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Confused about CAHs

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CBG23

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So I am confused two of the three Congential Adrenal Hyperplasias: 11B-hydroxylase deficiency and 17a-hydroxylase deficiency.

- Why do patients with 11B-hydroxylase deficiency have supranormal mineralocorticoid activity?

The books I've looked at site the increase in 11-Deoxycorticosterone (DOC) as the reason, while other sources say that DOC just has minor mineralocorticoid activity. If we don't have 11B-hydroxylase, we can't make corticosteron, which means that we can't make Aldosterone. If we are making little to no aldosterone (the major mineralocorticoid), how does an increase in a minor mineralocorticoid more than make up for it?

- Why do patients with 17a-hydroxylase deficiency have supranormal mineralocorticoid activity but decreased glucocorticoid activity?

If increased DOC is enough to make up for a lack of aldosterone, why isn't the increase corticosterone in this syndrome enough to make up for the lack of cortisol. Costanzo's physio text, Guyton, and Kaplan's lecture notes all mention Corticosterone as a weak glucocorticoid just as DOC is a weak mineralocorticoid. At one point in Cotanzo's text, she even mention that Corticosterone can substitute for cortisol when cortisol is deficient. But even though these patients make an excess of corticosterone, they still have reduced glucocorticoid activity!

So, is Costanzo wrong? Why do these sources bother mentioning the weak glucocorticoid activity of corticosterone if it can't make up for lost cortisol activity (as DOC can make up for lost Aldosterone activity)?
Last edited by CBG23; 03-18-2011 at 10:39 PM.
 

RySerr21

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So I am confused two of the three Congential Adrenal Hyperplasias: 11B-hydroxylase deficiency and 17a-hydroxylase deficiency.

- Why do patients with 11B-hydroxylase deficiency have supranormal mineralocorticoid activity?

The books I've looked at site the increase in 11-Deoxycorticosterone (DOC) as the reason, while other sources say that DOC just has minor mineralocorticoid activity. If we don't have 11B-hydroxylase, we can't make corticosteron, which means that we can't make Aldosterone. If we are making little to no aldosterone (the major mineralocorticoid), how does an increase in a minor mineralocorticoid more than make up for it?

- Why do patients with 17a-hydroxylase deficiency have supranormal mineralocorticoid activity but decreased glucocorticoid activity?

If increased DOC is enough to make up for a lack of aldosterone, why isn't the increase corticosterone in this syndrome enough to make up for the lack of cortisol. Costanzo's physio text, Guyton, and Kaplan's lecture notes all mention Corticosterone as a weak glucocorticoid just as DOC is a weak mineralocorticoid. At one point in Cotanzo's text, she even mention that Corticosterone can substitute for cortisol when cortisol is deficient. But even though these patients make an excess of corticosterone, they still have reduced glucocorticoid activity!

So, is Costanzo wrong? Why do these sources bother mentioning the weak glucocorticoid activity of corticosterone if it can't make up for lost cortisol activity (as DOC can make up for lost Aldosterone activity)?
Last edited by CBG23; 03-18-2011 at 10:39 PM.


levels of 11-DOC are pretty low in a healthy person. With a 11BH deficiency, the pt has low aldosterone/cortisol, so the body is probably continously trying to make it. B/c it cant, you get really high levels of 11-DOC and the other products before the block. I guess even a 'weak mineralocorticoid' at really high levels will have a strong enough effect.



To answer your last question, i have no clue. I looked up in a few sources trying to find the actions of corticosterone and the best explanation i could find was on uptodate.... it menntioned that the corticosterone levels do offset the lack of cortisone somewhat, reducing the symptoms you would normally see. Buuut for somereason its not enough to completely make up for the lack of cortisol...

"Although sufficient cortisol is not produced, large quantities of corticosterone (a steroid with both glucocorticoid and mineralocorticoid activities) are synthesized, reducing the symptoms associated with cortisol deficiency."


Seems like one of those things you just have to memorize and move on :confused:
 

gravitywave

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Costanzo's physio text, Guyton, and Kaplan's lecture notes all mention Corticosterone as a weak glucocorticoid just as DOC is a weak mineralocorticoid.

i like RySerr's answers. to add to them, i think maybe this is where you're getting tripped up. DOC is a weak mineralocorticoid that will blunt the effect of no aldosterone if present in large enough amounts. in a similar but not identical fashion, corticosterone will mask a cortisol deficiency. the pharmacodynamics of these two interactions could be quite different, however. corticosterone only binds glucocorticoid receptors with 1/100th the affinity that cortisol does.

also, i'd imagine that even though corticosterone does have a minor effect on glucocorticoid receptors, it's probably not present at the same levels that you'd see for 11-DOC in CYP11B1 deficiency, as here the aldosterone pathway is still functional and so a lot of the excess will be transformed into mineralocorticoid.
 
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