Modified Bethesda criteria for thyroid aspirates significantly decrease nondiagnostic rates without decreasing sensitivity.

INTRODUCTION: Previous studies suggest that the adequacy rate of thyroid aspirates can be improved by altering the adequacy criteria of the Bethesda System. We sought to measure the performance of these altered criteria in a prospective fashion. MATERIALS AND METHODS: Over a 6-year period, cases with 1 to 59 follicular cells were prospectively classified as "nondiagnostic, favor benign" or "scant but adequate". "Scant but adequate" cases were classified as either benign (Bethesda category 2) or atypia of undetermined significance (AUS) (Bethesda category 3). Bethesda category 3 cases were referred for Afirma testing (Veracyte, San Francisco, CA). RESULTS: Of 5147 cases, 131 (3%) were classified as "nondiagnostic, favor benign"; 45 (65%) of these had follow-up with a risk of malignancy of 2.6%. Additionally, 436 (8%) of all 5147 cases were classified as "scant but adequate" and "benign"; 49 (11%) of these had follow-up with a risk of malignancy of 0%. Lastly, 197 (4%) of all 5147 cases were classified as "scant but adequate" with AUS; 177 (90%) of these 197 cases had an adequate Afirma result. The "suspicious" rate was not significantly different than that of cases classified as "adequate" and AUS (Bethesda category 3 and 4) (35 of 197 [18%] versus 140 of 848 [17%] P = 0.67), and there was no significant difference in the risk of malignancy for these 2 categories ("scant but adequate" 9 of 18, "adequate" 50% versus 27 of 85, 32%, P = 0.10). Overall, the modified Bethesda criteria reduced the nondiagnostic rate from 22% to 10% (P <0.001) without lowering the sensitivity of the test. CONCLUSIONS: Modified Bethesda adequacy criteria can significantly lower nondiagnostic rates without lowering sensitivity.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Impact of Transoral Endoscopic Vestibular Approach Thyroidectomy on Pathologic Assessment.

CONTEXT.­: Since 2016, transoral endoscopic thyroid resection with vestibular approach (TOETVA) has been increasingly performed in the United States. Although guidelines for the procedure are evolving, indeterminate and malignant preoperative cytopathologic diagnoses are not a contraindication. There are limited data related to the pathologic examination of these specimens. OBJECTIVE.­: To examine the clinicopathologic features of TOETVA specimens with particular attention to limitations of interpretation of pathologic parameters and final diagnosis. DESIGN.­: We reviewed age, sex, preoperative imaging and cytologic diagnoses, surgical pathology, and clinical follow-up data in TOETVA resections from our institution for procedures performed between March 2016 and December 2019. RESULTS.­: Fifty cases of TOETVA were identified, comprising 48 women and 2 men with a mean age of 47 years. Preoperative cytologic diagnoses were available in 47 cases and included 19 nondiagnostic/benign (Bethesda I/II), 24 follicular lesion of undetermined significance/suspicious for follicular neoplasm (Bethesda III/IV), and 4 suspicious/malignant diagnoses (Bethesda V/VI). Thirty-four cases (68%) among the surgical resection specimens showed disruption and/or fragmentation. Thirty-nine cases were negative for carcinoma, including hyperplasias and benign/indolent neoplasms. Eleven cases exhibited papillary thyroid carcinoma. Final diagnoses were reached in all disrupted/fragmented cases. In 2 cases of papillary thyroid carcinoma, tumor size, microscopic extrathyroidal extension, and margin status could not be determined. CONCLUSIONS.­: A significant proportion of TOETVA specimens are disrupted/fragmented, which can compromise information about tumors, including size, number, margin status, and microscopic extrathyroidal extension. Given that these parameters inform treatment and follow-up, this should be considered when selecting patients for TOETVA.

Dietary patterns and thyroid cancer risk: a population-based case-control study.

