Leydig-like cells in the adrenals of a woman with ectopic ACTH syndrome

Abstract

A 36 year old woman with hypercorticism and markedly elevated blood ACTH levels underwent pituitary ablation because of suspected hypophysical Cushing's disease. Since no adenoma was detected in the anterior lobe and the hypercorticism persisted, a bilateral adrenalectomy was performed. Four months later lymph node and mediastinal metastases of an anaplastic small cell carcinoma, with the presence of argyrophil granulation, as well as immunoreactive 19–39ACTH, β-LPH and α-endorphin, were found. The primary site of ectopic ACTH production was not revealed. A light and electron microscopic study of the adrenals, in addition to cortical hyperplasia, disclosed numerous small cells associated with nonmyelinated sympathetic nerve fibers and containing cytoplasmic inclusions indistinguishable from Reinke craystals. The Leydig-like cell-nonmyelinated nerve complexes, noted in both the adrenal cortex and medulla, showed perivascular localization, and their morphologic features were similar to those of hilus cells of the ovaries or extraglandular Leydig cells of the testis. The underlying mechanism accounting for the development of Leydig-like cells remained obscure; cytodifferentiation from pluripotent mesenchymal cells, possibly mediated by secretory products of sympathetic nerve fibers, may provide an explanation for their formation.