New drug could help those with CAH reduce the use of corticosteroids

Congenital adrenal hyperplasia is a disorder that impacts the adrenal glands

5:00 AM

Author | Kelly Malcom

stethoscope blue yellow
Justine Ross, Jacob Dwyer, Michigan Medicine

People born with the common form of congenital adrenal hyperplasia lack an enzyme in the adrenal glands needed to make the hormones cortisol and aldorsterone, which are involved in the body’s response to stress and blood pressure regulation.  

The adrenals of children with this rare condition reroute hormone production to excess androgens, which tend to make them mature early and suffer from short stature and infertility as adults.

To make matters worse, a routine stomach virus can send CAH patients into what is known as an adrenal crisis, causing shock if not treated immediately. 

The go-to therapy for children and adults with CAH are high dose corticosteroids, which come with a host of side effects, including weight gain, diabetes, osteoporosis and cognitive dysfunction.  

A study, led by Richard Auchus, M.D., Ph.D., of the U-M Medical School Department of Pharmacology and internal medicine and investigators from the CAHtalyst Adult Trial provides strong evidence for an effective compound, crinecerfont, that could allow people with CAH to reduce their dose of replacement corticosteroids.  

Published in the New England Journal of Medicine, the study randomized adults with CAH to take crinecerfont or a placebo along with their normal corticosteroid regimen. 

A parallel study was conducted in children with CAH, and a companion paper reported these results.  

After a month, patients on the drug, but not placebo, had a reduction in the adrenal androgen, androstenedione, by half.

For the second part of the study, each group had their dose of glucocorticoid gradually reduced. 

The group on crinecerfont was able to maintain a reduction in the adrenal hormone after 24 weeks with a glucocorticoid dose close to that naturally produced by the body. 

“These patients are still cortisol deficient and thus will still need cortisol replacement, but with crinecerfont, they need much less and could be less likely to experience the longterm negative effects of current glucocorticoid dosing,” said Auchus. 

Additional investigators and authors include Kyriakie Sarafoglou, M.D., Mimi S. Kim, M.D., Maya Lodish, M.D., Eric I. Felner, M.D., Laetitia Martinerie, M.D., Ph.D., Natalie J. Nokoff, M.D., María Clemente, M.D., Ph.D., Patricia Y. Fechner, M.D., Maria G. Vogiatzi, M.D., Phyllis W. Speiser, M.D., Gelliza B.G. Rosales, M.P.H., Eiry Roberts, M.D., George S. Jeha, M.D., Robert H. Farber, Ph.D., and Jean L. Chan, M.D., Oksana Hamidi, D.O., Rosario Pivonello, M.D., Ph.D., Irina Bancos, M.D., Gianni Russo, M.D., Selma F. Witchel, M.D., Andrea M. Isidori, M.D., Ph.D., Patrice Rodien, M.D., Ph.D., Umasuthan Srirangalingam, Ph.D., Florian W. Kiefer, M.D., Ph.D., Henrik Falhammar, M.D., Ph.D., Deborah P. Merke, M.D.,Nicole Reisch, M.D., Gordon B. Cutler, Jr., M.D., Julia Sturgeon, M.S., Vivian H. Lin, M.D., Xin He, M.D. and Ming Chen, M.D. Ph.D. 

Auchus reports consulting fees from Neurocrine Biosciences, Crinetics Pharmaceuticals, Diurnal LTD, H Lundbeck A/S, and Novo Nordisk and contracted research support from Neurocrine Biosciences, Crinetics Pharmaceuticals, Diurnal LTD, and Spruce Biosciences. 

Papers cited:

“Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia,” New England Journal of Medicine. DOI: 10.1056/NEJMoa2404656 

“Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia,” New England Journal of Medicine. DOI: 10.1056/NEJMoa2404655 

Sign up for Health Lab newsletters today. Get medical tips from top experts and learn about new scientific discoveries every week by subscribing to Health Lab’s two newsletters, Health & Wellness and Research & Innovation. 

Sign up for the Health Lab Podcast: Add us on SpotifyApple Podcasts or wherever you get you listen to your favorite shows. 


More Articles About: All Research Topics Basic Science and Laboratory Research pharmacology Metabolism, Endocrinology & Diabetes
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories see through blue person with red lines running through neck to chest
Health Lab
What is phrenic neuropathy?
Phrenic neuropathy is a condition that impacts the nerve around the diaphragm making it harder to breathe, especially in situations such as lying down or being in water. The condition is treatable, with surgical intervention, physical therapy or by letting it heal over time.
Microscope
Health Lab
Nerve damage reduced in prediabetic mice with diet, exercise
A low calorie diet and high intensity exercise can reduce nerve damage in prediabetic mice, according to a Michigan Medicine study.
frozen dial with ice on it with red dial
Health Lab
Enzyme identified as new therapeutic target for “cold” tumors
A study identifies an enzyme as a new therapeutic target for “cold” tumors.
On left, a young boy in a wheelchair has his doctor standing to his left and his parent is standing to his right in a show of support. On the right side of the image, the boy is now an adult and is wondering about the cost of his care and if his questions will be answered.
Health Lab
Changing the definition of cerebral palsy
Cerebral palsy is defined as a childhood disorder, which fails to recognize adults living with the condition and the lack of care they receive once they age out of pediatric clinics.
kid screaming with fire coming out of mouth with smoke all around in grey and teddy bear panicked and parents legs on floor as if passed out or blown away
Health Lab
Does your child manage anger well?
One in seven parents think their child gets angrier than peers of the same age and four in 10 say their child has experienced negative consequences when angry, a national poll suggests. 
baby laying down with stethoscope over chest doctors hands
Health Lab
Comparing life threatening illness risk between two surgeries for infants with congenital heart disease
Newly presented data suggest that infants who receive a hybrid stage I palliation – a less invasive alternative for initial treatment – more commonly develop necrotizing enterocolitis compared to those who receive the standard Norwood operation, a complex open heart surgery.