McCullagh et al. (1953) described 5 patients with hypogonadotropic hypogonadism in the presence of normal testicular size and some degree of spermatogenesis. They designated the disorder fertile eunuch syndrome. One patient had a brother with eunuchoidal features who ... McCullagh et al. (1953) described 5 patients with hypogonadotropic hypogonadism in the presence of normal testicular size and some degree of spermatogenesis. They designated the disorder fertile eunuch syndrome. One patient had a brother with eunuchoidal features who refused examination. A deficiency of ICSH (interstitial cell-stimulating hormone), also known as luteinizing hormone (LH; see 152780) in the male, was postulated. The clinical picture is one of androgenic insufficiency with 'normal' spermatogenesis. The semen shows abnormalities of sperm count, morphology, and mobility, but at least 2 patients were said to have fathered children. Isolated deficiency of LH, in the presence of normal concentrations of FSH, was documented by radioimmunoassay by Faiman et al. (1968). Pitteloud et al. (2001) described a 26-year-old male with the fertile eunuch syndrome associated with a homozygous mutation in the GNRHR gene (Q106R; 138850.0001). The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with chorionic gonadotropin (CG; see 118860) alone, he developed sperm in his ejaculate and his wife conceived. Following cessation of CG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone secretion. The authors concluded that this case expands the clinical spectrum of GNRHR mutations, provides the first genetic basis for the fertile eunuch variant of hypogonadotropic hypogonadism, and documents the occurrence of reversible hypogonadotropic hypogonadism in a patient with a GNRHR mutation.
In a patient with fertile eunuch syndrome, Pitteloud et al. (2001) identified homozygosity for a gln106-to-arg (Q106R) mutation (138850.0001) in the GNRHR gene.