Re: Update (Spiro effect on MDD)

[Guest guest]

Hi Barb, here is the info in response to your questions 2 and 3. These are the

two studies I asked my Psycho Docs to review and tell me what is going on. You

might be a better resource for me! Thanks.

Source: http://archpsyc.ama-assn.org/cgi/content/full/60/1/24

Mineralocorticoid Receptor Function in Major Depression

In this study I found this: Results Spironolactone treatment resulted in a

significant increase in cortisol secretion levels in both groups. Depressed

patients demonstrated higher cortisol secretion levels than control subjects. In

addition, depressed patients demonstrated a different pattern of increase in

cortisol secretion levels after spironolactone administration. Furthermore, a

significant effect of spironolactone treatment on corticotropin secretion levels

can be observed in depressed patients, whereas controls show no such effect.

Conclusions Despite high baseline cortisol levels, patients with major

depression show high functional activity of the MR system. Paired with the body

of evidence regarding decreased sensitivity to GR agonists, these data suggest

an imbalance in the MR/GR ratio. The balance of MR and GR is known to affect

brain serotonin systems and may play an etiologic role in serotonin receptor

changes observed in patients with major depression.

This caused me to think I needed to understand something about Cortisol but I'm

starting to think I have created a tug-of-war with spironolactone increasing

serotonin through the above action while cymbalta is trying to reduce it !

I then went here to see if I could determine the " how " and that is when CYP11B1

and CYP11B2 came into play and I got lost! I think the key is in sections IX

and X but I was sort of like puppy chasing his tail trying to figure it out!

Source: http://edrv.endojournals.org/content/29/2/133.long#xref-ref-201-1

A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation

of Aldosterone Production for Cardiovascular Function

All help gretly appreciated so I can keep my psycho docs honest!

- 65 yo super ob., fastidious male - 12mm X 13mm rt. a.adnoma with

previous rt. flank pain. Treating with DASH. Stats w/o meds = BP 175/90 HR 59

BS 125. D/C Spironolactone 12/20/2011 due to adverse SX.

Other Issues/Opportunities: OSA w Bi-Pap settings 13/19, DM2, Gynecomastia, MDD

and PTSD.

Meds: Duloxetine hcl 80 MG, Metoprolol Tartrate 200 MG, AmlodipineBesylate

5mg, 81mg aspirin and Metformin 2000MG. Started washing Spironolactone 12/20/11

to prepare for AVS.

> >

> > Briefly, my adrenal history includes a right adenoma dx'd in 2000 and a

left adenoma dx'd in 2009 and drug-resistant HTN for 25 years. My right renal

artery is 70% stenosed (US dx) and the right kidney is atrophic. I had some

basic lab work done 2 weeks ago. Aldosterone was 25 (high). Renin 9.3 (high

normal). Started Spiro 25mg daily after labs were drawn. I have been on the

Spiro for 2 weeks now. After one dose, the brain fog lifted, my lungs were much

more clear, the trace LE peripheral edema started to diminish and my blood

pressure began to decrease.

> >

> > The second week on Spiro, I felt generally horrible and my BPs were

improving but not good. At the end of the second week, BP normalizing and K+

maintained on 20mEq BID (had been taking 40 BID and supplementing when the low

K+ PVCs cycled in - usually 160mEq over 24 hrs). The sum: I am feeling much

better.

> >

> > I was referred to endo. Saw him today. Super doc with a great big brain.

He says there is so much going on with me, now and historically, he is not sure

if it is primary or secondary aldosteronism because of the renal artery stenosis

or the long-term NSAID therapy (800mg BID for the issues with my lumbar

vertebrae and left hip). Based on the numbers and diagnostics, he is leaning

toward secondary. He ordered labs to check for Pheo, Cushing's, etc., and I will

see him in one month. He also wants a repeat CT because the last one was 3 years

ago. I won't do that until Medicare kicks in July 1. He's okay with that.

> >

> > He said it was up to me if I wanted to purge the drugs, do a salt loading

and then retest. He also said he would refer me to a university setting for an

AVS if I wanted a definitive diagnosis. The way I view it... I am 65, retired,

and Spiro is working. Kind of a no brainer.

