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Biomedical subjects

Steven I Sherman

Publications and source records attributed to Steven I Sherman.

9 recordsLinked to original sources

Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma.

Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of 131I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of 131I. A comparison of the 131I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that "stunning" from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study.

Adult↗

Prognostic factors in patients with Hürthle cell neoplasms of the thyroid.

BACKGROUND: Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS: The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS: The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS: Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy.

Adenoma, Oxyphilic↗

Thyroid carcinoma.

Thyroid carcinomas are fairly uncommon and include disease types that range from indolent localised papillary carcinomas to the fulminant and lethal anaplastic disease. Several attempts to formulate a consensus about treatment of thyroid carcinoma have resulted in published guidelines for diagnosis and initial disease management. Multimodality treatments are widely recommended, although there is little evidence from prospective trials to support this approach. Surgical resection to achieve local disease control remains the cornerstone of primary treatment for most thyroid cancers, and is often followed by adjuvant radioiodine treatment for papillary and follicular types of disease. Thyroid hormone replacement therapy is used not only to rectify postsurgical hypothyroidism, but also because there is evidence to suggest that high doses that suppress thyroid stimulating hormone prevent disease recurrence in patients with papillary or follicular carcinomas. Treatment for progressive metastatic disease is often of limited benefit, and there is a pressing need for novel approaches in treatment of patients at high risk of disease-related death. In families with inherited thyroid cancer syndromes, early diagnosis and intervention based on genetic testing might prevent poor disease outcomes. Care should be carefully coordinated by members of an experienced multidisciplinary team, and patients should be provided with education about diagnosis, prognosis, and treatment options to allow them to make informed contributions to decisions about their care.

Aftercare↗

Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationship.

HYPOTHESIS: Multiple endocrine neoplasia type 2 (MEN 2) is caused by RET proto-oncogene mutations and has a strong penetrance for medullary thyroid carcinoma (MTC). Subtypes are defined by the presence or absence of pheochromocytomas, hyperparathyroidism, and characteristic clinical stigmas. We hypothesize that specific RET mutations correlate with the MEN 2 phenotype and aggressiveness of MTC. DESIGN: Review of endocrine surgery database from 1951 through 2002. SETTING: Tertiary referral center. PATIENTS: Eighty-six patients from 47 kindreds were identified with MEN 2A, MEN 2B, or familial MTC. Patients were classified into 3 RET mutation risk groups: level 1, low risk for MTC (codons 609, 768, 790, 791, 804, and 891); level 2, intermediate risk (codons 611, 618, 620, and 634); and level 3, highest risk (codons 883 and 918). MAIN OUTCOME MEASURES: Stage of MTC at diagnosis and at last follow-up and frequency of pheochromocytomas and hyperparathyroidism. RESULTS: RET analysis was complete for 71 patients from 39 kindreds. Multivariate analysis identified an increased likelihood of stage III or IV MTC at diagnosis with increasing age (odds ratio, 1.12 per year of age at thyroidectomy; 95% confidence interval, 1.07-1.17; P<.001) and increasing risk group (odds ratio, 14.23 per incremental increase in MTC risk group from 1 to 3; 95% confidence interval, 3.05-66.55; P<.001). Pheochromocytomas were found in 21 patients from 12 kindreds; 20 of 21 patients had codon 634 or 918 mutations. Hyperparathyroidism was found in 10 patients from 7 kindreds; 7 of 10 patients had codon 634 mutations. CONCLUSION: Specific RET mutations predict the phenotypic expression of disease and the MTC aggressiveness in patients with MEN 2, guiding the timing of thyroidectomy and screening for pheochromocytoma.

Adolescent↗

Etiology, diagnosis, and treatment recommendations for central hypothyroidism associated with bexarotene therapy for cutaneous T-cell lymphoma.

Bexarotene is a synthetic retinoid X receptor (RXR)-selective retinoid recently approved for treatment of cutaneous T-cell lymphoma. In clinical trials, bexarotene was found to cause severe central hypothyroidism with high frequency, associated with marked reductions in serum concentrations of thyroid-stimulating hormone (TSH) and thyroxine. Further investigation demonstrated a novel mechanism causing this effect, namely reversible, RXR-mediated, thyroid hormone-independent suppression of TSH gene expression. Treatment of patients with bexarotene-induced hypothyroidism commonly requires high doses of thyroid hormone for replacement therapy, often twice the typical doses used to treat more common etiologies of hypothyroidism. These observations suggest that bexarotene probably has two fundamental effects on thyroid function: to suppress TSH production and to increase thyroid hormone metabolic clearance. Recommendations are provided for diagnosis and treatment of this syndrome.

Anticarcinogenic Agents↗

Genotype-phenotype analysis in multiple endocrine neoplasia type 1.

