The biochemical diagnosis of adrenal insufficiency with modern cortisol assays: Reappraisal in the setting of opioid exposure and hospitalization

We aimed to (1) examine the diagnosis of opioid-induced adrenal insufficiency, and (2) investigate the diagnostic value of a morning cortisol83 nmol/L (3 µg/dl) for the diagnosis of adrenal insufficiency, using newer more specific cortisol assays and cut-offs.Retrospective study (5/2015-10/2020).Cohort 1 (N = 75): adults who underwent cosyntropin stimulation testing and opioid exposure for30 days. Cohort 2 (N = 854): adults, with or without opioid exposure, who had a morning cortisol level measured the same day as stimulation testing.Peak cortisol during cosyntropin stimulation testing. Sensitivity and specificity of morning serum cortisol for adrenal insufficiency.The prevalence of adrenal insufficiency in patients with chronic opioid exposure who underwent cosyntropin stimulation testing was 4.0% using a cortisol cutoff of405 nmol/L (14.7 µg/dl) versus 19% using the traditional cutoff of500 nmol/L (18.1 µg/dl). For hospitalized patients with and without opioid-exposure, 14 of 22 (64%) patients with morning cortisol levels of83 nmol/L (3 µg/dl) passed cosyntropin stimulation testing. A morning cortisol level of348 nmol/L (12.6 µg/dl) had 100% sensitivity (95% confidence interval: 84.5%-100%) for the diagnosis of adrenal insufficiency.Applying a cutoff of405 nmol/L (14.7 µg/dl), opioid-induced adrenal insufficiency is rare. Nearly 1 out of 6 patients would be reclassified as having adrenal insufficiency applying the guideline-recommended cutoff of500 nmol/L (18.1 µg/dl). Serum morning cortisol83 nmol/L (3 µg/dl) is not a valid diagnostic test for adrenal insufficiency in hospitalized patients, whether or not receiving opioids.