title: Evaluation of gonadotrophin insufficiency in thalassemic boys with pubertal failure: spontaneous versus provocative test.
abstract: The objective of this study was to determine whether iron toxicity in blood transfusion dependent beta-thalassemic patients with pubertal failure was associated with gonadotrophin (GTH) insufficiency as assessed by spontaneous and dynamic tests. Gonadotrophin-releasing-hormone (GnRH)-GTH secretory dynamics were studied by serial ultradian GTH profiles and a 100 microg i.v. GnRH bolus test (GBT) in 28 male beta-thalassemia major patients with failed puberty (FP group). Five healthy, non thalassemic prepubertal males were studied for comparative purposes. According to the pulse profile, patients in the FP group were subdivided into apulsatile (no FSH and LH pulses, n = 16; AFP group) and pulsatile (defective pulse profile, n = 12; PFP group) subsets. The FP group had lower basal FSH (p < 0.01), LH (p < 0.01) and GnRH stimulated FSH (p < 0.001) and LH levels (p < 0.001) than the controls. However, basal and GnRH-stimulated FSH (p < 0.01 for basal and p < 0.001 for peak) and LH (p < 0.01 for both basal and peak) levels were lower in the AFP than the PFP group. Serum ferritin levels in GnRH-non-responders were higher than those in the responders (9,052.63 +/- 579.14 mg/l vs 5,933.33 +/- 1,819.65 mg/l; p < 0.05). Similarly, symptomatic organ damage was higher in the AFP than the PFP patients (81% vs 42%; p < 0.001). In conclusion, this study suggests that iron overloaded thalassemic patients with failed puberty had abnormal GnRH-GTH secretory dynamics. The severity of the defect was heterogeneous, ranging from very severe (apulsatile) to less severe (pulsatile) subsets. Comparison between spontaneous and dynamic test levels showed that there was concordance between the degree of pulse defect and magnitude of LH response to GBT. However, ultradian GTH profile was a more reliable method for identifying the degree of GTH insufficiency than GBT. Our data also showed that iron toxicity was the major cause of GnRH-GTH deficiency in thalassemic patients. Such information may be useful for better understanding of the pathophysiology of hypogonadotrophic hypogonadism (HH), thereby promoting therapeutic options for induction of puberty and spermatogenesis.
authors: Department of Obstetrics and Gynaecology, University College London, UK. ratnach@globalnet.co.uk
authors: R
authors: R
authors: Chatterjee
authors: M
authors: M
authors: Katz
mesh_terms: D000293:Adolescent; D000328:Adult; D005069:Evaluation Studies as Topic; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011627:Puberty; D013789:Thalassemia / Q000503:physiopathology*
chemical_list: D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone