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 ?

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 ???

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.

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 ? In which case 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. 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.

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