GLUCOCORTICOID AND MINERALOCORTICOID PATHWAYS IN TWO ADRENOCORTICAL CARCINOMAS: COMPARISON OF THE EFFECTS OF o,p′-DICHLORODIPHENYLDICHLOROETHANE, AMINOGLUTETHIMIDE AND 2-p-AMINOPHENYL-2-PHENYLETHYLAMINE IN VITRO

Abstract

SUMMARY The synthesis of glucocorticoids and mineralocorticoids in vitro was studied in an adrenocortical carcinoma after ablation from an 11·5-year-old boy. This patient had been unsuccessfully treated with high doses of o,p′-dichlorodiphenyldichloroethane (o,p′-DDD) and aminoglutethimide. These in-vitro results were compared with those obtained with another adrenocortical carcinoma removed from a 26-year-old woman who had received no preoperative treatment. The sensitivity of these adrenocortical carcinomas to o,p′-DDD, aminoglutethimide and 2-(p-aminophenyl)-2-phenylethylamine (SKF 12185) was investigated. Synthesis of cortisol (47%) and corticosterone (45%) in control incubations showed that 11β-hydroxylase activity was not affected by the treatment. This explains the raised level of plasma cortisol in the treated child. All three compounds inhibited both 11β-hydroxylase and 18-hydroxylase activities up to 95%, depending on the inhibitor. This study shows (a) an inhibitory effect of o,p′-DDD on the steroidogenesis of an adrenocortical carcinoma in vitro, an effect not previously reported in man or laboratory animals, and (b) the in-vitro efficacy of o,p′-DDD and aminoglutethimide on corticosteroidogenesis by a carcinoma unresponsive to treatment in vivo. This discrepancy between data obtained in vivo and in vitro could possibly be explained by either an insufficient ratio of ingested dose: tumour mass, or a malabsorption of the drugs in this patient.