A diagnosis of primary adrenal insufficiency requires demonstration of which finding?

• A. decreased urinary 17-keto and 17-hydroxysteroids
• B. decreased cortisol production
• C. impaired response to ACTH stimulation
• D. increased urinary cortisol excretion after metyrapone

Answer: (C)

The test hinges on how the adrenal cortex responds to ACTH. In primary adrenal insufficiency (Addison disease), the adrenal cortex is damaged and cannot make cortisol even when stimulated. When synthetic ACTH (cosyntropin) is given, the normal adrenal response is a rise in cortisol within about 30 to 60 minutes. In primary disease, this cortisol rise is blunted or absent, so the cortisol level remains low after stimulation. This impaired response to ACTH stimulation is the most direct, specific way to demonstrate adrenal dysfunction and distinguish primary adrenal insufficiency from other causes.

The other options aren’t as diagnostic on their own. Decreased urinary steroid metabolites or simply decreased cortisol production don’t specify the cause or the adrenal reserve. The metyrapone test is another investigative tool for the HPA axis, but it’s not the standard criterion for confirming primary adrenal insufficiency.