Sorry was rushing to get the post down as I keep disconnecting due to a problem at the moment here.

It certainly makes sense not to dose throughout the day in a standard fashion, however I do have some more questions about the circadian rythm.

1) In the Mayo extract it says that the cortisol peak will be affected by the time of rising. So it’s possible that for one child it can be at 6 am and for another at 8am and for the same child , even differ from day to day if his/her waking time is not consistent. Given that, can it somehow influence the peaking of ACTH at 3am as the Hindmarsh study suggests in a backward fashion. Meaning if the child were to wake everyday at 8 am or even later then if that is when the cortisol surge occurs and is needed then can the HPA axis start its work later, because the need for cortisol is much later ? Is that a possibility ?

I think that your right here actually.  It stands to reason that if a child rises earlier, that their cortisol needs to peak ealier.   However, it can work the other way around too.  The med’s and your routine will influence the wake, sleep cycle of a child also.  If your a family that rise early and the child does then it would make sense to give that first hydrocortisone dose earlier.  This then impacts on when you give the next dose though, but if your a family that goes to bed early, I guess that kids would be in bed around 7pm and thereabouts so that last dose would shift to from 5.30pm to slightly earlier.  Otherwise going to bed late and risisng early equals not enough sleep. 

I think the trick is to look at your personal family circumstances and slot the dosing in to suit--altering the times to fit your childs waking and sleeping patterns.  otherwise as you say if they are awake at 6am and not getting their tab until 7am, there is bound to be a deficit somewhere.  My kids get up at 7am so that is ok.  Ashley’s alarm goes off at that time and he wakes at that moment and takes his tablet.  So it would probably make sense for a child waking at 6am to take their at 6am.  The next one at 11am, the next one at 4.30pm and the early am one at 2am.  Thats because they are probably going to bed much earlier as they have to rise earlier, so really they are reaching those different stages of sleep an hour earlier. 

2) It says in the same extract that GH peaks at 2 hours after sleep approximately when deep sleep occurs. So that again would differ from child to child. So if the late night dose is timed in such way that it is given after about 3 hours after bed time so by the time it peaks in the system, the GH production has proceeded without hindrance, which means in my daughter’s case she goes to bed by 9pm , I would have to give her late night dose at about 12 midnight. Then this would have addressed the GH problem, or would it ???

Most children are in bed before 9pm.  I put my kids to bed way before that and if anything they are there before 8pm.  Ashley only stays up late because of his age and he does go at 9pm on the weekend though.  I still stick to the same times for the sake of his regime where dosing med’s is concerned though.  GH starts to be released two hours after deep sleep ensues.  It does not peak there.  The nature of GH is that in children with normal health it is released in pulses throughout the night on a negative feedback mechanism again like the HPA axis and cortisol release.  These pulses stop and start.  It is not one continuous stream of GH in the blood serum.  I think therefore that that may possibly tie in with the cortisol availability at the time where production is concerned.  I still think that cortisol in normal healthy people is produced at 8pm to 4am but it is so much lower due to the relaxed state before sleep and during sleep.  Look at the Mayo chart again and you will see that it is a flat steady rate it is produced at but nevertheless, it is at level "5" on that chart.  If you look at the highest peaks, they show at level "20." This obviously means that cortisol is STILL produced at midnight, but that it is at a quarter of it’s amount at 8am and also one third less in general than the daily production that has taken place.    The last small dose @ 5.30pm should really therefore reflect what is needed to carry the child through until the next dose at 3am say. 

Because our kids do not make cortisol themselves in the same way as normal kids--continuously and at the right rate for the time of day, this means that at one point in that 6-8 hour period on conventional dosing their levels of cortisol are high than at the other end before the next dose they are low to non-existent in some cases.    There unfortunately is no other way to keep it as steady as it is in that chart in normal folks without a drip and cortisol being continually administered at small amounts.  

