Case Report of Methadone-Induced Adrenal Insufficiency

Presentation Number: SUN 369
Date of Presentation: April 2nd, 2017

Rami Salameh, Siddique Chaudhary*, Farah Al Sabie, Halina Kusz and Susan Smith
McLaren Regional Medical Center, Flint, MI


Background: Opioids, have been widely used to treat chronic pain and have known side effects involving the endocrine system including hypogonadism, decreased libido, osteoporosis, fatigue, menstrual irregularities and erectile dysfunction. We report a case of methadone-induced adrenal insufficiency, a lesser known side effect.

Clinical Case: A 52 year old male nursing home resident, with a history of essential hypertension, osteoarthritis and chronic pain on a stable dose of methadone 5 mg every 8 hours for more than 3 years, developed episodes of hypoglycemia although he was not on hypoglycemics. Increased intake did not eliminate the episodes.

The patient was noted to have relative hypotension without a change in his anti-hypertensive meds. A CBC and BMP showed normal renal function, hyperkalemia, hyponatremia, hypoglycemia and eosinophilia. Adrenal insufficiency was suspected. AM cortisol blood level was 2.6 ug/dL(normal range: 10-20 ug/dL). TSH was elevated, but free T3 and free T4 were normal. Further testing was refused. The patient was treated presumptively for methadone-induced adrenal insufficiency with prednisone 5 mg/day and methadone was stopped. All abnormalities reversed supporting the diagnosis of methadone-induced adrenal insufficiency.

In the literature, cases of adrenal insufficiency have been reported secondary to fentanyl, heroin, tramadol, hydrocodone and methadone. Once opioids were stopped and patients started on steroids, symptoms resolved. Only one of the reported cases had follow-up testing of the HPA axis which was normal.

In the early 1980s, two studies reported that chronic exogenous opioid exposure may cause depletion of the endogenous endorphin system. Other studies around the same time concluded that chronic long acting opioids do not affect endogenous opioids and circadian rhythms of beta-endorphin, cortisol or ACTH. The reason for this inconsistency could be due to mu, delta and kappa opioid receptor polymorphism causing individual variability in the HPA axis response to opioids.

The mechanism of opioid-induced adrenal insufficiency is uncertain. But it is thought possibly to be due to a three-fold effect: 1) decrease of CRH secretion from the hypothalamus; 2) a direct interference with the pituitary capacity to respond to CRH; and 3) direct interference with the adrenal production of cortisol.

Conclusion: Opioids are commonly used in the treatment of pain. Their effect on the HPA axis is often overlooked. Clinicians need to be alert to this possible side effect. As of now, there are no official recommendations to screen chronic opioid patients for adrenal insufficiency or hypogonadism. Research with animal models may help elucidate the underlying mechanism while large publicly available databases that include medication administration, symptoms and labs may help to define the incidence.


Nothing to Disclose: RS, SC, FA, HK, SS