ORF28-03 - Incidence of Opioid-Induced Endocrinopathies and Associated Outcomes in a Large Population-Based Study

Background: Chronic opioid use remains prevalent in the United States and has been associated with various endocrinopathies and adverse long-term patient outcomes. However, the incidence of opioid-related endocrinopathies over time, as well as their potential impact on patient outcomes, remains incompletely characterized. We aimed to evaluate temporal changes in the incidence of chronic opioid use, endocrinopathies, and clinical outcomes in a population-based study.

Methods: We conducted a large retrospective population-based cohort study with 15 years of follow-up (2005-2021). Patients with ≥3 months of consecutive opioid use were identified as cases and paired 1:1 with age-, sex-, and calendar-year matched referent subjects. Outcomes of interest included the incidence of chronic opioid use, adrenal insufficiency, hypogonadism, hyperprolactinemia, hypothyroidism, inpatient hospitalization, and mortality during follow-up.

Results: The incidence of chronic opioid use declined four-fold between 2005 and 2021. In our cohort of 7,805 matched patients, the cumulative incidence of adrenal insufficiency was 11.3% among patients with chronic opioid use compared with 5.9% among referent subjects. Chronic opioid use was associated with a two-fold increased risk of incident adrenal insufficiency, even after adjustment for age, sex, comorbidity burden, and prior hospitalization. Chronic opioid use was also associated with higher incidence of hypogonadism [HR 2.57 (95% CI 1.69-3.91)], hyperprolactinemia [HR 1.67 (1.04-2.67)], hospitalization [HR 1.78 (95% CI 1.69-1.87)], and mortality [HR 1.74 (95% CI 1.61-1.88)]. Importantly, adrenal insufficiency alone was noted to be an independent risk factor for increased incidence of hospitalization [HR 1.48 (95% CI 1.29-1.69)] and mortality [HR 2.21 (95% CI 1.98-2.47)].

Conclusions: 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. 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 months.