Decreased Receptor Binding of Biologically Inactive Thyrotropin in Central Hypothyroidism

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Abstract
Previous studies have suggested that certain cases of idiopathic central hypothyroidism of hypothalamic origin may result from the secretion of biologically inactive thyrotropin. To investigate this possibility and to define the mechanism of defective hormone action, we measured the adenylate cyclase–stimulating bioactivity (B) and receptor-binding (R) activity of purified immunoreactive serum thyrotropin (I) from seven patients with hypothalamic hypothyroidism. We found a strikingly decreased R/I ratio (<0.15) in patients as compared with controls (0.6 to 2.7) and a similarly decreased B/I ratio (<0.2 vs. 2.8 to 5.6). After acute injection of thyrotropin-releasing hormone (TRH, 200 μg intravenously), the R/I ratio increased in two of three patients, but the B/I ratio became normal in only one. After administration of TRH for 20 to 30 days, an increase in immunoreactive serum thyrotropin was observed in all patients. Moreover, both ratios returned to normal in all but one patient, who had apparent desensitization. The increase in the amount and bioactivity of secreted thyrotropin after long-term TRH therapy resulted in enhanced secretion of serum thyroid hormones in all patients studied.