To determine the accuracy of noninvasive and invasive localization studies in patients with persi... more To determine the accuracy of noninvasive and invasive localization studies in patients with persistent or recurrent hyperparathyroidism (HPT). Reoperations based on patients who were treated surgically for recurrent or persistent HPT at the University of California-San Francisco Hospitals from 1982 to 1993. This study evaluated 174 localization studies performed in 152 patients before reoperation (110 women and 42 men). The accuracy of localization studies, including ultrasonography, thallous chloride T1 201-technetium Tc 99m pertechnetate scanning, technetium Tc 99m sestamibi scanning, magnetic resonance imaging, computed tomography, and selective venous catheterization, were evaluated, as were the results of parathyroid reoperations. A total of 174 consecutive reoperations were performed in 152 patients with HPT (persistent, 113; recurrent, 39; mean age, 54 years; range, 21 to 88 years). One hundred thirty-three patients had primary HPT, 15 had secondary HPT, and four had tertiary HPT. Overall, 141 (93%) became normocalcemic, two (1%) became hypocalcemic, and nine (6%) remained hypercalcemic. Abnormal parathyroid glands at reoperation were situated in a normal location in 77 cases (44%), in the mediastinum in 37 cases (22%), in a deep cervical location in 34 cases (19%), or in an intrathyroidal location in 14 cases (8%), or were undescended in four cases (2%); supernumerary glands were found in 26 cases (15%). Some patients had more than one remaining abnormal gland. Selective venous catheterization with a parathyroid hormone assay was done in cases in which the results of noninvasive localization studies were equivocal or negative, and it frequently converted an equivocal result of a localization study to a definitely positive result. There were no complications from the localization studies. At reoperation, permanent hypoparathyroidism that required parathyroid autotransplantation of cryopreserved tissue developed in two patients and two patients had recurrent laryngeal nerve palsies. We currently recommend using ultrasonography and technetium Tc99m sestamibi scanning and magnetic resonance imaging for patients with recurrent or persistent HPT. Selective venous catheterization with a parathyroid hormone assay is done selectively. Localization tests decrease morbidity and improve overall results in these patients.
Similarities exist in hormone receptors of breast, prostate, and thyroid tumors. HER2 oncogene ex... more Similarities exist in hormone receptors of breast, prostate, and thyroid tumors. HER2 oncogene expression is known to be present in breast and prostate tumors, but conflicting data have been published about its presence in thyroid tumors. This uncertainty prompted us to examine the incidence of HER2 overexpression in normal and malignant thyroid tissue. Normal and neoplastic thyroid tissue samples from 46 female and 9 male patients were assayed for HER2 expression by immunohistochemical assay. Of the 55 total samples, 36 were from neoplasms and 19 were from benign tissues. Significant HER2 overexpression was not found in any benign or malignant thyroid tissue. Two of 6 thyroid carcinomas from male patients showed 1+ reactivity for HER2 expression on immunohistochemistry assay, but remained negative on fluorescene in sito hybridization confirmatory testing. No significant expression of HER2 was noted in benign or malignant thyroid tissue. These results cast doubt on the value of HER2 as a prognostic factor or possible target for specific antitumor therapy for thyroid cancer.
Imaging of metastatic sites of medullary thyroid carcinoma (MTC) is successful in less than 60% o... more Imaging of metastatic sites of medullary thyroid carcinoma (MTC) is successful in less than 60% of cases of residual or recurrent disease. Positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) takes advantage of the fact that malignant tumors are capable of increased uptake and use of glucose, which is mediated by the members of the glucose transporter family of proteins (GLUT 1 through GLUT 5). FDG-PET images of 10 patients with recurrent or persistent MTC after primary operation were compared with images by computed tomography or magnetic resonance imaging. Identified metastatic lesions were assessed by intraoperative findings and pathology reports. Expression of GLUT 1 through GLUT 5 was examined by Western blot analysis of tumor tissue from eight of the patients evaluated and an additional panel of 10 MTCs and seven pheochromocytomas. FDG-PET identified 31 foci of FDG accumulation in 10 patients, and 16 of these metastatic sites were resected and confirmed by histologic analysis. Only 11 foci were demonstrated by computed tomographic or magnetic resonance imaging. None of the glucose transporters examined displayed significant expression. Two pheochromocytomas were successfully imaged by FDG-PET. FDG-PET imaging can be useful in the localization of cervicomediastinal MTC metastases and pheochromocytoma. The increased glucose uptake in these tumors, as evidenced by FDG-PET, does not appear to be attributable to the expression of the glucose transporter proteins GLUT 1 through GLUT 5.
Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techn... more Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techniques for localizing insulinoma. Retrospective review. A tertiary referral center. All patients with a biochemical diagnosis of organic hyperinsulinism who were referred to University of California, San Francisco, from 1975 to 1998. Sensitivities of the localization techniques for insulinoma were evaluated. The sensitivities of tumor localization with arteriography, computed tomography, preoperative ultrasonography, magnetic resonance imaging, magnetic resonance imaging with gadolinium, transhepatic venous sampling, palpation, and intraoperative ultrasonography were 47%, 24%, 50%, 30%, 40%, 55%, 76%, and 91%, respectively. Nine of the 11 nonpalpable and nonvisible tumors at operation were localized by intraoperative ultrasonography. The currently available preoperative localization tests are not reliable enough to be recommended when intraoperative ultrasonography is available.
Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and refe... more Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and referral patterns for sporadic, nonfamilial, non-multiple endocrine neoplasia, primary hyperparathyroidism (PHPT). The American Association of Clinical Endocrinologists membership was surveyed by mail (n=1406 members) regarding physician practices and surgical referral patterns for PHPT. Seven hundred eighty-eight respondents (56%) practiced 17.0+/-0.4 years and referred 63%+/-1% of patients with PHPT for operation. Most endocrinologists (90%) used localizing studies before surgical referral (sestamibi, ultrasound scanning, technetium/thallium scanning, magnetic resonance imaging, computed tomography). Respondents identified symptoms, calcium homeostasis, bone density, health status, age, and general anesthesia risk as the most important considerations for surgical referral. Most respondents (79%) indicated that MIP availability would increase the number of patients who were referred for operation (P<.001), although most of the respondents stated that MIP would change the extent and duration of preoperative evaluations (P<.001). Respondents in practice for fewer years were more likely to refer patients for MIP (P<.001) and minimize preoperative evaluation (P<.05). Endocrinologists who had a patient with a complication after traditional parathyroidectomy were more likely to embrace MIP (P<.05). MIP availability decreases the extent and duration of preoperative evaluation while decreasing the time from diagnosis to referral. MIP also lowers the endocrinologists' surgical referral threshold for PHPT, although it emphasizes the perceived shortcomings of traditional parathyroidectomy that are held by many physicians.
The reported incidence of recurrent laryngeal nerve (RLN) palsy/paralysis in thyroid and parathyr... more The reported incidence of recurrent laryngeal nerve (RLN) palsy/paralysis in thyroid and parathyroid operation ranges from 2% to 13%. Injury to the external branch of the superior laryngeal nerve (EBSLN) is less clearly documented. We hypothesized that a novel evoked electromyography system using an audio warning alarm might be beneficial for detection and preservation of the RLN and EBSLN. A total of 117 thyroid/parathyroid operations were performed using a nerve locator/monitor (Neurovision SE, RLN Systems Inc, Jefferson City, Mo). Dissection was performed using a stimulating hemostat with conduction to an endotracheal surface electrode. A total of 97 thyroidectomies (50 total, 47 lobectomies) and 20 parathyroidectomies (16 directed, 4 bilateral) were performed representing 176 RLN and 152 EBSLN at risk. Of 176 RLN, 161 were correctly identified by the nerve stimulator alarm including 2 nonrecurrent nerves. The cricothyroid space and the superior pole vessels were scanned to ident...
Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described p... more Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described pathologically, but there is little clinical information regarding tumor behavior. We retrospectively analyzed the course of our patient and 16 others reported in the literature to determine optimal management. We review the case history of our patient and the literature concerning patients with carcinosarcoma of the thyroid. Seventeen patients, 52 to 80 years of age (mean, 60 years), have had a thyroid carcinosarcoma of the thyroid. Five of seven patients for whom the information is available were treated by partial thyroidectomy and two by total thyroidectomy. Among these patients five (71%) died within the first 3 months and two (29%) survived more than 6 months. The mean survival was 5 months. At autopsy in seven patients, six had lymph node or distant metastases. Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. L...
Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathy... more Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathyroidectomy, but generally fail to consider neurocognitive and psychiatric symptoms because of the relative paucity of evidence. In this prospective study, patients with pHPT (PTX) and benign euthyroid thyroid disease (THY) referred for operation were evaluated pre- and postoperatively with validated psychometric and neurocognitive instruments to determine whether learning, memory, or concentration improved with after parathyroidectomy. Statistical comparisons between groups were performed with univariate analysis and repeated measures of analysis of variance. Fifty-five subjects, mean age of 54 years, were evaluated preoperatively; 41 returned postoperatively. There were no significant differences between groups by age and gender. PTXs reported more depression symptoms preoperatively (P = .04) that improved postoperatively. There were no differences between the 2 groups on verbal memory and trait anxiety. For PTXs, average preoperative serum calcium concentration (11.3 mg/dL) and serum PTH level (100 pg/mL) normalized postoperatively. Preoperatively PTXs showed greater delays in their spatial learning (P = .03). All subjects learned across the 5 trials, but PTXs were more delayed (P = .03). After operation, PTXs improved and functioned at a level equivalent to the THYs. There was an interaction between trial (neurocognitive testing), visit (pre- vs postoperative), status (PTX vs THY), and change in PTH level (P = .06), suggesting that individuals with greater change in PTH were more likely to improve in their learning efficiency postparathyroidectomy. PHPT may be associated with a spatial learning deficit and processing that improves after parathyroidectomy. While longer-term follow-up is necessary, neurocognitive symptoms perhaps should be considered as criteria for parathyroidectomy.
A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. ... more A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. We wanted to determine if some of these families represent early manifestations of full-blown syndromes such as multiple endocrine neoplasia type 1 (MEN-1), as early identification may alter surgical and medical management. Four small families with a family history of hyperparathyroidism without clear-cut MEN-1 features were screened for a MEN1 mutation. The 10 exons of the MEN1 gene were amplified and analyzed by single-strand conformation analysis (SSCA). Abnormal SSCA shifts were then sequenced using an automated sequencer. Two germline mutations were found: R527X and P277H. The former was detected in three members of a family consisting of two children and a mother. At the time of testing the youngest son was normocalcemic and clinically normal but subsequently developed hyperparathyroidism (HPT). Since the initial testing, the family has been confirmed to be a MEN-1 family as the mother has developed abdominal pain and an elevated serum pancreatic polypeptide and the younger brother an anterior pituitary tumor and recurrent HPT. The latter P277H mutation was identified in two of three members tested from another family. Manifestations of MEN-1 syndrome have also developed. The father now has developed diarrhea and elevated serum gastrin; and the daughter has developed recurrent HPT. Genetic screening of families who clinically have FIHP is important and may influence the type of medical and surgical treatment and follow-up, as some have MEN-1 syndrome. Long-term screening for MEN syndromes should be included in this set of patients. Positive screening may predict disease and allow early detection and appropriate treatment before initiation of symptoms.
Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an es... more Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake. Despite this key difference between tumor and normal cells, the mechanism which mediates increased glucose uptake is poorly understood. Several research studies have assessed the expression of different glucose transporter (GLUT) proteins and expression of the genes which code for them in thyroid tissues. While no consensus exists on the specifics of which GLUT genes or proteins are expressed, a picture has emerged that a single specific transporter, GLUT1, is expressed at higher levels in thyroid carcinomas compared to a variety of normal and nonmalignant forms of thyroid disease. Greater levels of GLUT1 expression may be associated with poorer prognosis. Experiments in established thyroid carcinoma cells lines may provide useful insights into glucose transport in the thyroid. Thyroid cells show increased glucose uptake in response to thyroid-stimulating hormone (TSH), but expression of GLUT genes does not appear to be significantly affected by TSH suggesting TSH affects glucose uptake by affecting GLUT localization/ translocation rather than through increased GLUT gene expression. Improving technologies are providing a stronger foundation for detailed analyses of glucose transporters in thyroid to better elucidate the mechanisms by which these genes and proteins are regulated in normal and pathogenic tissue.
Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and se... more Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and seven without previous surgery, had computed tomography (CT) examinations preoperatively to evaluate the use of CT in localizing parathyroid adenomas. The patients were scanned at 5 mm intervals from the level of the hyoid bone to the lung apex. Scanning of the mediastinum was performed at 10 mm intervals from apex to lung base. Computed tomography correctly identified prospectively the site of the adenoma in 10 of 13 patients (77%), with surgically proven adenomas. In retrospect, all 13 adenomas could be identified. One false positive diagnosis of adenoma was made. Our study suggests that CT may be beneficial in the preoperative localization of parathyroid tumors, particularly in ectopic locations.
