Noninvasive Skin Test May Aid in Cushing Diagnosis

Miriam E. Tucker

May 15, 2023

SEATTLE — Tissue accumulation of advanced glycation end products (AGEs) is associated with the presence of hypercortisolism, suggesting a potential future noninvasive method to assist in the diagnosis of Cushing syndrome, new research suggests.

Tissue accumulation of AGEs — harmful compounds formed by glycation of macromolecules — has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.

The findings were presented at the American Association of Clinical Endocrinology Annual Meeting 2023 by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minnesota.

"Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful," Sandooja told Medscape Medical News.

"After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional" instrument in the toolkit to reach a conclusive diagnosis, she added.  

Asked to comment, session moderator Anupam Kotwal, MD, told Medscape Medical News: "I think it's very exciting data...I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass...It might be used to guide care when there's not a clear-cut answer."

However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.

Moreover, "Skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step," added Kotwal, who is an assistant professor in the Division of Diabetes, Endocrinology and Metabolism at the University of Nebraska, Omaha.

More Work Will Be Needed

Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Sandooja explained.

"It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery."

Kotwal observed, "If the answer is clear for Cushing disease, I don't know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we're unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes."

But, he added, "Keeping in mind issues of skin...we don't want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I'm always hesitant to bring something into practice before there is a little more information on how it can be used."

Sandooja and Kotwal have reported no relevant financial relationships.

American Association of Clinical Endocrinology Annual Meeting. Abstract #1402218. Presented May 4, 2023.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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