High renin/aldosterone and norepinephrine? It’s backwards!

[Stacky]

I’ve been reading on here for like 5 hours and apparently have absorbed nothing.. 

First, I don’t have POTs... I mean, sometimes I do. But sometimes my heartrate is high while I lay down. And sometimes it doesn’t spike much when I stand. So... not POTs, but close. I also have very labile BP that tends to climb the longer I stand, but also sometimes doesn’t. And sometimes is high laying down! Yay!

Today I have high BP and my heartrate jumps over 30bpm when I stand. 

I also have very high renin and aldosterone, and a 24 hr urine catecholamine came back high for NE. Not tumor high. Just like regular high. 

No pheo, no renal artery stenosis, no fibromuscular dysplasia, no answers.

Blood work great. Lots of kidney stones. 

So for hyperadrenergic POTs, there’s hypovolemia, norepinephrine spillage, and low renin/aldo, right? 

Beta blockers usually work well? As do ARB’s or Ace inhibitors? SNRI’s? Beta blockers make my heartrate all crazy like with ups and downs but Corlanor does help lower it a little most days. Losartan helps with BP but doesn’t touch the spikes. They get as high as 180/130 on max dose. 

I can’t find a medication that works and now I have kidney disease and I’m so dang tired. I quit my job and sleep like 18 hours a day. I’m miserable. Can’t get into a study because it’s not real POTs, it’s innapropriate sinus tachycardia. My cardiologist told me to try eating breakfast. Like.... What? 

I would appreciate hearing the experiences of other members facing similar symptoms!

 

[haugr]

Couple of questions... What kidney disease do you have?  Is your high renin related to your kidney disease or were you dehydrated at the time?  Do you happen to know if your renin / aldosterone ratio was normal?

[Stacky]

It bounces between stage 2-3 chronic kidney disease. I have protein in my urine and sometimes a GFR in the 50s. They say it’s from the uncontrolled BP. Just diagnosed about a year ago.

The high renin and aldosterone have been around for 6+ years. I’m not sure about the ratio.. I’ll have to look back on my records when I get home. Renin hovers around 2-3 times normal and aldosterone is usually between 1.5-2 times normal.

 

[haugr]

The renin / aldosterone situation that you mentioned above isnt really an issue with low renin and aldosterone, its more of an issue with an imbalance of renin / angiotensin ii / aldosterone that results in abnormally high levels of angiotensin ii compared to the renin and aldosterone.  It's the high angiotensin ii levels that really messes you up.  High levels of angiotensin ii can lead to being in a hypovolemic state since it causes your kidneys to stop retaining fluids like they normally would. 

If your renin is high with an appropriate aldosterone ratio, then it's safe to conclude that you have high angiotensin ii levels too.  That would explain a lot of your symptoms.  

[haugr]

The body has 2 main ways to raise blood pressure.  The first is from the renin-angiotensin-aldosterone system, with angiotensin ii being the active blood pressure raiser.  ARBS or ACE inhibitors suppress angiotensin ii. 

The other is norepinephrine, which is primarily triggered by the brain as part of the sympathetic nervous system.  The brain can trigger norepinephrine in times of anxiety or from a lack of blood flow to the brain.  Norepinephrine also increases your heart rate.  High levels of angiotensin ii have been reported to exaccerbate the release of norepinephrine.  Beta blockers seem to be hit or miss for reducing the norepinephrine effects.  Some POTSies report that they help, others POTSies report that they exacerbate some symptoms.  Alpha2 agonists such as clonidine tend to be more helpful if you are experiencing high norepinephrine surges since it suppresses its release instead of blocking its effects.

My experience was that a combination of high angiotensin ii, low blood volume, and even a minor amount of activity or anxiety led led to some vicious norepinephrine attacks.  My BP would surge to as high as 180/125 when they would hit.  If i were a betting man, I would guess that you are experiencing something similar.  I would guess that the variance in POTS symptoms depends on how much fluids and sodium you have recently consumed, activity, and anxiety (which of course can vary throughout the day).  

The problem with an snri if you are hyperadrenergic is that they increase norepinephrine levels.

