An Overlooked Sequela of Long-Term Opioid Analgesic Use: A Case Report on Central Adrenal Insufficiency

Background: Opioid use began to surge since late 1990s and has evolved into a full-fledge opioid epidemic. 2 million Americans aged 12 or older are estimated to have opioid use disorder. We hereby present a case of opioid-induced adrenal insufficiency (OIAI), an overlooked endocrinopathy in which chronic opioid use suppresses the hypothalamic-pituitary-adrenal axis. Clinical Case: A 53-year-old African American female with past medical history of chronic pain syndrome presented with worsening fatigue and generalized weakness for a week, to the extent that she required full assistance to ambulate at home. Upon further inquiry, she also suffered from postprandial eipgastric pain and non-bloody diarrhea for several months. She has a 2-year use of Norco 10 mg/325 mg three times daily to manage her chronic pain. Her blood pressure was running low at 85/57 mmHg with no other abnormal vitals. Our first visual impression of her was a debilitated lady with low voice and slow body movements. Adrenal insufficiency was suspected and subsequently confirmed with low morning cortisol level (1.1 mcg/dL), low DHEAS level (25.3 mcg/dL) and subnormal response of cortisol (16.8 mcg/dL) to the cosyntropin stimulation test. Her ACTH level was less than 3 pg/mL. These laboratory findings were consistent with central adrenal insufficiency. Chronic steroid use, the most common culprit for adrenal insufficiency, was not found in her home medication list or prescription records. To further evaluate the underlying etiologies, we checked the pituitary hormones and found normal levels of LH, FSH, TSH, prolactin and IGF-1. Head CT 2 years prior was negative for any discernible mass. The suspicion for pituitary mass that markedly suppresses ACTH secretion only was reasonably low. The diagnosis of OIAI was made by excluding other causes. Endocrinology was consulted for the dosing of hydrocortisone. She improved physically after receiving hydrocortisone replacement therapy. Collaborative efforts were made to cut down her opioid dose. Conclusions: OIAI is a longstanding overlooked condition in chronic opioid users of which clinicians should raise their awareness. The estimated prevalence of OIAI ranges from 9% to 29% depending on the daily dosage and total duration of opioid use. The case reports of OIAI, however, are only a few. Patients with OIAI could present with fatigue, weight loss, gastrointestinal symptoms, headache or muscular aches. Not only does OIAI impair patients’ quality of life and potentially escalate their opioid dosage by inexperienced prescribers, it also leads to catastrophic adrenal crisis following acute insults. The challenge clinicians face is to uncover the clinical clues suggesting OIAI, which are often hidden in a myriad of symptoms caused by chronic pain and other co-morbidities. Timely diagnosing OIAI is thus never more important in the midst of the unprecedented opioid epidemic.