Re: Spironolactone effect at the CYP11B2/CYP11B1 Gene level in Channel 8

[Guest guest]

I will get that paper for you, , but couldn't get into the system yesterday and haven't tried yet today.

On cortisol, that doesn't always mean it will increase for everyone on spiro. Many have had very high aldosterone levels yet say they never had a low potassium (I surmise more did,. but the doc acted like all their labs were "normal" and/or ignored a borderline K or it was done wrong). Yet science says they should lose K.

I bet most Americans right now have high cortisols. Illness alone raises cortisol, independent of meds. So unless most have before and afters, it would be hard to say whether cortisol is high or not due to spiro. They must have factored that in a study like yours. But with the side effects anyway whats the debate for you as I wouldn't use it if I could get the epe.

Most seem to report less anxiety on spiro - again I think it 1. an answer to the problem so cortisol drops and 2. treating the HTN as the likely reason anxiety is less,....oh, but when that booby pain hits cortisol has to go up!

In theory, alot of the meds many of us are on/have been on affect some system. The SSRI's studied - prozac especially have been found to raise cortisol through blocking the negative feedback loop. It is assumed other likely do that to. So an SSRI would also be the wrong med for you too with that effect. But for many they relieve the symptoms related to depression and anxiety(in studies I mean). But the debate is still out on the SSRI's (not in my mind as I hate them and think they are bigger scams than anything ever done to us by big pharm). SSRI's are known to significantly raise cortisol in some very high, which greatly also reduces testosterone, which SSRI's do anyway, thus the advent of viagra came about the same time as prozac and especially zoloft.

It is a stressful time to many ere in our country, akin to the great depression. Just the stress of the illness could also likely raise cortisol in ALOT of us. I looked at my last labs before spiro and mine was high. Not bad, but high. And while I have said depression is not my thing, thank goodness.....anxiety sure can be But.......in chronic stress and anxiety cortisol is supposed to be a protective mechanism.

From: <jclark24p@...>Subject: Spironolactone effect at the CYP11B2/CYP11B1 Gene level in Channel 8hyperaldosteronism Date: Saturday, May 5, 2012, 11:14 PM

Dr. Grim, I am going to explain this one last time so read the whole post.Spironolactone antagonizes androgen causing a reduction (or elimination, I'm not sure) at the CYP11B2 gene. This process allows cortisol, which is CYP11B1, the gene next door to increase. This is all happening on channel 8.If you are producing excess cortisol for whtever reason you already have excess cortisol (CYP11B1). If you then apply the effects of spironolactone and antagonize androgen (CYP11B2) you increase cortisol (CYP11B1) even more (I call it a "double whammy"!)This is why NIH thought Spironolactone was the wrong medicine for me. This is why I would suggest Spironolactone is poor choice for anyone showing signs of excess cortisol. (Actually this is why I advocate proper testing and treating appropriately!)If anyone doesn't know what cortisol does, think "fight or flight" and depression compounds the problem.....

[Guest guest]

I am going to work on this summary as this does not really flow right somehow.'Here was our take on the aldo cortisol issue in African Americans from our 2007 article (attached). My current Ho is that AAs are descended and selective survivors of stresses from sodium intake and output during the slavery period of Hx. This genotype seems to possess better than average ability to retain (store) salt in a high salt environment. The failure to decrease aldo with high sodium intake leads to the high blood pressure. The increase in BP with salt loading is inherited based on our twin studies in blacks and whites. When sodium loaded both W and B lose K from the body. If the K is replaced as it is lost the BP does not increase. Prob one reason the DASH works so well but esp well in AAs. The higher cortisol and perhaps aldo may be related to the psychosocial stress exposure in todays society. Repeated busts of ACTH. I we could easiily measrue the cortisol/ACTH ratio as a screening test for automous adrenal cortisol production. Not one seems to have every done that. These observations raise a question about the stimulus forelevated plasma aldosterone and salivary cortisol concentrationsin the hypertensive subjects and about the potentialphysiological relationship of these steroids to hypertensionand the metabolic syndrome. Plasma and urine potassium didnot differ in normotensive and hypertensive subjects. Althoughadrenocorticotropic hormone (corticotropin [ACTH])may acutely stimulate aldosterone secretion, long-term sustainedelevations of ACTH do not.33,34 In the present study,there was no correlation between plasma aldosterone andsalivary cortisol, albeit measured at different times. However,we cannot exclude the possibility that elevations of aldosteroneand cortisol in the hypertensive subjects may be relatedto small variations of ACTH. Alternatively, genetic variationin the 2 closely related genes encoding for the 2 late pathwaysteroidogenic enzymes, 11 hydroxylase (CYP11B1) andaldosterone synthase (CYP11B2), may result in an increase incortisol and aldosterone production, respectively, independentof external regulators, such as angiotensin II, potassium,and ACTH.35It is also possible that the higher plasma aldosteroneconcentrations in hypertensive subjects and in subjects withthe metabolic syndrome are in some way related to theassociation of aldosterone with waist circumference. Freefatty acids released from visceral adipose tissue have beenshown to stimulate aldosterone production,36 perhaps to agreater extent in blacks than in whites.37 Alternatively, insulinhas been reported to stimulate aldosterone secretion in vitroand in experimental animals.38,39 Consistent with previousreports, we observed that centripetal obesity is associatedwith insulin resistance and hyperinsulinemia. Overall, plasmaaldosterone was correlated with plasma insulin and insulinresistance. Taken together, these data are consistent with thehypothesis that the elevated insulin levels or other adipokinesin individuals with centripetal obesity function as a secretagoguefor aldosterone.