These days, I take losartan, clonidine, a low dosage of an ssri, drink plenty of sports drinks and take a daily sodium chloride tablet to keep myself stable.  It's also important to get plenty of anti oxidants because angiotensin ii leads to abnormally high amounts of oxidative stress.  If you are male, I would highly suggest getting your testosterone levels checked too.

 

[Stacky]

Wow! Thanks so much for all the info. I feel like you know me!

The Losartan works best out of all meds I’ve tired but doesn’t seem to touch the spikes. I have a Clonidine rx that I take when diastolic goes above 110 and it also works really well but knocks me smooth out. And the rebound spikes are rough. One pill turns into another and I end up having to ween off over a day or two. I thought about asking for the patch but I don’t know if I can handle the drowsiness. I’m already so sleepy all the time. Do you take it daily and if so, did the fatigue disapate at all?

I’ve always been told to limit my sodium. I can’t tell if I feel better on a high or low salt diet... But low sodium doesn’t seem to help at all.

What are causes of high angiotensin? Anything structural or simply bad genes?

Thank you so much! 

 

[haugr]

I take .1mg of Clonidine just before going to bed, and then I carry some with me at all times in case I get an attack.  I was on the patch for a while and I really liked it, but it irritated my skin so bad that I ended up ditching it after I stabled a bit.

As for the sodium, I have to be very, very careful with it.  I keep a very close eye on my blood pressure and adjust the amount of sodium accordingly.  It is very important though because low blood flow is what triggers your kidneys to release renin.  Normally the kidneys start releasing renin when you get dehydrated.

In my case, the high angiotensin ii levels are from a defect in an enzyme called the ACE2 which is responsible for catabolizing the angiotensin ii.  I think its a genetic condition because i have several siblings that have symptoms.  I would guess in your case that the abnormally high renin results in high angiotensin ii.

 

 

[Stacky]

What a huge pain.. Did your Dr do genetic testing to find that? My sister has tachycardia and low swings in BP but no highs. I’ve always thought that we could have some kind of wonky gene, especially since it started when we were early 20s.

Yer smart! Haha. Thanks so much for the info. I feel like you’re the only person I’ve found that has pretty much my exact symptoms. How old were you when it started? I had moderately high BP at about 22 when I was on birth control but it leveled out when I stopped taking it. And then it came back when I was pregnant at 25 and has just gotten worse.

[haugr]

It leveled me about a year ago.  I was 39 at the time and ended up being bed ridden for about 10 weeks.  In hindsight I think I've always had symptoms though.  

I haven't had any genetic testing done, I just got very, very lucky and just by chance I happened to visit one of the few doctor's in my area that understood the condition and had experience treating it.  He recognized the symptoms and sent me on the right path.

[yogini]

The POTS treatments would only help if you have dysautonomia, and it sounds like you are unsure about that.  You may want to ask your kidney doctor whether the HR and BP issues could be caused entirely by the kidney condition, which is a possibility.  You could also see a POTS doctor to get tested, since you would need someone to figure out your meds anyway.  

[Stacky]

Haugr- Sounds like a fantastic Dr. I’m glad you’re feeling better. Have you had any imaging done? Do you have elevated renin and aldosterone as well?

 

Yogini- My Cardiologist and nephrologist have both done “tested” my by taking BP and pulse laying down, sitting, and standing but it’s usually not much of a change immediately. Typically takes a few minutes to start climbing.

The kidney disease is new. He thinks it’s most likely from the uncontrolled BP. I just had a CT and haven’t received the results yet but got a copy and it pretty clearly shows a small cyst and several small stones. Any idea if a cyst could be causing these problems?

[haugr]

I've had a lot of testing done.  Echo cariogram, a stress test, another stress test with imaging, a renal ultra sound, MRI, 2 week holter monitor, tons of blood work.  My renin and aldosterone were normal.

[yogini]

Dysautonomia does not require an immediate change, but rather a sustained change. If your HR Is high or BP low after 10 minutes or 30 minutes of standing, that would signal POTS.  I would recommend going to a POTS specialist to get tested. 

