{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:52:46Z","timestamp":1793494366717,"version":"4.5.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK121888"],"award-info":[{"award-number":["K23DK121888"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Cross-sectional study, 2016-2018.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Referral center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcome measure<\/jats:title>\n                  <jats:p>Diagnosis of OIAI was considered if positive case detection (cortisol\u2005&amp;lt;\u200510 mcg\/dL, ACTH\u2005&amp;lt;\u200515 pg\/mL, and dehydroepiandrosterone sulfate\u2005&amp;lt;\u200525 mcg\/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P\u2005=\u20050.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P\u2005=\u20050.03). No patient taking &amp;lt;MME of 20 mg\/day developed OIAI (sensitivity of 100% for MME\u2005&amp;gt;\u200520 mg); however, specificity of MME cutoff &amp;gt;20 mg was only 19%. After opioid discontinuation, 6\/7 patients recovered adrenal function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg\/day and above should be monitored for OIAI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa499","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T20:42:18Z","timestamp":1598906538000},"page":"e3766-e3775","source":"Crossref","is-referenced-by-count":46,"title":["Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids"],"prefix":"10.1210","volume":"105","author":[{"given":"Taoran","family":"Li","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota"},{"name":"Department of Medicine, Mount Sinai St. Luke\u2019s-Roosevelt Hospital, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Pharmacy; Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley P","family":"Gilliam","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Loukianova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M","family":"Donegan","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Indiana University, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9332-2524","authenticated-orcid":false,"given":"Irina","family":"Bancos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"2021122106034335200_CIT0001","year":"2019"},{"issue":"26","key":"2021122106034335200_CIT0002","doi-asserted-by":"crossref","first-page":"697","DOI":"10.15585\/mmwr.mm6626a4","article-title":"Vital signs: changes in opioid prescribing in the United States, 2006-2015","volume":"66","author":"Guy","year":"2017","journal-title":"MMWR Morb Mortal Wkly Rep."},{"issue":"15","key":"2021122106034335200_CIT0003","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1001\/jama.2016.1464","article-title":"CDC guideline for prescribing opioids for chronic pain\u2013United States, 2016","volume":"315","author":"Dowell","year":"2016","journal-title":"JAMA."},{"issue":"10","key":"2021122106034335200_CIT0004","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/pm\/pny247","article-title":"Prevalence of nonopioid and opioid prescriptions among commercially insured patients with chronic pain","volume":"20","author":"Miller","year":"2019","journal-title":"Pain Med."},{"key":"2021122106034335200_CIT0005","doi-asserted-by":"crossref","first-page":"107902","DOI":"10.1016\/j.drugalcdep.2020.107902","article-title":"Chronic non-cancer pain among adults with substance use disorders: prevalence, characteristics, and association with opioid overdose and healthcare utilization","volume":"209","author":"John","year":"2020","journal-title":"Drug Alcohol Depend."},{"issue":"10","key":"2021122106034335200_CIT0006","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.4158\/EP-2019-0177","article-title":"Current knowledge and practices of heath care professionals on opioid-induced adrenal insufficiency","volume":"25","author":"Saeed","year":"2019","journal-title":"Endocr Pract."},{"key":"2021122106034335200_CIT0007","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/j.psyneuen.2009.05.013","article-title":"Endocrine consequences of opioid therapy","volume":"34","author":"Aloisi","year":"2009","journal-title":"Psychoneuroendocrinology."},{"key":"2021122106034335200_CIT0008","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1744-8069-6-69","article-title":"Aromatase and 5-alpha reductase gene expression: modulation by pain and morphine treatment in male rats","volume":"6","author":"Aloisi","year":"2010","journal-title":"Mol Pain."},{"issue":"11","key":"2021122106034335200_CIT0009","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1068\/p6430","article-title":"Modulation of viewpoint effects in object recognition by shape and motion cues","volume":"38","author":"Vuong","year":"2009","journal-title":"Perception."