe also suggest that PHPT is associated with increased death rates from cardiovascular disease and cancer even in patients with mild HPT, although this finding was not substantiated in North American studies.Physical Findings Parathyroid tumors are seldom palpable, except in patients with profound hypercalcemia or parathyroid cancer. A palpable neck mass in a patient with PHPT is more likely to be thyroid in origin or a parathyroid cancer. Patients also may demonstrate evidence of band keratopathy, a depo-sition of calcium in Bowman’s membrane just inside the iris of the eye. This nonspecific condition generally is caused by chronic eye diseases such as uveitis, glaucoma, and trauma but also may |
Surgery_Schwartz_10982 | Surgery_Schwartz | depo-sition of calcium in Bowman’s membrane just inside the iris of the eye. This nonspecific condition generally is caused by chronic eye diseases such as uveitis, glaucoma, and trauma but also may occur in the presence of conditions associated with high calcium or phosphate levels. Fibro-osseous jaw tumors, and/or the presence of familial disease in patients with PHPT and jaw tumors, if present, should alert the physician to the pos-sibility of parathyroid carcinoma.Differential Diagnosis Hypercalcemia may be caused by a multitude of conditions, as listed in Table 38-9. PHPT and malignancy account for >90% of all cases of hypercalcemia. PHPT is more common in the outpatient setting, whereas malig-nancy is the leading cause of hypercalcemia in hospitalized patients. PHPT can virtually always be distinguished from other diseases causing hypercalcemia by a combination of history, physical examination, and appropriate laboratory investigations.Hypercalcemia associated with malignancy | Surgery_Schwartz. depo-sition of calcium in Bowman’s membrane just inside the iris of the eye. This nonspecific condition generally is caused by chronic eye diseases such as uveitis, glaucoma, and trauma but also may occur in the presence of conditions associated with high calcium or phosphate levels. Fibro-osseous jaw tumors, and/or the presence of familial disease in patients with PHPT and jaw tumors, if present, should alert the physician to the pos-sibility of parathyroid carcinoma.Differential Diagnosis Hypercalcemia may be caused by a multitude of conditions, as listed in Table 38-9. PHPT and malignancy account for >90% of all cases of hypercalcemia. PHPT is more common in the outpatient setting, whereas malig-nancy is the leading cause of hypercalcemia in hospitalized patients. PHPT can virtually always be distinguished from other diseases causing hypercalcemia by a combination of history, physical examination, and appropriate laboratory investigations.Hypercalcemia associated with malignancy |
Surgery_Schwartz_10983 | Surgery_Schwartz | always be distinguished from other diseases causing hypercalcemia by a combination of history, physical examination, and appropriate laboratory investigations.Hypercalcemia associated with malignancy includes three distinct syndromes. Although bone metastases may cause hypercalcemia, patients with solid tumors of the lung, breast, kidney, head and neck, and ovary often have humoral hyper-calcemia of malignancy, without any associated bony metas-tases. In addition, hypercalcemia also may be associated with hematologic malignancies such as multiple myeloma. Humoral hypercalcemia of malignancy is known to be mediated primar-ily by PTH-related peptide (PTHrP), which also plays a role in the hypercalcemia associated with bone metastases and multiple myeloma.Thiazide diuretics cause hypercalcemia by decreasing renal clearance of calcium. This corrects in normal patients within days to weeks after discontinuing the diuretic, but patients with PHPT continue to be hypercalcemic. Thiazide | Surgery_Schwartz. always be distinguished from other diseases causing hypercalcemia by a combination of history, physical examination, and appropriate laboratory investigations.Hypercalcemia associated with malignancy includes three distinct syndromes. Although bone metastases may cause hypercalcemia, patients with solid tumors of the lung, breast, kidney, head and neck, and ovary often have humoral hyper-calcemia of malignancy, without any associated bony metas-tases. In addition, hypercalcemia also may be associated with hematologic malignancies such as multiple myeloma. Humoral hypercalcemia of malignancy is known to be mediated primar-ily by PTH-related peptide (PTHrP), which also plays a role in the hypercalcemia associated with bone metastases and multiple myeloma.Thiazide diuretics cause hypercalcemia by decreasing renal clearance of calcium. This corrects in normal patients within days to weeks after discontinuing the diuretic, but patients with PHPT continue to be hypercalcemic. Thiazide |
