Sex-specific associations between the developmental alterations in the pituitary-thyroid hormone axis and thyroid nodules in Chinese euthyroid adults: a community-based cross-sectional study.

Background: Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults. Methods: 8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted. Results: TFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found. Conclusions: The trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.

Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross­sectional Study.

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations.