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Adrenal function in Smith–Lemli–Opitz syndrome

Authors

  • Simona E. Bianconi,

    Corresponding author
    1. Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland
    2. Inter-Institute Medical Genetics Training Program, National Institutes of Health (NIH), Bethesda, Maryland
    • Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Building 10, Room 9D42, 10 Center Drive, Bethesda, MD 20892.
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  • Sandra K. Conley,

    1. Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland
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  • Meg F. Keil,

    1. Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland
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  • Ninet Sinaii,

    1. Biostatistics and Clinical Epidemiology Service, NIH Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland
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  • Kristina I. Rother,

    1. Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland
    2. Inter-Institute Training Program on Pediatric Endocrinology, National Institutes of Health (NIH), Bethesda, Maryland
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  • Forbes D. Porter,

    1. Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland
    2. Inter-Institute Medical Genetics Training Program, National Institutes of Health (NIH), Bethesda, Maryland
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  • Constantine A. Stratakis

    1. Program in Developmental Endocrinology & Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland
    2. Inter-Institute Medical Genetics Training Program, National Institutes of Health (NIH), Bethesda, Maryland
    3. Inter-Institute Training Program on Pediatric Endocrinology, National Institutes of Health (NIH), Bethesda, Maryland
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  • How to Cite this Article: Bianconi SE, Conley SK, Keil MF, Sinaii N, Rother KI, Porter FD, Stratakis CA. 2011. Adrenal function in Smith–Lemli–Opitz syndrome. Am J Med Genet Part A 155: 2732–2738.

Abstract

Smith–Lemli–Opitz syndrome (SLOS) is a multiple malformation syndrome due to mutations of the 7-dehydrocholesterol reductase gene (DHCR7), which leads to a deficiency of cholesterol synthesis and an accumulation of 7-dehydrocholesterol. The SLOS clinical spectrum ranges from multiple major malformations to a mild phenotype with minor anomalies and intellectual disability. Several children with SLOS and adrenal insufficiency have been described. We performed ovine corticotropin (oCRH) testing in 35 SLOS patients and 16 age- and gender-matched controls. We reviewed prior adrenocorticotropin (ACTH) stimulation tests of our SLOS patients (19 of 35 available) and reviewed results of ACTH stimulation tests from 10 additional SLOS patients. Results from oCRH testing showed that patients with SLOS had significantly higher ACTH baseline values than healthy controls (24.8 ± 15.3 pg/ml vs. 17.8 ± 7.5 pg/ml, P = 0.034). However, no statistically significant differences were noted for peak ACTH values (74.4 ± 35.0 pg/ml vs. 64.0 ± 24.9 pg/ml, P = 0.303) and for baseline (14.2 ± 7.8 mcg/dl vs. 14.2 ± 6.3 mcg/dl, P = 0.992) and peak cortisol values (28.2 ± 7.9 mcg/dl vs. 24.8 ± 8.1 mcg/dl, P = 0.156). The area-under-the-curve (AUC) was not significantly different in SLOS patients compared to controls for both ACTH (250.1 ± 118.7 pg/ml vs. 195.3 ± 96.6 pg/ml, P = 0.121) as well as cortisol secretion (83.1 ± 26.1 mcg/dl vs. 77.8 ± 25.9 mcg/dl, P = 0.499). ACTH stimulation test results were normal in 28 of 29 tests. The individual with the abnormal test results had subsequent normal oCRH tests. The slightly increased baseline ACTH level seen during oCRH testing may be due to compensated adrenocortical insufficiency. However, we were able to show that our patients with SLOS had an adequate glucocorticoid response, and thus, in mild to moderate cases of SLOS stress steroid coverage may not be warranted. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

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