For a patient suspected of ectopic ACTH production, which test is most useful in substantiating this diagnosis?

The most useful test for substantiating the diagnosis of ectopic ACTH production is plasma cortisol. In cases of ectopic ACTH syndrome, an ectopic source (such as a tumor) produces adrenocorticotropic hormone (ACTH), leading to increased cortisol production from the adrenal glands.

Measuring plasma cortisol levels can indicate hypercortisolism, which is characteristic of this condition. Elevated cortisol levels in conjunction with undetectable or low levels of adrenocorticotropic hormone from the pituitary suggest the presence of ectopic ACTH secretion, as the normal physiological feedback mechanism would not be functioning correctly.

Tests like CA-50, alkaline phosphatase isoenzymes, and AFP serve different roles in clinical diagnostics, often associated with specific types of cancers or liver function tests, but they do not provide definitive evidence for ectopic ACTH production. Therefore, plasma cortisol is the most relevant and direct measurement for diagnosing suspected ectopic ACTH secretion.