The adrenal axis, the adrenal cortex, is a series of very well-tuned hormone production cycles, and if one of those cycles is not functioning properly, then an imbalance in the proper ratio of hormones begins to develop. And so in 21-hydroxylase deficiency, CAH, what you have is insufficient cortisol production, elevation in the level of corticotropin-releasing hormone from the hypothalamus, and adrenocorticotropic hormone, or ACTH, from the pituitary gland driving the production not of necessary hormone cortisol but of precursors to the sex hormones, predominantly androgens.

So our challenge is because often by the time the child or older patient is put on adequate treatment, this process has been ongoing. So it's rather hard to reset that hormone imbalance to get it back to a physiological state. So in order to treat our patients, we end up giving them glucocorticoids, medications such as hydrocortisone, prednisone, and rarely dexamethasone, to reset that balance.

Now, the medications that we administer to our patients orally are not the same as the hormones that are produced in the adrenal cortex, primarily for the reason of the circadian or daily pattern of secretion. The adrenal cortex has a very fine-tuned pattern of how it releases these hormones, predominantly in the very early morning hours, lower during the course of the day, and then low at night.

So when we give medications, we are actually not replacing in a physiologic schedule, and so that's why there is currently a push on to try and replicate the physiologic pattern of hormone administration to suppress the abnormal drive to the adrenal cortex to produce abnormal amounts of sex hormones or androgens and to allow the young child to grow properly, to encounter pubertal changes in a time honored fashion rather than at a very early age or even at a very late age.