title: Adrenal function in Smith-Lemli-Opitz syndrome.
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.
authors: Program in Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Simona E
authors: SE
authors: Bianconi
authors: Sandra K
authors: SK
authors: Conley
authors: Meg F
authors: MF
authors: Keil
authors: Ninet
authors: N
authors: Sinaii
authors: Kristina I
authors: KI
authors: Rother
authors: Forbes D
authors: FD
authors: Porter
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007223:Infant; D008297:Male; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D012016:Reference Values; D012720:Severity of Illness Index; D012756:Sheep; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*
chemical_list: D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D006854:Hydrocortisone