PURPOSE: Thyroid cancer (TC) incidence has increased greatly during the past decades with a few established risk factors, while the relationship between dietary factors and TC remains unclear. Limited literature has investigated the association with inconsistent findings. METHODS: We examined the association between dietary pattern and risk of TC in a population based case-control study conducted in Connecticut (2010-2011). Our study population included 390 historically confirmed incident TC cases and 436 population-based controls who completed baseline dietary history questionnaires (DHQ). We identified 3 distinct dietary patterns ("Starchy Foods and Desserts", "Fruits and Vegetables", "High Protein and Fat") through principal components analysis. Multivariate unconditional logistic regression models were used to investigate the association between each dietary pattern and risk of TC, controlling for potential confounders. RESULTS: A diet rich in fruits and vegetables was significantly associated with a reduced risk of overall TC (OR = 0.60, 95% CI: 0.39, 0.92; P trend = 0.02). Compared to younger women, a stronger protective effect was observed among women ≥ 50 years of age in overall TC and papillary TC risk. A diet rich in starchy foods and desserts was positively and negatively associated with an overall TC risk among men and women respectively. CONCLUSIONS: Our study found a significant negative association between diet patterns rich in fruits and vegetables and TC risk, especially among women aged 50 years or older. While high in starchy foods and desserts may be positively and negatively associated with TC risk among men and women respectively, these results require confirmation in other populations.

Genetic susceptibility may modify the association between cell phone use and thyroid cancer: A population-based case-control study in Connecticut.

Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P < 0.01 for interaction in all thyroid cancers. In the common homozygote groups, no association with cell phone use was observed. In the variant group (heterozygotes and rare homozygotes), cell phone use was associated with an increased risk for rs11070256 (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.30-4.30), rs1695147 (OR: 2.52, 95% CI: 1.30-4.90), rs6732673 (OR: 1.59, 95% CI: 1.01-2.49), rs396746 (OR: 2.53, 95% CI: 1.13-5.65), rs12204529 (OR: 2.62, 95% CI: 1.33-5.17), and rs3800537 (OR: 2.64, 95% CI: 1.30-5.36) with thyroid cancers. In small tumors, increased risk was observed for 5 SNPs (rs1063639, rs1695147, rs11070256, rs12204529 and rs3800537), In large tumors, increased risk was observed for 3 SNPs (rs11070256, rs1695147, and rs396746). Our result suggests that genetic susceptibilities modify the associations between cell phone use and risk of thyroid cancer. The findings provide more evidence for RFR carcinogenic group classification.

Phytoestrogens and Thyroid Cancer Risk: A Population-Based Case-Control Study in Connecticut.

BACKGROUND: Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. METHODS: We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. RESULTS: An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 µg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 µg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 µg/day compared with <40 µg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 µg/day compared with <760 µg/day) was associated with moderate genistein intake among women. CONCLUSIONS: Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. IMPACT: The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer.

Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.

Volume-outcome relationship in parathyroid surgery.

BACKGROUND: Since its first description, several studies have highlighted the role of the surgeon's experience in the outcome of parathyroid surgery, however, no uniform consensus exists regarding the minimum operative experience required for good surgical outcomes. This work aims to summarize the current data regarding the surgeon volume-outcome relationship for parathyroidectomy. METHODS: An electronic literature review identified 85 publications, and after study selection 11 were included. An additional nine publications were added based on reference review and inclusion of publications not initially captured. CONCLUSIONS: There are insufficient data to dogmatically conclude a minimum number of cases required to achieve optimal surgical results. However, extrapolation from the inclusive studies support the conclusions that higher operative volumes improve cure rates and decrease the rates of complications, recurrent disease, and perioperative costs. Endocrine Surgery fellowships or mentorships may help prepare the less experienced surgeon for successful outcomes. Although reticent to offer firm minimal volume requirements, we have made suggestions in this manuscript.

Cell phone use and risk of thyroid cancer: a population-based case-control study in Connecticut.

PURPOSE: This study aims to investigate the association between cell phone use and thyroid cancer. METHODS: A population-based case-control study was conducted in Connecticut between 2010 and 2011 including 462 histologically confirmed thyroid cancer cases and 498 population-based controls. Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between cell phone use and thyroid cancer. RESULTS: Cell phone use was not associated with thyroid cancer (OR: 1.05, 95% CI: 0.74-1.48). A suggestive increase in risk of thyroid microcarcinoma (tumor size ≤10 mm) was observed for long-term and more frequent users. Compared with cell phone nonusers, several groups had nonstatistically significantly increased risk of thyroid microcarcinoma: individuals who had used a cell phone >15 years (OR: 1.29, 95% CI: 0.83-2.00), who had used a cell phone >2 hours per day (OR: 1.40, 95% CI: 0.83-2.35), who had the most cumulative use hours (OR: 1.58, 95% CI: 0.98-2.54), and who had the most cumulative calls (OR: 1.20, 95% CI: 0.78-1.84). CONCLUSIONS: This study found no significant association between cell phone use and thyroid cancer. A suggestive elevated risk of thyroid microcarcinoma associated with long-term and more frequent uses warrants further investigation.

