Case Presentation: A 19-year-old female with a history of opioid use disorder (OUD) presented to the Emergency Department with abdominal pain, fever, and severe hypotension several days after relapsing with intravenous heroin following two years of successful maintenance on buprenorphine. She was admitted to the intensive care unit for treatment of severe sepsis including broad-spectrum antibiotics and vasopressors. Due to refractory hypotension she also received stress dose hydrocortisone. Her clinical condition improved dramatically over the next 24 hours and she was transferred to the general ward on hospital day 3. On hospital day 4 she developed new onset bradycardia and hypoglycemia.On physical exam, the patient was drowsy but arousable. Heart rate was regular and persistently less than 50 bpm with no murmurs or rubs. Blood pressure was within normal limits. Her extremities were mildly edematous but well perfused. There were no areas of rash or hyperpigmentation appreciated.Point of care glucose on hospital day 4 was 66 mg/dL. TSH and free T4 were normal. A random cortisol level was 5.1 ug/dL with ACTH of 12 pg/mL. Cosyntropin stimulation testing revealed minimal response to the low dose test and inadequate response to the high dose test (cortisol increased from 8.8 to 11.0 ug/dL where the threshold for a normal test is a peak cortisol >15.5 ug/dL). Blood and urine cultures, CT of the chest, abdomen, and pelvis, and transesophageal echocardiography did not reveal any etiology for her presentation of fever, abdominal pain, and shock. She was diagnosed with opioid-induced adrenal insufficiency (OIAI) and improved clinically with physiologic doses of hydrocortisone.
Discussion: Chronic opioid use is an increasingly common although still under-recognized etiology of HPA axis suppression. Among patients receiving chronic opioids, the prevalence of OIAI is estimated to be between 8.3% and 29%. No specific risk factors have been identified aside from a dose-dependent association with increasing morphine equivalent daily dose (MEDD) (1). The proposed mechanism for OIAI is the tonic inhibition of corticotropin releasing hormone and ACTH via hypothalamic and pituitary delta and kappa opioid receptors when chronically exposed to exogenous opioids. Limited studies suggest that full recovery of HPA axis function is common with complete discontinuation of opioid therapy. In this case, transient bacteremia from intravenous drug use likely precipitated an adrenal crisis with symptoms returning after stress dose steroids were weaned. The opioid crisis remains at epidemic levels in the US, with an estimated 2.7 million Americans living with OUD in 2020 (2). We know that patients with active intravenous drug use are at high risk for bacterial infections and may delay care until the onset of severe symptoms. This necessitates an awareness among clinicians of the risk for concurrent adrenal suppression to avoid delays in potentially life-saving interventions.
Conclusions: It’s important for both hospitalists and emergency physicians to be aware of OIAI and to recognize that septic and adrenal shock may co-present in patients with OUD.