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-0) 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-β was not detectable in serum (<0.5 ng/ml) before or after TRH; alpha was <0.5–2.0 ng/ml in men and premenopausal women and 1.0–5.0 ng/ml in post-menopausal women and did not increase after TRH. In 20 patients with primary hypothyroidism mean serum hTSH-β 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 hyper-functioning thyroid nodule, or hypothyrotropic hypothyroidism had detectable serum hTSH-β 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-β after TRH represented secretion of free subunits from the pituitary. In addition, L-thyroxine (L–T)4()administered to 2 hypothyroid patients deceased the serum concentrations of alpha and hTSH-β before and after TRH. Serum hTSH-β was fully suppressed with 100–300 fig (L–T)4 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-β, in addition to hTSH. The secretion of free subunits in hypo-thyroidism 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. (J Clin Endocrinol Metab40: 872, 1975)

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