title: Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion-dependent β-thalassemia major, with an emphasis on the impact of cardiac iron load.
abstract: 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. 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 dehydroepiandrosterone sulfate (DHEAS) levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function. The setting used was University hospital and government-based tertiary care center. 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. 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. 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.
authors.affiliation: Department of Paediatric Endocrinology & Diabetes, Şişli Hamidiye Etfal Education & Research Hospital, Istanbul, Turkey. aucar76@yahoo.com.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Uçar
authors.affiliation: Department of Paediatric Hematology & Oncology, Children's State Hospital of Sanliurfa, Sanliurfa, Turkey.
authors.forename: Nergiz
authors.initials: N
authors.lastname: Öner
authors.affiliation: Department of Paediatric Hematology & Oncology, Children's State Hospital of Sanliurfa, Sanliurfa, Turkey.
authors.forename: Gülcihan
authors.initials: G
authors.lastname: Özek
authors.affiliation: Department of Radiology, School of Medicine, Dicle University, Diyarbakir, Turkey.
authors.forename: Mehmet Güli
authors.initials: MG
authors.lastname: Çetinçakmak
authors.affiliation: Department of Paediatrics, Harran School of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Abuhandan
authors.affiliation: Department of Paediatric Cardiology, Children's State Hospital of Sanliurfa, Sanliurfa, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Yıldırım
authors.affiliation: Department of Paediatrics, Children's State Hospital of Sanliurfa, Sanliurfa, Turkey.
authors.forename: Cemil
authors.initials: C
authors.lastname: Kaya
authors.affiliation: Department of Paediatric Radiology, Children's State Hospital of Sanliurfa, Sanliurfa, Turkey.
authors.forename: Sena
authors.initials: S
authors.lastname: Ünverdi
authors.affiliation: Department of Paediatric Endocrinology & Diabetes, Trabzon Kanuni Education & Research Hospital, Trabzon, Turkey.
authors.forename: Hamdi Cihan
authors.initials: HC
authors.lastname: Emeksiz
authors.affiliation: Department of Paediatrics, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Yılmaz
authors.affiliation: Department of Adolescent Medicine, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Aylin
authors.initials: A
authors.lastname: Yetim
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000097:blood*; D000324:Adrenocorticotropic Hormone; D000450:Aldosterone / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007501:Iron / Q000097:blood*; D008297:Male; D012083:Renin / Q000097:blood*; D017086:beta-Thalassemia / Q000097:blood*
chemical_list: D000450:Aldosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D007501:Iron; D012083:Renin; D006854:Hydrocortisone
keywords: Adrenocortical; Cardiac MRI T2* iron; Cortisol; Dehydroepiandrosterone sulfate; Mineralocorticoid; Thalassemia major; Total body iron load
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