CHICAGO – Chronic opioid therapy raises the risk for several endocrine disturbances, but key biochemical testing for such complications remains rare, new data show.

“Although the incidence of chronic opioid use has progressively declined over the past decade, patients on chronic opioid therapy remain at increased risk for incident adrenal insufficiency, hypogonadism, hyperprolactinemia, inpatient hospitalization, and mortality,” Ashley J. Han, MD, a third-year internal medicine resident physician at Mayo Clinic, Rochester, Minnesota, said at ENDO 2026: The Endocrine Society Annual Meeting.

“Given that undiagnosed and untreated endocrinopathies can impair quality of life and are associated with negative clinical outcomes, clinicians should maintain heightened vigilance and consider appropriate biochemical testing in patients receiving opioid therapy for 3 or more months,” she added.

The data came from a large retrospective population-based cohort study with follow-up from 2005-2021. A total of 7805 patients (mean age, 60 years; 60% women) with 3 months or longer of consecutive opioid use were paired 1:1 with age-, sex-, and calendar-year-matched individuals without a history of chronic opioid use. During the study period, chronic opioid use declined fourfold.

Only 13.5% of the chronic opioid group had undergone cortisol testing, compared with 6.9% of the referent patients.

The cumulative incidence of adrenal insufficiency was higher among those with chronic opioid use than among non-users (11.3% vs 5.9%; hazard ratio [HR], 2.13). Chronic opioid use was also associated with significantly higher incidences of hypogonadism (4.3% vs 1.9%; HR, 2.59), hyperprolactinemia (1.2% vs 0.7%; HR, 1.87), hospitalization (77.7% vs 55.9%; HR, 1.79), and mortality (45% vs 23.9%; HR, 1.78).

Adrenal insufficiency was a significant independent risk factor for increased incidence of hospitalization and mortality, along with chronic opioid use, age per 10-year increase above 50, male sex, and morbidity index (comorbidities: 5+ vs 1).

Asked to comment, Roberto Salvatori, MD, professor of medicine at Johns Hopkins School of Medicine and director of the pituitary clinic at Johns Hopkins Hospital, Baltimore, questioned why the investigators randomized 1 to 1 rather than 1 to 3 or 4, as is typically done, and also noted that the study was retrospective. However, he said that because so few patients had been screened, the adrenal insufficiency was likely an underestimate, noting, “I think it’s probably true that it’s underrecognized.”

Han had no disclosures. Salvatori reported consulting for Crinetics, Chiasma, and Camurus. 

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social