Endocrine Abstracts

Background: Chronic opioid use may lead to adrenal insufficiency (AI) due to suppression of the hypothalamic-pituitary-adrenal axis. We aimed to determine incidence of AI and mortality in patients treated with chronic opioid therapy in a standardized geographically well-defined population.

Methods: In this population-based cohort study we assessed the standardized incidence rate of first time met chronic opioid use and adrenal insufficiency in adult residents of Olmsted County, MN, USA, from January 1, 2005, to December 31, 2021. The Rochester Epidemiology Project was used as a database since it links medical records for all patients in Olmsted County since 1966. Incidence rates were standardized for age and sex according to the 2020 US white population. Chronic opioid use was defined as opioid therapy for at least 3 months of consecutive use of either transdermal fentanyl or oral opioids based on prescription database. AI was defined based on presence of chronic (≥ 6 months) glucocorticoid therapy. Elixhauser morbidity index was used.

Findings: Between 2005 and 2021, 8359 patients (mean age 60.8 years, 60% women) were identified to have chronic opioid use. Standardized incidence rates for chronic opioid use decreased from 533 (95% Confidence Interval, CI 484-583) per 100 000 person-years in 2005 to 138 (95% CI 116-159) in 2021. After 15 years of follow-up and adjusting for the competing risk of death, an estimated 11.3% (95% CI 10.4-12.3%) of patients treated with chronic opioids met criteria for AI at a mean age of 64.8 years (61% women). When compared to referent subjects, and after adjusting for age, sex, prior hospitalizations, morbidity index, and year of index date, patients on chronic opioids were at higher risk to be diagnosed with AI (Hazard ratio, HR of 2.2, 95% CI 1.9-2.6). When compared to referent subjects, and after adjusting for morbidity index, history of hospitalizations, age, and sex, and AI, patients treated with opioids had a higher mortality (HR 1.74, 95% CI 1.61-1.87). Diagnosis of AI was independent predictor of mortality in patients treated with chronic opioids (HR 2.27, 95% CI 2-2.58).

Interpretation

We show a decrease in chronic opioid use between 2005 and 2021. Patients treated with chronic opioids demonstrated a 11.3% of cumulative incidence of AI. Patients treated with chronic opioids and concomitant AI had higher mortality even after adjusting for morbidity and prior hospitalizations.