Endocrine Abstracts

Beta thalassemia major (betaTM) is an inherited hematological disorder characterized by reduced or absent synthesis of beta-globin chains and anemia. Chronic transfusion treatment is necessary, exposing patients to iron overload comorbidities such as hypogonadism. It is due to iron accumulation in the pituitary gland and, more rarely, in testis and ovaries. HPG axis dysfunction can manifest as low estradiol or testosterone with low to normal serum LH and FSH, as commonly seen in hypogonadotropic hypogonadism (HH). The aim of our study was to verify the prevalence of hypogonadism in beta-TM patients (HH-betaTM), to evaluate the differences compared to a non-thalassemic hypogonadal population (HH), to assess the difference in cardiovascular risk (CVR) between beta-TM patients with and without hypogonadism. 47 patients (30 females, 17 males) with betaTM (22-60 years on average) were studied. Associated endocrinopathies included GH deficiency, thyroid nodules, osteoporosis. The control group consisted of 27 HH-nonthalassemic patients (8 women, 21 men), aged 19-73 years. Levels of testosterone, estradiol, LH and FSH were evaluated in both groups. CVR was assessed in betaTM patients using risk score calculators. In the total of 30 women betaTM patients 15 had HH, only six were receiving replacement therapy, while nine were refusing treatment. In the population of 17 male beta-TM patients, 6 had HH with a mean pre-therapy testosterone level of 204±22,118 ng/dl, FSH level of 4,167±2,073 IU/l and LH level of 3,55±3.92 IU/l. All were on replacement therapy with testosterone. In male HH-nonthalassemic controls, mean of FSH was 1,428±1,528 IU/l, of LH was 0.928±1,189 IU/l and of testosterone was 194±88,427 ng/dl. The difference between levels of FSH and LH in HH-betaTM and HH controls was significant only in the male population (P<0.01). No differences were found in CVR in 15 females with HH-betaTM compared to 15 female non-hypogonadal betaTM. CVR was significantly different in male with HH-betaTM compared to non-hypogonadal betaTM male (1.467% vs 0.633%)(P<0.05). Our data confirm the high incidence of hypogonadism in thalassemia, but in the male betaTM population there are higher gonadotropin levels compared to patients with HH, due to the mixed nature of the systemic damage. This characterizes HH in thalassemia as an intermediate clinical entity that deserves differentiated attention in terms of diagnosis, type of replacement therapy and follow-up. In the thalassemic male population, hypogonadism significantly worsens cardiovascular risk and highlights the importance of replacement therapy.