Multiple Endocrinologic Complications in Thalassemia Major

Abstract

Thalassemia major is a genetic disorder with a defective synthesis of either the alpha or the beta chain of hemoglobin A. Blood transfusion is crucial for the survival in these patients. Unfortunately, endocrine dysfunction is a very common complication in these patients and is principally due to excessive iron overload as a result of frequent blood transfusions. Although regular blood transfusion may increase life expectancy, disturbances in growth and pubertal development, abnormal gonadal functions, impaired thyroid, parathyroid and adrenal functions, diabetes, and disorderly bone growth are common side effects. We hereby present a case of a 23-year-old, unmarried woman with beta thalassemia major presenting with primary amenorrhea, poor development of secondary sexual character, and short stature. Thorough history, clinical examination, and laboratory investigation, including dynamic function test (insulin tolerance test) were conducted. These tests confirmed that she had multiple endocrinopathies, including hypogonadotropic hypogonadism, growth hormone deficiency, and subclinical adrenal insufficiency, which were caused by iron overload. She required hormone replacement therapy. Early recognition of possible deficiencies in hypothalamo-pituitary-end organ hormones caused by iron overload in thalassemia patients that undergo frequent blood transfusion procedures is essential. Appropriate treatments, including transfusion regimen and chelation therapy, as well as specific treatment of each complication are the crucial for the successful management and improvement of quality of life these patients.

Factors Associated to Growth Disorder in Children with Thalassemia Major

“…Iron accumulation in the endocrine glands causes endocrine disorders causing hypogonadotropic, adrenal insufficiency, growth hormone (GH) deficiency, hypothyroidism, hypoparathyroidism, hypogonadism, and diabetes mellitus. [16][17][18][19] Growth disturbances in thalassemia major patients due to hormonal disorders are very complex. This growth disturbance occurs due to iron overload in the endocrine and gonadal glands, which causes hypogonadotropic hypogonadism, hypothyroidism, hypoparatiorids, diabetes mellitus, growth hormone deficiency, adrenal insufficiency.…”

“…It will affect the speed of bone growth on the bone growth plate so that the child's stature is short. 17,18,23 Hypogonadotropic-hypogonadism happens due to damage to the hypothalamus and anterior pituitary caused by hemosiderosis. The gonadotropins produced by the anterior pituitary are very sensitive to oxidative damage caused by iron overload.…”

The key complications of beta thalassemia major: a review and update

“…19 Common endocrine complications include growth disturbance, impaired thyroid function, impaired gonadal dysfunction and diabetes mellitus. 20 Iron deposition in the endocrine glands lead to low production of hormones especially growth hormone (GH) and gonadotropin (LH and FSH). 21 A study done among 35 thalassemia major patients in India showed 87.5% of girls presented with primary amenorrhea and low FSH and LH level while 89.47% of boys had low free testosterone.…”