> >

> > Any thoughts?

> >

> > Barb

> >

>

[Guest guest]

Are you stereotyping depressed people? I wonder if they can do a 24h urine

collection correctly! I'm not sure that looking up info on cortisol and aldo in

blacks would be helpful, I'm little fair skinned for that and there must be

reason you were exclusively targetting blacks. Is it possibly the difference in

the way they process salt?

I simply was reading two studies and saw where spiro affected cortisol and

increased cortisol affected depressed ppl differently. I am still expecting an

answer from my Psychiatrist. When Barb gave me some other info it was obvious

she is knowledgable and she offered to look into it. Who knows, we both might

learn something!

Although I am off spiro, I'm still wondering why my treatment went awry. I

still think there should be a decision tree and maybe we can determine some

individuls that would be better off skipping directly to eplerenone, I quoted

one the other day - " children " . (Maybe a better measure would be age!) Who

knows, more might be willing to take the meds/DASH route and have success if we

moved it up to the 21st century!

.....

> > > >

> > > > Briefly, my adrenal history includes a right adenoma dx'd in 2000 and a

left adenoma dx'd in 2009 and drug-resistant HTN for 25 years. My right renal

artery is 70% stenosed (US dx) and the right kidney is atrophic. I had some

basic lab work done 2 weeks ago. Aldosterone was 25 (high). Renin 9.3 (high

normal). Started Spiro 25mg daily after labs were drawn. I have been on the

Spiro for 2 weeks now. After one dose, the brain fog lifted, my lungs were much

more clear, the trace LE peripheral edema started to diminish and my blood

pressure began to decrease.

> > > >

> > > > The second week on Spiro, I felt generally horrible and my BPs were

improving but not good. At the end of the second week, BP normalizing and K+

maintained on 20mEq BID (had been taking 40 BID and supplementing when the low

K+ PVCs cycled in - usually 160mEq over 24 hrs). The sum: I am feeling much

better.

> > > >

> > > > I was referred to endo. Saw him today. Super doc with a great big brain.

He says there is so much going on with me, now and historically, he is not sure

if it is primary or secondary aldosteronism because of the renal artery stenosis

or the long-term NSAID therapy (800mg BID for the issues with my lumbar

vertebrae and left hip). Based on the numbers and diagnostics, he is leaning

toward secondary. He ordered labs to check for Pheo, Cushing's, etc., and I will

see him in one month. He also wants a repeat CT because the last one was 3 years

ago. I won't do that until Medicare kicks in July 1. He's okay with that.

> > > >

> > > > He said it was up to me if I wanted to purge the drugs, do a salt

loading and then retest. He also said he would refer me to a university setting

for an AVS if I wanted a definitive diagnosis. The way I view it... I am 65,

retired, and Spiro is working. Kind of a no brainer.

> > > >

> > > > Any thoughts?

> > > >

> > > > Barb

> > > >

> > >

> >

> >

> > Reply to sender | Reply to group | Reply via web post | Start a New Topic

> > Messages in this topic (110)

> > RECENT ACTIVITY: New Files 1

> > Visit Your Group

>

[Guest guest]

I didn't know that I had to validate the study too, I thought that was why we

used Pubmed. The article I quoted was published in " Arch Gen Psychiatry.

2003;60:24-28 " so it has had 9 years to be reviewed and challenged by

professionls, I doubt I could add anything!

To validate it I referred it to my treating professionls. Dr. Bolton has

professor status at the University of Vermont (UVM) and she was going to the

library to see if there was any more info in the last 9 years. I expect to hear

back later this month.

I simply found a study that indicated that treatment with spironolactone caused

an increase in cortisol. Then I found another study that while the increase was

not a problem in " normals " , it increased serotonin in PTNs with MDD. Wouldn't

it be nice to know this in advance? Maybe there is another medicine, on either

side of the conflict, that would eliminte this problem. If not, maybe we need

to increase the SSRI or find something that reduces cortisol. (And at the

minimum the left hand should know what the right hand is doing!)

Don't worry about me, I eliminated the potential problem on Dec. 20th and hope I

don't have to see how it works with epleremone! :>)

....