Alcohol Consumption and Risk of Thyroid Cancer: A Population Based Case-Control Study in Connecticut.

BACKGROUND: Studies examining the association between alcohol consumption and thyroid cancer risk have been inconsistent, in part due to varying types and amounts of alcohol consumption, incomplete information on confounders, and variations in genetic susceptibility in study populations. METHODS: The present study analyzed data from a population-based case-control study in Connecticut in 2010-2011 including 462 histologically confirmed incident thyroid cancer cases and 498 population-based controls. Unconditional logistic regression was used to estimate associations between alcohol consumption and risk of thyroid cancer. Potential confounding variables were age, gender, race, education, body mass index, family history of cancer among first-degree relatives, history of benign thyroid disease, smoking status, and physical activity. RESULTS: Ever consumption of alcohol was associated with a reduced risk of thyroid cancer (OR = 0.71, 95% CI: 0.54-0.95). The younger age at initiation and increasing duration of alcohol consumption were also associated with a reduced risk of thyroid cancer in a dose-dependent manner (P for trend = 0.041 and 0.0065, respectively). Compared to people who never drank alcohol, people who drank alcohol for >31 years were 50% less likely to develop thyroid cancer (OR = 0.50, 95% CI: 0.32-0.80). Alcohol consumption was associated with a reduced risk of papillary thyroid cancer (OR = 0.66, 95% CI: 0.49-0.88) and thyroid cancer with lager tumor size (>1 cm), but no significant association was found between alcohol consumption and non-papillary thyroid cancer or thyroid microcarcinoma. Analyses stratified by specific subtypes of alcohol demonstrated an inverse association for beer (OR = 0.69, 95% CI: 0.49-0.96) and wine consumption (OR = 0.71, 95% CI: 0.53-0.96) as compared to participants who never consumed alcohol, but no significant association was found for liquor consumption (OR = 0.75, 95% CI: 0.53-1.04). CONCLUSIONS: The study findings suggest an inverse association between alcohol consumption and risk of thyroid cancer. Future mechanistic study is warranted to elucidate the underlying mechanisms.

Endocrine Surgery: A Hopkins Legacy.

: The field of Endocrine Surgery is linked to extraordinary contributions made by Hopkins leaders in surgery including William Stewart Halsted, Harvey Cushing, and John L Cameron. Halsted's contributions to the anatomic basis of thyroid and parathyroid surgery were based on his experimental and clinical work performed at Johns Hopkins Hospital. Halsted's disciple, Harvey Cushing, created the field of modern neurosurgery and recognized the disease and syndrome that are immortalized with his name. The Halstedian principles promulgated and transmitted by John L Cameron to subsequent generations of endocrine surgeons at Hopkins have transformed the field of Endocrine Surgery with the stamp of Johns Hopkins Hospital.

Germline Variants in DNA Repair Genes, Diagnostic Radiation, and Risk of Thyroid Cancer.

Background: Radiation exposure is a well-documented risk factor for thyroid cancer; diagnostic imaging represents an increasing source of exposure. Germline variations in DNA repair genes could increase risk of developing thyroid cancer following diagnostic radiation exposure. No studies have directly tested for interaction between germline mutations and radiation exposure.Methods: Using data and DNA samples from a Connecticut population-based case-control study performed in 2010 to 2011, we genotyped 440 cases of incident thyroid cancer and 465 population-based controls for 296 SNPs in 52 DNA repair genes. We used multivariate unconditional logistic regression models to estimate associations between each SNP and thyroid cancer risk, as well as to directly estimate the genotype-environment interaction between each SNP and ionizing radiation.Results: Three SNPs were associated with increased risk of thyroid cancer and with thyroid microcarcinoma: HUS rs2708896, HUS rs10951937, and MGMT rs12769288. No SNPs were associated with increased risk of larger tumor (>10 mm) in the additive model. The gene-environment interaction analysis yielded 24 SNPs with Pinteraction < 0.05 for all thyroid cancer, 12 SNPs with Pinteraction < 0.05 for thyroid microcarcinoma, and 5 SNPs with Pinteraction < 0.05 for larger tumors.Conclusions: Germline variants in DNA repair genes are associated with thyroid cancer risk and are differentially associated with thyroid microcarcinoma and large tumor size. Our study provides the first evidence that germline genetic variations modify the association between diagnostic radiation and thyroid cancer risk.Impact: Thyroid microcarcinoma may represent a distinct subset of thyroid cancer. The effect of diagnostic radiation on thyroid cancer risk varies by germline polymorphism. Cancer Epidemiol Biomarkers Prev; 27(3); 285-94. ©2017 AACR.