[bombsh3ll]

On 12/2/2017 at 4:10 AM, haugr said:

My experience was that a combination of high angiotensin ii, low blood volume, and even a minor amount of activity or anxiety led led to some vicious norepinephrine attacks.  My BP would surge to as high as 180/125 when they would hit.  If i were a betting man, I would guess that you are experiencing something similar.  I would guess that the variance in POTS symptoms depends on how much fluids and sodium you have recently consumed, activity, and anxiety (which of course can vary throughout the day).  

Is there a direct test available for angiotensin ii? I know there are some studies (Lowe i think?) showing low renin and aldosterone but high angiotensin ii in low flow POTS. I produce next to no renin or aldosterone and fit the clinical picture of low flow POTS, but cannot seem to find a test for angiotensin ii either NHS or private in the UK.

I have tried fludrocortisone, which has two actions 1) salt and water retention (what I desperately want) and 2) enhancement of noradrenaline's vasoconstricting effects on blood vessels (the opposite of what I want). I am already intensely vasoconstricted with symptoms of high noradrenaline. (pheo has been excluded). Unfortunately for me the vasoconstricting effect of fludrocortisone seemed to outweigh any salt & fluid retention. I was even more peripherally shut down, hypertensive and non-psychogenically anxious, and still presyncopal all the time. 

I am therefore considering pairing it with an angiotensin receptor blocker such as losartan to negate the vasoconstricting effects, as I have heard of someone else doing, but would like to know if I actually do have high angiotensin ii levels first.

 

[Clb75]

Have you tried an endocrinologist? They can test the Renin, aldosterone, angiotensin system. 

[bombsh3ll]

1 hour ago, Clb75 said:

Have you tried an endocrinologist? They can test the Renin, aldosterone, angiotensin system. 

Yes I have, they tested the renin and aldosterone but not angiotensin ii. He had heard of POTS but was not very knowledgeable about it.

I was supposed to stand for 15 minutes before the blood tests, but if I could do that I would be running around jumping for joy, not in hospital having tests! They had to just do it with me sitting. 

When I was tested for pheochromocytoma with a urine collection, the amount of urine I passed in 24hrs was over 6 litres, so I had a hypertonic saline test for diabetes insipidus (it was awful, really dehydrating!). That came back inconclusive so I have to repeat it, but I have already tried desmopressin to try and increase my plasma volume and although it stopped me from having to pee during the night, it didn't help me stand any. The endocrinologist explained to me that desmopressin does help you hold water but most of it goes into the cells rather than staying in the bloodstream. 

I have now found a place in the UK which does blood volume testing, so I have put the repeat diabetes insipidus test on hold for now while I get this done. 

 

[haugr]

None of the doctors that I visited directly tested me for angiotensin ii, and I'm not sure if there is a common test available. My doctor said it was more of a "lets try this treatment to see how you respond" type of a thing.  In my opinion though, if you are abnormally frequently urinating, and diabetes has already been ruled out, then I would say thats a pretty good indicator.  In fact, the frequent urination was really my first symptom.  My wife used to tease me mercilessly about my tiny bladder

[bombsh3ll]

1 hour ago, haugr said:

None of the doctors that I visited directly tested me for angiotensin ii, and I'm not sure if there is a common test available. My doctor said it was more of a "lets try this treatment to see how you respond" type of a thing.  In my opinion though, if you are abnormally frequently urinating, and diabetes has already been ruled out, then I would say thats a pretty good indicator.  In fact, the frequent urination was really my first symptom.  My wife used to tease me mercilessly about my tiny bladder

That's really helpful info, thanks. Did you ever have a blood volume test which confirmed hypovolaemia, or if not, did you or your doctors suspect you were hypovolaemic? As your aldosterone was normal I guess you didn't need to take fludrocortisone, but if I try losartan I'd take the two together it in the hope I can get some volume repletion whilst at the same time reducing the vasoconstriction, as I think expanding my blood vessels without expanding my volume would be a disaster! 

[haugr]

I never had any tests done to check if I was hypovolaemic, but my doctor was pretty confident that I was from early on.  Fludrocortisone never really came up, but I don't seem to need nearly as much extra sodium and fluids as some POTSies.  An extra 2 grams of sodium through sports drinks and sodium chloride tablets is enough for me.

