An article by Cotton et al1 relates recent etomidate exposure to an increased frequency of adrenal insufficiency in acutely ill patients, but Cotton and colleagues may have defined this association more accurately if analysis had included the recent use of opioids and corticosteroids by their subjects. Both classes of medication can independently and prominently lower cortisol levels. Opioids administered by intravenous,2 intrathecal,3 transdermal,4 and oral5 routes rapidly depress cortisol levels and occasionally have been reported to induce adrenal insufficiency in the absence of other apparent precipitating factors or underlying disease processes.3,4 Adrenal inhibition by synthetic corticosteroids has also been widely documented and is generally acknowledged. I have recently identified multiple patients with symptomatic adrenal insufficiency during long-term use of opioids, often in association with oral megestrol acetate, inhaled corticosteroids, or frequent intra-articular corticosteroid injections.
Daniell HW. Opioid Contribution to Decreased Cortisol Levels in Critical Care Patients. Arch Surg. 2008;143(12):1147-1148. doi:10.1001/archsurg.143.12.1147