Thyroid peroxidase antibodies, levels of thyroid stimulating hormone and development of hypothyroidism in euthyroid subjects

Thyroid peroxidase antibodies (TPOAbs) have been found to be related to the levels of thyroid stimulating hormone (TSH) and to predict future development of thyroid failure in selected populations. We investigated these relations in a euthyroid general population.

Cross-sectional investigation of the relationship of TPOAbs and levels of TSH in euthyroid subjects. Prospective investigation of the association of TPOAbs and TSH with development of hypothyroidism. Incident hypothyroidism was defined as initiation of l-thyroxine in the absence of thyreostatic medication.

The study was performed in a random sample of 2703 participants of the PREVEND study. A total of 309 subjects were excluded from analyses, mainly because of TSH outside the reference range (0.35-4.94 mIU/l; n=115).

Mean (SD) baseline age was 47.7 (12.5) years, with 50.8% females. Prevalence of positive TPOAbs (≥ 12 kU/l) was 8.4%. TSH concentrations were increased in subjects with TPOAbs (P<0.001). During a median follow-up of 9.1 years, 15 (0.6%) subjects developed hypothyroidism (3.5% in TPOAbs positive vs. 0.4% in TPOAbs negative subjects; P<0.001). Female sex (P=0.02), and TSH (P<0.001) were also significantly associated with incident hypothyroidism. In multivariate analysis, TSH and TPOAbs remained independent predictors (both P<0.001).

We confirmed the positive relationship of the presence of TPOAbs with levels of TSH and showed that TPOAbs and TSH predict future development of hypothyroidism. These results are consistent with the presence of TPOAbs necessitating a compensatory increase in levels of TSH for maintenance of euthyroidism, even in the euthyroid range.