Dear Maheran,

You had posted a bit ago, wondering how your son's bone age could have advanced in such an extreme fashion without his bloodwork having given any warning.  From what you wrote, it appears that it advanced almost 6 years in one year's time, is that correct? Sorry I haven't had the chance to respond to your note till now, though your story made a big impression on me, as soon as I read it.  My son also has a very advanced bone age (though his was as a result of late diagnosis), so I fully understand the helplessness you must be feeling right now.  I do have a couple of thoughts for you.

First, the bone age would advance if your son is overproducing androgens (male sex hormones) in an uncontrolled way.  In looking at the combination of your son's twice a day HC dosing, in conjunction with the timing and distribution of his meds (5 mg am/10 mg pm), it does seem to me that there was ample opportunity for breakthrough androgen secretion. 

HC is out of circulation in about 6 hours, meaning that it is normally recommended to be given 3-4 times/day.  In spite of this, many doctors have utilized twice/day dosing in many of their CAH patients.  We also briefly saw a doctor who recommended 2X/day HC dosing.  Several times while my son was her patient, I tried to find out the rationale behind this approach, since it seemed to contradict much of what I had previously understood about CAH treatment.  Quite frankly, I didn't think the answers given me made a whole lot of sense and, over time, I feel that they are even less defensible.  Recently, I've read that---not surprisingly---many doctors are going back to the 3X-4X/day dosing because of evidence of increased androgen breakthrough.  So, I would start by wondering if twice/day HC dosing is really the way to go with your son.

Secondly, I question why the doctors would choose to give your son a small dose in the morning and a dose twice as large, at night.  It is considered desirable, with replacement doses, to mimic the body's natural production of cortisol.  Generally, cortisol levels are highest in the early morning and gradually fall during the course of the day.  In essence, then, your son's medication regimen followed a pattern exactly opposite that of natural circadian rhythm, i.e.  he was getting a very big dose at a time he really didn't need it (pm), and probably not getting enough when he really could have used some help (am). 

Why didn't it show up in his bloodwork?  Again, I feel that the numbers could have lied in your son's case because of the size and distribution of his HC doses, and their relationship to when his tests were probably taken.  Were your child's tests generally gotten in the morning? Before or after medication?  Corticosteroids taken at night have the effect of being twice as potent as the same dose taken during the day, so your son's nighttime dose is even more potent than it appears---effectively 4X what he was getting in the morning.  So, an early morning reading could have falsely shown good control because I'm sure your son was quite suppressed, at that time.  In addition, if the tests were taken after the morning meds, the numbers would have been even more deceptively low.  If your child's tests were done in the afternoon, they might have been low, anyway, because of natural circadian rhythm.  So, either way, it seems like there are several possible ways that your son's numbers would have always been "good," even though it appears that just the opposite was true.

I think that is one of the biggest problems with using a single blood draw, to assess control, since blood is very specific to a particular point in time.  So, yes, your son could indeed have been very well suppressed at the very  moment that his blood was being drawn---for a variety of reasons---but, unfortunately, that doesn't account for what may have been happening in his body for the rest of the 23 hours and 59 minutes of his day. 

Increasing your child's morning HC dose to 10 mg. will undoubtedly halt some of your son's excess androgen production.  I still feel, however, that your doctor is treating the problem symptomatically, rather than trying to analyze its root cause.  I don't know how big your son is, but 20 mgs. total of HC/day for a child who is only 5 yo. sounds a bit on the high side.  Control can probably be achieved with a smaller total daily dose, differently distributed. 

Also, did your doctor test for anything besides 17-OHP?  If there was also a problem with precocious puberty, the 17-OHP could have been completely normal, though a potential problem would have been indicated by a high testosterone count.  If your child's doctor never ran a testosterone test, though, and only relied on the 17-OHP to assess control, this could have been missed completely, as a result.

A bone age advancement of 6 years, in one year's time, is something that really shouldn't happen, if one is paying attention.  It is hard for me to believe that there were no red flags in the whole of the last 12 months to clue your doctor to the fact that your child was wildly out of control, despite returning "good" numbers.  Sadly, your son's situation appears to be another case where a doctor treats "by the numbers," rather than looking at the total child and utilizing some good old common sense.  I believe they owe you some better answers than just that this is another unexplainable situation. 

I know the feeling of wishing that you could go back in time and reverse damage that has already been done.  Unfortunately, we can only go forward, so I hope this will help---at least a little---in preventing more of the same from happening with your son.