From a near future perspective, what do you believe are the most promising approaches to reducing metabolic, cardiometabolic, and related morbidities in adults with CAH?
I think we're at an exciting time point for novel therapies. To treat 21 hydroxylase deficiency resulting in classic CAH. I think for decades, and this is many decades, the success of giving glucocorticoid and mineral corticoid, of having a newborn survive into childhood, adolescence and adulthood. was considered the achievement in the management of congenital adrenal hyperplasia. And that was for decades, the end of the story. As the individuals who come tonal hyperplasia began to age, we realized it's not the end of the story because these individuals were developing metabolic disease in terms of Glucose dysregulation, dyslipidemia, and osteoporosis at rates that weren't being seen in their counterparts without 21 hydroxylase deficiency. And the focus switched from Yes, we still obviously want to keep these patients alive, but can we give them a dose of glucocorticoid or give them glucocoid corticoid in a different way, or interrupt some pathways that activate the androgen pathways? So that we can give the glucocorticoid in a way that the dose that's more physiologic and not get the adverse metabolic effects. And I think that's a big direction where things are going now. So, we talked about two different ways. One would be, you know, could there be a way to give the gene of 21 hydroxylase back? Or another approach is, can we give glucocorticide but turn off the CRH ACTH stimulation so that androgen production is not elevated and then cut, cut back on our glucocorticoid dose. I do want to mention that the treatments I'm talking about are specific to those two examples are specific to congenital adrenal hyperplasia. But a lot of the things that we're aggressive about doing for cardio metabolic health, as people get older, patients with CAH getting older, don't necessarily receive them at the same rate because people think there's something different going on. So, the traditional methods of modifying cardio metabolic risk of keeping people at a good weight through diet and exercise, eating low fat foods, treating hypertension, if it Involves treating and diagnosing diabetes early, treating lipids. We need to be sure that patients with congenital adrenal hyperplasia are receiving the same treatments that patients their age and with their wrists would be receiving. It may be in the patients with congenital adrenal hyperplasia that part of it is mediated by the therapy that we're giving the patient and that we're giving them excess glucocorticoid. And as we do work to come to a regimen of glucocorticoid that is lower, we still need to be paying attention to modifying traditional risk factors that are present in a lot of these individuals and are present in increased prevalence because of the excess glucocorticoids.
