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

T. HYODO^*, K. MEGYESI^,, C. R. KAHN^,||, J. P. McLEAN and H. G. FRIESEN^*

^* Department of Physiology, University of Manitoba Budapest, Hungary
Guest Worker, Semmelweis Medical University Budapest, Hungary Diabetes Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health Bethesda, Maryland 20014
Diabetes Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health Bethesda, Maryland 20014
St. Boniface Hospital Manitoba, Canada

^|| To whom reprint requests should be addressed.

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 x 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 related peptides was even more prominent (4 x normal) when the more specific NSILA-s/MSA 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 rumor 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 confirmed 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. These data again suggest that in some patients with tumor hypoglycemia, elevated levels of NSILA-s related peptides may play an important pathogenetic role and that these peptides are produced by the tumor itself.

Supported by the Medical Research Council of Canada and the National Institutes of Health.

Received October 19, 1976.

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