ADRENOCORTICOTROPIC HORMONE RECEPTOR-BLOCKING IMMUNOGLOBULINS IN SERUM FROM PATIENTS WITH ADDISONS-DISEASE - A REEXAMINATION

The presence of antibodies inhibitory to ACTH-stimulated cortisol secretion was investigated in patients with Addison's disease. In preliminary experiments, immunoglobulin G (IgG) samples from patients with Addison's disease and control subjects were prepared using diethylaminoethyl-cellulose ion exchange chromatography. Twelve of 29 Addison's IgGs and 1 of 3 control IgGs inhibited ACTH-stimulated cortisol secretion in an in vitro guinea pig adrenal cell bioassay. All but 1 of the samples that inhibited ACTH-stimulated cortisol secretion also inhibited dibutyryl cAMP-stimulated steroidogenesis. IgGs purified by protein-G immunoaffinity were similarly screened for inhibition of ACTH-stimulated cortisol secretion; samples from 5 controls and 5 patients with Graves' disease were without effect, and IgGs from only 2 of 25 patients with Addison's disease decreased ACTH bioactivity (by <12%). The effects of the IgGs on ACTH bioactivity in vitro were not concentration dependent. Our results suggest that Addison's disease is not caused by circulating antibodies to the ACTH receptor. The inhibitory effects seen with IgG prepared by diethylaminoethyl ion exchange chromatography were most likely attributable to the effects of non-IgG components in the preparations.