Syndromes Congenital disorders

Congenital idiopathic hypogonadotropic hypogonadism is characterized by isolated gonadotropin deficiency resulting in eunuchoidism (sexual infantilism and eunuchoidal body habitus) and sometimes impaired olfactory function (anosmia). Many of the men have in addition mid-line facial defects, color blindness, hearing difficulties, and cryptorchidism (Kallmann's syndrome). The underlying cause of the hypogonadism is a defect in gonadotropin-releasing hormone (GnRH) secretion. In some men, the disorder is X-linked, and is thought to be due to disordered migration of GnRH neurons from the olfactory region to the hypothalamus. In others the neurons may not develop normally. In rare cases, the disorder results from a mutation in the GnRH receptor.

Most of these patients have both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) deficiency, but a few have isolated deficiency of FSH or LH. The clinical manifestations of isolated LH deficiency are very similar to those of combined FSH and LH deficiency, except that some men with isolated LH deficiency are fertile (fertile eunuch syndrome). A rare cause is a mutation in the FSH ß-subunit gene that results in functional FSH deficiency.

Hemochromatosis is a genetic disorder of mucosal iron transport that results in increased deposition of iron in many tissues including the pituitary gland. It can therefore cause hypogonadotropic hypogonadism, nearly always of postpubertal onset.

Other genetic disorders of gonadotropin secretion include multiorgan genetic syndromes such as the Laurence-Moon-Biedl syndrome, Prader-Willi syndrome, Lowe syndrome, and familial cerebral ataxia.

Acquired hypogonadotropic hypogonadism Any hypothalamic or pituitary disease can cause hypogonadotropic hypogonadism and therefore infertility. This can be induced by destruction of GnRH neurons or of the gonadotrophs in the pituitary, by interruption the hypothalamic-pituitary portal circulation, or by functional inhibition of GnRH or gonadotropin secretion.

Among these disorders, the most common are pituitary macroadenomas (including nonsecreting macroadenomas), surgical therapy for pituitary macroadenomas, prolactinomas, and craniopharyngiomas. Vascular lesions (pituitary infarction, carotid aneurysm) may also cause hypopituitarism, as can a variety of infiltrative disorders such as sarcoidosis, histiocytosis, tuberculosis, and fungal infections.

Functional hypogonadotropic hypogonadism and infertility can be induced by hyperprolactinemia, androgen excess, estrogen excess, and cortisol excess.

   While any cause of hyperprolactinemia (drugs, hypothyroidism) may be incriminated, most men have prolactinomas. (See "Causes of hyperprolactinemia";).

   Androgen excess may be due to the administration of either testosterone or other anabolic steroids ,androgen overproduction due to congenital adrenal hyperplasia, or tumors of the testis or adrenal glands . Anabolic steroid use should be suspected in men with low sperm counts, low serum LH concentrations, and a well-androgenized phenotype.

   Estrogen excess may be due to estrogen therapy or to estrogen production by a testicular tumor.

Opioid-like or other central nervous system-activating drugs, including many psychotropic drugs, can inhibit GnRH or gonadotropin secretion. GnRH analogues (agonists and antagonists) usually are given to suppress gonadotropin secretion, as in men with prostatic carcinoma; infertility is an expected effect of treatment with these analogues.

Any serious systemic illness or chronic nutritional deficiency can cause hypogonadotropic hypogonadism and infertility Massive obesity has a similar effect.