Rashelle Ripa, MD: No financial relationships to disclose
Introduction: Secondary adrenal insufficiency (AI) is a recognized complication of exogenous glucocorticoid exposure; however, clinically significant hypothalamic-pituitary-adrenal (HPA) axis suppression from inhaled corticosteroids (ICS) is less commonly appreciated. ICS are generally considered to have minimal systemic effects except in patients receiving cytochrome P450 3A4 inhibitors (CYP3A4). We report a case of secondary AI in a healthy young adult associated with prolonged use of a fluticasone-containing inhaler (Trelegy Ellipta).
Presentation: A 27-year-old male with asthma, migraine with aura, generalized anxiety disorder, fibromyalgia, atopy, and GERD presented with seven years of fatigue, myalgias, salt craving, low libido, nausea, and orthostatic symptoms. His asthma had been managed with daily Trelegy Ellipta containing fluticasone furoate 100 µg for four years, along with as-needed albuterol. He also reported childhood inhaled fluticasone use and annual short prednisone tapers for asthma exacerbations, the most recent one month before presentation.
Initial labs showed a serum cortisol of 3.4 µg/dL (drawn at 11:53 AM after taking Trelegy that morning). After withholding Trelegy, a repeat morning cortisol was 10.7 µg/dL with an ACTH of 35.9 pg/mL, considered indeterminate. Cosyntropin stimulation testing demonstrated a peak cortisol of 13 µg/dL at 60 minutes, consistent with adrenal insufficiency. Thyroid function was normal. The patient was started on hydrocortisone 5 mg twice daily, counseled on sick-day rules, and advised to wear a medical alert bracelet.
Discussion: ICS-induced AI is uncommon but has been described, particularly in adults receiving high-dose fluticasone (≥750 µg/day) or concomitant CYP3A4 inhibitors. Our patient had neither risk factor aside from prolonged exposure and intermittent prednisone tapers. A meta-analysis has shown that fluticasone confers significantly greater dose-related adrenal suppression compared with other ICS agents including beclomethasone dipropionate, budesonide, and triamcinolone acetonide. This case highlights that long-term daily use of a high-potency ICS-even at manufacturer-recommended dosing and without chronic oral steroid use-can result in clinically meaningful HPA axis suppression. The low morning cortisol after withholding the inhaler and blunted response to cosyntropin provide strong evidence for secondary AI. Increased awareness is warranted to prevent delayed diagnosis in patients presenting with nonspecific symptoms while using potent ICS formulations.
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