Endocrine Abstracts

Graves’ hyperthyroidism (GH) and Hashimoto’s hypothyroidism (HH) are the opposite ends of the clinical expression of autoimmune thyroid diseases (AITD). AITD are multifactorial ‘complex’ diseases in which immune responses against thyroid antigens develop in genetic susceptible subjects, provoked by environmental factors. Susceptibility genes include immunoregulatory genes (HLA, CTLA-4, PTPN22, CD4 and FCRL3) and thyroid-specific genes (TSHR and Tg). Environmental factors include ambient iodine intake, stress, smoking, particular drugs (interferon, alemtuzumab and HAART), and possibly infections. Endogenous factors (female gender, parity and X-chromosome inactivation) contribute to the risk of AITD. We will focus on new data on the role of environmental factors.

Smoking is a well-established risk factor for GH and especially for Graves’ ophthalmopathy. Recent studies provide convincing evidence that smoking to a certain extent protects against HH. Cessation of smoking is associated with de novo development of TPO-Ab, and with a transient increase in the incidence of overt hypothyroidism. The remarkable divergent effects of smoking on GH and HH remain incompletely understood.

Alcohol consumption is associated with a decreased risk of de novo development of TPO-Ab. It also protects against the development of overt GH or HH, independent of smoking behaviour.

Selenium deficiency might be involved in the pathogenesis of AITD, but the evidence is less clear. Selenium supplementation in Hashimoto’s thyroiditis decreases serum TPO-Ab in some but not all studies. Selenium concentrations in GH patients are highest in patients who go into remission after a course of antithyroid drugs.

Vitamin D deficiency. In a prospective study the de novo development of TPO-Ab was not associated with low serum 25(OH)D. In view of paracrine effects of locally synthesized 1.25(OH)₂D and polymorphisms in the vitamin D receptor it is, however, premature to dismiss a role of vitamin D in the pathogenesis of AITD.