Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect

Abstract

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

Adult-Onset Idiopathic Hypogonadotropic Hypogonadism — A Treatable Form of Male Infertility

“…21 Hemochromatosis, the disease most likely to cause acquired isolated gonadotropin deficiency in relatively young men, was ruled out by the presence of normal serum ferritin concentrations, and in addition, responsiveness to GnRH is poor in men with hemochromatosis, because of the predominantly pituitary defect in gonadotropin secretion. 22 The importance of the finding of a partially empty sella turcica in 4 of the 10 men is uncertain; about 20 percent of normal subjects have an empty sella without an associated clinical syndrome. 23 One of the men with adult-onset hypogonadotropic hypogonadism had a history of head trauma.…”

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications

“…Hypogonadism is also a classical feature of hemochromatosis, which is predominantly the consequence of a pituitary lesion caused by the iron overload (227).…”

Conséquences endocrines des hémochromatoses

“…La raison de l'avidité spé-cifique des cellules gonadotropes hypophysaires pour le fer n'est pas encore comprise, elle pourrait s'expliquer par l'expression dans ces cellules antéhypophysaires de transporteurs du fer absents dans les autres lignées antéhypophysaires [38,39]. Cette atteinte pituitaire directe et isolée dans la grande majorité des cas [40] semble expliquer l'absence de réponse des gonadotrophines hypophysaires à l'administration pulsatile du peptide hypothalamique GnRH (GonadotropinReleasing Hormone) lorsque l'hypogonadisme hypogonadotrophique est sévère [41].…”