SHORT STATURE AND FAILURE OF PUBERTAL DEVELOPMENT IN THALASSEMIA MAJOR - EVIDENCE FOR HYPOTHALAMIC NEUROSECRETORY DYSFUNCTION OF GROWTH-HORMONE SECRETION AND DEFECTIVE PITUITARY GONADOTROPIN-SECRETION

In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved ra te of survival. Endocrine disorders related to secondary haemosiderosi s such as short stature, delayed puberty and hypogonadism are major pr oblems in both adolescent and adult patients. A total of 32 patients w ith P-thalassaemia major undergoing treatment at the Children's Hospit al, University of Gottingen were examined. Fourteen of these were shor t in stature. Growth hormone (GH) secretion was investigated in 13 pat ients exhibiting either a short stature or reduced growth rate. The st imulated GH secretion of 10 patients in this subgroup lay within the n ormal range. Studies of their spontaneous GH secretion during the nigh t revealed that these patients had a markedly reduced mean GH and redu ced amplitudes in their GH peaks. Low insulin-like growth factor (IGF) -I levels were seen in the growth-retarded thalassaemic patients. Eigh t were subjected to an IGF generation test and showed a strong increas e in both IGF-I and insulin-like growth factor binding protein (IGFBP) -3 levels indicating intact IGF-I generation by the liver. Hypogonadot ropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-rele asing hormone (GnRH) per pump in 2 female and 5 male patients, no chan ge in either their serum oestradiol or testosterone levels or in LH/FS H response to GnRH was observed suggesting that they were suffering fr om a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature, low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3-1 2 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3.Conclusion Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver d amage. Hypogonadotropic hypogonadism is caused by the selective loss o f pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be conside red either as an alternative or an additional treatment before startin g GH therapy.