Consequently, I beleive that their GH and other hormone release works differently to a normal childs.  Even dosing in the conventional way, I am sure you will realise that compared to the above it is very primitive.  Each dose during the day is doing the same really.  High at one part and lower at the other end.   The problem is, the night time one is not needed to be so high as what it is in conventional dosing and the whole conventional dosing thing needs to be tipped completely the other way around to get closer to it.   Circadian dosing  is the closest that we will ever get though without further medical intervention I would imagine. 

The whole point of circadian dosing is to recognise the fact that when we are not dosing similar to the way cortisol is produced , the parts where we over do this can cause side effects.   5-6 hours exposed to the highest dose of cortisol as opposed to the lower one needed is a big deal obviosly.  The only way that you can avoid that is by dosing at 3am instead of 10pm.   In fact the highest dose of cortisol is what they traditionally would give at 10pm  really and that is not the way it should be.  

We are not trying to be exact, but just to mimick things better and lessen the side-effects to our kids.  

3) That brings us the question of giving the dose when it is not needed. Upto midnight high doses of cortisol are not needed, but from that point on it is. So if the largest dose was given at 12midnight then by 1 am it has peaked in the system, which then starts to decrease. However by 3-4 am when the HPA axis is supposed to be in gear it is only 4 hours later and being as it is the largest dose I would think there are sufficient quantities to inhibit the ACTH to a level of over suppression.

You really are mixed up with the midnight thing.  Although it is active, your smaller dose at 5.30pm should have covered that and at some point it is bound to decline but atleast it is in an area of the day whereby there is not so much cotisol needed if it does.     The high doses are not needed at midnight though Sue.  Look on the chart for a normal persons cortisol levels.  They do not need high doses of cortisol until 3-4am when it peaks.  The point is is that it is some "6 hours" that you have given a very high dose to a child that didn;t even need that dose until 3am.  During that 6 hours they should have been at their lowest.  Because however, they had cortisol levels that were higher it suppresses GH I would imagine.  Someone needs to check this out in a study of some type, but we all know that cortisol suppresses GH.  That’s why our kids are shorter on average at the end of their growing period.  Most normal kids don’t have a surge of cortisol until 3-4am.  They are doing ALL their growing therefore in the period up to that compared to at other times of the day really.  Tissues and organs repair themselves better in a rested state and cells regenerate more in sleep.  Thats because of the conditions within the whole body allowing it.  Lowered cortisol fascilitates everything else being able to regenerate during the night when the body is rested.  So this regime really does mean that there are less side-effects because we know that high doses can stop these processes--side-effects such as poor wound healing and growth stunted.  Because you have given your lowest dose there at 5.30pm, it is less likely to cause problems than the larger dose your currently giving.  It also means that even if there IS some ACTH or 17 OHP there (more than ormal) then to be honest because the body is in deep sleep, it isn’t going to be as high as what it would be during the day if a child was not getting enough cortisol there.  The whole point is to just dose as Mother Nature intended and take advantage of less side-effects in every way and that includes exposure to androgens also.    