Surgery_Schwartz_10984 | Surgery_Schwartz | by decreasing renal clearance of calcium. This corrects in normal patients within days to weeks after discontinuing the diuretic, but patients with PHPT continue to be hypercalcemic. Thiazide diuretics can, therefore, exacerbate underlying PHPT and can be used to unmask PHPT in patients with borderline hyper-calcemia. Familial hypocalciuric hypercalcemia 1 (FHH1) is a rare autosomal dominant condition with nearly 100% pen-etrance and results from inherited heterozygous mutations in the CASR gene located on chromosome 3.54 Homozygous germline mutations at this locus result in neonatal severe pri-mary hyperparathyroidism and calcemia, a condition that can rapidly prove fatal. Patients with FHH1 generally have lifelong hypercalcemia, which is not corrected by parathyroidectomy. A milder form of the disease known as familial hypercalciu-ric hypercalcemia results from germline inactivating mutations in the intracytoplasmic tail domain of the CaSR gene. These patients have an appropriate | Surgery_Schwartz. by decreasing renal clearance of calcium. This corrects in normal patients within days to weeks after discontinuing the diuretic, but patients with PHPT continue to be hypercalcemic. Thiazide diuretics can, therefore, exacerbate underlying PHPT and can be used to unmask PHPT in patients with borderline hyper-calcemia. Familial hypocalciuric hypercalcemia 1 (FHH1) is a rare autosomal dominant condition with nearly 100% pen-etrance and results from inherited heterozygous mutations in the CASR gene located on chromosome 3.54 Homozygous germline mutations at this locus result in neonatal severe pri-mary hyperparathyroidism and calcemia, a condition that can rapidly prove fatal. Patients with FHH1 generally have lifelong hypercalcemia, which is not corrected by parathyroidectomy. A milder form of the disease known as familial hypercalciu-ric hypercalcemia results from germline inactivating mutations in the intracytoplasmic tail domain of the CaSR gene. These patients have an appropriate |
Surgery_Schwartz_10985 | Surgery_Schwartz | of the disease known as familial hypercalciu-ric hypercalcemia results from germline inactivating mutations in the intracytoplasmic tail domain of the CaSR gene. These patients have an appropriate hypercalciuric response to elevated calcium and PTH in addition to hypermagnesemia and hyper-phosphaturia. Some cases benefit from parathyroidectomy. Recently two new types of FHH (2 and 3) have been described. These are associated with germline inactivating mutations of GNA11(19p13.3) and AP2S1(19q12.2) genes. Both mutations cause hypocalciuric hypercalcemia through aberrant inactiva-tion of CaSR signaling. Although clinical presentation in FHH2 is similar to FHH1, those with FHH3 tend to have higher PTH levels and osteomalacia.71Table 38-9Differential diagnosis of hypercalcemiaHyperparathyroidismMalignancy—hematologic (multiple myeloma), solid tumors (due to PTHrP)Endocrine diseases—hyperthyroidism, Addisonian crisis, VIPomaGranulomatous diseases—sarcoidosis, tuberculosis, berylliosis, | Surgery_Schwartz. of the disease known as familial hypercalciu-ric hypercalcemia results from germline inactivating mutations in the intracytoplasmic tail domain of the CaSR gene. These patients have an appropriate hypercalciuric response to elevated calcium and PTH in addition to hypermagnesemia and hyper-phosphaturia. Some cases benefit from parathyroidectomy. Recently two new types of FHH (2 and 3) have been described. These are associated with germline inactivating mutations of GNA11(19p13.3) and AP2S1(19q12.2) genes. Both mutations cause hypocalciuric hypercalcemia through aberrant inactiva-tion of CaSR signaling. Although clinical presentation in FHH2 is similar to FHH1, those with FHH3 tend to have higher PTH levels and osteomalacia.71Table 38-9Differential diagnosis of hypercalcemiaHyperparathyroidismMalignancy—hematologic (multiple myeloma), solid tumors (due to PTHrP)Endocrine diseases—hyperthyroidism, Addisonian crisis, VIPomaGranulomatous diseases—sarcoidosis, tuberculosis, berylliosis, |
Surgery_Schwartz_10986 | Surgery_Schwartz | (multiple myeloma), solid tumors (due to PTHrP)Endocrine diseases—hyperthyroidism, Addisonian crisis, VIPomaGranulomatous diseases—sarcoidosis, tuberculosis, berylliosis, histoplasmosisMilk-alkali syndromeDrugs—thiazide diuretics, lithium, vitamin A or D intoxicationFamilial hypocalciuric hypercalcemiaPaget’s diseaseImmobilizationPTHrP = parathyroid hormone-related protein; VIP = vasoactive intestinal peptide.Brunicardi_Ch38_p1625-p1704.indd 166801/03/19 11:21 AM 1669THYROID, PARATHYROID, AND ADRENALCHAPTER 38Coexisting primaryhyperparathyroidismand malignancyIntact PTHNormalrangeHypo-parathyroidismPrimaryhyper-parathyroidismLimit ofdetectionHypercalcemiaassociatedwith malignancy968634Intact PTH (pg/mL of hPTH [1-84])Normal50020015010050Figure 38-30. Intact parathyroid hormone (PTH) measurement allows differentiation between the various causes of hypercalcemia. (Reproduced with permission from Endres DB, Villanueva R, Sharp CF, et al. Measurement of parathyroid hormone, | Surgery_Schwartz. (multiple myeloma), solid tumors (due to PTHrP)Endocrine diseases—hyperthyroidism, Addisonian crisis, VIPomaGranulomatous diseases—sarcoidosis, tuberculosis, berylliosis, histoplasmosisMilk-alkali syndromeDrugs—thiazide diuretics, lithium, vitamin A or D intoxicationFamilial hypocalciuric hypercalcemiaPaget’s diseaseImmobilizationPTHrP = parathyroid hormone-related protein; VIP = vasoactive intestinal peptide.Brunicardi_Ch38_p1625-p1704.indd 166801/03/19 11:21 AM 1669THYROID, PARATHYROID, AND ADRENALCHAPTER 38Coexisting primaryhyperparathyroidismand malignancyIntact PTHNormalrangeHypo-parathyroidismPrimaryhyper-parathyroidismLimit ofdetectionHypercalcemiaassociatedwith malignancy968634Intact PTH (pg/mL of hPTH [1-84])Normal50020015010050Figure 38-30. Intact parathyroid hormone (PTH) measurement allows differentiation between the various causes of hypercalcemia. (Reproduced with permission from Endres DB, Villanueva R, Sharp CF, et al. Measurement of parathyroid hormone, |
