A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review

Abstract

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.

Opioid-Induced Adrenal Insufficiency

“…Chronic opioid use affects more than 5% of the US population and is a widely accepted public health issue primarily linked to addiction and overdose. 1 However, recent research has shed light on a lesser-known yet important consequence-opioid-induced adrenal insufficiency (OIAI). OIAI is characterized by insufficient production of adrenal hormones due to chronic opioid use.…”

“…It occurs from opioid suppression of the hypothalamic-pituitaryadrenal (HPA) axis through antagonism of μ, δ, and κ receptors within the hypothalamus and pituitary gland. 1 OIAI may affect a considerable proportion of patients with chronic opioid use, with a recent meta-analysis 2 estimating prevalence to be around 15%. There is no universally established threshold of opioid use to induce OIAI, and it may be related to genetic differences in opioid receptor concentrations along the HPA axis.…”

“…However, the risk appears to be associated with both dosage and duration of opioid use, with patients taking high-dose opioids for an extended period at increased risk. 1 One cross-sectional study 3 including 102 patients with chronic opioid use found no OIAI when taking less than 20 morphine milligram equivalent (MME) daily, but the specificity was only 19%.…”

“…1 Concern for OIAI should be raised in a patient receiving chronic opioid therapy, particularly more than 20 MME daily, with signs of adrenal insufficiency, including fatigue, musculoskeletal pain, anorexia, abdominal discomfort, orthostatic hypotension, or electrolyte abnormalities. 1,2 The European Society of Endocrinology recommends morning cortisol testing as a first-line diagnostic approach for adrenal insufficiency (cortisol Յ3 μg/dL). 4 The guidelines suggest performing cosyntropin stimulation testing (CST) if the morning cortisol test is inconclusive (cortisol >3 μg/dL and <18 μg/dL).…”

“…Hydrocortisone is often used in divided doses at 15 to 25 mg/d, with careful dosing to prevent overreplacement. 1 Discontinuing opioids can reverse OIAI, but the recovery timeline is uncertain. Consideration should be given to alternative pain management strategies and opioid tapering.…”