},{"issue":"5","key":"2021122106034335200_CIT0010","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1054\/jpai.2002.126790","article-title":"Hypogonadism in men consuming sustained-action oral opioids","volume":"3","author":"Daniell","year":"2002","journal-title":"J Pain."},{"issue":"1","key":"2021122106034335200_CIT0011","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jpain.2007.08.005","article-title":"Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain","volume":"9","author":"Daniell","year":"2008","journal-title":"J Pain."},{"issue":"1","key":"2021122106034335200_CIT0012","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1055\/s-2008-1076715","article-title":"Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women","volume":"117","author":"Fraser","year":"2009","journal-title":"Exp Clin Endocrinol Diabetes."},{"issue":"6","key":"2021122106034335200_CIT0013","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1210\/jcem.85.6.6615","article-title":"Endocrine consequences of long-term intrathecal administration of opioids","volume":"85","author":"Abs","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122106034335200_CIT0014","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/j.1365-2796.2005.01483.x","article-title":"Chronic fentanyl application induces adrenocortical insufficiency","volume":"257","author":"Oltmanns","year":"2005","journal-title":"J Intern Med."},{"issue":"10","key":"2021122106034335200_CIT0015","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1055\/s-0029-1202851","article-title":"Secondary adrenal insufficiency due to opiate therapy\u2013another differential diagnosis worth consideration","volume":"117","author":"Schimke","year":"2009","journal-title":"Exp Clin Endocrinol Diabetes."},{"issue":"8","key":"2021122106034335200_CIT0016","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00228-011-0992-9","article-title":"Tramadol-induced adrenal insufficiency","volume":"67","author":"Debono","year":"2011","journal-title":"Eur J Clin Pharmacol."},{"key":"2021122106034335200_CIT0017","doi-asserted-by":"crossref","DOI":"10.4158\/EP-2020-0297","article-title":"Clinical presentation and outcomes of opioid induced adrenal insufficiency","author":"Li","year":"2020","journal-title":"Endocr Pract"},{"issue":"6","key":"2021122106034335200_CIT0018","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/cen.13125","article-title":"Adrenal insufficiency in patients on long-term opioid analgesia","volume":"85","author":"Gibb","year":"2016","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"5","key":"2021122106034335200_CIT0019","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/AJP.0b013e3181d1059d","article-title":"Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term oral opioid treatment","volume":"26","author":"Rhodin","year":"2010","journal-title":"Clin J Pain."},{"key":"2021122106034335200_CIT0020","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.psyneuen.2015.03.015","article-title":"Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial","volume":"56","author":"Nenke","year":"2015","journal-title":"Psychoneuroendocrinology."},{"issue":"4","key":"2021122106034335200_CIT0021","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/pme.12661","article-title":"Chronic spinal and oral morphine-induced neuroendocrine and metabolic changes in noncancer pain patients","volume":"16","author":"Valverde-Filho","year":"2015","journal-title":"Pain Med."},{"key":"2021122106034335200_CIT0022","article-title":"Opioids and their endocrine effects: a systematic review and meta-analysis","author":"de Vries","journal-title":"J Clin Endocrinol Metab."},{"issue":"12","key":"2021122106034335200_CIT0023","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.amjmed.2014.07.015","article-title":"Elucidating risk factors for androgen deficiency associated with daily opioid use","volume":"127","author":"Rubinstein","year":"2014","journal-title":"Am J Med."},{"issue":"6","key":"2021122106034335200_CIT0024","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1530\/EJE-18-0530","article-title":"Secondary adrenal insufficiency and pituitary dysfunction in oral\/transdermal opioid users with non-cancer pain","volume":"179","author":"Lamprecht","year":"2018","journal-title":"Eur J Endocrinol."},{"issue":"4","key":"2021122106034335200_CIT0025","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0304-3959(85)90004-1","article-title":"The West Haven-Yale Multidimensional Pain Inventory (WHYMPI)","volume":"23","author":"Kerns","year":"1985","journal-title":"Pain."},{"key":"2021122106034335200_CIT0026","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/1471-2474-13-155","article-title":"Reliability of the Multidimensional Pain Inventory and stability of the MPI classification system in chronic back pain","volume":"13","author":"Verra","year":"2012","journal-title":"BMC Musculoskelet Disord."