Prevalence of growth and puberty failure with respect to growth hormone and gonadotropins secretion in beta-thalassemia major.

BACKGROUND: Present transfusion protocols have increased the life expectancy of patients with beta-thalassemia major, but siderosis is a major clinical complication of the treatment. Short stature and hypogonadism are extremely frequent in patients with thalassemia. To investigate the influence of age at the onset of blood transfusion, iron chelation therapy, and serum ferritin levels on growth and pubertal development in thalassemic patients, and the prevalence of these endocrine complications with respect to pituitary somatotropic and gonadotropic functions, this study was designed.

METHODS: Clinical data of 158 patients (82 females and 76 males) with thalassemia major, aged 10 - 20 years (mean age: 15.1 +/- 4.8 years) were collected from a pediatric hematology clinic in Tehran. Height was measured and stages of puberty were determined by a pediatric endocrinologist. Serum ferritin concentration, liver function tests, serum calcium and phosphorus, blood sugar, free thyroxine (FT4), TSH, FSH, LH, dehydroepiandrosterone sulfate, testosterone (in boys), estradiol (in girls), and insulin-like growth factor I were measured after overnight fasting. In patients with a height more than 2 standard deviation below the mean, the growth hormone stimulation test was considered. Bone age was determined in all patients.

RESULTS: Thalassemic patients in this study showed a high prevalence of short stature (62%) and hypogonadism (69%). We found a low serum level of gonadotropins (FSH and LH) in over 14-year-old patients with impaired puberty, which indicated that hypogonadotropic hypogonadism is responsible for this complication. Results of growth hormone provocative tests and serum insulin-like growth factor I levels in short stature patients showed a reduced growth hormone response in 38% and low insulin-like growth factor I levels in 42% of thalassemic patients. Short stature and hypogonadism were more common in patients with serum ferritin levels above 2000 microg/L and these complications were significantly more frequent in patients who started treatment later than that of the patients who started treatment in the first years of life (P < 0.001).

CONCLUSION: Short stature and hypogonadism are extremely frequent in our patients with thalassemia, but correct blood transfusion and appropriate iron chelation therapy can prevent or limit these complications. These data support the need for vigilant follow-up of patients with thalassemia in order to treat endocrine dysfunction at an appropriate age.