1. If you look down the first pathway, this is the one concerning aldosterone production.   Cholesterol is converted to Pregnenolone with the enzyme Desmolase-->then with the aid of 3 beta dehydrogenase it is converted to Progesterone--> using  21 Hydroxylase it converts to Deoxycorticosterone-->using 11 Beta Hydroxylase it converts to Corticosterone---> then using 18-Hydroxylase it is converted to 18-OH Corticosterone.  Finally it then needs the enzyme18-Oxydase to convert it to aldosterone which is responsible for retaining sodium and is what florinef replaces.  Any of those enzymes within each step of the process being missing or affected would affect aldosterone production.  In 21-Hydroxylase deficiency it is 21 Hydroxylase and so on.

2. In children with total 21 Hydroxylase deficiency in both pathways the process can not get any further than Progesterone where making aldosterone is concerned.   In the case of cortisol, it is 17 OH Progesterone or 17 OHP.      They do not make aldosterone full stop.  If  a child has not got a total block  but nevertheless a substantial one where 21 Hydroxylase deficiency is concerned in both pathways,  then they would no doubt make "some" aldosterone but still not the required amount that they would normally make.  This then affects how much sodium is retained and means the electrolyte levels are never quite as they should be.    If  your child is diagnosed salt wasting at birth or diagnosis, either a partial or full deficiency, then they will always have that.  They will therefore always need replacement florinef as well as cortisol.  What determines the necessity for florinef is the lack of sodium retention and excess excretion in the urine.  A defiecient child will literally in some cases not be able to hold sodium at all and there will be very high levels of sodium in the urine.  The renin will be elevated.  Perhaps the progesterone levels are elevated too since as the process cannot continue any further due to lack of 21 Hydroxylase, it would then be released into the body as the incomplete hormone.  As the aldosterone levels are still not adequate though, the pituitary would sense that and signal the adrenals to make more aldosterone.  of course it will make more progesterone I would have thought.    Well I only assume this because if we apply the same theory where making cortisol is concerned and what is released there being 17 OHP as the incomplete hormone, you then get elevated production of adnrogens thereafter.  

3. Cortisol itself has some mineralocorticoid properties.  That is why when someone with non-salt wasting CAH does not get the right treatment, their renin show a problem, especially when sick or having a crisis.

4. Progesterone is a precursor for estrogens:     Progesterone is a steroid hormone made by the corpus luteum of the ovary at ovulation, and in smaller amounts by the adrenal glands.    Progesterone is manufactured in the body from the steroid hormone pregnenolone, and is a precursor to most of the other steroid hormones, including cortisol, androstenedione, the estrogens and testosterone.  Because progesterone is the precursor to so many other steroid hormones, its use can greatly enhance overall hormone balance after menopause. Progesterone also stimulates bone-building and thus helps protect against osteoporosis.  Hence the reason why it is possible during under treatment to not just advance bone growth, but that any low bone density is reversed.

           CONGENITAL ADRENAL HYPERPLASIA

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Enzymatic pathways for Cortisol and Aldosterone:

	Desmolase		17-alpha-Hydroxylase		C-17-Lyase
Cholesterol	--------------------->	Pregnenolone	----------------------->	17-oh-Pregnenolone	------------------->	Dehydroepiandrosterone
		|		|		|
	3-beta-oh-steroid dehydrogenase	|	3-beta-oh-steroid dehydrogenase	|	3-beta-oh-steroid dehydrogenase	|
		Progesterone		17-oh-Progesterone		Androstenedione
	21-Hydoxylase	|	21-Hydroxylase	|	Peripheral tissues	|
		Deoxycorticosterone		11-Deoxycortisol		Testosterone
	11-beta-Hydroxylase	|	11-beta-Hydoxylase	|
		Corticosterone		Cortisol
	18-Hydroxylase	|
		18-oh-Corticosterone
	18-Oxidase	|
		Aldosterone

 

Result of a 21-Hydroxylase Deficiency