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

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.