Surgery_Schwartz_10987 | Surgery_Schwartz | (PTH) measurement allows differentiation between the various causes of hypercalcemia. (Reproduced with permission from Endres DB, Villanueva R, Sharp CF, et al. Measurement of parathyroid hormone, Endocrinol Metab Clin North Am. 1989 Sep;18(3):611-629.)Hypercalcemia also is found in approximately 10% of patients with sarcoidosis secondary to increased 25-hydroxy vitamin D 1-hydroxylase activity in lymphoid tissue and pul-monary macrophages, which is not subject to inhibitory feed-back control by serum calcium. Thyroid hormone also has bone-resorption properties, thus causing hypercalcemia in thy-rotoxic states, especially in immobilized patients. Hemoconcen-tration appears to be an important factor in the hypercalcemia associated with adrenal insufficiency and pheochromocytoma, although the latter patients may have associated parathyroid tumors (MEN2A), and some pheochromocytomas are known to secrete PTHrP. Other endocrine lesions such as vasoactive intestinal peptide–secreting tumors | Surgery_Schwartz. (PTH) measurement allows differentiation between the various causes of hypercalcemia. (Reproduced with permission from Endres DB, Villanueva R, Sharp CF, et al. Measurement of parathyroid hormone, Endocrinol Metab Clin North Am. 1989 Sep;18(3):611-629.)Hypercalcemia also is found in approximately 10% of patients with sarcoidosis secondary to increased 25-hydroxy vitamin D 1-hydroxylase activity in lymphoid tissue and pul-monary macrophages, which is not subject to inhibitory feed-back control by serum calcium. Thyroid hormone also has bone-resorption properties, thus causing hypercalcemia in thy-rotoxic states, especially in immobilized patients. Hemoconcen-tration appears to be an important factor in the hypercalcemia associated with adrenal insufficiency and pheochromocytoma, although the latter patients may have associated parathyroid tumors (MEN2A), and some pheochromocytomas are known to secrete PTHrP. Other endocrine lesions such as vasoactive intestinal peptide–secreting tumors |
Surgery_Schwartz_10988 | Surgery_Schwartz | latter patients may have associated parathyroid tumors (MEN2A), and some pheochromocytomas are known to secrete PTHrP. Other endocrine lesions such as vasoactive intestinal peptide–secreting tumors may be associated with hypercalcemia due to increased secretion of PTHrP. Milk-alkali syndrome requires the ingestion of large quantities of calcium with an absorbable alkali such as that used in the treatment of peptic ulcer disease with antacids. Ingestions of large quantities of vitamins D and A are infrequent causes of hypercalcemia, as is immobilization.Diagnostic Investigations Biochemical Studies. The presence of an elevated serum cal-cium and intact PTH or two-site PTH levels, without hypocal-ciuria, establishes the diagnosis of PHPT with virtual certainty. These sensitive PTH assays use immunoradiometric or immu-nochemiluminescent techniques and can reliably distinguish PHPT from other causes of hypercalcemia. Furthermore, they do not cross-react with PTHrP (Fig. 38-30). In | Surgery_Schwartz. latter patients may have associated parathyroid tumors (MEN2A), and some pheochromocytomas are known to secrete PTHrP. Other endocrine lesions such as vasoactive intestinal peptide–secreting tumors may be associated with hypercalcemia due to increased secretion of PTHrP. Milk-alkali syndrome requires the ingestion of large quantities of calcium with an absorbable alkali such as that used in the treatment of peptic ulcer disease with antacids. Ingestions of large quantities of vitamins D and A are infrequent causes of hypercalcemia, as is immobilization.Diagnostic Investigations Biochemical Studies. The presence of an elevated serum cal-cium and intact PTH or two-site PTH levels, without hypocal-ciuria, establishes the diagnosis of PHPT with virtual certainty. These sensitive PTH assays use immunoradiometric or immu-nochemiluminescent techniques and can reliably distinguish PHPT from other causes of hypercalcemia. Furthermore, they do not cross-react with PTHrP (Fig. 38-30). In |
