Reversal of Primary Male Infertility and Testicular Adrenal Rest Tumors in Salt-Wasting Congenital Adrenal Hyperplasia

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A26-yr old male with a salt-wasting form of congenital adrenal hyperplasia presented with a 4-yr history of primary infertility. He had done well on deflazacort (range 6–18 mg/d) and fludrocortisone [0.05 mg twice a day (bid)] until late adolescence when he had several Addison’s crises due to decreased therapeutic adherence. He was lost to follow-up for several years before infertility work-up. LH and FSH were undetectable, whereas serum testosterone level was 37.4 nmol/liter normal (N): 8–26 , ACTH 501 ng/liter (N: 10 – 60), and 17-hydroxyprogesterone 1047 nmol/liter (N: 1.8 –9.2). Computed tomography scan showed massive bilateral adrenal hyperplasia (Fig. 1), and testicular ultrasonography multiple bilateral testicular adrenal rest tumors (TARTs). Semen analysis showed azoospermia. Congenital adrenal hyperplasia was shown to be due to a missense mutation in exon 8 of the 21hydroxylase gene. In response to dexamethasone (0.5 mg bid) and fludrocortisone (0.05 mg bid), ACTH and 17-hydroxyprogesterone levels fell (8 ng/liter and 2.5nmol/liter, respectively), whereas LH (4.2 U/liter) and FSH (9.3 U/liter) rose, followed by spontaneous conception. The patient’s wife delivered a healthy term male baby 12 months after the change of replacement therapy. However, repeat semen analysis and paternity confirmation were not performed. Repeat imaging studies after 13 months of treatment disclosed dramatic reduction of adrenal hyperplasia and the disappearance of TARTs. These data demonstrate the rapid reversibility of TARTs using dexamethasone as first described by Cunnah et al. (1) without side effects in contrast to previous reports (2). The chronological association of TART disappearance with pregnancy suggests that mechanical obstruction on seminal tubules might have caused this patient’s infertility, although gonadal axis suppression may also have contributed to infertility, as discussed recently (3, 4).