> > > > > >

> > > > > > Briefly, my adrenal history includes a right adenoma dx'd in

> > 2000 and a left adenoma dx'd in 2009 and drug-resistant HTN for 25

> > years. My right renal artery is 70% stenosed (US dx) and the right

> > kidney is atrophic. I had some basic lab work done 2 weeks ago.

> > Aldosterone was 25 (high). Renin 9.3 (high normal). Started Spiro

> > 25mg daily after labs were drawn. I have been on the Spiro for 2

> > weeks now. After one dose, the brain fog lifted, my lungs were much

> > more clear, the trace LE peripheral edema started to diminish and my

> > blood pressure began to decrease.

> > > > > >

> > > > > > The second week on Spiro, I felt generally horrible and my

> > BPs were improving but not good. At the end of the second week, BP

> > normalizing and K+ maintained on 20mEq BID (had been taking 40 BID

> > and supplementing when the low K+ PVCs cycled in - usually 160mEq

> > over 24 hrs). The sum: I am feeling much better.

> > > > > >

> > > > > > I was referred to endo. Saw him today. Super doc with a

> > great big brain. He says there is so much going on with me, now and

> > historically, he is not sure if it is primary or secondary

> > aldosteronism because of the renal artery stenosis or the long-term

> > NSAID therapy (800mg BID for the issues with my lumbar vertebrae and

> > left hip). Based on the numbers and diagnostics, he is leaning

> > toward secondary. He ordered labs to check for Pheo, Cushing's,

> > etc., and I will see him in one month. He also wants a repeat CT

> > because the last one was 3 years ago. I won't do that until Medicare

> > kicks in July 1. He's okay with that.

> > > > > >

> > > > > > He said it was up to me if I wanted to purge the drugs, do a

> > salt loading and then retest. He also said he would refer me to a

> > university setting for an AVS if I wanted a definitive diagnosis.

> > The way I view it... I am 65, retired, and Spiro is working. Kind of

> > a no brainer.

> > > > > >

> > > > > > Any thoughts?

> > > > > >

> > > > > > Barb

> > > > > >

> > > > >

> > > >

> > > >

> > > > Reply to sender | Reply to group | Reply via web post | Start a

> > New Topic

> > > > Messages in this topic (110)

> > > > RECENT ACTIVITY: New Files 1

> > > > Visit Your Group

> > >

> >

> >

>

[Guest guest]

I didn't know that I had to validate the study too, I thought that was why we

used Pubmed. The article I quoted was published in " Arch Gen Psychiatry.

2003;60:24-28 " so it has had 9 years to be reviewed and challenged by

professionls, I doubt I could add anything!

To validate it I referred it to my treating professionls. Dr. Bolton has

professor status at the University of Vermont (UVM) and she was going to the

library to see if there was any more info in the last 9 years. I expect to hear

back later this month.

I simply found a study that indicated that treatment with spironolactone caused

an increase in cortisol. Then I found another study that while the increase was

not a problem in " normals " , it increased serotonin in PTNs with MDD. Wouldn't

it be nice to know this in advance? Maybe there is another medicine, on either

side of the conflict, that would eliminte this problem. If not, maybe we need

to increase the SSRI or find something that reduces cortisol. (And at the

minimum the left hand should know what the right hand is doing!)

Don't worry about me, I eliminated the potential problem on Dec. 20th and hope I

don't have to see how it works with epleremone! :>)

....

> > > > > >

> > > > > > Briefly, my adrenal history includes a right adenoma dx'd in

> > 2000 and a left adenoma dx'd in 2009 and drug-resistant HTN for 25

> > years. My right renal artery is 70% stenosed (US dx) and the right

> > kidney is atrophic. I had some basic lab work done 2 weeks ago.

> > Aldosterone was 25 (high). Renin 9.3 (high normal). Started Spiro

> > 25mg daily after labs were drawn. I have been on the Spiro for 2

> > weeks now. After one dose, the brain fog lifted, my lungs were much

> > more clear, the trace LE peripheral edema started to diminish and my

> > blood pressure began to decrease.

