Journal of Clinical Endocrinology & Metabolism, Vol 52, 393-398, Copyright © 1981 by Endocrine Society

ARTICLES

Studies on the possible mechanism for deficiency of nonsuppressible insulin-like activity in thalassemia major

AC Herington, GA Werther, RN Matthews and HG Burger

Previous studies have shown that serum levels of the somatomedin, nonsuppressible insulin-like activity (NSILA-S), are extremely low in patients with thalassemia major. Since these patients are not GH deficient, several other possible mechanisms for the reduced levels of NSIL-S have been explored. No evidence for the presence of NSILA inhibitors was obtained either in mixing experiments of normal serum and thalassemic sera or after acid gel chromatography of thalassemic sera. The high iron and ferritin levels of thalassemia had no effects on the NSILA-S bioassay itself or on the binding of GH to its hepatic receptors. GH molecules secreted as a result of exercise-induced GH stimulation tests were shown to be both immunologically and biologically reactive. No circulating GH-binding proteins were present in thalassemic sera. Since the liver function in the group of patients included in this study was only slightly abnormal, it is considered unlikely that generalized hepatic damage due to the severe iron overload of thalassemia is a major cause. These results suggest that neither NSILA-S inhibitors, abnormal GH molecules, nor hepatic damage contribute to the failure of these patients to produce NSILA-S and that a specific defect may exist at the hepatic GH receptor or postreceptor level.