Will get back with you. Will be very interested in your NIH results and what they will recommend. I have sent Dr. Stratkis an email about our site and would hope maybe the might be interested in helping us with a good database.On May 5, 2012, at 11:14 PM, wrote: Dr. Grim, I am going to explain this one last time so read the whole post. Spironolactone antagonizes androgen causing a reduction (or elimination, I'm not sure) at the CYP11B2 gene. This process allows cortisol, which is CYP11B1, the gene next door to increase. This is all happening on channel 8. If you are producing excess cortisol for whtever reason you already have excess cortisol (CYP11B1). If you then apply the effects of spironolactone and antagonize androgen (CYP11B2) you increase cortisol (CYP11B1) even more (I call it a "double whammy"!) This is why NIH thought Spironolactone was the wrong medicine for me. This is why I would suggest Spironolactone is poor choice for anyone showing signs of excess cortisol. (Actually this is why I advocate proper testing and treating appropriately!) If anyone doesn't know what cortisol does, think "fight or flight" and depression compounds the problem. ....

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Kidambi Adrenal Steroids AA 2007.pdf

[Guest guest]

It is protective in the short run but damaging over time.CE Grim MDOn May 6, 2012, at 3:05 AM, Bingham wrote: I will get that paper for you, , but couldn't get into the system yesterday and haven't tried yet today. On cortisol, that doesn't always mean it will increase for everyone on spiro. Many have had very high aldosterone levels yet say they never had a low potassium (I surmise more did,. but the doc acted like all their labs were "normal" and/or ignored a borderline K or it was done wrong). Yet science says they should lose K. I bet most Americans right now have high cortisols. Illness alone raises cortisol, independent of meds. So unless most have before and afters, it would be hard to say whether cortisol is high or not due to spiro. They must have factored that in a study like yours. But with the side effects anyway whats the debate for you as I wouldn't use it if I could get the epe. Most seem to report less anxiety on spiro - again I think it 1. an answer to the problem so cortisol drops and 2. treating the HTN as the likely reason anxiety is less,....oh, but when that booby pain hits cortisol has to go up! In theory, alot of the meds many of us are on/have been on affect some system. The SSRI's studied - prozac especially have been found to raise cortisol through blocking the negative feedback loop. It is assumed other likely do that to. So an SSRI would also be the wrong med for you too with that effect. But for many they relieve the symptoms related to depression and anxiety(in studies I mean). But the debate is still out on the SSRI's (not in my mind as I hate them and think they are bigger scams than anything ever done to us by big pharm). SSRI's are known to significantly raise cortisol in some very high, which greatly also reduces testosterone, which SSRI's do anyway, thus the advent of viagra came about the same time as prozac and especially zoloft. It is a stressful time to many ere in our country, akin to the great depression. Just the stress of the illness could also likely raise cortisol in ALOT of us. I looked at my last labs before spiro and mine was high. Not bad, but high. And while I have said depression is not my thing, thank goodness.....anxiety sure can be But.......in chronic stress and anxiety cortisol is supposed to be a protective mechanism. From: <jclark24p@...>Subject: Spironolactone effect at the CYP11B2/CYP11B1 Gene level in Channel 8hyperaldosteronism Date: Saturday, May 5, 2012, 11:14 PM Dr. Grim, I am going to explain this one last time so read the whole post.Spironolactone antagonizes androgen causing a reduction (or elimination, I'm not sure) at the CYP11B2 gene. This process allows cortisol, which is CYP11B1, the gene next door to increase. This is all happening on channel 8.If you are producing excess cortisol for whtever reason you already have excess cortisol (CYP11B1). If you then apply the effects of spironolactone and antagonize androgen (CYP11B2) you increase cortisol (CYP11B1) even more (I call it a "double whammy"!)This is why NIH thought Spironolactone was the wrong medicine for me. This is why I would suggest Spironolactone is poor choice for anyone showing signs of excess cortisol. (Actually this is why I advocate proper testing and treating appropriately!)If anyone doesn't know what cortisol does, think "fight or flight" and depression compounds the problem.....