},{"key":"2021122106034335200_CIT0027","article-title":"Developing and testing the MOS 20-Item Short-Form Health Survey","author":"Ware"},{"issue":"3","key":"2021122106034335200_CIT0028","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/00005650-199303000-00006","article-title":"The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs","volume":"31","author":"McHorney","year":"1993","journal-title":"Med Care."},{"issue":"22","key":"2021122106034335200_CIT0029","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1097\/00007632-199811150-00011","article-title":"Psychometric characteristics and clinical usefulness of physical performance tests in patients with low back pain","volume":"23","author":"Simmonds","year":"1998","journal-title":"Spine (Phila Pa 1976)."},{"issue":"2","key":"2021122106034335200_CIT0030","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1210\/jc.2015-1700","article-title":"ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis","volume":"101","author":"Ospina","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122106034335200_CIT0031","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S2213-8587(14)70142-1","article-title":"Diagnosis and management of adrenal insufficiency","volume":"3","author":"Bancos","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"5","key":"2021122106034335200_CIT0032","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.3892\/etm.2016.3156","article-title":"Opioid endocrinopathy: a clinical problem in patients with cancer pain","volume":"11","author":"Merdin","year":"2016","journal-title":"Exp Ther Med."},{"issue":"9","key":"2021122106034335200_CIT0033","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1210\/jc.2002-021897","article-title":"Diagnosis of adrenal insufficiency: evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease","volume":"88","author":"Schmidt","year":"2003","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122106034335200_CIT0034","doi-asserted-by":"crossref","first-page":"E216","DOI":"10.25011\/cim.v36i4.19955","article-title":"The role of morning basal serum cortisol in assessment of hypothalamic pituitary-adrenal axis","volume":"36","author":"Yip","year":"2013","journal-title":"Clin Invest Med."},{"issue":"3","key":"2021122106034335200_CIT0035","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1530\/EJE-10-0229","article-title":"Can basal cortisol measurement be an alternative to the insulin tolerance test in the assessment of the hypothalamic-pituitary-adrenal axis before and after pituitary surgery?","volume":"163","author":"Karaca","year":"2010","journal-title":"Eur J Endocrinol."},{"key":"2021122106034335200_CIT0036","first-page":"42","article-title":"Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis","volume":"7","author":"Charoensri","year":"2017","journal-title":"J Clin Transl Endocrinol."},{"issue":"4","key":"2021122106034335200_CIT0037","first-page":"637","article-title":"Association between commonly prescribed opioids and androgen deficiency in men: a retrospective cohort analysis","volume":"18","author":"Rubinstein","year":"2017","journal-title":"Pain Med."},{"issue":"4","key":"2021122106034335200_CIT0038","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1530\/acta.0.1140509","article-title":"Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone","volume":"114","author":"Allolio","year":"1987","journal-title":"Acta Endocrinol (Copenh)."},{"issue":"4","key":"2021122106034335200_CIT0039","first-page":"269","article-title":"Effects of oral treatment with sustained release morphine tablets on hypothalamic-pituitary-adrenal axis","volume":"19","author":"Palm","year":"1997","journal-title":"Methods Find Exp Clin Pharmacol."},{"issue":"12","key":"2021122106034335200_CIT0040","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2019-230551","article-title":"Opioid-induced hypoadrenalism resulting in fasting hypoglycaemia","volume":"12","author":"Tabet","year":"2019","journal-title":"BMJ Case Rep."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa499\/33702245\/dgaa499.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/10\/e3766\/41828162\/dgaa499.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/10\/e3766\/41828162\/dgaa499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T06:04:24Z","timestamp":1640066664000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/10\/e3766\/5899818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,31]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,8,31]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa499","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,8,31]]}}}