To determine the accuracy of noninvasive and invasive localization studies in patients with persi... more To determine the accuracy of noninvasive and invasive localization studies in patients with persistent or recurrent hyperparathyroidism (HPT). Reoperations based on patients who were treated surgically for recurrent or persistent HPT at the University of California-San Francisco Hospitals from 1982 to 1993. This study evaluated 174 localization studies performed in 152 patients before reoperation (110 women and 42 men). The accuracy of localization studies, including ultrasonography, thallous chloride T1 201-technetium Tc 99m pertechnetate scanning, technetium Tc 99m sestamibi scanning, magnetic resonance imaging, computed tomography, and selective venous catheterization, were evaluated, as were the results of parathyroid reoperations. A total of 174 consecutive reoperations were performed in 152 patients with HPT (persistent, 113; recurrent, 39; mean age, 54 years; range, 21 to 88 years). One hundred thirty-three patients had primary HPT, 15 had secondary HPT, and four had tertiary HPT. Overall, 141 (93%) became normocalcemic, two (1%) became hypocalcemic, and nine (6%) remained hypercalcemic. Abnormal parathyroid glands at reoperation were situated in a normal location in 77 cases (44%), in the mediastinum in 37 cases (22%), in a deep cervical location in 34 cases (19%), or in an intrathyroidal location in 14 cases (8%), or were undescended in four cases (2%); supernumerary glands were found in 26 cases (15%). Some patients had more than one remaining abnormal gland. Selective venous catheterization with a parathyroid hormone assay was done in cases in which the results of noninvasive localization studies were equivocal or negative, and it frequently converted an equivocal result of a localization study to a definitely positive result. There were no complications from the localization studies. At reoperation, permanent hypoparathyroidism that required parathyroid autotransplantation of cryopreserved tissue developed in two patients and two patients had recurrent laryngeal nerve palsies. We currently recommend using ultrasonography and technetium Tc99m sestamibi scanning and magnetic resonance imaging for patients with recurrent or persistent HPT. Selective venous catheterization with a parathyroid hormone assay is done selectively. Localization tests decrease morbidity and improve overall results in these patients.
Similarities exist in hormone receptors of breast, prostate, and thyroid tumors. HER2 oncogene ex... more Similarities exist in hormone receptors of breast, prostate, and thyroid tumors. HER2 oncogene expression is known to be present in breast and prostate tumors, but conflicting data have been published about its presence in thyroid tumors. This uncertainty prompted us to examine the incidence of HER2 overexpression in normal and malignant thyroid tissue. Normal and neoplastic thyroid tissue samples from 46 female and 9 male patients were assayed for HER2 expression by immunohistochemical assay. Of the 55 total samples, 36 were from neoplasms and 19 were from benign tissues. Significant HER2 overexpression was not found in any benign or malignant thyroid tissue. Two of 6 thyroid carcinomas from male patients showed 1+ reactivity for HER2 expression on immunohistochemistry assay, but remained negative on fluorescene in sito hybridization confirmatory testing. No significant expression of HER2 was noted in benign or malignant thyroid tissue. These results cast doubt on the value of HER2 as a prognostic factor or possible target for specific antitumor therapy for thyroid cancer.
Imaging of metastatic sites of medullary thyroid carcinoma (MTC) is successful in less than 60% o... more Imaging of metastatic sites of medullary thyroid carcinoma (MTC) is successful in less than 60% of cases of residual or recurrent disease. Positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) takes advantage of the fact that malignant tumors are capable of increased uptake and use of glucose, which is mediated by the members of the glucose transporter family of proteins (GLUT 1 through GLUT 5). FDG-PET images of 10 patients with recurrent or persistent MTC after primary operation were compared with images by computed tomography or magnetic resonance imaging. Identified metastatic lesions were assessed by intraoperative findings and pathology reports. Expression of GLUT 1 through GLUT 5 was examined by Western blot analysis of tumor tissue from eight of the patients evaluated and an additional panel of 10 MTCs and seven pheochromocytomas. FDG-PET identified 31 foci of FDG accumulation in 10 patients, and 16 of these metastatic sites were resected and confirmed by histologic analysis. Only 11 foci were demonstrated by computed tomographic or magnetic resonance imaging. None of the glucose transporters examined displayed significant expression. Two pheochromocytomas were successfully imaged by FDG-PET. FDG-PET imaging can be useful in the localization of cervicomediastinal MTC metastases and pheochromocytoma. The increased glucose uptake in these tumors, as evidenced by FDG-PET, does not appear to be attributable to the expression of the glucose transporter proteins GLUT 1 through GLUT 5.
Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techn... more Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techniques for localizing insulinoma. Retrospective review. A tertiary referral center. All patients with a biochemical diagnosis of organic hyperinsulinism who were referred to University of California, San Francisco, from 1975 to 1998. Sensitivities of the localization techniques for insulinoma were evaluated. The sensitivities of tumor localization with arteriography, computed tomography, preoperative ultrasonography, magnetic resonance imaging, magnetic resonance imaging with gadolinium, transhepatic venous sampling, palpation, and intraoperative ultrasonography were 47%, 24%, 50%, 30%, 40%, 55%, 76%, and 91%, respectively. Nine of the 11 nonpalpable and nonvisible tumors at operation were localized by intraoperative ultrasonography. The currently available preoperative localization tests are not reliable enough to be recommended when intraoperative ultrasonography is available.
Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and refe... more Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and referral patterns for sporadic, nonfamilial, non-multiple endocrine neoplasia, primary hyperparathyroidism (PHPT). The American Association of Clinical Endocrinologists membership was surveyed by mail (n=1406 members) regarding physician practices and surgical referral patterns for PHPT. Seven hundred eighty-eight respondents (56%) practiced 17.0+/-0.4 years and referred 63%+/-1% of patients with PHPT for operation. Most endocrinologists (90%) used localizing studies before surgical referral (sestamibi, ultrasound scanning, technetium/thallium scanning, magnetic resonance imaging, computed tomography). Respondents identified symptoms, calcium homeostasis, bone density, health status, age, and general anesthesia risk as the most important considerations for surgical referral. Most respondents (79%) indicated that MIP availability would increase the number of patients who were referred for operation (P<.001), although most of the respondents stated that MIP would change the extent and duration of preoperative evaluations (P<.001). Respondents in practice for fewer years were more likely to refer patients for MIP (P<.001) and minimize preoperative evaluation (P<.05). Endocrinologists who had a patient with a complication after traditional parathyroidectomy were more likely to embrace MIP (P<.05). MIP availability decreases the extent and duration of preoperative evaluation while decreasing the time from diagnosis to referral. MIP also lowers the endocrinologists' surgical referral threshold for PHPT, although it emphasizes the perceived shortcomings of traditional parathyroidectomy that are held by many physicians.
The reported incidence of recurrent laryngeal nerve (RLN) palsy/paralysis in thyroid and parathyr... more The reported incidence of recurrent laryngeal nerve (RLN) palsy/paralysis in thyroid and parathyroid operation ranges from 2% to 13%. Injury to the external branch of the superior laryngeal nerve (EBSLN) is less clearly documented. We hypothesized that a novel evoked electromyography system using an audio warning alarm might be beneficial for detection and preservation of the RLN and EBSLN. A total of 117 thyroid/parathyroid operations were performed using a nerve locator/monitor (Neurovision SE, RLN Systems Inc, Jefferson City, Mo). Dissection was performed using a stimulating hemostat with conduction to an endotracheal surface electrode. A total of 97 thyroidectomies (50 total, 47 lobectomies) and 20 parathyroidectomies (16 directed, 4 bilateral) were performed representing 176 RLN and 152 EBSLN at risk. Of 176 RLN, 161 were correctly identified by the nerve stimulator alarm including 2 nonrecurrent nerves. The cricothyroid space and the superior pole vessels were scanned to ident...
Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described p... more Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described pathologically, but there is little clinical information regarding tumor behavior. We retrospectively analyzed the course of our patient and 16 others reported in the literature to determine optimal management. We review the case history of our patient and the literature concerning patients with carcinosarcoma of the thyroid. Seventeen patients, 52 to 80 years of age (mean, 60 years), have had a thyroid carcinosarcoma of the thyroid. Five of seven patients for whom the information is available were treated by partial thyroidectomy and two by total thyroidectomy. Among these patients five (71%) died within the first 3 months and two (29%) survived more than 6 months. The mean survival was 5 months. At autopsy in seven patients, six had lymph node or distant metastases. Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. L...
Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathy... more Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathyroidectomy, but generally fail to consider neurocognitive and psychiatric symptoms because of the relative paucity of evidence. In this prospective study, patients with pHPT (PTX) and benign euthyroid thyroid disease (THY) referred for operation were evaluated pre- and postoperatively with validated psychometric and neurocognitive instruments to determine whether learning, memory, or concentration improved with after parathyroidectomy. Statistical comparisons between groups were performed with univariate analysis and repeated measures of analysis of variance. Fifty-five subjects, mean age of 54 years, were evaluated preoperatively; 41 returned postoperatively. There were no significant differences between groups by age and gender. PTXs reported more depression symptoms preoperatively (P = .04) that improved postoperatively. There were no differences between the 2 groups on verbal memory and trait anxiety. For PTXs, average preoperative serum calcium concentration (11.3 mg/dL) and serum PTH level (100 pg/mL) normalized postoperatively. Preoperatively PTXs showed greater delays in their spatial learning (P = .03). All subjects learned across the 5 trials, but PTXs were more delayed (P = .03). After operation, PTXs improved and functioned at a level equivalent to the THYs. There was an interaction between trial (neurocognitive testing), visit (pre- vs postoperative), status (PTX vs THY), and change in PTH level (P = .06), suggesting that individuals with greater change in PTH were more likely to improve in their learning efficiency postparathyroidectomy. PHPT may be associated with a spatial learning deficit and processing that improves after parathyroidectomy. While longer-term follow-up is necessary, neurocognitive symptoms perhaps should be considered as criteria for parathyroidectomy.
A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. ... more A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. We wanted to determine if some of these families represent early manifestations of full-blown syndromes such as multiple endocrine neoplasia type 1 (MEN-1), as early identification may alter surgical and medical management. Four small families with a family history of hyperparathyroidism without clear-cut MEN-1 features were screened for a MEN1 mutation. The 10 exons of the MEN1 gene were amplified and analyzed by single-strand conformation analysis (SSCA). Abnormal SSCA shifts were then sequenced using an automated sequencer. Two germline mutations were found: R527X and P277H. The former was detected in three members of a family consisting of two children and a mother. At the time of testing the youngest son was normocalcemic and clinically normal but subsequently developed hyperparathyroidism (HPT). Since the initial testing, the family has been confirmed to be a MEN-1 family as the mother has developed abdominal pain and an elevated serum pancreatic polypeptide and the younger brother an anterior pituitary tumor and recurrent HPT. The latter P277H mutation was identified in two of three members tested from another family. Manifestations of MEN-1 syndrome have also developed. The father now has developed diarrhea and elevated serum gastrin; and the daughter has developed recurrent HPT. Genetic screening of families who clinically have FIHP is important and may influence the type of medical and surgical treatment and follow-up, as some have MEN-1 syndrome. Long-term screening for MEN syndromes should be included in this set of patients. Positive screening may predict disease and allow early detection and appropriate treatment before initiation of symptoms.
Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an es... more Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake. Despite this key difference between tumor and normal cells, the mechanism which mediates increased glucose uptake is poorly understood. Several research studies have assessed the expression of different glucose transporter (GLUT) proteins and expression of the genes which code for them in thyroid tissues. While no consensus exists on the specifics of which GLUT genes or proteins are expressed, a picture has emerged that a single specific transporter, GLUT1, is expressed at higher levels in thyroid carcinomas compared to a variety of normal and nonmalignant forms of thyroid disease. Greater levels of GLUT1 expression may be associated with poorer prognosis. Experiments in established thyroid carcinoma cells lines may provide useful insights into glucose transport in the thyroid. Thyroid cells show increased glucose uptake in response to thyroid-stimulating hormone (TSH), but expression of GLUT genes does not appear to be significantly affected by TSH suggesting TSH affects glucose uptake by affecting GLUT localization/ translocation rather than through increased GLUT gene expression. Improving technologies are providing a stronger foundation for detailed analyses of glucose transporters in thyroid to better elucidate the mechanisms by which these genes and proteins are regulated in normal and pathogenic tissue.
Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and se... more Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and seven without previous surgery, had computed tomography (CT) examinations preoperatively to evaluate the use of CT in localizing parathyroid adenomas. The patients were scanned at 5 mm intervals from the level of the hyoid bone to the lung apex. Scanning of the mediastinum was performed at 10 mm intervals from apex to lung base. Computed tomography correctly identified prospectively the site of the adenoma in 10 of 13 patients (77%), with surgically proven adenomas. In retrospect, all 13 adenomas could be identified. One false positive diagnosis of adenoma was made. Our study suggests that CT may be beneficial in the preoperative localization of parathyroid tumors, particularly in ectopic locations.
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