Autoimmune conditions in the World Trade Center general responder cohort: A nested case-control and standardized incidence ratio analysis.

BACKGROUND: The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. OBJECTIVES: Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. METHODS: Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. RESULTS: Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. CONCLUSIONS: The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

Increased postpartum thyroxine replacement in Hashimoto's thyroiditis.

BACKGROUND: The thyroidal response of pregnant patients with established Hashimoto's thyroiditis remains poorly described. The aim of this study was to determine the impact of pregnancy on Hashimoto's thyroiditis as revealed by changes in postpregnancy levothyroxine requirements. METHODS: We performed a retrospective study of 799 hypothyroid patients in a university hospital. We reviewed the clinical records and selected a group of well-documented pregnant (n = 34) and nonpregnant (n = 32) hypothyroid women for study. We reviewed levothyroxine intake and serum thyrotropin (TSH) levels during three consecutive 9-month time intervals that were immediately before, during, and after pregnancy. We compared the percent change in levothyroxine dose between the prepregnancy level and each trimester during and after pregnancy. RESULTS: There were two patterns of levothyroxine supplementation during gestation. In pattern 1 (n = 11) there was either no change or a single levothyroxine dose increase with no subsequent changes in each trimester (T1 = T2 = T3). In pattern 2 (n = 18), multistep levothyroxine dose increases were required throughout pregnancy (T1 < T2 < T3) to maintain desired TSH levels (<2.0 mU/L). Women with pattern 2 had mean TSH levels during gestation that differed significantly from pattern 1 (2.8 +/- 0.5 vs. 1.3 +/- 0.1 mU/L respectively; p < 0.03). Further, in multivariate logistic regression, women with pattern 2 were 62 times more likely than women with pattern 1 to have a levothyroxine dose at least 20% above baseline at 3 months postpartum (p = 0.04). CONCLUSIONS: We showed that >50% of hypothyroid women with Hashimoto's thyroiditis experienced an increase in levothyroxine requirements in the postpartum compared to pregestational doses. This pattern of enhanced levothyroxine need was most likely dependent on the preexisting thyroid functional reserve and postpartum progression of autoimmune destruction.

Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy.

OBJECTIVE: To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with (99m)technetium sestamibi scintigraphy. DESIGN: The results of ultrasonography for localization of enlarged parathyroid glands were determined in 120 consecutive patients with primary hyperparathyroidism and compared with findings at surgery (n = 86) and with the results of (99m)technetium sestamibi scintigraphy (n = 99). PATIENTS: All patients had biochemically documented primary hyperparathyroidism based on elevated serum calcium and 'intact' parathyroid hormone measured by immunoassay. Patients with prior parathyroid surgery or secondary hyperparathyroidism were excluded. MEASUREMENTS: High-resolution ultrasonography was performed by a single observer. (99m)Technetium sestamibi scintigraphy was performed using early and delayed (2-h) views, and correlated with simultaneous thyroidal 123I uptake in most patients. RESULTS: Ultrasonography detected putative enlarged parathyroid glands in 92 of 120 unselected patients (77%). It correctly predicted surgical findings in 64 of 86 patients undergoing surgery (74%), including 61 of 72 patients with solitary eutopic parathyroid adenomas (84%), but only two of eight patients with solitary ectopic adenomas, and only one of six patients with multigland parathyroid disease. Sestamibi scintigraphy was positive in 87 of 99 unselected patients (88%), a higher proportion than ultrasonography (P < 0.05), reflecting superior sensitivity for the detection of ectopic parathyroid adenomas. For 74 patients undergoing parathyroid surgery who underwent both imaging tests there was no statistically significant difference between ultrasonography and sestamibi scintigraphy in ability to correctly predict surgical findings (74%vs. 82%, respectively) or in positive predictive value (93%vs. 90%, respectively). However, sestamibi scintigraphy was clearly more sensitive for ectopic parathyroid adenomas, providing correct localization in 8/8 cases. When one test was negative, testing with the second method was usually positive, improving the likelihood of a positive result to 98% when both tests were employed. CONCLUSIONS: Ultrasonography can be a sensitive and accurate method for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, comparable in overall utility to sestamibi scintigraphy. These results suggest that a strategy of initial testing with one or the other method, followed by the alternate imaging test if the first test is negative, would provide correct parathyroid imaging in most patients without prior parathyroid surgery.

Radioguidance is not necessary during parathyroidectomy.

