ROCHESTER — Researchers reported findings at ENDO 2026, the annual meeting of the Endocrine Society, indicating that measuring adrenocorticotropic hormone (ACTH) after a 1-mg overnight dexamethasone suppression test (DST) may improve the diagnosis of hypercortisolism in patients whose baseline ACTH levels fall into a diagnostic gray zone.

Kai Yu, a research fellow at the Mayo Clinic in Rochester, Minnesota, presented the findings from a large international multicenter study evaluating post-dexamethasone ACTH as a biomarker to distinguish adrenal, pituitary, and other causes of hypercortisolism.

"In clinical practice, I think a lot of endocrinologists will know when patients with hypercortisolism present to us, usually for ACTH-independent hypercortisolism, their ACTH level should be low 10," Yu said. "And then for ACTH-dependent hypercortisolism, their ACTH should be above 20. But in real clinical practice, we actually see a lot of patients with ACTH-independent and ACTH-dependent hypercortisolism. Their baseline ACTH actually falls into a gray zone, which is between 10 and 40."

"So this study is meaning to understand if there is any new biomarker that can help us for the subtyping of hypercortisolism whose baseline ACTH falls into the gray zone between 10 and 40," Yu said. "I think the most interesting and practical finding from our study is that we show a new marker, which is the post 1-mg DST ACTH. It shows excellent discrimination on the adrenal disease from the pituitary disease. And we also show excellent discrimination of post 1-mg DST ACTH in patients with pituitary disease versus the non-neuroplastic hypercortisolism."

"So the post 1-mg DST ACTH showed discrimination, the AUC was 0.99, so 99% accuracy in distinguishing adrenal disease from the pituitary," Yu said. "And with a cutoff below 8, we can be very confident to say, 'Hey, here is adrenal disease.' And with a cutoff above 9, then we can be sure it is pituitary disease. And when we check those patients with baseline ACTH, only when it falls into the 10 and 40 [range], which is the gray zone, the diagnostic accuracy still remained above 90%, at 94%."

"So we find this biomarker as the best we can recommend for a first-line marker that when we cannot use baseline ACTH to distinguish, we recommend to use post 1-mg DST ACTH," Yu said. "So our next step for this study is we try to establish a clinical strategy. So the first thing for hypercortisolism is always starting from establishing the diagnosis for hypercortisolism. After that is established, we will use ACTH below 10, 10 to 40, and above 40. And then we will firstly apply the post 1-mg DST ACTH to see how many patients we can screen out. We can confirm to be adrenal versus pituitary versus non-neoplastic hypercortisolism. And then if we still see some false positives, then in that case we will introduce the delta cortisol and also the percentile delta cortisol into the whole diagnostic algorithm. So that's our next step and we are still working on that."