Endocrine dysfunction in homozygous beta-thalassemia: An underrecognized and undertreated consequence of prolonged survival

Abstract

The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of long-term care. While iron overload remains a central mechanism, additional contributors such as hypothalamic dysfunction, neurosecretory disturbances, and chronic inflammation have been identified. Endocrine disorders including hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, hypoparathyroidism, osteoporosis, and growth axis impairment - are prevalent and often underdiagnosed. Diagnostic challenges include normal hormone levels in early stages, necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction. Risk is modulated by sex, age, and chelation adherence. Early identification and proactive, multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.

Keywords: Thalassemia, Endocrine dysfunction; Iron overload; Hypogonadotropic hypogonadism; Adrenal insufficiency; Thyroid dysfunction; Bone disease

Core Tip: Endocrine dysfunction is a major source of long-term morbidity in transfusion-dependent beta-thalassemia. Subtle hypothalamic-pituitary axis abnormalities, such as neurosecretory growth hormone dysfunction and tertiary adrenal insufficiency, may precede overt clinical signs. Pituitary magnetic resonance imaging and dynamic hormone testing improve early detection. Integrating routine endocrine screening into thalassemia care enables timely interventions that can prevent irreversible complications and enhance quality of life.