Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study

Objective: To evaluate the progression in time from euthyroidism to overt autoimmune hypothyroidism or to overt autoimmune hyperthyroidism. Subjects and methods: The design is that of a nested case-control study within the prospective Amsterdam autoimmune thyroid disease (AITD) cohort study in which 790 healthy euthyroid women with at least one first or second degree relative with documented AITD were followed for 5 years. Thyroid function tests were assessed annually. Contrast between cases (overt hypothyroidism - TSH > 5.7 mU/l and free thyroxine (FT4) < 9.3 pmol/l and overt hyperthyroidism - TSH < 0.4 mU/l and FT4 > 20.1 pmol/l, also referred to as events) and controls (matched for age and duration of follow-up). Results: At baseline, the 38 hypothyroid cases had already higher TSH and lower FT4 concentrations than their 76 controls, and the difference between both the groups persisted 1 year before occurrence of the event. In contrast, neither TSH nor FT4 values differed between the 13 hyperthyroid cases and their 26 controls at baseline or 1 year before the event. The prevalence of thyroid peroxidase-Ab was higher in both hypothyroid and hyperthyroid cases than in controls. At the time of event, hypothyroid cases were less common among current smokers (P = 0.083) and more common in the postpartum period (P = 0.006) than their controls, whereas hyperthyroid cases were pregnant more frequently (P = 0.063). Conclusions: The data suggest that progression toward overt autoimmune hypothyroidism is a gradual process taking several years, but in contrast overt autoimmune hyperthyroidism develops faster in terms of months.