4) The time period between this HPA axis and waking is where I am totally confused.  If the HPA axis starts acting at 3-4 in ALL children but the cortisol peak occurs only at waking  then then the time period could be anywhere between 3 -5 hours and this is definitely a LONG period in terms of cortisol excretion time.  My question is " Is it sufficient if the body has enough cortisol AT 3-4 am when the HPA axis is active and would that be sufficient to suppress further production of androgens and 17-OHP. Or does the HPA axis START becoming active at 4 am and continues to remain active until the early morning surge is satisfied ? It is active all the time on and off but we cannot mimick that exactly without going to the extremes above as I said.  The best that we can do is just curdely mimick it and beleive me it is crude what we are doing dosing some 4-6 hours apart---EVEN--with the circadian dosing.  But the whole point is that it is far more closer than the conventioanl dosing when you look at the logical repercussions of dosing high amounts of cortisol when there should be low amounts and vice versa.  Like I said cortisol production works off a fast feedback loop and normally is probably released every few seconds to maintian the levels it is at.  We cannot possibly do that.  One thing is for sure though, we can certainly try to get the "measure for measure" right where dosage at certain times of day is concerned.  Of course when a child is ill, we need to make the doses more equal and regular, but apart from that, when a CAH child is well, all they need is what they would nromally make but for this deficiency or as near as we can get it on a 4-6 hourly basis.   e surely the late night dose will not stay in the body and BETWEEN 3 am and "waking time" the HPA axis will cause more ACTH secretion and in turn more androgens and 17-ohp since cortisol is low. However if the HPA axis goes into gear at say 3 am and at THAT point the hypothalamus senses enough cortisol to inhibit excessive ACTH secretion then we can overcome the androgen issue. And then upon waking if not enough cortisol in given immediately it could cause the ACTH to act again. That is how it normally works all the time but on a constant basis.  So it is constantly active at night but producing much much less because we are rested and when we are active it meets that demand too.  Can this scenario be a possibility ?  Looking at the graphs it seems that cortisol starts to rise at midnight and peaks at waking, so if the maximum need of cortisol upon waking is met and the dose given at midnight that will peak at 1 or so is large and sufficient enough to meet the slightly increasing need then the ACTH be adequately suppressed. Of course, this is only if the body does an internal check mechanism at 3am and then does a recheck at waking. Any ideas as to how this mechanism precisely works.

5) In my daughter’s case I have been doing the thrice daily with largest dose at night for 9 months now. In the beginning she was gaining 2 pounds a month and also growing well but certainly looks chubby and round. I was convinced she is oversuppressed and a lot of physicians who looked at her felt the same. Her levels after the Feb level of 434ng/dl went to 19ng/dl and now it is at 10ng/dl.  Her blood work is always done 3 hours after morning meds at 7am.  Now she is less round since I weaned her and she is mobile too . My question is , if she was oversuppressed as her levels seem to indicate then how did that happen if I was dosing her at 11 pm and then again at 7 am. That brings me to my second question, so if she was undersuppressed because of her dosing time and if 17-oHP was produced in abundance how long does it stay in the system. Will giving the morning dose at 7 am and doing the test 3 hours after, flush the 17-ohp out and give a false picture of oversuppression wherein actually androgens are being made and metabolised between 4am and 7 am. Is this technically possible.

There are less of these side-effects when you dose in a more natural way.

I will let other’s answer you lower questions apart from the fact that any exposure to androgens even at night will cause clitoral tissue to change in size on a gradual basis.  I think though that you are benefited by this regime in that sense and there will be less chance for that to occur if you switch.  There is an Endo here in NZ that has been dosing two of his girls this way for a year or two to avoid that androgen exposure from 3-4am.  Maybe other’s will be best to answer some of your questions though.  i think you have done well considering that many of us only stumbed on such sites when our children had had some considerable side-effects already.  You can look forwards to avoiding those things much ealier, and will do ok I feel.  The growth issue is something that we all obsess about and I do sometimes wish I had done this a lot sooner and researched instead of accepting all answers from the Doctor as gospel.  Common sense theories are probably worth more than anything they trained hard to get really.  All the questions I evr had never had the correct answer, though I would say here, they probably thought at the time that it was the right answer.  Things have moved on really in that sense--though I wish they would do more studies with cortisol and GH in these children to prove some of these theories.   

6) I’m so lost as to what is the correct way to know what’s going on. Our ped endo says the growth chart is where he will look first and then the blood work. We are of Asian origin, my husband is 5’10’’ and I am 5’4’’, so the growth chart, meant mainly for Caucasian children is not going to be an accurate predictor in terms of percentile and because in the first year children grow in spurts sometimes she goes up and other times she is down, but since birth in 9 months she has grown 9 inches approx.Is that considered a good amount of growth ?

7) Lastly, I’m petrified that her clitoris will continue to grow if she is undersuppressed and everytime I change her I imagine that it has grown some. This is so traumatic for me.

I really appreciate all your comments and suggestions.

Thanks