Great questions, Chris.  Wish I knew for sure any of the answers!

The supposed benefit of shorter acting steroids is that it allows us to specialize the amount of support for specific times of the day.  Those of us who dose 3x a day generally do it in a ratio of 2-1-2.  For example, my daughter gets 2.5 mg at 7 am, 1.25 mg at 3 pm, and 2.5 mg at 11 pm.  The larger morning and nighttime doses are designed to imitate the natural ramping up the body does overnight, with a cortisol peak around 8 am.  There is a natural lull in the need for cortisol in the midday hours, thus the lower dose.  In theory, having constant levels throughout the day would mean that there is too much steroid support in the late afternoon hours.  The result could be some physical signs of over-suppression, even though there may not be enough support in the hours of greatest need (which could potentially result in high labs).

The problem with all of this is that it really is just theory.  I get irritated by the lack of hard, cold facts – but I am not going to volunteer my child for hourly blood draws over a period of days and all the rest that it would take to put some real data on paper.  How many of us would?  In addition, each of our children is so different that it would take large studies to see patterns emerging.  My own two girls have exactly the same mutations, but very different experiences with the disorder.  Compund that with all of the different combinations of mutations and you can see how hard it is to generalize, even with good test data.

There seems to be growing acceptance that the longer acting steroids (used very carefully) can result in satisfactory height outcomes.  I believe some of this data was presented at the MAGIC convention, and I know that studies have been published.  It is especially helpful if compliance is an issue.  Once a day meds sound great to me!  The fact that Carol believes in her doctor and the course of treatment that he is advocating speaks volumes to me about its merits.  We have spoken to our endo about making the switch for my older daughter, and I believe we’ll do that soon.

Why switch to longer acting meds after linear growth is complete?  Compliance is one of the reasons I’ve heard.   People will take one dose a day more predictably than they will take three.  Another argument is that Cortef has a much greater effect on the mineralocorticoid axis than the longer acting steroids.  Salt wasters benefit from this effect, but most simple virilizers don’t need it and switching may eliminate some of the fluid retention and accompanying puffiness that Cortef users can experience.  We ladies hate to feel puffy after puberty!

Thanks for continuing a great thread, Chris.  If y'all see any mistakes in my info, let me have it.