SUN-415 Medical Therapy to Restore Male Fertility in Classic Congenital Adrenal Hyperplasia

Abstract A.J. Newman: None. L.C. Tsai: None. A. Vaidya: None. Classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) causes excess adrenal androgens that may suppress the hypothalamic-pituitary-gonadal axis leading to male infertility. A 35-year-old man with classic CAH presented with his wife after 2 years of inability to conceive and an extensive evaluation for female factors of infertility that was unrevealing. He had been diagnosed with CAH in infancy after a salt-wasting crisis. At the time of this evaluation, his medication regimen included hydrocortisone 20 mg in the morning and 5 mg in the afternoon, plus fludrocortisone 0.2 mg daily. He felt well on this regimen, with good strength, energy and sexual function. He was normally virilized and ultrasound showed testes of normal size without evidence of testicular adrenal rest tumors (TARTs). Semen analysis demonstrated sperm count of 14.7 million/mL (normal > 15 million/mL) with 98% abnormal morphology. Labs were notable for elevated 17-hydroxyprogesterone (17-OHP) 18,400 ng/dL (<220) and androstenedione (A4) 1,390 ng/dL (40-150); low total testosterone (T) 199 ng/dL (240-950) and free T 3.38 ng/dL (4.65-18.1); and low luteinizing hormone (LH) 0.2 IU/L (1.7-8.6) and follicle stimulating hormone (FSH) 1.1 IU/L (1.5-12.4). Androstenedione to total testosterone ratio (A:T) was 7.7 (reference < 1). His infertility was attributed to high adrenal androgens resulting in suppression of gonadotropins. He was treated with a nighttime dose of methylprednisolone 3 mg in addition to his current regimen. Five months later, his labs showed 17-OHP 3100 ng/dL, A4 160 ng/dL, total T 550 ng/dL (A:T ratio 0.29), free T 9.90, FSH 6.9 IU/L and LH 4.3 IU/L; repeat semen analysis demonstrated sperm count of 125 million/mL with normal morphology and motility. The patient’s wife achieved a spontaneous pregnancy 3 months later with subsequent delivery of a healthy baby girl. Of note, while addition of nighttime methylprednisolone restored the patient’s fertility, it also led to 15 lb. weight gain in 6 months, and therefore nocturnal methylprednisolone was discontinued. In all patients with classic CAH, treatment entails glucocorticoid and mineralocorticoid replacement to treat adrenal insufficiency and to partially lower ACTH, adrenal hyperandrogenism, and the risk of TARTs. This therapy must be balanced with the risk of iatrogenic Cushing syndrome, as ACTH suppression invariably requires supraphysiologic glucocorticoids. Though adrenal hyperandrogenism contributes to infertility, in male patients not seeking fertility, adrenal androgens may adequately support virilization and sexual function, so suppression may not be needed to achieve patient goals. However, in those seeking fertility, temporary use of nocturnal glucocorticoids can effectively reverse hyperandrogenemia and restore spermatogenesis and fertility. Sunday, June 2, 2024