> > > > > >

> > > > > > The second week on Spiro, I felt generally horrible and my

> > BPs were improving but not good. At the end of the second week, BP

> > normalizing and K+ maintained on 20mEq BID (had been taking 40 BID

> > and supplementing when the low K+ PVCs cycled in - usually 160mEq

> > over 24 hrs). The sum: I am feeling much better.

> > > > > >

> > > > > > I was referred to endo. Saw him today. Super doc with a

> > great big brain. He says there is so much going on with me, now and

> > historically, he is not sure if it is primary or secondary

> > aldosteronism because of the renal artery stenosis or the long-term

> > NSAID therapy (800mg BID for the issues with my lumbar vertebrae and

> > left hip). Based on the numbers and diagnostics, he is leaning

> > toward secondary. He ordered labs to check for Pheo, Cushing's,

> > etc., and I will see him in one month. He also wants a repeat CT

> > because the last one was 3 years ago. I won't do that until Medicare

> > kicks in July 1. He's okay with that.

> > > > > >

> > > > > > He said it was up to me if I wanted to purge the drugs, do a

> > salt loading and then retest. He also said he would refer me to a

> > university setting for an AVS if I wanted a definitive diagnosis.

> > The way I view it... I am 65, retired, and Spiro is working. Kind of

> > a no brainer.

> > > > > >

> > > > > > Any thoughts?

> > > > > >

> > > > > > Barb

> > > > > >

> > > > >

> > > >

> > > >

> > > > Reply to sender | Reply to group | Reply via web post | Start a

> > New Topic

> > > > Messages in this topic (110)

> > > > RECENT ACTIVITY: New Files 1

> > > > Visit Your Group

> > >

> >

> >

>

[Guest guest]

I thought I was searching on ONE item, Cortisol. First I checked the effect

that Spironolactone had on cortisol and found it raised it (the CYP11B1/CYP11B2

effect). Then I checked the effect of increased cortisol in MDD and found it

increased serotonin. Knowing I was on a SNRI, Cymbalta, and knowing the " S " is

for Serotonin and the " I " is for Inhibitor I decided I should check the

relationship and referred it to my Psychiatry doctors. When Barb came online a

month ago I found she was knowledgable in this area and had worked with a very

prestigious doctor in Texas so I presumed she probably knew how to do it right!

(I figured he didn't get to the top of his field by surrounding himself with

mediocre associates!)

I missed the androgen/testosterone connection and don't plan to miss

cortisol/serotonin connection if I can help it! (I don't consider that I was

the only one, there were 7 doctors at the VA also!)

.....

> > > > > > > >

> > > > > > > > Briefly, my adrenal history includes a right adenoma

> > dx'd in

> > > > 2000 and a left adenoma dx'd in 2009 and drug-resistant HTN for 25

> > > > years. My right renal artery is 70% stenosed (US dx) and the right

> > > > kidney is atrophic. I had some basic lab work done 2 weeks ago.

> > > > Aldosterone was 25 (high). Renin 9.3 (high normal). Started Spiro

> > > > 25mg daily after labs were drawn. I have been on the Spiro for 2

> > > > weeks now. After one dose, the brain fog lifted, my lungs were

> > much

> > > > more clear, the trace LE peripheral edema started to diminish

> > and my

> > > > blood pressure began to decrease.

> > > > > > > >

> > > > > > > > The second week on Spiro, I felt generally horrible and my

> > > > BPs were improving but not good. At the end of the second week, BP

> > > > normalizing and K+ maintained on 20mEq BID (had been taking 40 BID

> > > > and supplementing when the low K+ PVCs cycled in - usually 160mEq

> > > > over 24 hrs). The sum: I am feeling much better.

> > > > > > > >

> > > > > > > > I was referred to endo. Saw him today. Super doc with a

> > > > great big brain. He says there is so much going on with me, now

> > and

> > > > historically, he is not sure if it is primary or secondary

> > > > aldosteronism because of the renal artery stenosis or the long-

> > term

> > > > NSAID therapy (800mg BID for the issues with my lumbar vertebrae

> > and

> > > > left hip). Based on the numbers and diagnostics, he is leaning

> > > > toward secondary. He ordered labs to check for Pheo, Cushing's,

> > > > etc., and I will see him in one month. He also wants a repeat CT

> > > > because the last one was 3 years ago. I won't do that until

> > Medicare

> > > > kicks in July 1. He's okay with that.

