Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, Dahl KD. Delayed puberty in males with β-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Eur J Endocrinol 1995;133:48–56. ISSN 0804–4643
Patients with β-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary–gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6–19.0 years) affected by β-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepian-drosterone and 17 β-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9–26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary–gonadal function.
Sandra Valenti, Department of Endocrinology and Metabolism, 6 Viale Benedetto XV, 16132 Genoa, Italy