Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations. We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers. TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025). The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations.

Background: Sleep duration is an identified risk factor for adverse health outcomes. As the endocrine system is closely intertwined with sleep duration and quality, the association between endocrine dysfunction and sleep has been evaluated. Thyroid function, particularly that related to thyrotropin (TSH), is also known to be influenced by the sleep/awake status and circadian rhythm. Additionally, a link between sleep duration and autoimmunity, which is a common cause of thyroid dysfunction, has been suggested; however, depending on the sleep deprivation method used in studies, the effects of sleep on thyroid function vary. The relationship between subclinical thyroid dysfunction and sleep duration is poorly documented. Thus, to elucidate the impact of sleep on thyroid function, we investigated the association of subclinical thyroid dysfunction with sleep duration using representative data from the sixth Korea National Health and Nutrition Examination Survey, conducted from 2013 to 2015. Methods: In all, 4945 participants (2543 male and 2402 female) were included after excluding subjects using the following criteria: <19 years of age, free T4 level outside the normal range, history of thyroid disease, or incomplete data. The population was classified into three groups: short sleeper (8 h/day). The odds ratio (OR) for subclinical hypothyroidism or hyperthyroidism according to sleep duration was evaluated. Results: The short, normal, and long sleeper groups consisted of 2097, 2514, and 334 subjects, respectively. On multiple logistic regression analysis, compared to normal sleepers, short sleepers showed a significantly increased risk of subclinical hyperthyroidism (OR 1.37, 95% confidential interval (CI) 1.02–1.84, p = 0.036), while the risk of subclinical hypothyroidism in short sleepers was not elevated. Comparing long sleepers to normal sleepers, the OR for subclinical hyperthyroidism and hypothyroidism was 1.79 (95% CI 1.12–2.86, p = 0.015) and 1.91 (95% CI 1.03–3.53, p = 0.039), respectively. Conclusions: Both shorter and longer sleep durations were associated with an increase in the risk of subclinical thyroid dysfunction compared to the optimal sleep duration. This analysis of representative population data shows that sleep duration could intertwine with thyroid function resulting in increased risk of subclinical thyroid dysfunction.

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear.Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC.BRAFmutation was tested with pyrosequencing.Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto’s thyroiditis than classic PTCs (93% versus 36%, resp.,P< 0.001) and showed significantly lower rate ofBRAFmutation when compared to classic PTCs (65% versus 84%, resp.,P= 0.007). In classic PTC, the frequency ofBRAFmutations was negatively correlated with coexisting Hashimoto’s thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto’s thyroiditis, there were no significant differences in clinicopathologic characteristics or theBRAFmutational rate between the two groups.Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto’s thyroiditis.

Yun KJ, et al. Endocrinol Metab. 2014 Sep;29(3):388-393. https://doi.org/10.3803/EnM.2014.29.3.388

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.

Fine needle aspiration cytology (FNAC) and washout thyroglobulin (Tg) measurements are the standard for evaluating a metastatic lymph node (LN) in thyroid cancer. However, patients rarely benefit from these procedures due to false results. This study aims to identify a reliable biomarker that significantly improves the diagnosis of metastatic LNs, in addition to FNAC and washout Tg. This study analyzed 130 LNs that were suspected to have metastases on thyroid ultrasonography, from June 2016 to December 2017. All subjects underwent FNAC, washout Tg measurements and a new biomarker, washout Cytokeratin fragment 21-1 (CYFRA 21-1) measurement. The final LN outcomes were confirmed by surgical histology, repeat FNAC, or follow-up image. The diagnostic values of the presence of washout CYFRA 21-1 for diagnosing metastatic LNs were evaluated according to final LN outcomes. Among the 130 LNs, 42 were metastatic lesions and 88 were benign. The washout CYFRA 21-1 levels were significantly higher in metastatic LNs than in benign LNs. In contrast to the findings of washout Tg, washout CYFRA 21-1 showed little overlap between benign and malignant LNs, and its diagnostic cutoff values were not affected by surgery. The combinations of FNAC and washout CYFRA 21-1 showed higher sensitivity (91.9%), specificity (96.5%), negative predictive value (98.8%), and diagnostic accuracy (94.2%) than FNAC with washout Tg. The combination of FNAC, washout Tg, and washout CYFRA 21-1 showed the best sensitivity (98.8%). When washout CYFRA 21-1 was applied to the discordant results that were observed between FNAC and washout Tg, 20 of 22 LNs were correctly diagnosed. Washout CYFRA 21-1 measurements in thyroid LNs provide a diagnostic modality.