Identification of asymptomatic patients with subtle dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is a diagnostic challenge. HPA axis response to hypoglycemia during an insulin tolerance test (ITT) is considered the gold standard in the evaluation of suspected adrenal insufficiency, especially in the setting of growth hormone deficiency (GHD). The short 1 μg cortroysn stimulation test (CST) is also an accurate and practical screening test for the adequacy of ACTH reserve.
The aim of this study was to determine the utility of ITT and CST in determining adrenal insufficiency in children undergoing evaluation for GHD.
Retrospective analysis of the integrity of the HPA axis in subjects evaluated for potential GHD during the 5-year period from January 2005 to December 2009 was performed. A total of 520 children underwent ITT for potential GHD, of which 388 (75%) were boys. The mean age was 10.9 years (SD = 3.6 years), and the mean maximum cortisol was 18.3 μg/dL (SD = 5.6).
Of the 520 children who underwent ITT, 240 (46%) had a peak cortisol less than 18 μg/dL and were considered positive for possible adrenal insufficiency. Of those with a positive ITT, 131 underwent a CST, of which 44 (34%) continued to remain positive. Of these 44 children, 17 had a second CST, and 12 (71%) remained positive. Fourteen children who had cortisol levels less than 18 μg/dL following the initial ITT underwent a metyrapone test, all of whom proved adrenally sufficient.
In participants with a peak cortisol level less than 18 μg/dL during ITT, a subsequent 1 μg CST excluded adrenal insufficiency in two thirds of the subjects. Furthermore, a second CST in participants with a peak cortisol level of less than 18 μg/dL during the first CST was unlikely to exclude adrenal insufficiency.
The ITT is useful in the evaluation of participants with potential GHD because it assesses the adequacy of both the growth hormone and HPA axis. In those children with subnormal cortisol response during ITT, only a single 1 μg CST is needed for further assessment of adrenal insufficiency.
© 2012 Published by Elsevier Inc.