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.
Adrenal function in Smith–Lemli–Opitz syndrome†
Article first published online: 11 OCT 2011
Published 2011 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.
American Journal of Medical Genetics Part A
Volume 155, Issue 11, pages 2732–2738, November 2011
How to Cite
Bianconi, S. E., Conley, S. K., Keil, M. F., Sinaii, N., Rother, K. I., Porter, F. D. and Stratakis, C. A. (2011), Adrenal function in Smith–Lemli–Opitz syndrome. Am. J. Med. Genet., 155: 2732–2738. doi: 10.1002/ajmg.a.34271
- Issue published online: 20 OCT 2011
- Article first published online: 11 OCT 2011
- Manuscript Accepted: 27 JUL 2011
- Manuscript Received: 24 JAN 2011
- U.S. National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development. Grant Numbers: HD-000642-04, HD-008825-04
- National Institutes of Health (NIH)
- adrenal gland;
- adrenocortical insufficiency;
- pituitary gland;
- adrenocorticotropin (ACTH);
- Smith–Lemli–Opitz syndrome (SLOS);
- inborn error of cholesterol synthesis;
- corticotropin releasing hormone (CRH)
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.