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


METHODS
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.


METHODS
A clinical research center was the setting for the study.


METHODS
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.


CONCLUSIONS
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.
Batista
Dalia L
DL
Section on Endocrinology and Genetics, Program in Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Courcoutsakis
Nikos
N
Riar
Jehan
J
Keil
Margaret F
MF
Stratakis
Constantine A
CA
D000293:Adolescent; D000818:Animals; D001827:Body Height; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone; D003480:Cushing Syndrome / Q000150:complications* / Q000175:diagnosis*; D003907:Dexamethasone; D003937:Diagnosis, Differential; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D012189:Retrospective Studies; D012756:Sheep
D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone