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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.

Introduction: Lymphocytic hypophysitis is an uncommon inflammatory disorder of the pituitary gland. Peripartum women are most often affected, but it can be seen in a wide range of patients. Patients can present with pituitary dysfunction or mass effect symptoms, making it difficult to differentiate from a pituitary adenoma. Pituitary apoplexy is an acute syndrome due to hemorrhage into the pituitary gland causing headache, visual deficits, and hypoadrenalism. We present a case of a woman with a pituitary mass presenting with symptoms mimicking pituitary apoplexy, in whom surgical pathology later revealed lymphocytic hypophysitis without evidence of hemorrhage. Clinical Case: A 27-year-old non-pregnant female presented with severe headaches, nausea, vomiting, and diplopia for four days. A presumed pituitary macroadenoma was diagnosed two years previously during a workup for irregular menses. An emergency evaluation with a CT angiogram of the head showed enhancement at the superior aspect of and surrounding the pituitary gland. MRI of the pituitary revealed an enhancing 17 x 17 mm sellar and suprasellar mass compressing the optic chiasm, without evidence of the normal pituitary posterior bright spot. Visual field testing was normal. She was referred for transsphenoidal resection of the pituitary mass due to persistent headaches, optic chiasm impingement, and suspicion of pituitary apoplexy. Intraoperatively, there was no evidence of hemorrhage. Central diabetes insipidus and hypothyroidism developed in the post-operative period. She was discharged on hydrocortisone replacement therapy (20 mg in the morning, 10 mg in the afternoon). An outpatient random cortisol level of 1.2 mcg/dL (reference: 6.7 - 22.6 mcg/dL) while off hydrocortisone for twenty-four hours confirmed hypocortisolism. Surgical pathology showed moderate lymphocytic infiltrate and focal germinal centers in the adenohypophysis consistent with lymphocytic hypophysitis. Conclusion: Although lymphocytic hypophysitis is well-described in the literature, its association with symptoms suggesting pituitary apoplexy has been reported only rarely. This atypical case shows that lymphocytic hypophysitis can present with acute symptoms mimicking pituitary apoplexy. The case highlights the difficulties in recognizing lymphocytic hypophysitis prior to surgery and emphasizes the need to consider the diagnosis in patients presenting with pituitary masses and/or symptoms of pituitary apoplexy.

Summary objective To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with 99mtechnetium 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 99mtechnetium 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. 99mTechnetium 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

En combinant l'information obtenue en preoperatoire sur la localisation des glandes et en peroperatoire, a partir du monitorage de la parathormone (PTH), on peut realiser une parathyroidectomie dite «ciblee». Pour ce faire, on a developpe de multiples approches, allant de l'exploration cervicale unilaterale (ECU) a la parathyroidectomie radioguidee (PR) et a la parathyroidectomie laparoscopique (PL). Le but de cette etude a ete d'evaluer l'efficacite de ces differentes approches dans la prise en charge de l'hyperparathyroidie primitive. Entre juin 1998 et novembre 2000, on a realise 110 interventions «ciblees» sur la parathyroide dans un centre medical universitaire. Tous les patients ont eu une scintigraphie au technetium-99m-sestamibi et/ou une echographie avant l'intervention. Le monitorage peroperatoire de la PTH a ete utilise dans tous les cas. Trente-sept patients ont eu une ECU, 59, une PR, et 14, une PL. Avec un suivi entre 1 et 24 mois, tous les patients ont ete gueris apres leur parathyroidectomie comme le laissait prevoir une reduction superieure a 50% du dosage peroperatoire de la PTH apres ablation de toutes les glandes hypersecretantes. Cent trois patients avaient un adenome solitaire (95%) et un patient avait un cancer de la parathyroide. Six patients (5%) avaient une maladie multiglandulaire, y compris quatre cas d'hyperplasie et deux patients porteurs d'un adenome double. Quatre-vingt-trois patients (75%) ont pu quitter l'hopital le jour de leur intervention. La localisation preoperatoire et l'utilisation du monitorage peroperatoire de la PTH permettent une approche «ciblee» dans le traitement de l'hyperparathyroidie primitive. Les chirurgiens endocrines devraient etre familiers avec toutes les techniques mini-invasives de la parathyroidectomie afin de pouvoir adapter l'approche operatoire a chaque cas individuel.

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. Cancer 2002;94:1078–82. © 2002 American Cancer Society. DOI 10.1002/cncr.10280

Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid nodules. However, cytologic interpretation of FNA specimens is often difficult, especially in the presence of indeterminate microfollicular cytologic patterns, which are thought to suggest follicular neoplasm (adenoma or carcinoma). To assess the risk of malignancy associated with specific cytologic patterns, we correlated preoperative FNA cytologic patterns (n = 484 reports including repeat aspirations) with final histological diagnoses for 368 surgical thyroid specimens obtained during the period 1994-1998. The overall prevalence of malignancy in the surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%). Nodules with indeterminate cytologic patterns in the absence of nuclear atypia (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia consistent with follicular neoplasm were malignant (60%), including specimens with or without microfollicular cytology. Nodules with frankly malignant cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses of papillary carcinoma were confirmed at surgery in all 49 cases. These results indicate that indeterminate microfollicular cytologic patterns in the absence of nuclear atypia are associated with a low risk of malignancy, at least in this series. This finding suggests that many nodules with such microfollicular cytology might be managed conservatively with observation. In contrast, cytologic nuclear atypia consistent with a follicular neoplasm confers a high risk of cancer. In addition, frankly malignant cytologic diagnoses, especially papillary carcinoma, are highly reliable, and thus may be used as a guide for planning surgery appropriate for thyroid cancer.

