International consensus on the diagnosis and management of endocrine complications of β and α thalassemia in children and adolescents.

Abstract

β-thalassemia (βT) and α-thalassemia (αT) are chronic hemolytic anemias caused by hereditary defects in the β or α chains of hemoglobin respectively. According to the clinical picture, both forms of thalassemia are subdivided into minor, intermedia or major. Previous guidelines focused on growth and endocrine dysfunctions in βT major, where the complications reported are consequences of iron toxicity. However emerging evidence shows that patients with other forms of thalassemia are also at risk of some endocrinopathies. This guideline provides consensus on the screening and management of endocrine complications of children and adolescents with different forms of thalassemia. The panel has 14 experts from 13 countries representing 8 societies. They reviewed literature up to 2024 for the highest available evidence on the subject and 42 recommendations were modified until at least 70% vote for agreement was achieved. Hypogonadism, delayed growth and puberty are common in βT major and transfusion dependent (TD) αT HbH disease and they are also reported in βT intermedia and non-TD αT HbH disease. Osteopenia, adrenal insufficiency and reproductive dysfunction are reported only in βT major and TD αT HbH disease. In addition, hypothyroidism, diabetes and hypoparathyroidism are also reported in TD and non-TD thalassemia. Adherence to modern transfusion, and iron chelation can prevent or reverse endocrine complications. Regular screening should be conducted before the age of 10 years in patients with TD thalassemia, and from 11 years onwards in non-TD thalassemia. Those who received hematopoietic stem cell transplantation for βT major are at risk of endocrinopathies and should be managed similarly to individuals with TD thalassemia.