Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with
Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for
thyroid disease in this group of patients to assure early diagnosis of
hypothyroidism. Methods. In a 25-year-old man diagnosed with
Down's syndrome, clinical manifestations of
hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of
thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH
antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled
TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in
hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative
thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the
carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the
hormone as in the present case.