Case Presentation: Central Adrenal Insufficiency (CAI) is a rare and often late diagnosis due to nonspecific signs, such as fatigue, hyponatremia, electrolyte abnormalities and fever of unknown origin (FUO). CAI suspicion arises in patients with pituitary tumors, cranial irradiation, surgery, injury, infection, exogenous glucocorticoid withdrawal, and less commonly known, opioid use disorder. A 31-year-old male with a history of hidradenitis suppurativa (HS), alpha thalassemia, remote history of opioid use disorder with current methamphetamine use disorder and multiple hospitalizations for sepsis secondary to HS presented with worsening pain and drainage from multiple hidradenitis wounds. His physical exam was notable for extensive wounds tracking along the scrotum, buttocks, and thighs. On hospital day 2, he was febrile, tachycardic, and hypotensive, necessitating transfer to the ICU for vasopressor support and initiation of broad-spectrum antibiotics. CT Abdomen & Pelvis demonstrated asymmetric skin thickening overlying the left inguinal and right sacral regions with possible small fluid collections consistent with his diagnosis of HS. For pain management, he was prescribed oxycodone ER 30 mg, q12h, Roxicodone 30 mg, q6h PRN, and acetaminophen 1000 mg, q8h PRN. Dermatology was consulted, and he was started on topical clindamycin and oral doxycycline for anti-inflammatory effect, however, fevers and hypotension persisted. Antibiotics were escalated to include: daptomycin, piperacillin-tazobactam, and metronidazole due to concern for superimposed soft tissue infection. Despite this, his fevers continued. A thorough infectious work-up was performed, including 8 blood cultures over a course of 17 days and a repeat CT Chest/Abdomen/Pelvis, which was unremarkable. Infectious Disease was consulted, and all antibiotics were stopped to rule out drug fever. However, the patient remained febrile and relatively hypotensive. Further lab evaluation revealed hypovolemic hyponatremia, cortisol 2.0 ug/dL, TSH 2.69 m[iU]/L, free T4 0.56 ng/dL, total T3 53.90 ng/dL, and positive Co-syntropin stimulation test. MRI brain pituitary protocol was obtained and demonstrated an incidental pituitary microadenoma. Endocrinology was consulted, and he was started on hydrocortisone for newly diagnosed CAI with subsequent abatement of fevers and hyponatremia. He was discharged on a hydrocortisone taper and suboxone for his opioid use disorder.

Discussion: The incidence of CAI in the United States has been cited to be approximately 5 cases per 100,000.(1) The scarcity of cases leaves CAI an easily overlooked diagnosis for FUO. It has been established that IL-1, an endogenous pyrogen, stimulates pituitary secretion of ACTH, which suppresses the immune response, including IL-1 production.(2) However, in CAI this feedback mechanism is ineffective, leading to persistent pyrexia and subsequently a diagnosis of FUO. It is estimated that 9 percent of chronic opioid users have been diagnosed with CAI due to opioid-induced suppression of the hypothalamic-pituitary axis, if daily opioid use is >20 mg/ml morphine equivalents (MME). (3) Though our patient had a remote history OUD, he required 80 MME per day to control his pain.

Conclusions: This case highlights the importance of careful attention to a patient’s history, medications, particularly opioids, as well as a thorough investigation of the origin of fevers.