EVALUATION OF THE INTEGRITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BY INSULIN HYPOGLYCEMIA TEST

We retrospectively reviewed dynamic ACTH and cortisol responses to ins ulin hypoglycemia in 193 subjects with suspected ACTH deficiency to as certain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 mu g/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-ad renal (HPA) axis, and 60 subjects were determined to have ACTH deficie ncy. Baseline and peak cortisol concentrations were strongly correlate d (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 mu g/dL at peak ACTH lev els above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortiso l values above 17 mu g/dL or below 4 mu g/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axi s integrity, defined as an increment in plasma cortisol of more than 7 mu g/dL above the baseline or as a doubling of the baseline cortisol value, were associated with high false positive and false negative rat es. We conclude that 1) the baseline morning serum cortisol concentrat ion has very limited predictive power in differentiating between norma l and impaired HPA function; 2) the use of criteria based on increment al changes in serum cortisol from baseline leads to unacceptably high false positive and false negative rates; and 3) insulin hypoglycemia i s still the best indicator of the integrity of the response of the HPA axis to stress.