Surgery_Schwartz_10989 | Surgery_Schwartz | use immunoradiometric or immu-nochemiluminescent techniques and can reliably distinguish PHPT from other causes of hypercalcemia. Furthermore, they do not cross-react with PTHrP (Fig. 38-30). In patients with Table 38-10Biochemical features of primary hyperparathyroidismSERUM TESTSALTERATIONCalciumIncreased, except in normocalcemic primary hyperparathyroidismIntact PTHIncreased or inappropriately highChlorideIncreased or high normalPhosphateDecreased or low normalChloride-to-phosphate ratioIncreased (usually >33)MagnesiumUnchanged or decreased (in patients with osteitis fibrosa cystica)Uric acidNormal or increasedAlkaline phosphataseNormal or increased (in the presence of high turnover bone disease)Acid-base statusMild hyperchloremic metabolic acidosisCalcium-to-creatinine clearance ratioGenerally >0.02 (vs. <0.01 in FHH) but there are exceptions1,25-dihydroxy vitamin DNormal or increasedUrine tests 24-h urinary calciumNormal or increasedBFHH = benign familial hypocalciuric | Surgery_Schwartz. use immunoradiometric or immu-nochemiluminescent techniques and can reliably distinguish PHPT from other causes of hypercalcemia. Furthermore, they do not cross-react with PTHrP (Fig. 38-30). In patients with Table 38-10Biochemical features of primary hyperparathyroidismSERUM TESTSALTERATIONCalciumIncreased, except in normocalcemic primary hyperparathyroidismIntact PTHIncreased or inappropriately highChlorideIncreased or high normalPhosphateDecreased or low normalChloride-to-phosphate ratioIncreased (usually >33)MagnesiumUnchanged or decreased (in patients with osteitis fibrosa cystica)Uric acidNormal or increasedAlkaline phosphataseNormal or increased (in the presence of high turnover bone disease)Acid-base statusMild hyperchloremic metabolic acidosisCalcium-to-creatinine clearance ratioGenerally >0.02 (vs. <0.01 in FHH) but there are exceptions1,25-dihydroxy vitamin DNormal or increasedUrine tests 24-h urinary calciumNormal or increasedBFHH = benign familial hypocalciuric |
Surgery_Schwartz_10990 | Surgery_Schwartz | ratioGenerally >0.02 (vs. <0.01 in FHH) but there are exceptions1,25-dihydroxy vitamin DNormal or increasedUrine tests 24-h urinary calciumNormal or increasedBFHH = benign familial hypocalciuric hypercalcemia; PTH = parathyroid hormone.metastatic cancer and hypercalcemia, intact PTH levels help to determine whether the patient also has concurrent PHPT. Although extremely rare, a patient with hypercalcemia may have a tumor that secretes PTH. FNAB of such a tumor for PTH levels or selective venous catheterization of the veins draining such tumors can help clarify the diagnosis.Patients with PHPT also typically have decreased serum phosphate (∼50%) and elevated 24-hour urinary calcium con-centrations (∼60%). A mild hyperchloremic metabolic acidosis also is present (80%), thereby leading to an elevated chloride-to-phosphate ratio (>33). Urinary calcium levels need not be measured routinely, except in patients who have not had previ-ously documented normocalcemia or have a family history | Surgery_Schwartz. ratioGenerally >0.02 (vs. <0.01 in FHH) but there are exceptions1,25-dihydroxy vitamin DNormal or increasedUrine tests 24-h urinary calciumNormal or increasedBFHH = benign familial hypocalciuric hypercalcemia; PTH = parathyroid hormone.metastatic cancer and hypercalcemia, intact PTH levels help to determine whether the patient also has concurrent PHPT. Although extremely rare, a patient with hypercalcemia may have a tumor that secretes PTH. FNAB of such a tumor for PTH levels or selective venous catheterization of the veins draining such tumors can help clarify the diagnosis.Patients with PHPT also typically have decreased serum phosphate (∼50%) and elevated 24-hour urinary calcium con-centrations (∼60%). A mild hyperchloremic metabolic acidosis also is present (80%), thereby leading to an elevated chloride-to-phosphate ratio (>33). Urinary calcium levels need not be measured routinely, except in patients who have not had previ-ously documented normocalcemia or have a family history |
Surgery_Schwartz_10991 | Surgery_Schwartz | an elevated chloride-to-phosphate ratio (>33). Urinary calcium levels need not be measured routinely, except in patients who have not had previ-ously documented normocalcemia or have a family history of hypercalcemia to rule out FHH. In patients with FHH, 24-hour urinary calcium excretion is characteristically low (<100 mg/d). Furthermore, the serum calcium-to-creatinine clearance ratio (24-hour urine calcium/plasma total calcium/24-hour urine creatinine/plasma creatinine) usually is <0.01 in patients with FHH, whereas it is typically >0.02 in patients with PHPT, although there are exceptions to this. Other biochemical features of PHPT are listed in Table 38-10. Elevated levels of alkaline phosphatase may be found in approximately 10% of patients with PHPT and are indicative of high-turnover bone disease. These patients are prone to developing postoperative hypocal-cemia due to bone hunger. Serum and urine protein electropho-resis may be necessary to exclude multiple | Surgery_Schwartz. an elevated chloride-to-phosphate ratio (>33). Urinary calcium levels need not be measured routinely, except in patients who have not had previ-ously documented normocalcemia or have a family history of hypercalcemia to rule out FHH. In patients with FHH, 24-hour urinary calcium excretion is characteristically low (<100 mg/d). Furthermore, the serum calcium-to-creatinine clearance ratio (24-hour urine calcium/plasma total calcium/24-hour urine creatinine/plasma creatinine) usually is <0.01 in patients with FHH, whereas it is typically >0.02 in patients with PHPT, although there are exceptions to this. Other biochemical features of PHPT are listed in Table 38-10. Elevated levels of alkaline phosphatase may be found in approximately 10% of patients with PHPT and are indicative of high-turnover bone disease. These patients are prone to developing postoperative hypocal-cemia due to bone hunger. Serum and urine protein electropho-resis may be necessary to exclude multiple |
