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. 2020 Oct 1;105(10):e3766-e3775.
doi: 10.1210/clinem/dgaa499.

Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids

Taoran Li  1   2 , Julie L Cunningham  3 , Wesley P Gilliam  4 , Larissa Loukianova  4 , Diane M Donegan  1   5 , Irina Bancos  1
Affiliations

Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids

Taoran Li et al. J Clin Endocrinol Metab. .

Abstract

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.

Keywords: MME; cortisol; diagnosis; morphine; pain; pituitary.

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Figures

Figure 1.
Figure 1.
Association of cortisol to (A) ACTH and to (B) DHEAS. am cortisol, morning cortisol; DHEAS, dehydroepiandrosterone sulfate.
See this image and copyright information in PMC

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