Evaluation of gonadotrophin insufficiency in thalassemic boys with pubertal failure: Spontaneous versus provocative test

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 spontaneo us and dynamic tests. Gonadotrophin-releasing-hormone (GnRH)-GTH secretory dynamics were studied by serial ultradian GTH profiles and a 100 mug i.v. G nRH bolus test (GBT) in 28 male beta -thalassemia major patients with faile d 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; PPP group) subse ts. The FP group had lower basal FSH (p < 0.01), LH (p < 0.01) and GnRH sti mulated FSH (p < 0.001) and LH levels (p < 0.001) than the controls. Howeve r, 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 th an the PFP group. Serum ferritin levels in GnRH-non-responders were higher than those in the responders (9052.63 +/- 579.14 mg/l vs 5933.33 +/- 1819.6 5 mg/l; p < 0.05). Similarly, symptomatic organ damage was higher in the AF P than the PFP patients (81% vs 42%; p < 0.001). In conclusion, this study suggests that iron overloaded thalassemic patient s with failed puberty had abnormal GnRH-GTH secretory dynamics. The severit y of the defect was heterogeneous, ranging from very severe (apulsatile) to less severe (pulsatile) subsets. Comparison between spontaneous and dynami c test levels showed that there was concordance between the degree of pulse defect and magnitude of LH response to GET. However, ultradian GTH profile was a more reliable method for identifying the degree of GTH insufficiency than GET. Our data also showed that iron toxicity was the major cause of G nRH-GTH deficiency in thalassemic patients. Such information may be useful for better understanding of the pathophysiology of hypogonadotrophic hypogo nadism (HH), thereby promoting therapeutic options for induction of puberty and spermatogenesis.