Surgery_Schwartz_10992 | Surgery_Schwartz | of high-turnover bone disease. These patients are prone to developing postoperative hypocal-cemia due to bone hunger. Serum and urine protein electropho-resis may be necessary to exclude multiple myeloma.Brunicardi_Ch38_p1625-p1704.indd 166901/03/19 11:21 AM 1670SPECIFIC CONSIDERATIONSPART IIOccasionally, patients present with normocalcemic PHPT due to vitamin D deficiency, a low serum albumin, excessive hydration, a high-phosphate diet, or a low normal blood calcium set point. These patients have increased total PTH levels with or without increased blood ionized calcium levels and must be distinguished from patients with renal leak hypercalciuria who also have increased PTH levels due to excessive calcium loss in the urine. This can be accomplished by administering thiazide diuretics. In patients with idiopathic hypercalciuria, the urinary calcium level falls, and the secondary increase in the blood PTH level also decreases to normal, whereas patients with normocal-cemic HPT | Surgery_Schwartz. of high-turnover bone disease. These patients are prone to developing postoperative hypocal-cemia due to bone hunger. Serum and urine protein electropho-resis may be necessary to exclude multiple myeloma.Brunicardi_Ch38_p1625-p1704.indd 166901/03/19 11:21 AM 1670SPECIFIC CONSIDERATIONSPART IIOccasionally, patients present with normocalcemic PHPT due to vitamin D deficiency, a low serum albumin, excessive hydration, a high-phosphate diet, or a low normal blood calcium set point. These patients have increased total PTH levels with or without increased blood ionized calcium levels and must be distinguished from patients with renal leak hypercalciuria who also have increased PTH levels due to excessive calcium loss in the urine. This can be accomplished by administering thiazide diuretics. In patients with idiopathic hypercalciuria, the urinary calcium level falls, and the secondary increase in the blood PTH level also decreases to normal, whereas patients with normocal-cemic HPT |
Surgery_Schwartz_10993 | Surgery_Schwartz | In patients with idiopathic hypercalciuria, the urinary calcium level falls, and the secondary increase in the blood PTH level also decreases to normal, whereas patients with normocal-cemic HPT continue to have elevated urine calcium and blood PTH levels and may, in fact, become hypercalcemic.Radiologic Tests. In patients with profound hypercalcemia or PHPT associated with vitamin D deficiency, hand and skull X-rays may demonstrate osteitis fibrosa cystica, but this is rare in current clinical practice. BMD studies using dual-energy absorptiometry are being increasingly used to assess the effects of PHPT on bone. PHPT primarily leads to one loss at cortical sites such as the distal radius while bone density is preserved at sites such as the lumbar spine. Current evaluation of patients with PHPT includes vertebral imaging by X-ray or vertebral fracture assessment (VFA) or CT scan in addition to BMD stud-ies. Measurement of trabecular bone score (TBS) is optional. In addition, renal | Surgery_Schwartz. In patients with idiopathic hypercalciuria, the urinary calcium level falls, and the secondary increase in the blood PTH level also decreases to normal, whereas patients with normocal-cemic HPT continue to have elevated urine calcium and blood PTH levels and may, in fact, become hypercalcemic.Radiologic Tests. In patients with profound hypercalcemia or PHPT associated with vitamin D deficiency, hand and skull X-rays may demonstrate osteitis fibrosa cystica, but this is rare in current clinical practice. BMD studies using dual-energy absorptiometry are being increasingly used to assess the effects of PHPT on bone. PHPT primarily leads to one loss at cortical sites such as the distal radius while bone density is preserved at sites such as the lumbar spine. Current evaluation of patients with PHPT includes vertebral imaging by X-ray or vertebral fracture assessment (VFA) or CT scan in addition to BMD stud-ies. Measurement of trabecular bone score (TBS) is optional. In addition, renal |
Surgery_Schwartz_10994 | Surgery_Schwartz | with PHPT includes vertebral imaging by X-ray or vertebral fracture assessment (VFA) or CT scan in addition to BMD stud-ies. Measurement of trabecular bone score (TBS) is optional. In addition, renal imaging by ultrasound, X-ray, or CT scan is also recommended. Parathyroid localization studies are not used to confirm the diagnosis of PHPT, but rather to aid in identify-ing the location of the offending gland(s), as discussed later in “Preoperative Localization Tests.”Treatment Indications for Parathyroidectomy and Role of Medical Management. Most authorities agree that patients who have developed complications and have “classic” symptoms of PHPT should undergo parathyroidectomy. However, the treatment of patients with asymptomatic PHPT has been the subject of con-troversy, due, in part, to the fact that there is little agreement on what constitutes an asymptomatic patient.At the National Institutes of Health consensus conference in 1990, “asymptomatic” PHPT was defined as “the | Surgery_Schwartz. with PHPT includes vertebral imaging by X-ray or vertebral fracture assessment (VFA) or CT scan in addition to BMD stud-ies. Measurement of trabecular bone score (TBS) is optional. In addition, renal imaging by ultrasound, X-ray, or CT scan is also recommended. Parathyroid localization studies are not used to confirm the diagnosis of PHPT, but rather to aid in identify-ing the location of the offending gland(s), as discussed later in “Preoperative Localization Tests.”Treatment Indications for Parathyroidectomy and Role of Medical Management. Most authorities agree that patients who have developed complications and have “classic” symptoms of PHPT should undergo parathyroidectomy. However, the treatment of patients with asymptomatic PHPT has been the subject of con-troversy, due, in part, to the fact that there is little agreement on what constitutes an asymptomatic patient.At the National Institutes of Health consensus conference in 1990, “asymptomatic” PHPT was defined as “the |
Surgery_Schwartz_10995 | Surgery_Schwartz | part, to the fact that there is little agreement on what constitutes an asymptomatic patient.At the National Institutes of Health consensus conference in 1990, “asymptomatic” PHPT was defined as “the absence of common symptoms and signs of PHPT, including no bone, renal, gastrointestinal, or neuromuscular disorders.” To deter-mine the best course of action for these patients, it is important to consider the natural history of untreated PHPT and the out-comes of treatment options, both medical and surgical.With respect to the natural history, the panel advocated nonoperative management of these patients with mild PHPT based on observational studies, which suggested relative stabil-ity of biochemical parameters over time. However, the consen-sus panel considered certain patients to be candidates for surgery based on testing or other information indicating end-organ effects or a higher likelihood of disease progression, and this led to the establishment of initial guidelines for | Surgery_Schwartz. part, to the fact that there is little agreement on what constitutes an asymptomatic patient.At the National Institutes of Health consensus conference in 1990, “asymptomatic” PHPT was defined as “the absence of common symptoms and signs of PHPT, including no bone, renal, gastrointestinal, or neuromuscular disorders.” To deter-mine the best course of action for these patients, it is important to consider the natural history of untreated PHPT and the out-comes of treatment options, both medical and surgical.With respect to the natural history, the panel advocated nonoperative management of these patients with mild PHPT based on observational studies, which suggested relative stabil-ity of biochemical parameters over time. However, the consen-sus panel considered certain patients to be candidates for surgery based on testing or other information indicating end-organ effects or a higher likelihood of disease progression, and this led to the establishment of initial guidelines for |
Surgery_Schwartz_10996 | Surgery_Schwartz | be candidates for surgery based on testing or other information indicating end-organ effects or a higher likelihood of disease progression, and this led to the establishment of initial guidelines for parathyroidectomy.74 Subsequently, another observational study on the natural history of treated versus untreated HPT was published by Silverberg and colleagues.75 In their cohort of 52 patients with asymptomatic HPT followed without surgery, levels of serum and urinary calcium, PTH, alkaline phosphatase, and vitamin D metabolites remained relatively stable over a 10-year period in most patients. Average bone mass also remained relatively stable. However, the study also reported development of a new indication for surgery in 14 (27%) of 52 of their asymptom-atic patients and, because approximately 50% of their patients were initially treated surgically, overall, about 75% of patients were underwent parathyroidectomy. Age <50 years was predic-tive of progression, and patients undergoing | Surgery_Schwartz. be candidates for surgery based on testing or other information indicating end-organ effects or a higher likelihood of disease progression, and this led to the establishment of initial guidelines for parathyroidectomy.74 Subsequently, another observational study on the natural history of treated versus untreated HPT was published by Silverberg and colleagues.75 In their cohort of 52 patients with asymptomatic HPT followed without surgery, levels of serum and urinary calcium, PTH, alkaline phosphatase, and vitamin D metabolites remained relatively stable over a 10-year period in most patients. Average bone mass also remained relatively stable. However, the study also reported development of a new indication for surgery in 14 (27%) of 52 of their asymptom-atic patients and, because approximately 50% of their patients were initially treated surgically, overall, about 75% of patients were underwent parathyroidectomy. Age <50 years was predic-tive of progression, and patients undergoing |
