Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome

A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.