BACKGROUND: Improvements in the accuracy of preoperative localization and the availability of the rapid parathyroid hormone assay have permitted minimally invasive parathyroidectomy in patients with primary hyperparathyoidism. HYPOTHESIS: The use of intraoperative radioguidance is beneficial during targeted parathyroid operations. DESIGN: A retrospective analysis of a prospective database of patients. SETTING: Tertiary care referral center. PATIENTS: During a 2(1/2)-year period, 130 patients underwent minimally invasive, targeted parathyroidectomy with intraoperative monitoring of the parathyroid hormone level. Of these, 60 patients underwent radioguided parathyroidectomy. Prior to surgery, a solitary parathyroid adenoma was visualized on technetium Tc 99m sestamibi scintigraphy in all patients selected for radioguided parathyroidectomy. A gamma probe was used to guide the surgical dissection. RESULTS: All patients were cured following radioguided parathyroidectomy. In 29 patients (48%), the probe provided confusing or inaccurate information; however, a unilateral neck exploration with excision of a parathyroid adenoma was successfully completed in each of these patients. Forty-three cases were completed under local anesthesia and 85% were discharged home on the same day of surgery. There was 1 temporary recurrent laryngeal nerve palsy. CONCLUSION: In the era of improved preoperative localization and intraoperative parathyroid hormone monitoring, the routine use of radioguidance is not recommended during parathyroidectomy.

Targeted parathyroidectomy in the era of intraoperative parathormone monitoring.

A combination of preoperative localization and intraoperative parathormone (PTH) monitoring permits targeted parathyroidectomy. Multiple approaches have been developed, ranging from unilateral neck exploration (UE) to radio-guided parathyroidectomy (RP) to endoscopic parathyroidectomy (EP). The purpose of this study was to evaluate the efficacy of these approaches in the management of primary hyperparathyroidism. From June 1998 to November 2000 a total of 110 targeted parathyroid operations were performed at a university medical center. All patients underwent technetium-99m-sestamibi scanning, ultrasonography, or both prior to surgery. Intraoperative PTH monitoring was utilized in all cases. Thirty-seven patients underwent UE, 59 underwent RP, and 14 underwent EP. Follow-up ranged from 1 to 24 months. All patients were cured following parathyroidectomy as predicted by a more than 50% reduction of the intraoperative PTH level following removal of all hypersecreting glands. Altogether, 103 patients had a solitary adenoma (95%), and 1 patient had a parathyroid carcinoma. Six patients (5%) had multigland disease, including four cases of hyperplasia and two patients with a double adenoma. Eighty-three patients (75%) were discharged the day of surgery. The use of preoperative localization and intraoperative PTH monitoring permits a targeted approach to the treatment of primary hyperparathyroidism. Endocrine surgeons should be facile in all minimally invasive parathyroid techniques to individualize the operative approach.

Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia.

BACKGROUND: Aberrant expression of the facilitative glucose transporter GLUT1 is found in a wide spectrum of epithelial malignancies. The authors describe an immunohistochemical study of GLUT1 expression in benign, borderline, and malignant ovarian epithelia. METHODS: One hundred forty one formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 using the streptavidin-biotin method. The samples were as follows: 3 endometriotic cysts, 9 serous cystadenomas, 15 mucinous cystadenomas, 17 noninvasive borderline implants, 3 invasive borderline implants, and 3 endosalpingiosis. In addition, 35 borderline tumors (26 serous, 7 mucinous, 2 seromucinous) and 56 adenocarcinomas (50 serous, 4 endometrioid, 2 mucinous) were stained. RESULTS: Benign serous and mucinous cystadenomas and endosalpingiosis were non-staining with GLUT1 antiserum. Twenty-eight of 35 borderline tumors (80%) stained positively, with weak to moderate (1-2+ out of 3) staining intensity and focal or patchy distribution. Seventeen noninvasive serous borderline implants were negatively stained; however, three invasive serous borderline implants were positively stained with GLUT1 antiserum. Fifty four of 56 ovarian carcinomas (96%) stained positively, with moderate to strong (2-3+ out of 3) intensity and multifocal distribution. CONCLUSIONS: GLUT1 is a consistent marker of ovarian epithelial malignancy. GLUT1 staining is absent in benign ovarian epithelial tumors, and shows progressively more staining in invasive tumors as compared to borderline tumors. Anti-GLUT1 antibody may be useful in distinguishing invasive from noninvasive serous borderline implants.