Cortisol is at it’s lowest at midnight and stays that way until around 3-4am where it starts to climb.  Giving a pill at 3am means you get the peak around half an hour to an hour after ingestion.  After that it decreases in the blood serum.  However, a dose of 5mg is a considerable dose at 3am in the morning if you consider that the body is rested.  It says in the bio-availability abstract that cortisol is excreted more slowly during the night.  Takes around an hour longer.  So effectively there is still traces of the 3am dose in the system at 7am.  Around 7-8am  is where the largest peak of cortisol usually occurs within a whole 24 hour period.  On this dosing, the last dose before they go to sleep is 5.30pm.  It is being taken when they are winding down and just before bedtime.  It therefore sees them through and effectively, would be getting very low by 12 midnight.  However, due to the fact that there is little call for cortisol at that time, what little there is I would imagine covers a child.  There is no activity at 12 midnight, so therefore there is not call for cortisol.  At that point the body is in a very deep state of sleep so even if the hypothalmus did sense a lowered amount Sue, the amount of 17 OHP made before the 3am dose would  be far less than what would be made if you gave the largest dose at 10pm and it wore off at around 3-4am.  that is because at 3-4 am the hypothalmic-pituitary-adrenal axis is far more active than it is at midnight.  Which means you need the steroid there not at 10pm. 

The article is referring to 17 OHP levels which are made after 3-4am in kids on late night dosing.  The fact that they start to make too much 17 OHP after that time proves that the late dosing at 10pm is not adequate enough to cover the children, and in fact given at that time is of little use where suppressing the HPA axis is concerned from 3am where it is really needed.

If you look at the diagram for 17 OHP you will see that the levels start to climb at 4am.  This indicates that at that time the HPA became active and ACTH, and then 17 OHP was released, which is where the child would have made cortisol.  So the trick is to dose the cortisol as per the demand.  Because it takes an hour to peak, this means giving the hydrocortisone at 3am so that it can firstly stop problems occuring, but mainly so that whatever you give is beneficial and is not having to deal with an accumulation of 17 OHP levels before it can start to work for the child and peak when it should.  

Have you changed the timing of your daughters blood tests.  Also what are those readings in?  Nmol/L or ng/dl?   If the levels are ng/dl she is within the ranges.  if they are nmol/L she is out of control.  That is where the 454 result is concerned.  If you have done her last few blood tests after a morning dose, this is in the blood serum when they take her levels and can make it look like she is over treated.  If she has not had her med’s since 10pm and the result is 10 (ng/dl) it is very low and have you altered the night time dose at all?  Or is it the same and the other lower?