Confirmatory Testing for Adrenal Insufficiency

Introduction to Adrenal Insufficiency Diagnosis

The high-dose (250-μg) ACTH stimulation test is the most appropriate confirmatory test for adrenal insufficiency, as recommended by the Endocrine Society 1
A peak cortisol level below 18 μg/dL (or 550 nmol/L) at 30 or 60 minutes indicates adrenal insufficiency, according to the Journal of Internal Medicine 1

The Endocrine Society confirms that the high-dose (250-μg) ACTH stimulation test is superior to other diagnostic tests for establishing primary adrenal insufficiency 2
The high-dose test is easier to perform and has comparable accuracy to the low-dose test, as stated by the Intensive Care Medicine journal 3

In primary adrenal insufficiency, baseline ACTH levels are typically elevated, and a baseline morning cortisol <100 nmol/L with elevated ACTH may be sufficient for diagnosis, according to the Journal of Internal Medicine 1
Additional pituitary testing may be required in secondary adrenal insufficiency, as recommended by the Journal for ImmunoTherapy of Cancer 4

In critically ill patients with suspected critical illness-related corticosteroid insufficiency (CIRCI), the task force makes no definitive recommendation between delta cortisol (change in baseline cortisol at 60 min of <9 μg/dl) after cosyntropin administration or a random plasma cortisol of <10 μg/dl, as stated by the Intensive Care Medicine journal 5, 2
However, the high-dose test is still suggested over the low-dose test in critically ill patients, according to the Intensive Care Medicine journal 3

Delaying treatment in suspected acute adrenal crisis to perform diagnostic testing is not recommended, and treatment should never be delayed, as emphasized by the Journal of Internal Medicine 1, 6
Failing to collect baseline cortisol and ACTH samples before administering treatment is a common pitfall to avoid, as recommended by the Journal of Internal Medicine 1

Random cortisol measurements may be useful in emergency situations, but are less reliable, as stated by the Intensive Care Medicine journal 5