Category: Adrenal Disorders
Objective : Opioid induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due suppression of the hypothalamic-pituitary-adrenal axis. Despite the prevalent use of opioids, limited data are available on the clinical presentation and management of OIAI. Our objective was to describe clinical manifestations, biochemical presentation and clinical course of OIAI.
A retrospective study of adults diagnosed with OIAI between 2006-2018 at an academic center. Inclusion criteria were: 1) intermittent or continuous opioid ≥90 days, 2) diagnosis of OIAI with initiation of glucocorticoid (GC) replacement. Exclusion criteria were: 1) comorbidity or medication affecting adrenal function within the last 3 months. Opioid daily dose was converted into morphine mg equivalent (MME).
Results : OIAI was diagnosed in 40 patients (75% women) at a median age of 49 years (38-55). Patients used daily (37, 95%) or as needed (2, 5%) opioids at a daily median MME dose of 105 mg (60-200) and median duration of 96 months (24-120). Patients reported symptoms suggestive of OIAI for a median of 12 months (1-132) prior to diagnosis: fatigue (29, 73%), musculoskeletal pain (21, 53%), weight loss (17, 43%), headache (12, 30%), and nausea (8, 20%). Only 3 patients were identified with OIAI through case detection. No patient presented in adrenal crisis, but 1 patient developed adrenal crisis after the diagnosis of OIAI was made. Biochemical diagnosis of OIAI was based on 1) low morning cortisol (CORT), baseline ACTH and/or DHEAS in 26 (59%) patients or 2) abnormal Cosyntropin stimulation test (CST) in 17/28 (61%) patients. Median serum CORT was 3 (1.4-5) mcg/dL (normal >7), ACTH 9.7 (5.7-15) pg/mL (normal > 10) and DHEAS of 20 (15-32)mcg/dL (normal >50). The median peak CORT of patients with an abnormal CST was 14 mcg/dL (12-16). In addition to OIAI, 9 (21%) patients (7 men), were diagnosed with opioid induced hypogonadism. Hydrocortisone was the most common GC prescribed for OIAI (38, 95%) and among those with follow-up (33, 83%), 14(42%) experienced improvement in symptoms. At last follow-up, opioids were tapered or discontinued in 21 (48%) patients, of whom 8(38%) recovered from OIAI based on follow up testing.
Discussion : OIAI causes significant morbidity including fatigue, pain, and weight loss. Recognition requires a high level of clinical suspicion as only 8% were identified by a case detection strategy.
Conclusion : Appropriate GC treatment is vital to avoid adrenal crisis and can lead to improvement of symptoms. Resolution of OIAI is possible following opioid cessation or reduction and should be recommended if possible.
Taoran Li– Research Trainee, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, San Antonio, Texas
Diane Donegan– Assistant Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Indiana University, Indianapolis, IN, Indiana
Irina Bancos– Consultant, Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Minnesota
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN
San Antonio, Texas
Dr. Taoran Li is the Research Fellow in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic, Rochester. He graduated from Shanghai Jiao Tong University School of Medicine in Shanghai, China in 2017 and received his M.B.B.S. degree. Dr. Li started his research fellowship at Mayo Clinic in August 2018 where he is mentored by Dr. Irina Bancos. Dr. Li’s primarily leads several projects studying presentation, diagnosis, and outcomes of opioid-induced adrenal insufficiency. In addition, Dr. Li is involved as a co-investigator in several other research projects in the field of pituitary, adrenal and gonadal endocrinology.
Assistant Professor of Medicine
Division of Endocrinology, Diabetes, and Metabolism, Indiana University, Indianapolis, IN, Indiana
Dr. Diane Donegan is an Assistant Professor of Medicine and holds a joint position in the division of Endocrinology, Diabetes, and Metabolism as well as Neurosurgery at Indiana University. She earned her medical degree from University College, Dublin, Ireland and is a member of the Royal College Of Physicians, Ireland. Dr. Donegan completed her residency and fellowship at Mayo Clinic, Rochester during which she earned her Master’s in Clinical and Translational Science from the Mayo Graduate School of Medicine. She has a special interest in pituitary related pathology.
Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester MN, Minnesota
Dr. Irina Bancos is an Assistant Professor of Medicine and works in the Pituitary-Adrenal-Gonadal subdivision of Endocrinology division at Mayo Clinic, Rochester. She also serves as Director of the Endocrine testing center. Dr. Bancos received her M.D. from the Iuliu Hatiegany Medical University in Cluj-Napoca, Romania. She has completed her Internal Medicine Residency at Danbury Hospital in CT and Endocrinology Fellowship at Mayo Clinic, Rochester. In addition, Dr. Bancos completed a two year research fellowship (Mayo Foundation Scholarship) at the University of Birmingham, United Kingdom where she received training in steroid profiling and adrenal disorders. In 2015 she returned to Mayo Clinic, where her clinical and research interests include adrenal and pituitary tumors, adrenal insufficiency, congenital adrenal hyperplasia, Cushing syndrome, and mechanisms of steroid regulation of bone metabolism. Between 2016 and 2018, Dr. Bancos was the principal investigator and leader of the Transform the Adrenal Practice team at Mayo Clinic and currently holds several grants in the field of steroid regulation of aging, metabolism and body composition.