Does a patient with fatigue, poor appetite, and weight loss on fluticasone (fluticasone propionate) inhaler, with a normal morning cortisol level and undetectable Dehydroepiandrosterone sulfate (DHEAS), require a cosyntropin stimulation test?

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Does This Patient Need a Cosyntropin Stimulation Test?

Yes, this patient absolutely requires a cosyntropin stimulation test despite the morning cortisol of 17 µg/dL, because the undetectable DHEAS on fluticasone inhaler strongly suggests HPA axis suppression, and a cortisol of 17 µg/dL falls in the indeterminate range that requires confirmatory testing. 1, 2, 3

Why the Morning Cortisol Alone Is Insufficient

  • A morning cortisol of 17 µg/dL (approximately 469 nmol/L) is in the indeterminate "gray zone" - it's neither clearly normal (>18-20 µg/dL) nor clearly diagnostic of adrenal insufficiency (<5 µg/dL), making confirmatory testing medically necessary 1, 3

  • The undetectable DHEAS is a critical red flag - DHEAS is an ACTH-dependent adrenal androgen that becomes suppressed with chronic inhaled corticosteroid use, often before cortisol production is affected, and serves as an early indicator of HPA axis dysfunction 4, 1

  • Fluticasone propionate is specifically associated with adrenal suppression even at moderate doses, with studies showing that high-dose fluticasone (880 µg/day) caused adrenal impairment in 14 of 19 patients (74%), and suppression has been documented even at doses as low as 550 µg/day 5, 6

The Clinical Context Demands Testing

  • The patient's symptoms (tiredness, poor appetite, weight loss) are classic for adrenal insufficiency, occurring in 50-95% (fatigue), 20-62% (nausea/poor appetite), and 43-73% (weight loss) of patients with this condition 3, 1

  • Inhaled fluticasone can suppress the HPA axis without causing obvious Cushingoid features, and the combination of symptoms plus undetectable DHEAS creates a high pretest probability that warrants definitive testing 7, 6

The Cosyntropin Stimulation Test Protocol

  • Administer 250 µg cosyntropin (high-dose test) intramuscularly or intravenously - this is the gold standard confirmatory test recommended over the low-dose test due to easier administration, comparable accuracy, and FDA approval 2, 8

  • Measure serum cortisol at baseline and at 30 and/or 60 minutes post-administration 1, 2

  • **Interpretation: A peak cortisol <18 µg/dL (500-550 nmol/L) is diagnostic of adrenal insufficiency**, while >18-20 µg/dL is considered normal 1, 2, 3

Critical Management Considerations

  • Do NOT delay testing to taper the fluticasone - the patient needs the diagnosis established first to guide safe management 1

  • If the test confirms adrenal insufficiency, the patient will require:

    • Glucocorticoid replacement therapy (hydrocortisone 15-25 mg daily or prednisone 3-5 mg daily) 3, 1
    • Education on stress dosing for illness, surgery, or physical stress 3, 1
    • Injectable hydrocortisone 100 mg for emergency use 3
    • Medical alert bracelet or identification 1, 3
  • The fluticasone inhaler should be continued at the current dose until after testing - stopping it abruptly could precipitate adrenal crisis, and changing the dose will confound interpretation 1, 9

What Happens After the Test

  • If adrenal insufficiency is confirmed, initiate glucocorticoid replacement and work with pulmonology to transition to the lowest effective dose of inhaled corticosteroid or consider alternative asthma controllers 1, 7

  • If the test is normal, the symptoms may be due to other causes, but the undetectable DHEAS still warrants monitoring and consideration of reducing fluticasone dose if clinically feasible 4

  • Recovery of adrenal function after fluticasone reduction can take 2-10 months, so patients require ongoing monitoring with repeat testing 6

Common Pitfall to Avoid

  • Do not assume a "normal-appearing" morning cortisol of 17 µg/dL rules out adrenal insufficiency - this is a dangerous misconception that can lead to missed diagnoses, particularly in patients with secondary adrenal insufficiency from exogenous steroids where cortisol levels often fall in the 5-10 µg/dL range but can be higher 1, 3

References

Guideline

Diagnosing Adrenal Insufficiency in Hypo-osmolar Hyponatremia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Confirmatory Testing for Adrenal Insufficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Adrenal suppression secondary to inhaled fluticasone propionate.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 1999

Research

The effect of a steroid "burst" and long-term, inhaled fluticasone propionate on adrenal reserve.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2003

Research

Inhaled corticosteroids and secondary adrenal insufficiency.

The open respiratory medicine journal, 2014

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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