Severe obesity confounds the interpretation of low-dose dexamethasone test combined with the administration of ovine corticotrophin-releasing hormone in childhood Cushing syndrome

J Clin Endocrinol Metab. 2008 Nov;93(11):4323-30. doi: 10.1210/jc.2008-0985. Epub 2008 Aug 26.

Abstract

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 microg/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 microg/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 microg/dl (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding values for a cutoff of 2.2 microg/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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Animals
  • Body Height
  • Body Mass Index
  • Child
  • Child, Preschool
  • Corticotropin-Releasing Hormone*
  • Cushing Syndrome / complications*
  • Cushing Syndrome / diagnosis*
  • Dexamethasone*
  • Diagnosis, Differential
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism
  • Obesity / complications*
  • Retrospective Studies
  • Sheep

Substances

  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone