SAT-435 When The Cure Becomes The Cause: Adrenal Insufficiency In Cushing’s Management

Abstract Disclosure: J. Kalluru: None. S. Majumdar: None. Introduction: The therapeutic approach to hormonal disorders like Cushing’s syndrome requires meticulous balance, as interventions aimed at resolving hypercortisolism risk precipitating secondary adrenal insufficiency or exacerbating other hormonal imbalances. We report a patient with severe hypercortisolism who developed adrenal insufficiency after starting ketoconazole. Case: A 69-year-old woman with a medical history of asthma (intermittent glucocorticoid treatment), type 2 diabetes, hypertension, congestive heart failure, and recent compression fractures was admitted for a fall. On admission exam, her temperature was 98.3°F, pulse 77 bpm, respirations 22 bpm, oxygen saturation 100%, and blood pressure 160/98 mmHg. Findings included hair loss, bruising, thinning skin, and muscle weakness. She had elevated random cortisol levels: 44.9 µg/dL (normal range: 2.6-10.5 µg/dL) at 5 pm and 30.6 µg/dL at 11 pm the following day. A 24-hour urine cortisol collection revealed a cortisol of 630 µg/24h (normal range: 3.5 - 45 µg/24h) in 900 mL of urine. ACTH was 84.1 pg/mL (normal: 7.2-63.3 pg/mL). Serum creatinine 0.6 mg/dL (normal: 0.60 - 1.00 mg/dL), potassium of 3.5 mmol/L (normal: 3.3 - 5.3 mmol/L), and bicarbonate of 32 mmol/L (normal: 20-30 mmol/L). Pituitary MRI revealed asymmetry in the pituitary with a small hypodensity, raising concern for Cushing’s disease. In anticipation of inferior petrosal sinus sampling and surgical intervention, ketoconazole 200 mg twice daily was initiated to decrease cortisol biosynthesis. However, the subsequent day the patient developed hypotension and altered mental status, with a cortisol drop to 8 µg/dL. Ketoconazole was held, and 50 mg of IV hydrocortisone was given. Serum cortisol levels were monitored and once they stabilized at approximately 20 µg/dL, ketoconazole was cautiously restarted and adjusted to 100 mg twice daily. Although outpatient endocrine follow-up was scheduled the patient passed from complications of other comorbid conditions. Conclusion: Ketoconazole’s role in managing hypercortisolism, particularly in Cushing’s disease, lies in its ability to inhibit cytochrome P450 enzymes (like CYP17 and CYP11A1) in cortisol biosynthesis. However, it carries the risk of precipitating acute adrenal insufficiency. This underscores the need for careful titration and close monitoring of adrenal function in patients with prior glucocorticoid exposure, as past steroid excess may increase cortisol metabolism and heighten the risk of adrenal insufficiency when biosynthesis is abruptly suppressed. Therefore, either starting ketoconazole at the lowest dose in treatment-naive patients with titration to goal or using a block and replace strategy with supplemental hydrocortisone, would be reasonable strategies to avoid iatrogenic adrenal insufficiency. Presentation: Saturday, July 12, 2025