[KiminOrlando]

4 hours ago, bombsh3ll said:

I was supposed to stand for 15 minutes before the blood tests, but if I could do that I would be running around jumping for joy, not in hospital having tests! They had to just do it with me sitting. 

I couldn't do this either. My doc told me that I still needed to stand for the test for as long as I could, then when I felt like I didn't have much time before I passed out, they drew the blood. All the hormones get stirred up and he needed to know my specific make up just prior to fainting. One time I fainted before he got blood, so he stopped the test. He said this test is VERY sensitive and norepinephrine would give false readings very easily. I don't know if adrenals are the same way or what standing test you were doing, but wanted to pass that along.

[bombsh3ll]

 

2 hours ago, KiminOrlando said:

I couldn't do this either. My doc told me that I still needed to stand for the test for as long as I could, then when I felt like I didn't have much time before I passed out, they drew the blood. All the hormones get stirred up and he needed to know my specific make up just prior to fainting. One time I fainted before he got blood, so he stopped the test. He said this test is VERY sensitive and norepinephrine would give false readings very easily. I don't know if adrenals are the same way or what standing test you were doing, but wanted to pass that along.

Did you have the cannula placed in your arm ready before you stood up? How was your norepinephrine level, was it helpful to know the result?

I've never had plasma norepinephrine tested - just urine over 24 hours to exclude pheochromocytoma. I suspect I have high adrenergic output (probably to try and compensate for low blood volume) due to my symptoms when upright - tachycardia, clammy hands, sense of non-psychogenic anxiety/panic/impending doom/ heart pounding, shaking etc. 

It took the nurse several tries to get into my veins lying down as they are so tiny and thin - I had veins like drainpipes prior to becoming unwell, another sign to me of hypovolaemia - that they would never have managed it with me standing!

[KiminOrlando]

Yes, they had it ready to go, because I am a hard draw now too. My first one the norepinephrine was high, which he said was odd. I told him I passed out and that was when he said, 'this test is invalid'. They also had me on Celexa for anxiety which elevated my blood norepinephrine levels. Again, he said, 'why did they even run this test?' He took me off the anti anxiety med because I didn't really have anxiety and waited 6 months before trying again. Then I fainted on him, so we stopped again. When we finally got it, my norepinephrine levels were low. My morning cortisol levels are very low, but rebound by the afternoon, so I don't have Addison's disease. The cortisol stimulation test was normal. They also ruled out pheo with urine test. 

They put me on Northera (droxydopa) but my norepinephrine levels got too high, so they took me off. I did feel better, but started having BP spikes.

I don't have the panic side of the problem unless something happens. The smoke alarm goes off, and I can barely stand up. The same thing with my morning wake up alarm. I am shaking for the rest of the day. They know I have adrenal problems, but don't know what to call it yet.

I went in for surgery a couple of years ago. They wouldn't let me drink water for 12 hours. I told them how bad this would be and they wouldn't be able to get an IV. They tried 6 times and couldn't get me. Then they tried to convince me to let them go in at my neck because my veins were so collapsed. I wouldn't let them. Sometimes you have to listen to the patient when they tell you their blood volume, pressure and heart rate will be bad if they do what they are told. The anesthesiologist was a little concerned. They finally got it and I got TWO bags of fluids. I felt GOOD that day, even post op.

[bombsh3ll]

I would really love a couple of bags of fluid!!

Have you ever had a blood volume test? That is what I am currently trying to arrange so I can PROVE how volume deplete I am!

It is interesting that the Northera helped you feel better,  I feel like more noradrenaline would be my worst nightmare - did it not make your heart race even faster?

 

[KiminOrlando]

2 hours ago, bombsh3ll said:

It is interesting that the Northera helped you feel better,  I feel like more noradrenaline would be my worst nightmare - did it not make your heart race even faster?

Eventually, that is exactly what started happening, but I was on it for a year first. It has been six months and I still haven't dropped as low as I was before the med. They aren't sure why or if it will wear off. There are a lot of things they don't know about that drug yet. Cortisol is still at the bottom. Nobody tested anything else since.