Session: SUN 1-16-Adrenal Insufficiency
Poster Board SUN-3
Case: 64 yo man with history of depression, allergic rhinitis and ten year history of syncope of unclear etiology, presented for endocrine evaluation of episodic sympathomimetic symptoms, concerning for hypoglycemia. He is a nondiabetic on no oral hypoglycemic agents. 72-hour continuous glucose monitor revealed normoglycemia. Biochemistry revealed normal plasma metanephrines and thyroid function studies, negative anti-adrenal antibody and random serum cortisol of 6 mg/dL. Patient failed a 250 microgram cosyntropin stimulation test with baseline cortisol 1.1 mg/dL, ACTH 5.8 ng/mL and peak cortisol of 11.1mg/dL. Additional pituitary biochemical work-up and magnetic resonance imaging were unremarkable. Medication review revealed 10-year history of nefazodone for depression and intermittent intranasal fluticasone for allergic rhinitis. Time course of co-administetered therapies coincided with onset of symptoms. Physiologic steroid replacement therapy with hydrocortisone resolved syncopal and sympathomimetic symptoms.
Interpretation: Timely clearance of corticosteroid medications, whether systemic, topical or inhaled, requires an intact cytochrome P450 3A4 pathway. Medications, such as nefazodone which inhibit the P450 3A4 pathway, reduce clearance of exogenous steroids, resulting in supraphysicologic corticosteroid levels and consequent suppression of the HPA axis. Among inhaled corticosteroids, fluticasone has a high risk for HPA suppression due to longer plasma elimination half life, greater tissue binding, and prolonged receptor binding, which accentuates its greater glucocorticoid potency, particularly when used chronically.
Conclusion: This is the first known case describing adrenal insufficiency in a patient co-treated with nefazodone and fluticasone. Co-treatment with cytochrome P450 3A4 inhibitors, such as nefazodone, and fluticasone can suppress the HPA axis and predispose to secondary adrenal insufficiency. Intermittent use or withdrawal from fluticasone can unmask endogenous cortisol insufficiency and result in life-threatening adrenal crisis. Greater patient and physician awareness of the risks associated with combined medication profiles should be instituted, with endocrinologic monitoring of HPA axis, as long as the patient remains on fluticasone and nefazodone.
Nothing to Disclose: JL, MM, MV
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