ENDOCRINE COMPLICATIONS OF THALASSEMIA MAJOR

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ndocrine abnormalities are among the common complications of thalassemia despite early establish-ment of appropriate chelation therapy, problems such as delayed sexual maturation and impaired fertility may persist. Determining the prevalence of endocrine compli-cations is difficult because of difference in the age of the first exposure to chelation  therapy, and the continuing improvement in survival in well-chelated patients (De Sanctis, 2004).

In a report of 342 North American patients who had thalassemia major, 38% of subjects had at least one endocrinopathy, most commonly hypogonadism, and 13% had more than one endocrinopathy (Kwiatkowski, 2008). 

Growth retardation:

Growth retardation is common in thalassemia major. Patterns of growth are relatively normal until the age of 9-10 years when growth velocity begins to slow. The key contributing factors to stunted growth in patients with thalassemia may include chronic anemia, transfusional iron overload, hypersplenism, and chelation toxicity (De Sanctis 1991).

Before the introduction of hypertransfusion and chelation therapy in the routine management of patients with β-thalassemia major, chronic tissue hypoxia and iron toxicity from transfusion hemosiderosis have been implicated as major causes of growth retardation (Low, 2001).

Causes of short stature in thalassemia:  Causes of

Genetic, malnutrition, socioeconomic status, chronic anemia, GH insufficiency, associated endocrine complications, zinc deficiency, DFX "toxicity", chronic liver disease and  poor compliance to DFX (De Sanctis 2008).

Progressive accumulation of iron in the body in thalassemic patients results from repeated blood transfusion and increased absorption of dietary iron because of increased ineffective erythropoiesis. Without chelation, hemosiderosis can lead to tissue damage due to free radical formation, lipid peroxidation resulting in mitochondrial, lysosomal and sarcolemal damage and increased collagen deposition secondary to increased activity of the iron-dependent protocollagen proline hydroxylase enzyme activity (Low, 2001).

Modern medical therapy has allowed thalassemic children to grow normally in the first decade of life but growth retardation continues to be observed in a significant proportion of these adolescents (Low, 2001).

Several mechanisms have been suggested to cause disorders of GH secretion:

1.     Neurosecretory dysfunction

2.     Hypothalamic growth-hormone-releasing hormone deficiency

3.     Pituitary GH deficiency

4.     Increased somatostatin activity (De Sanctis, 2008).