UCLH researchers find way to reduce side effects of treatment for adrenal disorder

A research team involving UCLH clinicians has found a way to reduce the side effects of treatment for a disorder of the adrenal glands.

In the research trial, published in the New England Journal of Medicine, the team found that use of the drug crinecerfont enabled patients with congenital adrenal hyperplasia (CAH) to safely reduce their dose of glucocorticoids, which can lead to immunosuppression, bone loss and metabolic complications.

The classic form of CAH affects around one in every 10,000 to 15,000 people worldwide. It is caused by genetic mutations which impair the production of cortisol and aldosterone – hormones critical in the body’s response to stress. When adrenal function is impaired, there is an excessive build-up of androgens (testosterone-like hormones).  

To counteract the impaired production of cortisol, patients must take daily doses of replacement steroid known as glucocorticoids. Often patients with CAH have to take higher doses of glucocorticoids than are naturally present in the body – so-called supraphysiologic doses. Long term use of glucocorticoids – particularly at supraphysiologic doses – can lead to side effects and is a cause of safety concerns for patients.

Data from the first 24 weeks of the trial was reported. All patients took glucocorticoids. One group took crinecerfont alongside their glucocorticoids and the other group did not. Participants did not know which group they were in.

After 24 weeks, the group taking crinecerfont were able to reduce their dose of glucocorticoid by 27.3%. This compared with 10.3% for the placebo group.

At the same time point, 63% of participants in the crinecerfont group took doses of glucocorticoids which were no longer supraphysiologic, compared with just 18% in the placebo group.

Dr Umasuthan Srirangalingam, trial principal investigator at UCLH, said: “We are pleased to be able to report that crinecerfont could be used to safely reduce the glucocorticoids patients need, while still maintaining CAH control. In the longer term this should reduce side effects they may face and make long-term treatment for patients safer. This is an important step forward.”

The study was supported by the NIHR UCLH BRC and was run at the NIHR UCLH Clinical Research Facility.