Circadian rythym dosing is when you dose the child as close to the natural production of cortisol over a 24 hour period or normal sleep wakinh patterns.  For example, at night time cortisol levels are low in people who have normal functioning adrenal glands. They are at their highest  around 7am when we rise and then they slowly decline throughout the day until at midnight where they re said to be at their lowest.  At this time because cortisol is so low, hormones like HGH and other anabolics are higher genrally, and this is where healthy children with normal functioning adrenals would do most of their growing and where most injuries and tissue repair takes place also. So the question is why are we directed to give such a large dose of cortisol late at night when normally the levels should be low anyway to allow for growth?

At 3am the adrenals start to ramp up and make cortisol again.  So imagine giving a dose of steroid at 10pm. If your child metabolises cortisol quickly (it only lasts 6-8 hours in the blood--maybe 9 hours at night in some children-each child varies), then it is often very low by 3am and up to 7-8am where the next dose is due.  So technically there what should be happening is a rise in cortisol and instead it is rapidly declining.  This leaves the child exposed to higher than would be normal GH and anabolic hormones when ormally growth at this point would be slowing it is speeding up as those hormones creep higher.  In sharp contrast from 10am where most growth would take place due to the very low levels of cortisol, the hydrocortisone suppresses the GH hormones etc.   So in the first part of the evening the cortisol levels are too high and there is little to no growth. Then from 3am, the cortisol levels are quite low and there are lot’s if too many growth hormones for correct type or rate of growth and for the childs body.

So the only way around that is to gradually lower the cortisol dose during the day and stop at 5pm so that it can be lower, and then dose the next dose at 3am where it is really needed.  

I give Ashley 2.50mg at 5pm and then nothing until 3am and then he gets 5mg hydrocortisone. This mimicks where the proper peaks for cortisol manufacture are in a healthy CAH child. (When ill this may change). I then give him another boost of cortisol at 7am.

This has improved Ashleys growth patterns and he now follows the curve on the growth chart. More information about the way of dosing on PubMed in a study done over 15 years ago and then also in 2000 in the UK.

How does it affect weight?  If a child does not grow upwards much and has too much cortisol at certain times in the day for their needs then as we know they gain weight and look cushing.  How that works is if a childs cortisol levels are high last thing at night when they are asleep, they are missing the normal spurt of HGH and anabolic hormones which are helpful in muscle growth and we all know that muscle is important for metabolism.  If you lose muscle mas your metabolism slows.  Now the children are in very deep sleep with a high cortisol level which will catabolize muscle.  Not only this but they have high blood sugar and because they are not burning off the cortisol levels and making efficient use of it, any excess calories are stored as fat.  Fluid is stored in the tissues and they look puffy.  All this happens in what should be the deepest and most growth effcient part of sleep.  That is slow wave sleep. 

They say REM sleep often occurs after 3am and I feel it could be linked to when the adrenals start making cortisol.  So whilst a CAH child does get a dose of GH and other hormones there,  by that time, they have stored excess calories as fat and muscle has been catbolised and although it may be reversed to some extent for some children if their levels climb high enough, for some whom had too large a 10pm dose, this can often not take place at all or in very minimal amounts.  

So its far better to give small doses 3 to 4 times a day than to have large periods of exposure to both cortisol AND anabolic hormones.  Basically a normal healthy childs cortisol and anabolic hormone levels will be changing rapidly from one minute to the next dependant upon time of day, activity levels or stress levels etc.   The further that you get away from that (i.e. dosing every 12 hours) the more crude a growth pattern your going to effect.  The closer together those doses and smaller they are, the closer to natural they’ll appear to be for both cortisol and anabolic or growth hormones.  This coupled with giving them at the peak times in appropriate doses seems a more sensible approach.  Here are some links for more info:

   
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4076253&dopt=Abstract


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11600525&dopt=Abstract


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11994370&dopt=Abstract

Hope that helps,

Regards

Anne-Marie