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Severe Obesity Confounds the Interpretation of Low-Dose Dexamethasone Test Combined with the Administration of Ovine Corticotrophin-Releasing Hormone in Childhood Cushing Syndrome

Section on Endocrinology and Genetics, Program in Developmental Endocrinology and Genetics (D.L.B., N.C., J.R., M.F.K., C.A.S.), National Institute of Child Health & Human Development, Bethesda, Maryland 20892; Pediatric Endocrinology Inter-Institute Training Program (D.L.B., J.R., C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Department of Radiology (N.C.), University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece

Address all correspondence and requests for reprints to: Constantine A. Stratakis, M.D., D(Med)Sci, Section on Endocrinology and Genetics, Program in Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC (East Laboratories), Room 1-3330, 10 Center Drive, MSC1103, Bethesda, Maryland 20892. E-mail: stratakc{at}mail.nih.gov.

Context: Suppression of cortisol secretion with a low-dose dexamethasone (Dex) followed by the administration of ovine CRH (Dex-oCRH) is used in the evaluation of adults with a pseudo-Cushing syndrome state (PCSS) vs. Cushing syndrome (CS).

Objective: The aim of the study was to determine the value of Dex-oCRH testing in the investigation of childhood CS.

Design: We conducted a retrospective analysis of data from children evaluated for CS vs. PCSS from 1998–2006; body mass index Z (BMIZ) and height-for-age Z (HAZ) scores were estimated.

Setting: A clinical research center was the setting for the study.

Main Outcome Measures: The main outcomes were confirmation of the diagnosis of CS by histology and response to Dex-oCRH.

Results: Thirty-two children (ages 3–17 yr) were studied: 11 had CS and 21 had PCSS; of the latter, 11 had a BMIZ score greater than 2. Children with CS had a mean HAZ score of –1.3 ± 0.51 vs. 0.31 ± 0.38 in nonobese and 0.71 ± 0.39 in obese children (P < 0.001). The previously established criterion of a cortisol of 1.4 µg/dl (38 nmol/liter) after Dex-oCRH identified all 10 normal children who were not very obese and those with CS; 5 of 11 normal children with more severe obesity had cortisol values greater than 1.4 µg/dl (38 nmol/liter) after Dex-oCRH, lowering the test specificity to 55%. Without consideration for obesity, an increase of the cutoff cortisol value after Dex-oCRH to 3.2 µg/dl (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding values for a cutoff of 2.2 µg/dl (61 nmol/liter) were 100 and 90.5%, respectively.

Conclusion: Our study showed that height gain is a simple way of distinguishing children with PCCS from those with CS; the interpretation of Dex-oCRH in children is confounded by severe obesity, which limits the utility of this test.