The Medicine Forum, Volume 22 | 27 5 Opioid-Induced Secondary Adrenal Insufciency in a Young Patient with Chronic Pancreatitis Amry Majeed, Nicholas Noverati, MD, Christine Kurian, MD, Shirin Jaggi, DO INTRODUCTION Opioid misuse is a national public health crisis that has contributed to a decrease in life expectancy in men and women in the US. From 1999-2017, the rate of drug overdose deaths tripled, largely due to the rise in opioid use 1 . Despite widespread misuse, chronic opioid therapy still has a role in the clinical setting. Adverse effects include dizziness, nausea, vomiting, respiratory depression, and dependence 2 . While these side effects are well- documented, other effects of opioids are less explored, including opioid- induced adrenal insufficiency 3,7 . The typical presentation of adrenal insufficiency from any cause can include fatigue, nausea, vomiting, weight loss, abdominal pain and muscle aches. Laboratory findings might include hyponatremia and hyperkalemia. This case, however, presents a patient with atypical presentation but confirmed diagnosis of adrenal insufficiency in the setting of chronic opioid use. Ultimately, given chronic opioid use both prescribed and unprescribed, it is imperative that healthcare providers understand the endocrine effects of opioids as adrenal insufficiency is associated with higher morbidity and mortality 3 . The adrenal gland is made up of a cortex and medulla which each produce vital hormones. Specifically, the cortex is responsible for producing glucocorticoids, mineralo- corticoids, and androgens. Destruction or dysfunction of the adrenal gland may lead to deficiency of these hormones. Adrenal insufficiency can be classified into primary, secondary, or tertiary types. Primary adrenal insufficiency denotes malfunctioning of the adrenal gland itself. Secondary adrenal insufficiency is characterized by a decreased level of adrenocorticotropin (ACTH) released by the pituitary gland. Tertiary adrenal insufficiency is defined by a decreased level of corticotropin-releasing hormone (CRH) from the hypothalamus 15 . Opioids bind to mu, kappa, and delta opioid receptors to create effects throughout the body, including on the hypothalamus and pituitary. This is the proposed mechanism for opioid-induced suppression of the hypothalamus-pituitary-adrenal (HPA) axis noted in some studies 3 . NARRATIVE A 33 year-old man with a past medical history of chronic pancreatitis secondary to heavy alcohol use presented to the hospital with a chief complaint of abdominal pain, nausea, vomiting, and poor appetite. During the hospital- ization, the patient was hydrated with intravenous fluids and pain control was optimized. Since his initial diagnosis of pancreatitis, his home analgesics included oxycodone 10 mg, gabapentin 800 mg and duloxetine 60 mg. On admission his oxycodone was discontinued and he was started on hydromorphone through a patient-controlled analgesia pump as well as a ketamine infusion titrated by an acute pain management team. During endoscopy to perform a celiac plexus nerve block, findings consistent with chronic calcific pancreatitis were noted. With this procedure, his pain was better controlled and he was transitioned back onto an oral opioid-containing pain control regimen with oxycodone 10 mg, gabapentin 900 mg, and duloxetine 60 mg. However, his hospital course was further complicated by uncontrolled hypertension and fluctuating blood sugars. His blood glucose readings were initially as high as 500 mg/dL, at which point an insulin infusion was initiated for better control. The patient did not have evidence of diabetic ketoacidosis. The infusion was eventually discontinued and the patient was transitioned to a basal bolus insulin regimen. The patient’s blood pressure was also difficult to control. His home medications included carvedilol 3.125 mg, hydralazine 100 mg, nifedipine 60 mg, losartan 100 mg, and a clonidine patch 0.3 mg. Due to his inability to tolerate medications by mouth secondary to nausea, the patient was taking these medications inconsistently. Although his poorly controlled blood sugars and pressures were thought to be in part due to his abdominal pain, a secondary workup was pursued, especially considering his extensive multi-drug regimen. This workup included an aldosterone:renin ratio, urine and serum metanephrines, and a morning cortisol level. Due to hypertension and hyperglycemia, as well as normal serum sodium (136 mmol/L) and potassium (4.0 mmol/L), suspicion for adrenal insufficiency was low. However, the morning cortisol level was low at 2.3 mcg/dL. A cosyntropin stimulation test confirmed adrenal insufficiency; cortisol levels only increased to 10.8 mcg/dL after 60 minutes. A baseline ACTH level was found to be low at <9 pg/mL. Other lab findings were significant for normal values of sodium (136 mmol/L) and potassium (4.0 mmol/L). Since this was a surprising finding given the lack of clinical signs and symptoms of adrenal insufficiency, the stimulation test was repeated with similar results. The patient was GENERAL MEDICINE