The aims of this study were to evaluate: (1) associations of vitamin D with the presence/severity of Hashimoto’s thyroiditis (HT) and (2) correlations of vitamin D with thyroid-related phenotypes. Total 25(OH)D (vitamin D in the text) was measured from stored serum samples of 461 HT patients and 176 controls from a Croatian Biobank of HT patients (CROHT). (1) Vitamin D levels, and proportions of vitamin D deficiency, were compared between HT cases and controls. HT patients were additionally divided into two groups (MILD and OVERT) to take into account HT severity. (2) Correlations between vitamin D and 10 clinical phenotypes in all HT patients and two subgroups of HT patients were tested using the Spearman correlation test. Our analyses were adjusted for age, gender, BMI, smoking status and seasonality of blood sampling. (1) No significant differences in vitamin D levels, or proportions of vitamin D deficiency, were detected between HT patients of all disease stages and controls. However, a nominally significant difference in vitamin D levels between MILD and OVERT subgroups (OR = 1.038, p = 0.023) was observed. Proportions of individuals with vitamin D deficiency during winter–spring were high: all HT cases (64.69%), MILD (60.64%), OVERT (68.7%), controls (60.79%). (2) A nominally significant negative correlation between vitamin D and TSH in all HT patients (r = −0.113, p = 0.029) and a positive correlation between vitamin D and systolic blood pressure in OVERT HT patients (r = 0.205, p = 0.025) were identified. Our study indicates that there is no association between vitamin D and HT; however, there may be a subtle decrease in vitamin D levels associated with overt hypothyroidism.

Objective: We evaluated correlations of occupational physical activity (OPA) and recreational exercise (RE), respectively, with thyroid function in patients with Hashimoto’s thyroiditis (HT). Methods: We included 438 individuals with clinically diagnosed HT. Information on OPA and RE were collected through a self-report questionnaire. We assessed correlations between clinical phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume, vitamin D) and physical activities (OPA and RE) in all HT patients (ALL) and in two severity-based subgroups of patients (MILD and OVERT). Results: The main novel findings are significant correlations between increase in OPA and (i) a decrease in fT4 (OVERT, r = −0.265, p = 0.0002 and ALL, r = −0.138, p = 0.006); (ii) an increase in TSH (ALL, r = 0.124, p = 0.014 and OVERT, r = 0.183, p = 0.013) and (iii) an increase in TPOAb antibodies (ALL, r = 0.101, p = 0.045). In contrast, we observed correlations between increase in RE and: (i) a decrease in TSH (OVERT, r = −0.238, p = 0.001); (ii) a decrease in TgAb antibodies (OVERT, r = −0.194, p = 0.01) and (iii) an increase in vitamin D levels (ALL, r = 0.146, p = 0.005 and OVERT, r = 0.173, p = 0.023). Conclusions: Our results suggest that, unlike RE, OPA correlates with decreased thyroid function and increased thyroid autoimmunity. Our study proposes that the PA health paradox also applies for the thyroid health.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

In this cross-sectional observational study, we investigated whether recreational exercise (RE) influences systemic inflammation in Hashimoto’s thyroiditis (HT) across different disease severity groups. We analyzed 403 participants from the Croatian Biobank of Patients with HT (CRO-HT), including 173 controls and 230 HT patients (euthyroid, levothyroxine [LT4]-treated, and hypothyroid). Serum levels of 92 inflammatory proteins were measured using the Olink^® Target 96 Inflammation panel, and exercise status was assessed via structured questionnaires. Linear regression revealed distinct protein associations depending on thyroid status. In controls, RE was associated with reduced MMP-10 and FGF-5, reflecting cardiovascular and muscle benefits. In euthyroid patients, RE was associated with decreased CXCL9 and TRAIL, implicating reduced type 1 inflammation and vascular risk. LT4-treated patients showed increases in IL-15RA and IL-24 with RE, suggesting improved muscle metabolism and anti-inflammatory effects. In hypothyroid patients, RE was associated with reduced CCL20 and increased HGF, while changes in TRANCE and TWEAK indicated mixed effects on bone and immune regulation. Notably, RE was associated with reduced CXCL9 and CCL20, two proteins previously linked to HT risk. Overall, RE is associated with distinct changes in inflammatory profiles across HT disease severity groups, with the most favourable responses observed in LT4-treated patients, suggesting synergy with hormone therapy.

Diffuse toxic goiter, as the most common cause of hyperthyroidism, is usually initially treated with thyrostatic drugs such as methimazole, followed by radioiodine therapy or surgery which may be indicated as definitive treatment....