New biomarker of glucocorticoid action could help clinicians tailor treatments

Researchers have discovered pathways involved in the body’s response to glucocorticoid treatments and identified a new biomarker that could be used to monitor how these drugs work in patients, according to a clinical study published today in eLife.

A more reliable indicator of an individual’s response to glucocorticoid drugs could be used to develop a clinically applicable test that could help tailor treatments and potentially minimize side effects.

Glucocorticoids, like cortisol, are a type of hormone that plays a key role in the body’s response to stress. Glucocorticoid drugs are one of the most commonly prescribed treatments for a range of conditions, including for patients whose adrenal glands are unable to produce enough cortisol. The effects of glucocorticoids are complex, which means that the level of cortisol in the blood does not reliably reflect what is happening in the tissues. It is therefore difficult for healthcare professionals to know how to adapt treatments.

Side effects of glucocorticoid therapy are common in patients, indicating that current methods of monitoring their action, which generally focus on clinical response or disease activity, are inadequate. We wanted to find some sort of biomarker that could be measured to monitor the action of glucocorticoids in individuals, in the hope that this will help clinicians understand the best way to treat patients. “

Dimitrios Chantzichristos, first author, Chief Physician, Endocrinology-Diabetes-Metabolism Section, Sahlgrenska University Hospital, Sweden

The team studied patients with Addison’s disease who lack the ability to produce their own cortisol. This allowed them to compare the activity in the tissues of the same patient both when their cortisol levels were low and when they were restored by glucocorticoid treatments, thus helping to account for variations between individuals.

Rather than focusing only on the metabolic products associated with exposure to glucocorticoids, they also examined gene expression and microRNAs in patients using new computational approaches developed in collaboration with Dr. Adam Stevens of the University. from Manchester, UK. MicroRNAs are short strands of ribonucleic acid (RNA) that can regulate gene expression by interfering with protein production. The team analyzed these different factors in blood cells and body fat, an important metabolic tissue because patients’ cortisol levels were altered, revealing close relationships between the different elements involved in the action of glucocorticoids.

Among the elements they identified, a microRNA called miR-122-5p is closely correlated with genes and metabolites regulated by glucocorticoid treatments. To test this correlation, the team looked at the levels of miR-122-5p in the blood of patients exposed to different levels of glucocorticoids from three independent studies and found the same pattern, supporting the idea that this microRNA could be a useful biomarker of glucocorticoid action.

“This potential biomarker can now be studied in larger groups of patients with the aim of developing a clinically applicable test,” concludes lead author Gudmundur Johannsson, professor in the Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Sweden . “Our work has also improved our understanding of the action of glucocorticoids, which may help discover their role in many common diseases such as diabetes, obesity and cardiovascular disease.”

This study was the result of a collaborative effort between researchers from the universities of Manchester (UK), Edinburgh (UK), Copenhagen (Denmark) and Göteborg (Sweden), as well as University of Newcastle (UK) and Sahlgrenska University Hospital (Sweden).