Pituitary secretion of free alpha and beta subunit of human thyrotropin in patients with thyroid disorders

Abstract

Utilizing sensitive and specific radioimmunoassays, serum concentrations of human thyrotropin (hTSH), the immunologically common alpha subunit of the glycoprotein hormones, and the specific beta subunit of hTSH ( hTSH-beta) have been measured in normal individuals, in patients with primary hypothyroidism, and in patients with other disorders of thyroid function before and after intravenous administration of thyrotropin releasing hormone (TRH). In 29 normal individuals hTSH-beta was not detectable in serum (smaller than 0.5 ng/ml) before or after TRH; alpha was smaller than 0.5-2.0 ng/ml in men and premenopausal women and 1.0-5.0 ng/ml in postmenopausal women and did not increase after TRH. In 20 patients with primary hypothyroidism mean serum hTSH-beta was 1.3 ng/ml and increased to a peak value of 3.7 ng/ml after TRH; mean alpha was 4.3 ng/ml and increased to 6.3 ng/ml after TRH. None of the patients with Graves' disease, a hyperfunctioning thyroid nodule, or hypothyrotropic hypothyroidism had detectable serum hTSH-beta concentrations or alpha concentrations higher than the normals before or after TRH. In 3 patients with primary hypothyroidism given an intravenous bolus of labeled hTSH, no dissociation of hTSH into subunits was detectable for at least 3 h, indicating that the increment in serum alpha and hTSH-beta after TRH represented secretion of free subunits from the pituitary. In addition, L-thyroxine (L-T4) administered to 2 hypothyroid patients decreased the serum concentrations of alpha and hTSH-beta before and after TRH. Serum hTSH-beta was fully suppressed with 100-300 mug L-T4 daily, but there was a residual serum alpha component, which could not be suppressed with thyroid hormone and probably represented alpha subunits arising from gonadotropin-secreting pituitary cells. Normal pituitary glands also contained a predominance of free alpha subunit relative to hTSH-beta, in addition to hTSH. The secretion of free subunits in hypothyroidism may represent only a quantitative difference from the normal state, and subunits of hTSH appear to respond to the same control mechanisms as complete hTSH.