Opioid-Induced Adrenal Insufficiency

Abstract

The target audience for Mayo Clinic Proceedings is primarily internal medicine physicians and other clinicians who wish to advance their current knowledge of clinical medicine and who wish to stay abreast of advances in medical research. Statement of Need: General internists and primary care physicians must maintain an extensive knowledge base on a wide variety of topics covering all body systems as well as common and uncommon disorders. Mayo Clinic Proceedings aims to leverage the expertise of its authors to help physicians understand best practices in diagnosis and management of conditions encountered in the clinical setting. Accreditation Statement: In support of improving patient care, Mayo Clinic College of Medicine and Science is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. Credit Statements: AMA: Mayo Clinic College of Medicine and Science designates this journalbased CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. MOC: Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1 MOC point in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Learning Objectives: On completion of this article, you should be able to (1) review the pathophysiology of opioid-induced adrenal insufficiency, (2) evaluate a patient with suspected opioid-induced adrenal insufficiency, and (3) implement optimal treatment for opioid-induced adrenal insufficiency.

Novel medications inducing adrenal insufficiency

“…For example, a substantial proportion of patients with alcoholic liver disease have impaired adrenal function, as do patients with chronic infections (for example, viral hepatitis, HIV or Mycobacterium tuberculosis) 1 . In addition, up to 30% of patients receiv ing opioids have a suppressed HPA axis 9 . Opioids exert a tonic inhibition on the HPA axis, blocking hypo thalamic corticotropin releasing hormone (CRH) release and subsequent ACTH and cortisol produc tion.…”

Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling

“…For example, exposure to high levels of opioid antagonists in healthy human controls produced elevated levels of corticosterone, suggesting that opioid signalling may exert baseline inhibitory signalling on the HPA axis . This observation is supported by clinical observations of adrenal insufficiency in patients with chronic exposure to opioids . Alternatively, in animal and in vitro models, opioid exposure can stimulate CRH secretion.…”

“…As a caveat, however, the mechanism of this influence is likely somewhat dependent on the type of exogenous opioid, receptors involved, regardless of whether effects are studied in humans or animals, and the duration of exposure . For example, exposure to high levels of opioid antagonists in healthy human controls produced elevated levels of corticosterone, suggesting that opioid signalling may exert baseline inhibitory signalling on the HPA axis . This observation is supported by clinical observations of adrenal insufficiency in patients with chronic exposure to opioids .…”

“…It is therefore not surprising that exposure to exogenous opioids alters various outcomes of HPA axis‐mediated signalling. As a caveat, however, the mechanism of this influence is likely somewhat dependent on the type of exogenous opioid, receptors involved, regardless of whether effects are studied in humans or animals, and the duration of exposure . For example, exposure to high levels of opioid antagonists in healthy human controls produced elevated levels of corticosterone, suggesting that opioid signalling may exert baseline inhibitory signalling on the HPA axis .…”

Isolated Adrenocorticotropic Hormone Deficiency Secondary to Chronic Opiate Use

“…The true prevalence of opiate-induced secondary adrenal insufficiency remains unclear and currently available data are primarily from few retrospective studies and case reports [10]. Few studies have suggested that chronic use of opiates can disrupt the normal circadian rhythm of cortisol secretion as well [11].…”