Hypogonadism in Thalassemia Major.

Thalassemia is one of the commonest hereditary hemolytic anemia. 3% to 17% of the population in Indian subcontinent carries beta thalassemia gene. Every year about 100,000 children are born with thalassemia major in the world. Out of these 8000 to10,000 are born in India. With the introduction of moderate -transfusion programs and chelation therapy with subcutaneous desferrioxamine and/or Deferiprone, survival of patients with thalassemia major has greatly improved. The need for repeated transfusions in thalassemics, leads to deposition of iron in different tissues, which in turn leads to damage and dysfunction of various organs. If chelation is sub optimal, this can lead to delayed puberty/ arrested puberty or hypogonadism in these subjects. Absence of sexual characteristics in girls till the age of 13 years and a testicular volume<4ml in boys till the age of 14 years is defined as delayed puberty. Arrested puberty is the non-progression of puberty for a period of 12 months and complete absence of puberty is known as hypogonadism. Hypogonadism also results in worsening of the bone mineral density, since sex steroids are also responsible for bone mineralization. Delayed puberty /hypogonadism is usually due to deposition of iron in the anterior pituitary gland since even moderate amount of iron deposition can affect this gland. Other factors that are responsible for delay in puberty are chronic anemia and delayed bone age. The gonads (testes in males and ovaries in females) are usually healthy with no significant iron deposition. All patients with Thalassemia major enrolled at our center are assessed for their pubertal status at every visit. The purpose of this study was to see the effect of beta thalassemia major on the onset and progression of puberty and its relation to chelation. A retrospective analysis of our case records of children and young adults between the age of 16 to 25 years was done. A diagnosis of hypogonadism was made on the basis of clinical assessment of puberty by a pediatric endocrinologist, levels of LH, FSH and testosterone in males and estradiol in females. Constitutional delay of puberty was ruled out before the laboratory evaluation.76 subjects in this group, of which 47 (62%) were males and 29 (38%) were females, had been assessed for their pubertal status at the Thalassemia endocrinology clinic. These patients were on moderate -transfusion regimen, maintaining a hemoglobin concentration of 8- 9 gm %. Most were on chelation with desferrioxamine or deferiperone or both, but compliance was not good in many patients. Average serum ferritin levels were calculated by averaging the ferritin levels over the last 5 years. Puberty was staged according to Tanner’s stages of puberty. 39 of the 76 patients (51%) had normal onset of puberty i.e. before 13 years in females and 14 years in males. 28/47 (59.6%) males and 11/29 (37.9%) females had normal onset of puberty. Average mean serum ferritin for the group with normal puberty was 4127 ng/ml (976–7484ng/ml).37 of the 76 (49%) patients had hypogonadism. 18/29 (62%) females and 19/47 (40.4%) males were affected. Mean S. ferritin for this group was 5234 ng/ml (Range 1248–10900). In conclusion 51% of our patients had hypogonadism which did not correlate with the serum ferritin levels. It is possible that the anterior pituitary gland may be sensitive to lower ferritin levels. Age of onset of chelation and the effects of the 2 drugs used for chelation may indirectly affect puberty. These factors are currently being evaluated in our study subjects.