STEROID SECRETORY CHARACTERISTICS OF A VIRILIZING ADRENAL ADENOMA IN A WOMAN

A tumour of the left adrenal gland was identified in a woman who prese nted with virilization and secondary amenorrhea. Preoperatively, the p lasma levels of dehydroepiandrosterone sulphate, dehydroepiandrosteron e, androstenedione, testosterone, 5alpha-dihydrotestosterone and 5-and rostene-3beta,17beta-diol were elevated two- to fourfold whereas those of urinary 17-ketosteroids were elevated more than tenfold. The produ ction rate of dehydroepiandrosterone sulphate was more than 16 times t hat in normal women whereas those of dehydroepiandrosterone, testoster one and androstenedione were approximately twofold greater; plasma tes tosterone was derived almost entirely from the peripheral conversion o f androstenedione. Blood was obtained by catheterization of the ovaria n veins, left adrenal gland vein and inferior vena cava (at two differ ent sites) and plasma steroid levels were determined: testosterone and cortisol levels were elevated in all blood samples whereas those of a ndrostenedione, dehydroepiandrosterone sulphate and 11-desoxycortisol were approximately six- to eightfold, 1.5-fold and nine- to 22-fold hi gher in the effluent of the left adrenal gland/tumour compared with th e levels in the other compartments. Blood was collected hourly for 24 h to determine steroid levels under basal conditions and, also, after ACTH treatment. Plasma cortisol levels increased markedly upon ACTH ad ministration and fell to very low levels 11 h later, but those of andr ostenedione, testosterone, dehydroepiandrosterone, 5-androstene-3beta, 17beta-diol and dehydroepiandrosterone sulphate were not affected by A CTH treatment. A histological diagnosis of cortical adenoma of the ext irpated tumour was made. Tissue explants and adenoma cells were mainta ined in culture to characterize the steroid-metabolizing properties of the tumour. The secretion of dehydroepiandrosterone sulphate by tissu e explants was high initially, but declined to almost undetectable lev els after 5 days in culture. In the presence of ACTH, dehydroepiandros terone sulphate secretion remained elevated throughout the entire stud y up to 5 days. Basal secretion of dehydroepiandrosterone sulphate, an drostenedione, 11-desoxycortisol, cortisol, testosterone and 11beta-hy droxyandrostenedione by adenoma cells was either very low or undetecta ble. In the presence of ACTH, dibutyryl cyclic AMP or cholera toxin th e secretion of dehydroepiandrosterone sulphate, androstenedione and 11 -desoxycortisol increased markedly with time in culture up to 3 days, whereas the other steroids were undetected in the medium. A homogenate of adenoma tissue metabolized testosterone to androstenedione, but th e conversion of androstenedione to testosterone was minimal. The findi ngs of this study served to establish that virilization in this woman was due, at least in part, to excess testosterone - and testosterone-d erived 5alpha-dihydrotestosterone - produced at extra-adrenal tissue s ites almost exclusively through metabolism of tumour-secreted androste nedione. The excess production of steroid prohormones in this woman wa s due to autonomous tumour steroidogenesis. The remarkable feature was the degree of virilization resulting from a modest increase in biolog ically potent androgens.