A 38-year-old woman with moderate persistent asthma has been on inhaled fluticasone propionate 250 μg twice daily for 6 months. She reports occasional hoarseness and oral candidiasis. Her physician suspects local adverse effects from the inhaled corticosteroid. Which investigation is most appropriate to assess for steroid-induced suppression of the hypothalamic-pituitary-adrenal (HPA) axis?

Explanation

## Assessment of HPA Axis Suppression in ICS Use ### Clinical Context Inhaled corticosteroids (ICS) can cause systemic absorption and HPA axis suppression, particularly at higher doses or with prolonged use. The patient is on fluticasone propionate 500 μg/day (250 μg twice daily), which is a moderate-to-high dose with meaningful systemic bioavailability. When HPA axis suppression is clinically suspected, a structured approach to investigation is required. ### Investigation Comparison | Investigation | Role | Interpretation | |---|---|---| | **ACTH stimulation test (250 μg cosyntropin)** | **Gold standard for HPA reserve/suppression** | Directly tests adrenal cortical response; most sensitive and specific for clinically significant HPA suppression from exogenous corticosteroids | | Serum morning cortisol (8 AM) | Initial screening | Useful if very low (<100 nmol/L suggests suppression); insensitive for mild-moderate suppression | | Low-dose dexamethasone suppression test (1 mg overnight) | Screens for Cushing's syndrome (endogenous hypercortisolism) | Not appropriate for detecting ICS-induced suppression | | 24-hour urinary free cortisol | Screens for hypercortisolism (Cushing's) | Reflects integrated cortisol production; useful for detecting excess, not suppression | ### Key Point: **The ACTH stimulation test (250 μg cosyntropin / Synacthen test) is the most appropriate investigation to assess for steroid-induced HPA axis suppression.** It directly evaluates the functional reserve of the HPA axis by measuring the adrenal cortex's ability to respond to exogenous ACTH. A peak cortisol <500 nmol/L (18 μg/dL) at 30–60 minutes indicates impaired adrenal reserve consistent with HPA suppression. This is the standard recommended by endocrinology guidelines (Endocrine Society) for assessing HPA suppression from exogenous corticosteroids including ICS. ### Why Other Options Are Incorrect: - **Morning serum cortisol** is a useful initial screen but lacks sensitivity for mild-to-moderate suppression; it is not the most appropriate definitive test. - **Low-dose dexamethasone suppression test** is designed to diagnose Cushing's syndrome (endogenous hypercortisolism), not to detect suppression from exogenous steroids. - **24-hour urinary free cortisol** measures integrated cortisol output and is used to screen for hypercortisolism (Cushing's syndrome), not for detecting HPA suppression. ### Clinical Pearl: HPA axis suppression risk increases with ICS doses >800 μg/day beclomethasone equivalent (fluticasone 500 μg/day ≈ beclomethasone 1000 μg/day equivalent in systemic potency). The ACTH stimulation test is the recommended investigation when clinical suspicion of HPA suppression exists (Harrison's Principles of Internal Medicine, 21e; Endocrine Society Clinical Practice Guidelines). ### High-Yield: - **ACTH stimulation test** = gold standard for HPA axis suppression from exogenous corticosteroids - **Morning serum cortisol** = initial screen only; insensitive for mild suppression - **24-hour urinary free cortisol / low-dose DST** = for Cushing's syndrome (hypercortisolism), NOT suppression [cite: Harrison's Principles of Internal Medicine 21e, Ch. 379; KD Tripathi 8e Ch 48]