> > > > > > > >

> > > > > > > > He said it was up to me if I wanted to purge the drugs,

> > do a

> > > > salt loading and then retest. He also said he would refer me to a

> > > > university setting for an AVS if I wanted a definitive diagnosis.

> > > > The way I view it... I am 65, retired, and Spiro is working.

> > Kind of

> > > > a no brainer.

> > > > > > > >

> > > > > > > > Any thoughts?

> > > > > > > >

> > > > > > > > Barb

> > > > > > > >

> > > > > > >

> > > > > >

> > > > > >

> > > > > > Reply to sender | Reply to group | Reply via web post |

> > Start a

> > > > New Topic

> > > > > > Messages in this topic (110)

> > > > > > RECENT ACTIVITY: New Files 1

> > > > > > Visit Your Group

> > > > >

> > > >

> > > >

> > >

> >

> >

>

[Guest guest]

I would think a increase in cortisol would decrease stress. If this is the case

does decreasing stress increase depression?

> > > > > > > > >

> > > > > > > > > Briefly, my adrenal history includes a right adenoma

> > > dx'd in

> > > > > 2000 and a left adenoma dx'd in 2009 and drug-resistant HTN for 25

> > > > > years. My right renal artery is 70% stenosed (US dx) and the right

> > > > > kidney is atrophic. I had some basic lab work done 2 weeks ago.

> > > > > Aldosterone was 25 (high). Renin 9.3 (high normal). Started Spiro

> > > > > 25mg daily after labs were drawn. I have been on the Spiro for 2

> > > > > weeks now. After one dose, the brain fog lifted, my lungs were

> > > much

> > > > > more clear, the trace LE peripheral edema started to diminish

> > > and my

> > > > > blood pressure began to decrease.

> > > > > > > > >

> > > > > > > > > The second week on Spiro, I felt generally horrible and my

> > > > > BPs were improving but not good. At the end of the second week, BP

> > > > > normalizing and K+ maintained on 20mEq BID (had been taking 40 BID

> > > > > and supplementing when the low K+ PVCs cycled in - usually 160mEq

> > > > > over 24 hrs). The sum: I am feeling much better.

> > > > > > > > >

> > > > > > > > > I was referred to endo. Saw him today. Super doc with a

> > > > > great big brain. He says there is so much going on with me, now

> > > and

> > > > > historically, he is not sure if it is primary or secondary

> > > > > aldosteronism because of the renal artery stenosis or the long-

> > > term

> > > > > NSAID therapy (800mg BID for the issues with my lumbar vertebrae

> > > and

> > > > > left hip). Based on the numbers and diagnostics, he is leaning

> > > > > toward secondary. He ordered labs to check for Pheo, Cushing's,

> > > > > etc., and I will see him in one month. He also wants a repeat CT

> > > > > because the last one was 3 years ago. I won't do that until

> > > Medicare

> > > > > kicks in July 1. He's okay with that.

> > > > > > > > >

> > > > > > > > > He said it was up to me if I wanted to purge the drugs,

> > > do a

> > > > > salt loading and then retest. He also said he would refer me to a

> > > > > university setting for an AVS if I wanted a definitive diagnosis.

> > > > > The way I view it... I am 65, retired, and Spiro is working.

> > > Kind of

> > > > > a no brainer.

> > > > > > > > >

> > > > > > > > > Any thoughts?

> > > > > > > > >

> > > > > > > > > Barb

> > > > > > > > >

> > > > > > > >

> > > > > > >

> > > > > > >

> > > > > > > Reply to sender | Reply to group | Reply via web post |

> > > Start a

> > > > > New Topic

> > > > > > > Messages in this topic (110)

> > > > > > > RECENT ACTIVITY: New Files 1

> > > > > > > Visit Your Group

> > > > > >

> > > > >

> > > > >

> > > >

> > >

> > >

> >

>