title: Restoration of fertility by gonadotropin replacement in a man with hypogonadotropic azoospermia and testicular adrenal rest tumors due to untreated simple virilizing congenital adrenal hyperplasia.
abstract: BACKGROUND
  Classical congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated.
  
  
  METHODS
  A 30-year-old male was referred to our clinic for endocrine and fertility assessment after undergoing unilateral orchiectomy for a suspected testicular tumor. Histopathological evaluation of the removed testis revealed atrophy and testicular adrenal rest tumors (TARTs) and raised the suspicion of underlying CAH. The remaining testis was also atrophic (5 ml) with minor TARTs. Serum 17-hydroxyprogesterone levels were elevated, cortisol levels were at the lower limit of normal range, and gonadotropins at prepubertal levels, but serum testosterone levels were within the normal adult range. Semen analysis revealed azoospermia. CAH was confirmed by a homozygous mutation g.655A/C>G (IVS2-13A/C>G) in CYP21A2. Hydrocortisone (24 mg/m(2)) administered to suppress ACTH and adrenal androgen overproduction unmasked deficient testicular testosterone production. As azoospermia persisted due to sustained hypogonadotropic hypogonadism, a combined s.c. gonadotropin replacement with human chorionic gonadotropin (hCG) (1500 IU twice weekly) and FSH (human menopausal gondadotropin (hMG) 150 IU three times weekly) was initiated.
  
  
  RESULTS
  Normalization of testosterone levels and a stable low sperm concentration (0.5 mill/ml) with good sperm motility (85% A+B progressive) were achieved within 21 months of treatment. Despite persisting TARTs, while receiving treatment, the patient successfully impregnated his wife twice, the latter impregnation leading to the birth of a healthy girl.
  
  
  CONCLUSIONS
  TARTs in unrecognized (simple virilizing) CAH may lead to unnecessary orchiectomy. In hypogonadotropic, azoospermic CAH, a combined treatment with oral corticosteroids and subcutaneously administered hCG and FSH can successfully restore testicular testosterone production and fertility, even if only one hypoplastic and atrophic testis with adrenal rest tumors is present.
authors.affiliation: Center of Reproductive Medicine and Andrology, Clinical Andrology, University of Muenster, Albert-Schweitzer-Campus 1, Building D11, D-48149 Muenster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohayem
authors.forename: Frank
authors.initials: F
authors.lastname: Tüttelmann
authors.forename: Con
authors.initials: C
authors.lastname: Mallidis
authors.forename: Eberhard
authors.initials: E
authors.lastname: Nieschlag
authors.forename: Sabine
authors.initials: S
authors.lastname: Kliesch
authors.forename: Michael
authors.initials: M
authors.lastname: Zitzmann
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000150:complications*; D000314:Adrenal Rest Tumor / Q000150:complications / Q000601:surgery*; D000328:Adult; D053713:Azoospermia / Q000188:drug therapy* / Q000209:etiology; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007006:Hypogonadism; D008297:Male; D008596:Menotropins / Q000627:therapeutic use*; D009919:Orchiectomy; D012102:Reproductive Control Agents / Q000627:therapeutic use*; D013736:Testicular Neoplasms / Q000150:complications / Q000601:surgery*
chemical_list: D006063:Chorionic Gonadotropin; D012102:Reproductive Control Agents; D008596:Menotropins