THALASSAEMIA AND ABERRATIONS OF GROWTH AND PUBERTY

Abstract

Endocrine dysfunction in Thalassaemia major (TM) is a common and disturbing complication, which requires prompt recognition and treatment. The contribution of the underlying molecular defect in TM to the development of endocrinopathies is significant because the patients with the more severe genetic defects have a greater rate of iron loading through higher red cell consumption. TM patients frequently present delay of growth and puberty with reduction of final height. The pathogenesis of growth failure is multifactorial and is mainly due to chronic anemia and hypoxia, chronic liver disease, zinc and folic acid deficiency, iron overload, intensive use of chelating agents, emotional factors, and endocrinopathies (hypogonadism, delayed puberty, hypothyroidism) and GH-IGF-1 axis dysregulation. Although appropriate iron chelation therapy can improve growth and development, TM children and adolescents treated intensively with desferrioxamine remain short as well, showing body disproportion between the upper and lower body segment. Body disproportion is independent of prepubertal or pubertal period of greater height gain. Treatment with recombinant GH (rhGH) is recommended when GH deficiency is established, and even so, the therapeutic response is often non satisfactory. Growth acceleration is mostly promoted with sex steroids in children with associated pubertal delay. Sexual complications in TM, which include Delayed Puberty, Arrested Puberty and Hypogonadism, present the commonest endocrine complication. Iron deposition on gonadotroph cells of the pituitary leads to disruption of gonadotrophin production which is proven by the poor response of FSH and LH to GnRH stimulation. In the majority of patients gonadal function is normal as most women with Amenorrhea are capable of achieving pregnancy with hormonal treatment and similarly men with azoospermia become fathers. Secondary Hypogonadism appears later in life,    and is manifested in women as Secondary Amenorrhea and in men as decline in sexual drive and azzoospermia. The damage to the hypothalamus and pituitary is progressive, even when intensive chelating therapy is given and the appearance of Hypogonadism in both sexes is often unavoidable. Close follow up and proper management is crucial for every patient with TM. Early recognition of growth disturbance and prevention of hypogonadism by early and judicious chelation therapy is mandatory for the improvement of their quality of life. Patients with TM can now live a better life due to modern advances in their medical care and our better understanding in the pathogenesis, manifestation and prevention of endocrine complications.