Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort

Abstract

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3–13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1–1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1–1.4, P

Good Clinical Practice of the Italian Society of Thalassemia and Haemoglobinopathies (SITE) for the Management of Endocrine Complications in Patients with Haemoglobinopathies

“…Endocrine disorders are currently the most frequent complications and those with the greatest impact on the quality of life of subjects affected by haemoglobinopathy, with a risk of developing a new endocrine complication after five years equal to approx. 10%, even in subjects with a good control of their iron balances [ 1 ].…”

“…Hypogonadotropic hypogonadism is the most frequent complication, together with bone metabolism disorders, in adult women with transfusion-dependent haemoglobinopathy, reaching prevalences of over 50% in historical cohorts, and lower but still relevant prevalences in more recent cohorts [ 1 , 16 , 28 ].…”

“…In the population affected by transfusion-dependent thalassaemia the average reported percentage of hypogonadism is 35% to 80%, with important differences in the various case studies depending on the average age of the population studied, on the age at the beginning of transfusion therapy and on the efficacy of chelation therapy [ 1 , 3 , 44 , 45 ].…”

“…In spite of the outstanding advances in the care of cardiovascular and hepatic complications due to blood transfusions, the management of endocrine complications has been left behind and, nowadays, they are the most frequent and the most resource-draining complications in haemoglobinopathies [ 1 ]. The Italian Society of Thalassemia and Haemoglobinopathies (SITE) has therefore undertaken a project aimed at integrating available evidence with experts’ opinions through a systematic method, in order to reach an adequate degree of consensus on the recommendations for the clinical practice.…”

Endocrinopathies in thalassemia - a review

“…The Thalassemia International Federation Study Group on Growth and Endocrine Complications reported that hypogonadism was the most common endocrinopathy (40.8%), closely followed by growth retardation (30.8%) with hypothyroidism being the least common (3.2%) in 3817 patients with thalassemia major (TM) [1]. Another study in 426 patients with TM showed that the risk of developing an endocrine complication was 9.7% in 5 years, despite adequate chelation [2].…”