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Introduction/Objective. Hypothyroidism is a common disease and treatment with levothyroxine (LT4) is effective. However, variations in management are frequent. The aim of this study was to identify practices and attitudes of Serbian physicians relating to the treatment of hypothyroidism. Methods. An anonymized questionnaire was distributed electronically to members of the Serbian Thyroid Society, Serbian Association of Endocrine Surgeons, and Section for Endocrinology of the Serbian Medical Society. Results. Out of 170 invitations, 99 responses were received. LT4 was the first choice for the treatment of hypothyroidism in 90% of patients. After starting LT4 replacement therapy most respondents would recheck thyroid-stimulating hormone (TSH) in 4–6 weeks (n = 51, 62%) and in eight weeks (n = 29, 35%). In total, 61% of respondents (n = 60) indicated that they would consider treating euthyroid patients with LT4, the commonest indication being female infertility with high levels of thyroid antibodies (54%, n = 50). More than half respondents (58%, n = 45) would recommend combined LT4 + LT3 therapy for patients on LT4 with normal serum TSH who still complain of symptoms of hypothyroidism. 53% (n = 41/77), reported that the frequency of patients with normal serum TSH who still complain of hypothyroid symptoms is less than 5%. Conclusion. LT4 was the first choice of therapy for the treatment of hypothyroid patients, whereas LT3 + LT4 combination treatment is considered in patients with persistent symptoms of hypothyroidism despite normalization of TSH. The most common indication for thyroid hormone treatment in euthyroid patients was female infertility with high levels of thyroid antibodies. Alternative LT4 formulations like liquid solution or soft-gel capsules –formulations presently not available in Serbia, were largely reserved for specific conditions (interfering drugs, malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0–1.9], "daily" [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4. Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment. [ABSTRACT FROM AUTHOR]

Objective: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. Design and Participants: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. Measurements: We analysed questionnaires that had complete demographic data. Results: Eighty‐seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. Conclusions: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires. [ABSTRACT FROM AUTHOR]

Context Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD). Objective This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD. Methods Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized β values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs. Results We identified epigenome-wide significant differences (P < 9E-8) and replicated (P <.05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis. Conclusion Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential. [ABSTRACT FROM AUTHOR]