Adrenocortical Carcinoma and Hypoglycemia: Evidence for Production of Nonsuppressible Insulin-Like Activity by the Tumor

Abstract

Serum and tumor extracts from a patient with adrenocortical carcinoma and hypoglycemia were studied using conventional bioassay and radioreceptor assays. Immunoreactive insulin in all sera and extracts was low or undetectable. Increased insulin-like activity (about 2 .times. normal) was detected in the insulin radioreceptor assay and in the fat cell bioassay, suggesting the presence of some other insulin-like material in blood. An increased level of NSILA-s [nonsuppressible insulin-like activity soluble in acid ethanol]-related peptides was even more prominent (4 .times. normal) when the more specific NSILA-s/MSA [multiplication stimulating activity] radioreceptor assay was employed. Delineation of the tumor as the probable source of the NSILA-s related peptides was highly dependent on studying the proper type of extract. Acetone-ethanol extracts of tumor were 4- to 20-fold more active in the NSILA-s/MSA receptor assay than unaffected tissues; these elevated levels of NSILA-s related peptides were conformed by insulin radioreceptor assay and fat cell bioassay. Acid-ethanol extracts showed the same general pattern, but due to the much lower activity material obtained by this method, it was detectable only in the more sensitive NSILA-s/MSA receptor assay. The great variability observed among extraction methods and the lack of specific and sensitive assays in the past may have accounted for the difficulty in detecting this insulin-like peptide in previously reported patients. In some patients with tumor hypoglycemia, elevated levels of NSILA-s related peptides may play an important pathogenetic role and these peptides are produced by the tumor itself.