Cortisol status in patients with chronic non-malignant pain treated with opioids

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 50-71-HPA Axis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-69
Warrick J Inder*1, Frank Thomas1, Jane Sorbello1, Ken Ho1, David J Torpy2 and Jennifer Martin3
1Princess Alexandra Hospital, Woolloongabba QLD, Australia, 2Royal Adelaide Hospital, Adelaide SA, Australia, 3University of Queensland, Brisbane, Australia
Introduction: Opioid analgesics such as morphine, fentanyl and oxycodone are being increasingly used in primary care for chronic pain. While previously this was in the setting of malignancy, they are now commonly used for back pain, osteoarthritis and neurogenic pain. Opioid modulation of the hypothalamic-pituitary-adrenal (HPA) axis is well described. Acutely, morphine inhibits adrenocortical tropic hormone (ACTH) and cortisol secretion, while the opioid antagonist naloxone stimulates ACTH and cortisol. While there have been case reports of clinically significant adrenal insufficiency in people treated chronically with oral or transdermal opioids, the extent of the problem has not been well studied.

Methods: We have examined 14 patients (11 male, mean age: 53 years, range 40-67 years) attending a hospital-based Persistent Pain Service, treated with oral or transdermal opioids (mean morphine equivalent daily dose: 104.7 mg, range 30-225 mg). Each subject had an estimate of cortisol, ACTH and DHEA-sulphate before 0900h, having taken their normal morning medication beforehand. Those who had a 0900h cortisol of <250 nmol/L then underwent a 250 μg ACTH 1-24 test (normal response: cortisol >500 nmol/L at 60 min) and an overnight metyrapone test (OMT), dose 30 mg/kg (normal response: 11-deoxycortisol >200 nmol/L). Recruitment is ongoing.

Results: 8/14 participants had a 0900h cortisol of <250 nmol/L, and overall the mean 0900h cortisol was 217 nmol/L (range 29-389 nmol/L). 6/14 participants had an undetectable 0900h ACTH (<10 ng/L). The mean (±SEM) DHEA-S concentration was 1.9±0.3 μmol/L (laboratory reference range 1-11 μmol/L). Of the subjects with a low basal cortisol, 6/7 passed the 250 μg ACTH 1-24 test with a mean 60 minute cortisol of 665 nmol/L (range 412-847). 3/7 participants had an impaired 11-deoxycortisol response to the OMT of <200 nmol/L. The participant with the impaired response to ACTH 1-24 passed the OMT. One is yet to complete the stimulation testing.

Conclusion: Over 50% of chronic opioid users had low basal cortisol levels, of whom half failed at least one standard stimulation test of the HPA axis. These patients meet criteria which in the setting of structural pituitary disease would lead to glucocorticoid replacement. These findings have important implications for the identification of hormone deficiency and optimal management of patients receiving opioids for chronic non-malignant pain.

Nothing to Disclose: WJI, FT, JS, KH, DJT, JM

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