Search PubMed⌕ Search

Biomedical subjects

Steven I Sherman

Publications and source records attributed to Steven I Sherman.

28 records · Page 2Linked to original sources
PubMed2003

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↗
PubMed2003

Fine-needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients.

BACKGROUND: False-positive, false-negative, and indeterminate fine-needle aspiration (FNA) biopsy results complicate the management of patients with thyroid nodules. METHODS: Thyroid FNA results from 240 consecutive patients (seen 1991 to 2002) were categorized into four groups: positive for malignancy, negative for malignancy, indeterminate for malignancy, and nondiagnostic. Indeterminate results included follicular neoplasm, Hürthle cell neoplasm, and suspicious for papillary carcinoma. The FNA results were compared with histopathologic analysis after thyroidectomy. RESULTS: The FNA results were 76 (32%) positive for malignancy, 53 (22%) negative for malignancy, 100 (42%) indeterminate for malignancy, and 11 (5%) nondiagnostic. There were 3 (4%) false-positive and 2 (4%) false-negative FNA results. Among the 100 indeterminate FNA results, carcinoma was found in 11 (15%) of 73 follicular neoplasms, 2 (20%) of 10 Hürthle cell neoplasms, and 14 (82%) of 17 suspicious for papillary carcinoma. For the 73 patients with follicular neoplasms, nodule diameter >2 cm was associated with an increased risk of malignancy (P <0.03). CONCLUSIONS: False-negative FNA results are uncommon, supporting the practice of observation in most of these patients. Among those with indeterminate biopsy results, high-risk subgroups include patients with FNA results suspicious for papillary carcinoma and follicular neoplasms >2 cm.

Adenoma, Oxyphilic↗
PubMed2003

Potential role for intraoperative gamma probe identification of normal parathyroid glands.

BACKGROUND: Patients undergoing central neck surgery are at risk for hypoparathyroidism. We hypothesized that gamma probe identification of sestamibi-labeled parathyroid glands might help maximize parathyroid preservation. METHODS: Records of 351 patients who underwent central neck surgery were reviewed. A subgroup of patients underwent sestamibi injection followed by gamma probe-directed parathyroid gland identification. RESULTS: Operation was performed for malignancy in 73% of patients and represented a reoperation in 34%. Persistent hypoparathyroidism was more common in patients who underwent reoperation versus a primary operation (6.8% versus 1.7%; P = 0.02). Thirteen patients underwent gamma probe-directed identification of sestamibi-labeled parathyroid glands; in 6 of these patients, sestamibi-labeled parathyroid glands were salvaged from the resected specimens and autografted. None of these 13 patients developed persistent hypoparathyroidism. CONCLUSIONS: Patients undergoing reoperative central neck surgery are at increased risk for postoperative hypoparathyroidism. Gamma probe-directed salvage of sestamibi-labeled parathyroid glands may help maximize parathyroid preservation, especially in complex or reoperative central neck surgery.

Gamma Cameras↗
PubMed2003

Medullary thyroid carcinoma: results of a standardized surgical approach in a contemporary series of 80 consecutive patients.

BACKGROUND: The surgical management and follow-up strategy in patients with medullary thyroid carcinoma (MTC) remain controversial because of the lack of data on the natural history of these tumors and their patterns of progression. METHODS: We reviewed the records of all patients who underwent a cervical operation for MTC between 1991 and 2002. Compartment-oriented surgery (COS) was performed to minimize the risk of cervical recurrence. RESULTS: We identified 92 consecutive patients who underwent a cervical operation for MTC: 80 had invasive MTC, and 12 had C-cell hyperplasia after prophylactic thyroidectomy for familial MTC. Ten (13%) of the 80 patients with invasive MTC presented with distant metastases and underwent COS to achieve local-regional control; cervical recurrence developed in none, but three have died of MTC. The remaining 70 patients underwent COS for primary (n=23) or recurrent (n=47) MTC. Disease recurred in 18 (26%) of these 70 patients at a median follow-up of 35 months, with 10 (14%) of the recurrences being cervical. Recurrent disease was associated with a basal calcitonin level of >250 pg/mL in all but four patients, two of whom showed tumor dedifferentiation. In contrast, only 5 (11%) patients without evidence of recurrence had basal calcitonin levels of >250 pg/mL at last follow-up. CONCLUSIONS: Complete COS minimizes cervical recurrence. Radiographic evidence of recurrent disease is unlikely when the calcitonin level is < or =250 pg/mL. These data could be used to develop a logical, cost-effective treatment and follow-up strategy for patients with MTC.

Adolescent↗
PubMed2003

Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.

BACKGROUND: Cervical recurrence occurs in up to 30% of patients with differentiated thyroid carcinoma. We retrospectively compared preoperative transcutaneous ultrasonography and physical examination (PE) results in the detection of local-regional metastases (lymph node and soft tissue) in patients with thyroid cancer. METHODS: Data were collected retrospectively from the medical records of patients with thyroid carcinoma who underwent preoperative ultrasonography. Patients were divided into 3 groups: group 1, those undergoing primary thyroid/neck surgery; group 2, those undergoing reoperation for persistent disease; and group 3, those undergoing reoperation for recurrent thyroid carcinoma. For each group, we recorded the frequencies with which ultrasonography detected disease in a neck compartment (central or lateral) that was normal on PE. RESULTS: Two hundred twelve patients underwent operation for primary, persistent, or recurrent papillary (n=130), medullary (n=61), or follicular/Hürthle cell (n=21) carcinoma. Ultrasonography detected additional sites of metastatic disease not appreciated on PE in 21 (20%) of 107 group 1 patients, 9 (32%) of 28 group 2 patients, and 52 (68%) of 77 group 3 patients. The surgical procedure performed was altered by the information obtained from preoperative ultrasonography in 82 (39%) of the 212 patients. Of the 107 group 1 patients, cervical recurrence has been detected in only 6 (6%) at a median follow-up of 36 months, in spite of 67 (63%) having tumors larger than 2 cm or lymph node metastases. CONCLUSIONS: Preoperative high-quality ultrasonography detected lymph node or soft-tissue metastases in neck compartments believed to be uninvolved by PE in 39% of patients. Ultrasound findings altered the operative procedure in these patients, facilitating complete resection of disease and potentially minimizing local-regional recurrence.

Adenocarcinoma↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