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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

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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.

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Acknowledgments

The authors would like to thank all of the patients and parents included in the study. The authors would also like to thank Dr. Hüseyin Demirbilek for his critical review of the manuscript and David Chapman for editing the manuscript. The authors also thank Omega Statistics, Ltd., and Mark Behar for the statistical analyses, the Sanliurfa Thalassemia Society for partial financial support, and the thalassemia nurses Ayfer Aşkın and Harun Cagan for their active involvement in recruiting patients for the study.

Author contributions

A.U. conceptualized and designed the study. A.U., N.O., G.O., A.Y., M.A., A.Y., Y.Y. M.G.C., and C.K. participated in the recruitment of the study subjects. A.U., H.C.E., N.O. and G.O. participated in the data interpretation, statistical analysis, writing, and critical review of the manuscript.

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Authors and Affiliations

  1. Department of Paediatric Endocrinology & Diabetes, Şişli Hamidiye Etfal Education & Research Hospital, Istanbul, Turkey

    Ahmet Uçar

  2. Department of Paediatric Hematology & Oncology, Children’s State Hospital of Sanliurfa, Sanliurfa, Turkey

    Nergiz Öner & Gülcihan Özek

  3. Department of Radiology, School of Medicine, Dicle University, Diyarbakir, Turkey

    Mehmet Güli Çetinçakmak

  4. Department of Paediatrics, Harran School of Medicine, Harran University, Sanliurfa, Turkey

    Mahmut Abuhandan

  5. Department of Paediatric Cardiology, Children’s State Hospital of Sanliurfa, Sanliurfa, Turkey

    Ali Yıldırım

  6. Department of Paediatrics, Children’s State Hospital of Sanliurfa, Sanliurfa, Turkey

    Cemil Kaya

  7. Department of Paediatric Radiology, Children’s State Hospital of Sanliurfa, Sanliurfa, Turkey

    Sena Ünverdi

  8. Department of Paediatric Endocrinology & Diabetes, Trabzon Kanuni Education & Research Hospital, Trabzon, Turkey

    Hamdi Cihan Emeksiz

  9. Department of Paediatrics, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey

    Yasin Yılmaz

  10. Department of Adolescent Medicine, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey

    Aylin Yetim

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  1. Ahmet Uçar
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Correspondence to Ahmet Uçar.

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Uçar, A., Öner, N., Özek, G. et al. 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. Endocrine 53, 240–248 (2016). https://doi.org/10.1007/s12020-016-0872-2

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