Cosyntropin Stimulation Test is the Next Step
This patient requires a cosyntropin (ACTH) stimulation test to definitively diagnose or exclude adrenal insufficiency. Her low morning cortisol falls in the indeterminate range (5-10 μg/dL or 140-275 nmol/L), and with her history of recurrent steroid exposure, she is at high risk for secondary adrenal insufficiency requiring confirmatory dynamic testing 1, 2.
Why Dynamic Testing is Medically Necessary
A morning cortisol that is neither clearly normal (>18-20 μg/dL) nor clearly diagnostic (<5 μg/dL) requires ACTH stimulation testing to definitively rule in or rule out adrenal insufficiency 2, 3.
The cosyntropin stimulation test is the gold standard confirmatory test when basal cortisol levels are inconclusive 1, 4, 5.
Her recurrent steroid exposure creates significant risk for HPA axis suppression and secondary adrenal insufficiency, making this evaluation critical rather than optional 2, 3.
Cosyntropin Stimulation Test Protocol
Administer 0.25 mg (250 μg) cosyntropin intramuscularly or intravenously 1, 2.
Measure serum cortisol at baseline and 30 minutes (and/or 60 minutes) post-administration 1, 2.
A peak cortisol <500-550 nmol/L (<18-20 μg/dL) is diagnostic of adrenal insufficiency, while >550 nmol/L (>18-20 μg/dL) is considered normal 1, 2.
Obtain baseline ACTH level before cosyntropin administration to distinguish primary (high ACTH) from secondary (low/normal ACTH) adrenal insufficiency 6, 2, 3.
Critical Diagnostic Considerations
Do not rely on electrolyte abnormalities to make or exclude the diagnosis—hyponatremia is present in 90% of cases, but hyperkalemia occurs in only ~50% of primary adrenal insufficiency cases and is typically absent in secondary adrenal insufficiency 2, 3.
Her weight gain, fatigue, and hair loss are consistent with both adrenal insufficiency and hypothyroidism, so check TSH and free T4 simultaneously, as these conditions frequently coexist 7, 6.
If both adrenal insufficiency and hypothyroidism are confirmed, corticosteroids must be started several days before thyroid hormone replacement to prevent precipitating adrenal crisis 7, 6, 1.
What Happens Based on Test Results
If Test Confirms Adrenal Insufficiency (Peak Cortisol <18 μg/dL):
Initiate hydrocortisone 10-20 mg in the morning and 5-10 mg in early afternoon for secondary adrenal insufficiency (no mineralocorticoid needed) 6, 1.
Provide immediate education on stress dosing: double the dose for minor illness, triple for moderate illness, and use injectable hydrocortisone 100 mg IM for severe illness or inability to take oral medications 1, 3.
All patients require a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by emergency services 7, 6, 1.
Lifelong glucocorticoid replacement therapy will be necessary 2, 3.
If Test Rules Out Adrenal Insufficiency (Peak Cortisol >18-20 μg/dL):
This definitively excludes adrenal insufficiency, allowing safe exploration of other causes for her symptoms without risk of missing a life-threatening condition 2, 4.
Pursue alternative diagnoses such as hypothyroidism, chronic fatigue, or other endocrine disorders 7.
Important Pitfalls to Avoid
Never delay treatment if she develops signs of adrenal crisis (hypotension, severe vomiting, altered mental status)—immediately administer IV hydrocortisone 100 mg and 0.9% saline without waiting for test results 1, 2, 8.
Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained symptoms should be presumed to have adrenal insufficiency until proven otherwise 2.
Be aware that exogenous steroid use can confound cortisol measurements—hydrocortisone must be held for 24 hours before testing, and other steroids for longer 7, 2.
ACTH stimulation testing can give false-negative results early in hypophysitis, as adrenal reserve declines slowly after pituitary stimulation is lost—if clinical suspicion remains high despite normal testing, consider repeat evaluation in 3 months 7.
Why This Cannot Wait
Undiagnosed adrenal insufficiency is life-threatening, especially during physiologic stress such as infections (which she has already experienced requiring hospitalization) 2, 3.
Adrenal crisis carries high mortality if untreated, and this patient's history of recurrent infections and hospitalizations places her at ongoing risk 2, 4.
This is not a chronic fatigue syndrome evaluation—she has objective laboratory abnormalities (documented low cortisol) that mandate investigation 2.