Endocrinology and Metabolism

Original Article

THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Questionnaire Survey of Medical Thyroid Specialists in Korea on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: Jee Hee Yoon, Dong Yeob Shin, Hee Kyung Kim, Roberto Attanasio, Enrico Papini, Petros Perros, Endre V. Nagy, Laszlo Hegedüs, Sun Wook Kim, Ho-Cheol Kang; Received December 18, 2025 Accepted February 27, 2026 Published online July 8, 2026; DOI: https://doi.org/10.3803/EnM.2025.2868 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Recent surveys have highlighted substantial variability in the management of hypothyroidism that is associated with physician demographic and geo-economic characteristics. This study aimed to assess preferences for thyroid hormone therapy among medical thyroid specialists in Korea.
Methods
An online survey was conducted using the Treatment of Hypothyroidism in Europe by Specialists: An International Survey (THESIS) questionnaire. Participants were medical thyroid specialists who were members of the Korean Thyroid Association (KTA).
Results
Among the 349 regular members of the KTA who were physicians, 53 (15.2%) completed the survey. All respondents reported prescribing levothyroxine (LT4) as the initial treatment of choice for hypothyroidism. For patients with biochemical euthyroidism, 64.2% of respondents indicated that treatment was unnecessary; however, several conditions were cited as potential indications for thyroid hormone use (multiple responses were allowed), including female infertility with elevated thyroid antibody levels (30.2%), enlarging simple goiter (17.0%), and severe hypercholesterolemia as adjunctive therapy (9.4%). Although 24.5% of respondents reported avoiding LT4+liothyronine (LT3) therapy because of low-quality evidence, 62.3% indicated that they would consider it for symptomatic patients receiving LT4 monotherapy with normal thyroid-stimulating hormone levels.
Conclusion
Korean thyroid specialists generally adhere to current clinical guidelines, favoring LT4 as the standard treatment for hypothyroidism. However, there is considerable willingness to use LT4+LT3 combination therapy and to prescribe thyroid hormones for certain non-thyroid conditions. Ongoing educational efforts are needed to improve understanding that many persistent symptoms despite biochemical euthyroidism are influenced by psychosocial factors and to facilitate consistent implementation of evidencebased, guideline-aligned clinical practice.

Review Article

Thyroid
T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity: Wilmar M. Wiersinga; Endocrinol Metab. 2021;36(5):938-951. Published online September 30, 2021; DOI: https://doi.org/10.3803/EnM.2021.501

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Thyroxine (T4)+triiodothyronine (T3) combination therapy can be considered in case of persistent symptoms despite normal serum thyroid stimulating hormone in levothyroxine (LT4)-treated hypothyroid patients. Combination therapy has gained popularity in the last two decades, especially in countries with a relatively high gross domestic product. The prevalence of persistent symptoms has also increased; most frequent are complaints about energy levels and fatigue (80% to 90%), weight management (70% to 75%), memory (60% to 80%), and mood (40% to 50%). Pathophysiological explanations for persistent problems are unrealistic patient expectations, comorbidities, somatic symptoms, related disorders (Diagnostic and Statistical Manual of Mental Disorders [DSM-5]), autoimmune neuroinflammation, and low tissue T3. There is fair circumstantial evidence for the latter cause (tissue and specifically brain T3 content is normalized by T4+T3, not by T4 alone), but the other causes are viewed as more relevant in current practice. This might be related to the ‘hype’ that has emerged surrounding T4+T3 therapy. Although more and better-designed trials are needed to validate the efficacy of T4+T3 combination, the management of persistent symptoms should also be directed towards alternative causes. Improving the doctor-patient relationship and including more and better information is crucial. For example, dissatisfaction with the outcomes of T4 treatment for subclinical hypothyroidism can be anticipated as recent trials have demonstrated that LT4 is hardly effective in improving symptoms associated with subclinical hypothyroidism.

Citations

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Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study
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Original Article

Clinical Study
High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly: Youngmi Kim Pak, Hoon Sung Choi, Wook Ha Park, Suyeol Im, P. Monica Lind, Lars Lind, Hong Kyu Lee; Endocrinol Metab. 2021;36(2):436-446. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2020.883

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Background
High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time.
Methods
Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up.
Results
AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose.
Conclusion
These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

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Review Article

Miscellaneous
Evidence of the Possible Harm of Endocrine-Disrupting Chemicals in Humans: Ongoing Debates and Key Issues: Duk-Hee Lee; Endocrinol Metab. 2018;33(1):44-52. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.44

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Evidence has emerged that endocrine-disrupting chemicals (EDCs) can produce adverse effects, even at low doses that are assumed safe. However, systemic reviews and meta-analyses focusing on human studies, especially of EDCs with short half-lives, have demonstrated inconsistent results. Epidemiological studies have insuperable methodological limitations, including the unpredictable net effects of mixtures, non-monotonic dose-response relationships, the non-existence of unexposed groups, and the low reliability of exposure assessment. Thus, despite increases in EDC-linked diseases, traditional epidemiological studies based on individual measurements of EDCs in bio-specimens may fail to provide consistent results. The exposome has been suggested as a promising approach to address the uncertainties surrounding human studies, but it is never free from these methodological issues. Although exposure to EDCs during critical developmental periods is a major concern, continuous exposure to EDCs during non-critical periods is also harmful. Indeed, the evolutionary aspects of epigenetic programming triggered by EDCs during development should be considered because it is a key mechanism for developmental plasticity. Presently, living without EDCs is impossible due to their omnipresence. Importantly, there are lifestyles which can increase the excretion of EDCs or mitigate their harmful effects through the activation of mitohormesis or xenohormesis. Effectiveness of lifestyle interventions should be evaluated as practical ways against EDCs in the real world.

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Original Article

Diabetes, Obesity and Metabolism
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study: Yu Hyun Kwon, Seul-Ki Kim, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2018;33(1):55-61. Published online January 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.55

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Background

Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time.

Methods

A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014.

Results

Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80).

Conclusion

In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

Citations

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