HYPOTHESIS: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is an autosomal dominant disorder caused by germline mutations in the MEN1 gene and characterized by multiple endocrine tumors, most notably in the parathyroid glands, pituitary, and pancreas. The syndrome demonstrates variable expressivity and considerable genetic heterogeneity. Patient data were examined for possible associations between genotype and phenotype. DESIGN: We reviewed recorded medical data from 1975 to 2001 on patients with MEN 1 and compared specific types and locations of MEN1 gene mutations with manifestations of the syndrome. PATIENTS AND RESULTS: We identified 109 affected patients from 24 MEN 1 kindreds. The phenotypic expression of MEN 1 in affected individuals included hyperparathyroidism in 74%, pancreatic endocrine tumors in 51%, and pituitary tumors in 35%. Twelve of 14 insulinomas occurred in patients with pituitary tumors. Mutation analysis was completed in 14 of 24 kindreds (80 of the 109 patients). Mutations were most common in exons 2 (31%), 9 (15%), and 10 (23%). All 21 patients with frameshift mutations (and known pancreatic endocrine tumor status) had such tumors. Pituitary tumors were associated with frameshift mutations in exon 2. CONCLUSIONS: The type and location of MEN1 mutations may be associated with the phenotypic expression of specific tumors. Such information may assist in the genetic counseling and surveillance of at-risk patients. A specific genotype-phenotype correlation is unlikely because of the heterogeneity of the mutations in the MEN1 gene.

Adult↗

Improving the yield of preoperative parathyroid localization: technetium Tc 99m-sestamibi imaging after thyroid suppression.

BACKGROUND: Preoperative localization is essential for successful directed, minimally invasive or reoperative parathyroidectomy. Standard technetium Tc 99m-sestamibi imaging is the most sensitive modality for localization. We reviewed our experience with (99m)Tc-sestamibi imaging and specifically investigated the effect of thyroid suppression on repeat imaging of patients who had initially nonlocalizing scans. METHODS: . The records of patients who underwent (99m)Tc-sestamibi imaging during evaluation for primary hyperparathyroidism were reviewed. A subset of patients with initially nonlocalizing scans underwent thyroid suppression with either thyroxin or liothyronine and then had their scans repeated. RESULTS: Ninety-nine patients with primary hyperparathyroidism underwent (99m)Tc-sestamibi imaging followed by parathyroidectomy (initial operation, 78; reoperation, 21). Successful parathyroid localization was obtained on standard imaging in 67 patients. Fourteen of 32 patients who had nonlocalizing (99m)Tc-sestamibi imaging studies underwent an additional scan after thyroid suppression. In 10 of 14 patients (71%), repeat (99m)Tc-sestamibi imaging after thyroid suppression successfully localized abnormal parathyroid tissue. CONCLUSIONS: Thyroid suppression may improve the yield of (99m)Tc-sestamibi imaging in patients with hyperparathyroidism who have an initially nonlocalizing study. This diagnostic strategy may be helpful in patients motivated to undergo a directed, minimally invasive operation, as well as in the evaluation of patients for reoperative parathyroidectomy.

Humans↗

Socioeconomic factors and the presentation, management, and outcome of patients with differentiated thyroid carcinoma.

To determine whether patients from disadvantaged socioeconomic groups present with more advanced thyroid carcinoma or experience differing management and clinical outcomes, we retrospectively reviewed the charts of 292 patients seen at MD Anderson Cancer Center and Ben Taub General Hospital between 1987 and 1994. At diagnosis, the mean age was 42 +/- 16 years, 78% of patients were female, 76% of patients were low risk (TNM stage I or II), and 22% high risk (stage III or IV). Neighborhood income (+/- standard error of the mean [SEM]) (1990 census data) was lower in the high-risk group compared with the low-risk group (US dollars 26200 +/- 1670 vs. US dollars 30900 +/- 870, p = 0.012). Men were more likely than women to present at an older age (47.5 +/- 16.7 vs. 40.2 +/- 16.0, p = 0.0014) and in the high-risk group (46% vs. 15%, p < 0.0001). No socioeconomic factor (ethnicity, marital status, occupation prestige, neighborhood income, insurance type) influenced initial diagnostic assessment. Similarly, no socioeconomic factor influenced initial disease management or the type of follow-up received over the 12-year period. Married patients had a lower 5-year recurrence rate than those unmarried (18% vs. 32%, p = 0.03); however, this did not affect overall or disease-specific survival. Similarly, ethnicity, marital status, occupation prestige, and insurance type did not influence overall or disease-specific survival. Although 10-year overall survival rates were lower in patients in the lowest income quartile (57% vs. 70% for upper, p = 0.0024) and in men compared with women (39% vs. 76%, p < 0.0001), gender alone influenced 10-year disease-specific survival (80% for men, 89% for women, p = 0.047). In summary, no socioeconomic factor appears to affect initial treatment or follow-up pattern in patients with differentiated thyroid cancer. Income and gender may affect stage at initial disease presentation and may be risk factors affecting eventual clinical outcomes.

Adult↗