Wang C, Tso S C, Todd D
Department of Medicine, University of Hong Kong Queen Mary Hospital.
J Clin Endocrinol Metab. 1989 Mar;68(3):511-6. doi: 10.1210/jcem-68-3-511.
We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.
我们研究了11名男性和5名女性患者（年龄在12至30岁之间）的垂体-性腺功能，这些患者患有严重的β-地中海贫血和慢性铁过载。所有患者的基础血清皮质醇、T4和PRL浓度均正常，血清皮质醇和GH对胰岛素诱导的低血糖的反应以及TSH对TRH的反应也正常。在11名男性患者（均超过17岁）中，只有3人达到了完全青春期发育，4人的血清LH和FSH对GnRH的反应低于正常水平。作为一个群体，他们的平均基础血清睾酮（T）水平较低[11.7±4.9（±SE）nmol/L；正常范围为10 - 40 nmol/L]，11名男性患者中有9人对hCG有血清T升高的反应。3名17岁以上的女性患者中有2人处于青春期前，血清雌二醇（E2）水平检测不到，血清LH和FSH对GnRH无反应；另一名女性患者月经周期规律，血清E2水平正常，血清LH和FSH对GnRH反应正常。6名青春期前患者（4名男性和2名女性，年龄在17至30岁之间）在开始螯合治疗后连续3年接受研究。尽管血清铁蛋白中位数从11,910降至1,303 pmol/L，但青春期没有进展，他们的基础和GnRH刺激的血清LH和FSH以及血清T或E2水平没有变化。其中3名患者（1名男性和2名女性）随后除了接受螯合治疗外，还接受了6个月的皮下脉冲式GnRH治疗，但没有改善。我们得出结论，严重地中海贫血患者的慢性铁过载导致不同程度的低促性腺激素性性腺功能减退，在疾病后期给予螯合治疗对此无反应。大多数患者的性腺功能减退是由于垂体对GnRH反应低下所致。
