Prevalence of opioid-induced adrenal insufficiency in patients taking chronic opioids
Open accessAbstract
Context: Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear. Objective: To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain. Design: Cross-sectional study, 2016-2018. Setting: Referral center. Patients: Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center. Main outcome measure: Diagnosis of OIAI was considered if positive case detection (cortisol < 10 mcg/dL, ACTH < 15 pg/mL, and dehydroepiandrosterone sulfate < 25 mcg/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated. Results: In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking <MME of 20 mg/day developed OIAI (sensitivity of 100% for MME > 20 mg); however, specificity of MME cutoff >20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function. Conclusion: The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.
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In a cross-sectional study of 102 patients on various opioids, 9 patients (9%) were diagnosed with secondary adrenal insufficiency, and their minimum MME dose was 20 mg daily.
“Nine patients (9%) were diagnosed with secondary adrenal insufficiency (6 based on a combination of clinical assessment, basal morning cortisol, ACTH, and DHEAS levels and 3 after an ACTH1-24 stimulation test), and their minimum MME dose was 20 mg daily.”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [117]
Other studies have reported secondary adrenal insufficiency in people on lower opioid doses, including a cross-sectional study of 102 patients on various opioids.
“However, other studies have reported secondary adrenal insufficiency in people on lower opioid doses, including a cross-sectional one examining the hypothalamic-pituitaryadrenal axis function of 102 patients on various opioids (117).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [117]
In a group of 7 patients, 6 successfully weaned off opioids completely and were able to cease their hydrocortisone.
“In a group of 7 patients, 6 successfully weaned off opioids completely and were able to cease their hydrocortisone (117).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [117]
Roughly one in ten individuals on opioids at a morphine-equivalent dose above 20 mg daily face adrenal insufficiency risk.
“approximately 10% of patients taking opioids at a morphineequivalent dose of >20 mg/d are at risk of adrenal insufficiency.5”
From Home waking salivary cortisone to screen for adrenal insufficiency (2023) · cites this paper as [5]
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- Authors
- Li, T., Cunningham, J. L., Gilliam, W. P., Loukianova, L., Donegan, D. M., & Bancos, I.
- Affiliations
- St. Luke's-Roosevelt Hospital Center (US)
- Mayo Clinic (US)
- Corresponding author
- Bancos, Irina
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-08-31
- Volume
- 105
- Issue
- 10
- Pages
- e3766-e3775
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC7470471
- OpenAlex
- W3081528745
- Cited by
- 51
- References
- 39
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 9 · 2021: 9 · 2013: 1
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (K23DK121888)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- chronic opioid use, hypothalamic-pituitary-adrenal axis suppression, morphine milligram equivalents, chronic pain, prevalence, cortisol, ACTH, dehydroepiandrosterone sulfate, opioid discontinuation, adrenal function recovery
- MeSH terms
- Adrenal Insufficiency, Adult, Aged, Aged, 80 and over, Analgesics, Opioid, Cross-Sectional Studies, Dose-Response Relationship, Drug, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Prospective Studies, Prevalence, Dehydroepiandrosterone Sulfate, Young Adult, Chronic Pain
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