Diagnosing Primary vs Secondary Adrenal Insufficiency

Diagnostic Approach

The high-dose ACTH stimulation test (cosyntropin 250 mcg IV) is recommended by clinical guidelines for differentiating between primary and secondary adrenal insufficiency in suspected hypopituitarism, as stated by the American College of Endocrinology 1
Initial assessment should include morning serum cortisol and ACTH levels to establish baseline adrenal function, according to the Endocrine Society 2
A normal response to the high-dose ACTH stimulation test is a cortisol value exceeding 18 μg/dl at 30 or 60 minutes, as defined by the American Association of Clinical Endocrinologists 1

In primary adrenal insufficiency, cortisol response will be blunted or absent, and baseline ACTH levels will be elevated, as indicated by the American College of Endocrinology 4
In secondary adrenal insufficiency, cortisol response will be blunted or absent, but baseline ACTH levels will be low or inappropriately normal, according to the Endocrine Society 4
A delta cortisol of less than 9 μg/dl after cosyntropin administration suggests adrenal insufficiency, as stated by the American College of Endocrinology 1

The patient should discontinue adrenal supplements for 1-2 weeks before testing, as recommended by the American Association of Clinical Endocrinologists 5
Morning testing is preferred, with cortisol measured at baseline, 30, and 60 minutes after cosyntropin administration, according to the European Society of Endocrinology 3

For confirmed adrenal insufficiency, replacement therapy with hydrocortisone (typically 15-25 mg daily in divided doses) is indicated, as stated by the American College of Endocrinology 5
Patient education regarding stress dosing during illness or surgery is essential, according to the Endocrine Society 4