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Therapy Insight: metabolic and endocrine disorders in sickle cell disease

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 102–109 (2008)Cite this article

Abstract

Sickle cell disease (SCD) is an autosomal, recessive hemoglobinopathy characterized by hemolytic anemia, intermittent occlusion of small vessels leading to acute and chronic tissue ischemia, and organ dysfunction. Red blood cell transfusions are a therapeutic mainstay in SCD and repeated transfusions can result in iron overload. Endocrine dysfunction is the most common and earliest organ toxicity seen in subjects with chronic iron-induced cellular oxidative damage and can be seen in those without clinical evidence of iron overload. The predicted risks of iron overload and endocrine organ failure increase with both the duration of disease requiring transfusion therapy and the number of transfusions. Assessing the state of iron-overload in patients with SCD constitutes a diagnostic challenge because of the unreliability of serum ferritin levels and the risks associated with liver biopsy. In turn, MRI is the preferred noninvasive screening tool for iron overload. This article describes the endocrine and metabolic disorders reported in patients with SCD, discusses their management, and identifies gaps in current knowledge and opportunities for future research.

Key Points

  • Sickle cell disease is an autosomal, recessive hemoglobinopathy that can be complicated by endocrine dysfunction that is most commonly caused by iron overload in these patients

  • MRI, rather than the serum ferritin assay, is the most useful noninvasive screening technique for the detection of the distribution of iron stores

  • Increased disease duration and number of blood transfusions (>8 per year) are predictors of iron overload and have been associated with greater risk of endocrine organ failure

  • The most common types of endocrine and metabolic disorders seen in patients with sickle cell disease include growth failure, osteopenia, hypogonadism, carbohydrate intolerance, and primary hypothyroidism

  • Treatment of endocrine dysfunction includes replacement of particular hormone deficiency and improvement of nutritional status; the goals of hormone replacement therapy for patients with sickle cell disease are to achieve normal levels of circulating hormones, restore normal physiology, and to avoid symptoms of deficiency with minimal side effects

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Acknowledgements

D Smiley is supported by a research grant from the NIH (K12 RR-017643). S Dagogo-Jack is supported by research grants from the NIH (R01 DK-067269) and the General Clinical Research Center (M01 RR-00211). G Umpierrez is supported by research grants from the American Heart Association (0555306B), the NIH (R03 DK 073190-01) and the General Clinical Research Center (M01 RR-00039). Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. S Dagogo-Jack is a Professor of Medicine and Director of the Endocrinology Fellowship Training Program at the University of Tennessee College of Medicine, Memphis, TN, USA.

Authors and Affiliations

  1. D Smiley is an Assistant Professor of Medicine, and G Umpierrez is a Professor of Medicine, at Emory University School of Medicine, Atlanta, GA, USA;,

    Dawn Smiley, Samuel Dagogo-Jack & Guillermo Umpierrez

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Correspondence to Guillermo Umpierrez.

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Smiley, D., Dagogo-Jack, S. & Umpierrez, G. Therapy Insight: metabolic and endocrine disorders in sickle cell disease. Nat Rev Endocrinol 4, 102–109 (2008). https://doi.org/10.1038/ncpendmet0702

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