16 CUSHING'S SYNDROME DUE TO PIGMENTED MICRODULAR ADRENOCRTICAL DYSPLASIA: FAMILLIAL PRESENCE OF ADDRENAL STIMULATING IMMUNOGLOBULINES

Abstract

Immunoglobulins (Ig's) stimulating the thyroid (TSI) have been described in Graves' disease. By analogy, we earlier reported on the presence of Ig's stimulating adrenal DNA synthesis and/or steroidogenesis in patients with pituitary non dependent Cushing's syndrome due to Pigmented Adrenocortical Micronodular Dysplasia (PAMD)(1)In some of the patients with this syndrome, cardiac myxomas and spotly skin pigmentation are also present and a familial occurrence of this complex of symptoms has heen described. We now report on a familial occurrence of Ig's stimulating the adrenal in this syndrome. Sera were obtained from 2 sisters with PAMD, their parents and 2 remaining sibs (all clinically unaffected by PAMD). Guinea-pig adrenal segments were kept in organ culture (37°C, 95% O2 and 5% CO2, for 5 b) with protein A sephrose purified IgG added in concentrations of 15-25 μg IgG per ml culture fluid. At the end of the culture period the cortisol present in the culture fluid was determined by RIA. The culture segments were soap frozen and sectioned. Feulgen densitometry was performed on 50 randomly chosen nuclei residing in th zona fasciculata to calculate the percentage of cells in S-phase.IgG's of both patients with PAKD stimulated in vitro adrenal DNA synthesis and cortisol production. IgG's from their mother who is clinically unaffected also stimulated adrenal DNA synthesis and cortisol production in vitro. IgG's from the remaining family members were negative for these effects.The positive findings of lg's stimulating the adrenal in the clinically unaffected mother suggest that separate mechanisms (immune? metabolic? are necessary to bring about overt Cushing's syndrome.(1) JCEM, february ′88.