Objective To review the role of ultrasonography in the detection and management of thyroid cancer Methods Viewpoints are presented on the appropriate applications and the advantages of ultrasonography, based on an extensive personal experience with more than 1,500 ultrasound examinations for assessment of thyroid nodules and for follow-up surveillance of patients with thyroid cancer. Results Ultrasonography is ideal for thyroid imaging because of the high echogenicity of thyroid tissue, the superficial site of the thyroid that allows the use of high- frequency transducers yielding high resolution, and the low expense compared with other techniques. In patients with a thyroid nodule, ultrasonography can assist in distinguishing benign from malignant disease. Ultrasound studies will characterize the presence of cystic versus solid elements, the degree of echogenicity of solid elements, the existence of calcifications, and the regularity and definition of the nodule borders. Although individual sonographic features of thyroid nodules are not specific for benign or malignant lesions, a constellation of typical features has more diagnostic value. Hypoechogenicity, poorly defined irregular margins, and microcalcifications are characteristics that should increase the index of suspicion for a malignant nodule. Cytologic examination of fine- needle aspirates is the optimal diagnostic test, and ultrasonographic guidance for performance of the aspiration biopsy is often helpful and sometimes critical. Ultrasonography is also useful for detection of cervical lymph node metastatic lesions. Lymph nodes involved with metastatic thyroid cancer tend to become rounded and bulging, and they lose their hilar echoes as their structure becomes disrupted. Conclusion Because of its high resolution and relatively reasonable cost, ultrasonography is valuable in the diagnosis and management of thyroid cancer. (Endocr Pract. 2000;6:396-400)

BACKGROUND Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance. METHODS GLUT1 glucose transporter immunostaining was studied in normal colon and benign colon adenomas and in 112 colorectal carcinomas from patients for whom long term clinical outcome was known. RESULTS GLUT1 immunostaining was absent in normal colorectal epithelium and tubular adenomas, and absent or only weakly apparent in tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1 immunostaining. Tumors from 92 patients had low GLUT1 expression ( 50% of cells were GLUT1 positive) and 9 of these patients (45%) died of disease during follow-up. Disease specific mortality was greater in patients with high GLUT1 tumors (relative risk of 2.4; P = 0.02). In a multivariate analysis to assess whether high GLUT1 staining correlated with increased mortality independently of Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1 staining was 2.3 times that in the group with low GLUT1 staining, a difference that approached statistical significance (P = 0.07). CONCLUSIONS GLUT1 glucose transporter expression is associated strongly with neoplastic progression in the colon, and assessment of the extent of GLUT1 immunostaining in colorectal carcinoma identifies patients with a poorer prognosis. Cancer 1998;83:34-40. © 1998 American Cancer Society.

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.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.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 (T1T2T3) 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; p0.03). 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).We showed that50% 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.

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.

Cytologic examination of fine needle aspiration (FNA) specimens from thyroid nodules is the key test for the evaluation of thyroid nodules, and the results are critical in the selection of patients with nodules for thyroid surgery. Although needle placement for FNA is traditionally and most commonly guided by nodule palpation alone, the widespread availability of thyroid ultrasonography has made possible a technical refinement of this technique, needle placement under ultrasonographic guidance. Ultrasound-guided FNA is often valuable, and sometimes essential, in obtaining accurate diagnostic material. This chapter reviews the role of ultrasound-guided fine needle aspiration (UG FNA) in the diagnosis of thyroid nodules.

Malignant cells exhibit increased rates of glycolysis and glucose uptake, the latter of which is mediated by glucose transport proteins. Because several types of cancer have been shown to express high levels of the GLUT1 glucose transporter isoform, we hypothesized that expression of GLUT1 might distinguish malignant from benign thyroid tissue. Archival thyroid tissue obtained at surgery was immunostained for GLUT1 protein. There were 38 benign cases (24 follicular adenoma, 1 Hurthle cell adenoma, 8 nodular goiter, 3 Hashimoto's thyroiditis, 2 Graves' disease) and 28 cases of thyroid cancer (17 papillary and its follicular variant, 6 follicular, 1 Hurthle cell, 2 anaplastic, 2 medullary). Normal thyroid tissue adjacent to nodules showed no thyrocyte staining in any case. No GLUT1 staining was seen in thyrocytes in benign nodular tissue, except for a single case of Hashimoto's thyroiditis in which a few Hurthle cells showed weak staining. Among the thyroid cancers, 13 of 28 (46%) showed tumor cell GLUT1 staining in at least some areas. This included 9 of 17 cases of papillary carcinoma and its follicular variant, 2 of 6 cases of follicular carcinoma and 2 of 2 cases of anaplastic carcinoma. Tumor cell GLUT1 staining was seen in two patterns: circumferential plasma membrane staining focally within the tumor, or asymmetric staining of the basilar aspect of tumor cells adjacent to stroma in some cases of papillary carcinoma. We conclude that GLUT1 expression is frequently detectable by immunostaining in thyroid cancer, but not in benign nodules or normal thyroid. GLUT1 expression may be a clinically useful molecular marker for thyroid cancer.