[Guest guest]

It will be interesting if Dr. Stratakis can help you. I signed many psges of

confidentially pages. (Their promises to me, not me to them!) Also, his

current research appears to be in a very specific area but he may be into

something else or know someone who is.

>

> > Dr. Grim, I am going to explain this one last time so read the whole

> > post.

> >

> > Spironolactone antagonizes androgen causing a reduction (or

> > elimination, I'm not sure) at the CYP11B2 gene. This process allows

> > cortisol, which is CYP11B1, the gene next door to increase. This is

> > all happening on channel 8.

> >

> > If you are producing excess cortisol for whtever reason you already

> > have excess cortisol (CYP11B1). If you then apply the effects of

> > spironolactone and antagonize androgen (CYP11B2) you increase

> > cortisol (CYP11B1) even more (I call it a " double whammy " !)

> >

> > This is why NIH thought Spironolactone was the wrong medicine for

> > me. This is why I would suggest Spironolactone is poor choice for

> > anyone showing signs of excess cortisol. (Actually this is why I

> > advocate proper testing and treating appropriately!)

> >

> > If anyone doesn't know what cortisol does, think " fight or flight "

> > and depression compounds the problem.

> >

> > ....

> >

> >

>

[Guest guest]

I suggested I can help her team as well. Stressed the lack of a discussion that for aldo to do its damage it must be accompanied by a high salt diet.CE Grim MDOn May 6, 2012, at 12:24 PM, wrote: It will be interesting if Dr. Stratakis can help you. I signed many psges of confidentially pages. (Their promises to me, not me to them!) Also, his current research appears to be in a very specific area but he may be into something else or know someone who is. > > > Dr. Grim, I am going to explain this one last time so read the whole > > post. > > > > Spironolactone antagonizes androgen causing a reduction (or > > elimination, I'm not sure) at the CYP11B2 gene. This process allows > > cortisol, which is CYP11B1, the gene next door to increase. This is > > all happening on channel 8. > > > > If you are producing excess cortisol for whtever reason you already > > have excess cortisol (CYP11B1). If you then apply the effects of > > spironolactone and antagonize androgen (CYP11B2) you increase > > cortisol (CYP11B1) even more (I call it a "double whammy"!) > > > > This is why NIH thought Spironolactone was the wrong medicine for > > me. This is why I would suggest Spironolactone is poor choice for > > anyone showing signs of excess cortisol. (Actually this is why I > > advocate proper testing and treating appropriately!) > > > > If anyone doesn't know what cortisol does, think "fight or flight" > > and depression compounds the problem. > > > > .... > > > > >

[Guest guest]

You probably could but you will probably loose your creditabilty if you start by

advocating Spironolactone and invalidting further testing, IMHO!

> > >

> > > > Dr. Grim, I am going to explain this one last time so read the

> > whole

> > > > post.

> > > >

> > > > Spironolactone antagonizes androgen causing a reduction (or

> > > > elimination, I'm not sure) at the CYP11B2 gene. This process

> > allows

> > > > cortisol, which is CYP11B1, the gene next door to increase. This

> > is

> > > > all happening on channel 8.

> > > >

> > > > If you are producing excess cortisol for whtever reason you

> > already

> > > > have excess cortisol (CYP11B1). If you then apply the effects of

> > > > spironolactone and antagonize androgen (CYP11B2) you increase

> > > > cortisol (CYP11B1) even more (I call it a " double whammy " !)

> > > >

> > > > This is why NIH thought Spironolactone was the wrong medicine for

> > > > me. This is why I would suggest Spironolactone is poor choice for

> > > > anyone showing signs of excess cortisol. (Actually this is why I

> > > > advocate proper testing and treating appropriately!)

> > > >

> > > > If anyone doesn't know what cortisol does, think " fight or flight "

> > > > and depression compounds the problem.

> > > >

> > > > ....

> > > >

> > > >

> > >

> >

> >

>