7432 Secondary Adrenal Insufficiency Caused By Concurrent Treatment With Budesonide And Itraconazole

Abstract Disclosure: F. Anjum: None. M.G. Jakoby: None. Introduction: Inhaled corticosteroids (ICS) are unlikely to affect corticotroph axis function even at high doses due to low systemic absorption. However, co-treatment with drugs that reduce hepatic clearance of ICS may predispose patients to secondary adrenal insufficiency (AI). We report a case of secondary AI that occurred during concurrent treatment with budesonide and itraconazole. Case presentation: A 42-year-old female with longstanding asthma managed with inhaled budesonide (160 μg twice daily) was started on itraconazole (200 mg twice daily) for management of pulmonary histoplasmosis. Over the next three months, she experienced severe fatigue, and laboratory evaluation was notable for an undetectable (< 0.4 μg/dL) 8 AM cortisol level. Serum sodium (140 mM, 136-145) and potassium (4.6 mM, 3.5-5.1) were unremarkable, and a diagnosis of drug induced secondary AI was made. Treatment with hydrocortisone (15 mg in the morning, 5 mg in the evening) was started, and the patient’s infectious disease specialist stopped itraconazole, substituting posaconazole (300 mg daily) for an additional six months. Her pulmonologist substituted fluticasone (250 μg twice daily) for budesonide. After an approximate two-month hydrocortisone taper, 8 AM ACTH level was easily detectable (37.2 pg/mL, 7.2-63.3), though 30 min stimulated cortisol level was subnormal (11.1 μg/dL, expected > 18). Hydrocortisone was successfully tapered off over an additional two-months (30 min stimulated cortisol 23.4 μg/dL). Discussion: The literature on ICS induced secondary AI is generally case reports and series, and the incidence is very low (1.1/10,000 patient-years at risk). Limited oral bioavailability, high deposition in lungs, extensive protein binding, and robust hepatic clearance are factors that minimize the effects of ICS on corticotroph axis function. However, concurrent treatment with potent CYP3A4 inhibitors like itraconazole can significantly reduce hepatic clearance of ICS and predispose to systemic effects, including Cushing syndrome when high dose ICS are prescribed or secondary AI at lower doses. In a series of 25 cystic fibrosis patients co-treated with itraconazole and budesonide, 11/25 (44%) developed secondary AI. Our patient likely developed secondary AI but not Cushing syndrome due to treatment with low dose budesonide. This case illustrates the importance that endocrinologists recognize CY3A4 inhibiting drugs as a risk factor for secondary AI in patient treated with ICS. Presentation: 6/3/2024