Effects of mitotane on testicular adrenal rest tumors size, sperm count and adrenal steroidogenesis in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Anne Bachelot1, Sylvie Salenave2, Raphaelle Renard1, Laurence Rocher2, Jérome Dulon1, Christiane Coussieu1, Sylvie Brailly-Tabard2, Yves Morel3, Philippe Touraine1 & Jacques Young2
Testicular adrenal rest tumors (TART), described in patients with classic congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency, are responsible for Leydig cell failure and impaired spermatogenesis. These tumors, often unresponsive to intensified glucocorticoid therapy and surgical resection, may lead to infertility or even sterility. Here, we studied the effects of long term treatment with mitotane (Lysodren), a specific adrenolytic agent, on TART in 4 CAH adult patients. These patients were 2426 years old at the beginning of the study. Patient 1, 2 and 3 were diagnosed as newborns with a salt-wasting form of CAH and patient 4 was affected by a simple virilising form. Testicular ultrasonography revealed bilateral TART in all patients. Semen analysis showed azoospermia in 2 patients and severe oligoasthenoteratospermia in the 2 other. All patients were treated before with high glucocorticoid doses with important side effects (hypertension, weight gain and osteopenia) in response to this therapy whereas none had optimal adrenal ACTH and suppression. After 2454 months of Lysodren treatment, a dramatic decrease of both serum 17OHprogesterone and androstenedione levels was noted in all patients, despite persistent increase in serum ACTH levels. Testicular sonograms showed 41100% reduction of TART volume. Sperm count improved clearly in patients 1, 2 and 3, enabling cryopreservation of the subjects semen. Weight loss was observed for all patients during treatment. One episode of moderate adrenal insufficiency was noted in 2 patients, which required transient withdrawal of mitotane treatment and a substantial increase in steroid replacement therapy. Circulating total and LDL cholesterol increased in all patients. On the basis of these preliminary results, we suggest that mitotane might represent a new conservative approach in the management of patients with TART, and a pharmacological tool to improve fertility in men with CAH and TART.