Surgery_Schwartz_10997 | Surgery_Schwartz | 50% of their patients were initially treated surgically, overall, about 75% of patients were underwent parathyroidectomy. Age <50 years was predic-tive of progression, and patients undergoing parathyroidectomy showed not only normalization of calcium and PTH levels but also improved BMD at the spine and hip. Based on these and other studies, the guidelines were reassessed at a second work-shop on asymptomatic PHPT held at the National Institutes of Health in 2002.76Since that time, additional studies have provided further insights into the natural history of treated and untreated HPT. Three of these were randomized, controlled, prospective studies ranging in duration from 1 to 3.5 years. One was an observa-tional study (a continuation of the Columbia University PHPT Project) but was notable for its long duration of follow-up of 15 years.77 These studies confirmed the relative stability of vari-ous biochemical indices, thus validating the need for guidelines. However, the long-term | Surgery_Schwartz. 50% of their patients were initially treated surgically, overall, about 75% of patients were underwent parathyroidectomy. Age <50 years was predic-tive of progression, and patients undergoing parathyroidectomy showed not only normalization of calcium and PTH levels but also improved BMD at the spine and hip. Based on these and other studies, the guidelines were reassessed at a second work-shop on asymptomatic PHPT held at the National Institutes of Health in 2002.76Since that time, additional studies have provided further insights into the natural history of treated and untreated HPT. Three of these were randomized, controlled, prospective studies ranging in duration from 1 to 3.5 years. One was an observa-tional study (a continuation of the Columbia University PHPT Project) but was notable for its long duration of follow-up of 15 years.77 These studies confirmed the relative stability of vari-ous biochemical indices, thus validating the need for guidelines. However, the long-term |
Surgery_Schwartz_10998 | Surgery_Schwartz | for its long duration of follow-up of 15 years.77 These studies confirmed the relative stability of vari-ous biochemical indices, thus validating the need for guidelines. However, the long-term study suggested that the stability was not indefinite as calcium levels tended to rise in years 13 to 15. In addition, the study also demonstrated that bone density mea-surements remained stable for 8 to 10 years, but cortical bone density worsened after year 10. More concerning was the fact that 60% of patients lost >10% of their BMD over the 15-year observation period. Furthermore, whether patients met the 2002 guidelines for surgery did not appear to predict the risk of pro-gressive disease, with 40% of patients undergoing follow-up eventually needing surgery. Although there are no randomized trials, registry data also suggest that fracture risk is increased for PHPT up to 10 years prior to diagnosis and treatment.Medical options for treating PHPT and its complications include | Surgery_Schwartz. for its long duration of follow-up of 15 years.77 These studies confirmed the relative stability of vari-ous biochemical indices, thus validating the need for guidelines. However, the long-term study suggested that the stability was not indefinite as calcium levels tended to rise in years 13 to 15. In addition, the study also demonstrated that bone density mea-surements remained stable for 8 to 10 years, but cortical bone density worsened after year 10. More concerning was the fact that 60% of patients lost >10% of their BMD over the 15-year observation period. Furthermore, whether patients met the 2002 guidelines for surgery did not appear to predict the risk of pro-gressive disease, with 40% of patients undergoing follow-up eventually needing surgery. Although there are no randomized trials, registry data also suggest that fracture risk is increased for PHPT up to 10 years prior to diagnosis and treatment.Medical options for treating PHPT and its complications include |
