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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.

Food is considered as important environmental factor that plays a role in development of Hashimoto's thyroiditis (HT). The goal of our study was to identify food groups, assessed by food frequency questionnaire, that differ in consumption frequency between 491 patients with HT and 433 controls. We also analysed association of food groups with the wealth of HT-related clinical traits and symptoms. We found significantly increased consumption of animal fat (OR 1.55, p < 0.0001) and processed meat (OR 1.16, p = 0.0012) in HT cases, whereas controls consumed significantly more frequently red meat (OR 0.80, p < 0.0001), non-alcoholic beverages (OR 0.82, p < 0.0001), whole grains (OR 0.82, p < 0.0001) and plant oil (OR 0.87, p < 0.0001). We also observed association of plant oil consumption with increased triiodothyronine levels in HT patients (β = 0.07, p < 0.0001), and, association of olive oil consumption with decreased systolic blood pressure (β = − 0.16, p = 0.001) in HT patients on levothyroxine (LT4) therapy. Analysis of food consumption between HT patients with and without LT4 therapy suggest that patients do not tend to modify their diet upon HT diagnosis in our population. Our study may be of relevance to nutritionists, nutritional therapists and clinicians involved in developing dietary recommendations for HT patients. Environmental factors, in addition to genetic factors, play important role in Hashimoto's thyroiditis (HT) development 1. HT is a chronic autoimmune thyroid disorder (AITD) characterized by the production of thyroid autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) 2. Other main characteristics of HT include infiltration of lymphocytes and ruination of thyroid tissue, which usually leads to hypothyroidism 3. This disease predominantly affects female population and is considered as one of the most frequent endocrine disorders 4. The estimated incidence of HT is 350/100,000 for females and 80/100,000 per year for males 5. It is most often diagnosed in women between the age of 30 and 60 6. High iodine intake (median urinary iodine concentration ≥ 300 μg/L) 7 , especially in areas with sufficient iodine supply, is one of the most known factors that increase the incidence of HT 8. Also, low vitamin D levels (below 30 ng/mL) 9 and low selenium intake (bellow 40 µg/day) 10 are proposed to be risk factors for HT development, albeit a role of these factors in HT still needs to be confirmed. Conversely, alcohol intake was proposed to decrease the risk for HT 11. Other dietary factors are also considered as potential environmental modifiers of the clinical appearance of HT 12-15. A diet low in gluten has been recently proposed to have beneficial effects on the disease course in a study of 34 women with HT 13. Another study of 83 patients with HT indicated that restriction of lactose intake in lactose-intolerant HT patients resulted with decreased thyroid-stimulating hormone (TSH) levels 14. However, the current knowledge of this topic is scarce and only the following two studies ...

Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10 −9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10 −8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, p < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.

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