SUN-445 - Fluconazole-Induced Adrenal Insufficiency: A Rare Endocrine Complication of Long-Term Therapy for Coccidioidomycosis

Background: Adrenal insufficiency (AI) is a serious endocrine disorder characterized by impaired cortisol production, most often due to autoimmune disease, pituitary dysfunction, or exogenous steroid withdrawal. Drug-induced AI is uncommon, but azole antifungals have been reported as rare contributors due to their inhibitory effect on adrenal steroidogenesis. This effect is well established with ketoconazole but has been reported less frequently with fluconazole. We describe a rare case of fluconazole-associated AI in a patient receiving therapy for pulmonary coccidioidomycosis.

Case Presentation: A 52-year-old man with a past medical history of type 2 diabetes mellitus insulin-dependent, hypertension, hyperlipidemia, atrial fibrillation, and a recent pulmonary coccidioidomycosis (on fluconazole 400 mg daily for two months) presented with generalized weakness, lightheadedness, headaches, vomiting, and presyncope. He reported progressive fatigue, anorexia, and an unintentional 6-pound weight loss over the past two months, along with episodes of hypotension (systolic BP in the 70s) requiring reduction of his antihypertensive medications. On admission, his blood pressure was labile (90/71 mmHg). He denied any history of steroid use. Laboratory evaluation revealed a cortisol level < 0.4 µg/dL, consistent with adrenal insufficiency. Cosyntropin stimulation testing was also positive for AI. 21-hydroxylase antibody was negative, ruling out autoimmune Addison’s disease. The patient was started on intravenous hydrocortisone (100 mg every 8 hours), with subsequent improvement in symptoms and stabilization of blood pressure. Fluconazole was held during hospitalization. At discharge, he was transitioned to oral hydrocortisone, and fluconazole was resumed at a reduced dose of 200 mg daily after discussion with infectious disease specialists, given the temporal relationship between fluconazole initiation and the onset of AI.

Conclusion: This case illustrates an uncommon but clinically significant adverse effect of fluconazole therapy. Clinicians should have a high suspicion for adrenal insufficiency in patients receiving prolonged azole antifungal therapy, particularly in endemic regions where long-term fluconazole use is common for conditions such as coccidioidomycosis.

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