ESPE Abstracts (2016) 86 P-P1-11

Evaluation of the Glucocorticoid, Mineralocorticoid, and Adrenal Androgen Secretion Dynamics in A Large Cohort of Patients Aged 6-18 Years with Transfusion-dependent [beta]-Thalassemia Major, with an Emphasis on the Impact of Cardiac Iron Load

Ahmet Uçara, Nergiz Önerb, Gülcihan Özekb, Mehmet Guli Çetincakmakc, Mahmut Abuhandand, Ali Yildirime, Cemil Kayaf, Sena Unverdig, Hamdi Cihan Emeksizh, Yasin Yilmazi & Aylin Yetimj


aDepartment of Pediatric Endocrinology and Diabetes, Sisli Hamidiye Etfal Education and Research Hosipital, Istanbul, TR, Turkey; bDepartment of Hematology and Oncology, Sanliurfa, Sanliurfa Children’s State Hospital, TR, Turkey; cDepartment of Radiology, School of Medicine, Dicle University, Diyarbakir, TR, Turkey; dDepartment of Pediatrics, School of Medicine, Harran University, Sanliurfa, TR, Turkey; eDepartment of Pediatric Cardiology, Sanliurfa Children’s State Hospital, Sanliurfa, TR, Turkey; fDepartment of Pediatrics, Sanliurfa Children’s State Hospital, Sanliurfa, TR, Turkey; gDepartment of Radiology, Sanliurfa Children’s State Hospital, Sanliurfa, TR, Turkey; hDepartment of Pediatric Endocrinology and Diabetes, Trabzon Kanuni Education and Research Hospital, Trabzon, TR, Turkey; iDepartment of Pediatrics, School of Medicine, Istanbul University, Istanbul, TR, Turkey; jDepartment of Adolescent Medicine, School of Medicine, Istanbul University, Istanbul, TR, Turkey


Background: The variable presence of adrenal insufficiency (AI) due to hypocortisolemia (HC) in patients with thalassemia is well established; however, the prevalence of adrenocortical hypofunction (ACH) in the zona glomerulosa and zona reticularis of the adrenal cortex is unknown.

Objective and hypotheses: To establish the prevalence of ACH, we examined the cortisol response to 1 μg- and 250 μg- ACTH tests, plasma aldosterone (A)/plasma renin activity (PRA) ratio, and serum DHEAS levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function.

Method: One hundred twenty-one (52 females) patients with β-thalassemia major (β-TM) and 72 healthy peers (38 females) were enrolled. The patients underwent a 250-μg cosyntropin test if their peak cortisol was <500 nmol/l in a 1-μg cosyntropin test. Magnetic resonance imaging (MRI) was performed to assess the MRI based liver iron content and cardiac MRI T2* iron. The associations between ACH and TBIL were investigated.

Results: The patients with thalassemia had lower ACTH, cortisol, DHEAS, and A/PRA values compared with the controls (P<0.001). Thirty-nine patients (32.2%) had HC [primary (n=1), central (n=36), combined (n=2)], and 47 (38.8%) patients had reduced DHEAS levels; 29 (24.0%) patients had reduced A/PRA ratios. Forty-six (38.0%) patients had hypofunction in one of the adrenal zones, 26 (21.5%) had hypofunction in two adrenal zones, and 9 (7.4%) had hypofunction in all three zones. Patient age and TBIL surrogates were significant independent parameters associated with ACH. Cardiac MRI T2* iron was the only significant parameter that predicted the severity of ACH at a cut-off of 20.6 ms, with 81% sensitivity and 78% specificity.

Conclusions: Patients with thalassemia have a high prevalence of AI due to HC and zona glomerulosa and zona reticularis hypofunction. TBIL surrogates can predict ACH, but cardiac iron was the only surrogate that was adequately sensitive to predict the severity of ACH.