Context: The regulation of TSH bioactivity in humans is not completely understood.

Objective: To investigate the role of serum thyroid hormones in regulating the bioactivity of TSH.

Design: We determined in vitro TSH bioactivity and glycosylation in 9 patients (41.3 y; 6F/3M) with primary hypothyroidism before and after L-thyroxine replacement, in 11 age and sex comparable controls (37.6y; 7F/4M) and in 2 thyroidectomized patients with TSH-secreting adenomas during and after L-thyroxine withdrawal.

Methods: In vitro TSH bioactivity was measured by a sensitive and specific bioassay based on cAMP generation by CHO cells transfected with human TSH receptor. TSH glycosylation was assessed by concanavalin-A lectin and by ricin column affinity chromatography.

Results: In vitro TSH bioactivity in hypothyroid patients was low as compared to controls (0.48 ± 0.1 vs 1.1 ± 0.2, P = 0.004) and increased during L-thyroxine (0.48 ± 0.1 vs 0.8 ± 0.1, P = 0.01). A strong significant correlation (r = + 0.80, P = 0.004, Spearman) was observed between the absolute increments of serum TSH bioactivity and T3 during L-thyroxine replacement. The degree of sialylation was elevated in hypothyroid patients before treatment (47% ± 2.4 vs 29% ± 4.3, P = 0.002) and decreased significantly after L-thyroxine (47% ± 2.4 vs 33% ± 4.3, P = 0.02). The mannose content of serum TSH in hypothyroid patients was similar to controls and did not change during L-thyroxine. In vitro TSH bioactivity also decreased in patients with TSH-secreting adenomas during L-thyroxine withdrawal.

Conclusion: These data indicate that serum thyroid hormone level is a positive regulator of TSH bioactivity.