ABNORMAL THYROXINE METABOLISM IN HYPOSOMATOTROPHIC DWARFISM AND INHIBITION OF RESPONSIVENESS TO TRH DURING GH THERAPY

Abstract

Thyrotropin (TSH) release and thyroxine metabolism have been studied in order to determine whether human growth hormone (GH) administration is causally related to the occasional development of secondary hypothyroidism in GH-deficient dwarfs. Five hyposomatotrophic dwarfs and one normal child were studied. The TSH response to synthetic thyrotropin-releasing hormone (TRH) was normal in all, regardless of thyroid functional status. Before GH administration, two of the three clinically euthyroid dwarfs were found to have daily thyroxine degradation rates in the hypothyroid range although serum total and free thyroxine levels were normal. Following six to ten days of GH treatment, TSH levels fell slightly and the TSH response to TRH was blunted. During long-term GH treatment of four dwarfs no significant change in thyroid function was observed. In addition, TSH responsiveness to TRH recovered in three of these four chronically treated patients, including one who was frankly hypothyroid. The growth rate of the three clinically euthyroid dwarfs improved during long-term GH therapy; nevertheless, the addition of 50µg triiodothyronine to the treatment regimen of the dwarf in whom the thyroxine degradation rate was lowest resulted in a markedly improved growth rate. These studies indicate that a state of hypothyroidism that is undetectable by measurement of total serum thyroxine and free thyroxine exists in some GH-deficient patients. GH may be necessary for normal thryoxine metabolism and action. Such a GH effect might explain the observed influence of GH on TSH release. On the other hand, the demonstrated abnormality in thyroxine metabolism may result from mild, preexisting TSH deficiency.