Thyroid-Stimulating Hormone, Thyroid Hormones, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

Background: The effects of thyroid-stimulating hormone (TSH) and thyroid hormones on the development of human papillary thyroid cancer (PTC) remain poorly understood.Methods: The study population consisted of 741 (341 women, 400 men) histologically confirmed PTC cases and 741 matched controls with prediagnostic serum samples stored in the Department of Defense Serum Repository. Concentrations of TSH, total T3, total T4, and free T4 were measured in serum samples. Conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI).Results: The median time between blood draw and PTC diagnosis was 1,454 days. Compared with the middle tertile of TSH levels within the normal range, serum TSH levels below the normal range were associated with an elevated risk of PTC among women (OR, 3.74; 95% CI, 1.53-9.19) but not men. TSH levels above the normal range were associated with an increased risk of PTC among men (OR, 1.96; 95% CI, 1.04-3.66) but not women. The risk of PTC decreased with increasing TSH levels within the normal range among both men and women (Ptrend = 0.0005 and 0.041, respectively).Conclusions: We found a significantly increased risk of PTC associated with TSH levels below the normal range among women and with TSH levels above the normal range among men. An inverse association between PTC and TSH levels within the normal range was observed among both men and women.Impact: These results could have significant clinical implications for physicians who are managing patients with abnormal thyroid functions and those with thyroidectomy. Cancer Epidemiol Biomarkers Prev; 26(8); 1209-18. ©2017 AACR.

Occupational exposure to pesticides and other biocides and risk of thyroid cancer.

OBJECTIVES: To assess the associations between occupational exposure to biocides and pesticides and risk of thyroid cancer. METHODS: Using data from a population-based case-control study involving 462 incident thyroid cancer cases and 498 controls in Connecticut collected in 2010-2011, we examined the association with occupational exposure to biocides and pesticides through a job-exposure matrix. We used unconditional logistic regression models to estimate OR and 95% CI, adjusting for potential confounders. RESULTS: Individuals who were occupationally ever exposed to biocides had an increased risk of thyroid cancer (OR=1.65, 95% CI 1.16 to 2.35), and the highest risk was observed for the high cumulative probability of exposure (OR=2.18, 95% CI 1.28 to 3.73). The observed associations were similar when we restricted to papillary thyroid cancer and well-differentiated thyroid cancer. Stronger associations were observed for thyroid microcarcinomas (tumour size ≤1 cm). No significant association was observed for occupational exposure to pesticides. CONCLUSIONS: Our study provides the first evidence linking occupational exposure to biocides and risk of thyroid cancer. The results warrant further investigation.

Primary hyperparathyroidism with normal baseline intraoperative parathyroid hormone: A challenging population.

BACKGROUND: Patients with primary hyperparathyroidism and baseline intraoperative parathyroid hormone levels in the normal range are challenging. This study compares the predictive value of a commonly used intraoperative parathyroid hormone algorithm, a software model for cure prediction, and surgeon judgment in this population. METHODS: This was a retrospective review of consecutive patients who underwent parathyroidectomy for primary hyperparathyroidism at a single institution from March 2013 to October 2014. RESULTS: Of 541 operative patients, 114 (21.1%) had a mean normal baseline intraoperative parathyroid hormone of ≤69 pg/mL (median 59.0 ± 10.3; range 26-69). Of the 114 patients, 93 (81.6%) were women, median age was 61 years (range 18-88). Overall, 107/108 (99.1%) patients were cured; 47 (41.2%) patients had single adenomas, 16 (14%) had double adenomas, and 51 (44.7%) had multigland hyperplasia. Using the 50% decline algorithm, a correct prediction was made in 86 (75.4%) patients. Using the computer software, a correct prediction was made in 88 (77.2%) patients. Surgeon judgment, however, was 99.1% accurate. CONCLUSION: Patients with normal baseline intraoperative parathyroid hormone have a high incidence of multigland disease (58.8%), greater than reported previously. Current software modeling and the 50% decline algorithm are insufficient to predict cure in this population; intraoperative parathyroid hormone interpretation combined with operative findings and surgical judgment yield optimal outcomes.