Assessment of glucose homeostasis in young adult female β-thalassemia major patients (β-TM) with acquired hypogonadotropic hypogonadism (AHH) never treated with sex steroids compared to eugonadal β-TM patients with spontaneous menstrual cycles.

Abstract

Acquired ypogonadotropic hypogonadism (AHH) is the most prevalent endocrine complication in thalassemia major (TM). Considering the detrimental effect of estrogen deficiency on glucose metabolism, the ICET-A Network promoted a retrospective study on the long-term effects of estrogen deficiency on glucose homeostasis in female β-TM patients with HH without hormonal replacement therapy (HRT). Seventeen β-TM patients with AHH (4 had arrested puberty; Tanners' breast stage 2-3), never treated with sex steroids, and 11 eugonadal β-TM patients with spontaneous menstrual cycles at the time of referral were studied. A standard 3-h OGTT was performed in the morning, after an overnight fast. Six-point plasma glucose and insulin level determinations, indices of insulin secretion and sensitivity, early-phase insulin insulinogenic index (IGI), HOMA-IR and β-cell function (HOMA-β), oral disposition index (oDI), glucose and insulin areas under the OGTT curves were evaluated. Abnormal glucose tolerance (AGT) or diabetes was observed in 15 (88.2%) of 17 patients with AHH and 6 (54.5%) of 11 patients with eumenorrhea. The difference between the two groups was statistically significant (P: 0.048). However, the group of eugonadal patients was younger compared to AHH patients (26.5 ± 4.8 years vs. 32.6 ± 6.2 years ; P: 0.010). Advanced age, severity of iron overload, splenectomy, increased ALT levels and reduced IGF-1 levels were the main clinical and laboratory risk factors for glucose dysregulation observed in β-TM with AHH compared to eugonadal β-TM patients with spontaneous menstrual cycles. These data further support the indication for an annual assessment of OGTT in patients with β-TM. We believe that a registry of subjects with hypogonadism is necessary for a better understanding of the long-term consequences of this condition and refining treatment options.