Surgery_Schwartz_10999 | Surgery_Schwartz | randomized trials, registry data also suggest that fracture risk is increased for PHPT up to 10 years prior to diagnosis and treatment.Medical options for treating PHPT and its complications include antiresorptive treatments such as bisphosphonates, hor-mone replacement therapy (HRT), and selective estrogen recep-tor modulators such as raloxifene.78 Bisphosphonates and HRT are reasonable options in patients for whom skeletal protection is needed, as evidence from randomized, placebo-controlled trials indicates that these medications are very effective at decreasing bone turnover and increasing BMD in PHPT, with the effects being comparable to patients undergoing parathyroidectomy. Caution needs to be exercised due to the nonskeletal effects of HRT, and hence, bisphosphonates are preferred. There are no clinical studies regarding the effects of raloxifene on BMD in HPT, and none of these agents affects calcium or PTH levels. More recently, calcimimetics (modifiers of the sensitivity of | Surgery_Schwartz. randomized trials, registry data also suggest that fracture risk is increased for PHPT up to 10 years prior to diagnosis and treatment.Medical options for treating PHPT and its complications include antiresorptive treatments such as bisphosphonates, hor-mone replacement therapy (HRT), and selective estrogen recep-tor modulators such as raloxifene.78 Bisphosphonates and HRT are reasonable options in patients for whom skeletal protection is needed, as evidence from randomized, placebo-controlled trials indicates that these medications are very effective at decreasing bone turnover and increasing BMD in PHPT, with the effects being comparable to patients undergoing parathyroidectomy. Caution needs to be exercised due to the nonskeletal effects of HRT, and hence, bisphosphonates are preferred. There are no clinical studies regarding the effects of raloxifene on BMD in HPT, and none of these agents affects calcium or PTH levels. More recently, calcimimetics (modifiers of the sensitivity of |
Surgery_Schwartz_11000 | Surgery_Schwartz | There are no clinical studies regarding the effects of raloxifene on BMD in HPT, and none of these agents affects calcium or PTH levels. More recently, calcimimetics (modifiers of the sensitivity of the CASR) have been used in randomized, multicenter controlled trials and have been shown to decrease both serum calcium and PTH levels in both symptomatic and asymptomatic PHPT patients. Unfortunately, bone density failed to improve in medi-cally treated patients. Although this therapy shows promise, long-term outcome data are lacking, and their routine use is not advocated at this time, except in patients who are very poor operative risks or refuse surgery.Successful parathyroidectomy results in resolution of oste-itis fibrosa cystica and decreased formation of renal stones in symptomatic (classic) patients. In addition, it results in improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and 30% overall) after | Surgery_Schwartz. There are no clinical studies regarding the effects of raloxifene on BMD in HPT, and none of these agents affects calcium or PTH levels. More recently, calcimimetics (modifiers of the sensitivity of the CASR) have been used in randomized, multicenter controlled trials and have been shown to decrease both serum calcium and PTH levels in both symptomatic and asymptomatic PHPT patients. Unfortunately, bone density failed to improve in medi-cally treated patients. Although this therapy shows promise, long-term outcome data are lacking, and their routine use is not advocated at this time, except in patients who are very poor operative risks or refuse surgery.Successful parathyroidectomy results in resolution of oste-itis fibrosa cystica and decreased formation of renal stones in symptomatic (classic) patients. In addition, it results in improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and 30% overall) after |
Surgery_Schwartz_11001 | Surgery_Schwartz | (classic) patients. In addition, it results in improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and 30% overall) after adjustment for age, sex, and previous frac-tures over a 20-year observation period.75 There are also data to show that it improves a number of the nonspecific manifesta-tions of PHPT such as fatigue, polydipsia, polyuria and nocturia, Brunicardi_Ch38_p1625-p1704.indd 167001/03/19 11:21 AM 1671THYROID, PARATHYROID, AND ADRENALCHAPTER 38Table 38-11Indications for parathyroidectomy in patients with asymptomatic primary HPT (2014 NIH consensus conference guidelines)• Serum calcium >1 mg/dL above the upper limits of normal• GFR <60 mL/min; 24-h urine for calcium >400 mg/d (>10 mmol/d) and increased stone risk by biochemical stone risk analysis; presence of nephrolithiasis or nephrocalcinosis by X-ray, ultrasound, or CT• Substantially decreased bone mineral density at the lumbar spine, total hip, | Surgery_Schwartz. (classic) patients. In addition, it results in improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and 30% overall) after adjustment for age, sex, and previous frac-tures over a 20-year observation period.75 There are also data to show that it improves a number of the nonspecific manifesta-tions of PHPT such as fatigue, polydipsia, polyuria and nocturia, Brunicardi_Ch38_p1625-p1704.indd 167001/03/19 11:21 AM 1671THYROID, PARATHYROID, AND ADRENALCHAPTER 38Table 38-11Indications for parathyroidectomy in patients with asymptomatic primary HPT (2014 NIH consensus conference guidelines)• Serum calcium >1 mg/dL above the upper limits of normal• GFR <60 mL/min; 24-h urine for calcium >400 mg/d (>10 mmol/d) and increased stone risk by biochemical stone risk analysis; presence of nephrolithiasis or nephrocalcinosis by X-ray, ultrasound, or CT• Substantially decreased bone mineral density at the lumbar spine, total hip, |
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