My Hyperadrenergic POTS Story

My POTS kicked in August of 2016.  At the time, I was trying to be a bit healthier that I had been by cutting out soda and eating better.  I think that the first symptom was that I had to pee a lot more often.  I remember that my wife kept making fun of my tiny bladder during that phase.  Then the light headedness and tachycardia started slowly increasing over the next couple of weeks.  In September it really hit me hard.  I was in my office at work and nearly passed out, which was followed shortly after by a super intense adrenaline storm.  I went to the ER complaining of chest pressure and dizziness, but I was feeling a bit better by the time I got there.  My blood pressure was high and I did in fact have tachycardia.  They also took an ekg and some basic labs that came back normal and he told me that he thought that it could possibly be either SVT, AFib, or just acid reflux.  He told also told me that I should set up an appointment with a cardiologist.  

The next day I called and set up appointments with a general practitioner and a cardiologist, and literally the way I chose them was that I called the offices that were nearest to my house and asked for the doctors with the next available appointments.  I got in to see the general practitioner the following day, and it turns out that he was one of the most experienced POTS doctors in Utah and actually dedicates 1 day per week to treating POTS patients.  I still can't believe how lucky I got by finding him the way that I did.  He said that he wanted to see the outcome of the cardiologist appointment before he did anything.  After visiting him, he said that he wanted to see the results of the cardiologist before he did anything else.

During the next week before my cardiologist appointment, I started taking my blood pressure regularly and I noticed that I would get some crazy swings.  One day when I was worried about a problem at work that I couldn't get there to address, I took my blood pressure and it came in at 180/125.  This was before I knew much about blood pressure and I didn't realize that my blood pressure was high enough that I should have called 911.  I also tried going back to work in this week, but I only lasted one day back.  My co-workers were all extremely concerned about how pale I was, and the tachyardia and light headedness was more than I could handle.

Based on my description of what happened in my office the previous week, the cardiologist assumed that I had SVT, so he put me on a calcium channel blocker, a 2 week holter monitor at the same time, and scheduled me for a echocardiogram.  My blood pressure was still crazy during those 2 weeks, but the calcium channel blocker helped keep my blood pressure from crisis levels.  The results of the holter and echo didn't show anything useful other than bouts of tachycardia, fairly frequent skipped heart beats, and that my heart was showing signs high blood pressure.  I asked the cardiologist about the rest of the symptoms and he said that it just sounded to him like anxiety and that I should take some anti-anxiety meds for it. 

I then went back to the GP the next week during one of my adrenaline storms and he took my pulse while lying down and again standing up.  He didn't say anything to me at this point other than he wanted to run a ton of labs.  The most interesting test was the lying down vs standing catecholamines blood draw which measured my norepinephrine at about 250 while lying down and about 850 while standing up.  I also had low testosterone.  After getting the results a week later, had me come back into his office where he diagnosed me with hyperadrenergic pots.  He told me to start the mediterranean diet, to stop taking the calcium channel blocker, to start taking .1mg of clonidine, and to start regularly exercising.  Unfortunately, he didn't mention anything about salt, and he printed out some documentation on the mediterranean diet that included going salt free.  About a week later, all of my symptoms were much worse.  I ended up in the emergency room again after constantly being on the verge of passing out and blood pressure that kept repeatedly spiking to crisis levels.  I also was having some strange tingling in my feet, legs, hands, arms, and face.  The ER did an ekg, an MRI, and a bunch of lab work but again didn't find anything. 

The next day I went back to my GP where he then told me that he messed up the print out and that to go up to 8Gs of salt supplements per day, about half of which coming from sports drinks and the rest coming from sodium chloride tablets.  He also put me on 100mg of Losartan, .2 mg Clonidine patch, .2mg of Clonidine pills, and zoloft.  This was obviously a huge jump up from where I was at and a lot of new meds to take on at a single time.  Things got really confusing at this point.  My brain fog went away and light headedness went away, but my blood pressure got extremely high constantly - like 150-160 / 100-110, and any activity or anxiety would put me into crisis mode.  That dosage of Clonidine gave me bradycardia and chest pains too.  My sleeping heart rate at this point came all the way down to about 40.

I went to a second cardiologist at this point who had me do a stress test.  The first round that I did with him showed what he said were some anomalies so he told me to start taking a daily aspirin and that he wanted to do a second stress test combined with an echocardiogram.  I cut back significantly on the salt after the stress test since the cardiologist indicated that I might have angina, so by the second stress test everything came back normal.  My blood pressure started coming back down to reasonable levels as well.

I went back to my GP, explained everything that had happened, and he basically told me at that point that I needed to play around with the Clonidine and salt dosages until I found what worked for me.  He also sent me to do a renal ultrasound to check for any abnormalities with my adrenal glands.  That ultrasound didn't turn up anything and they tried to get me to get a renal cat scan, but my insurance denied it so I never had it done.

I was about 2 months into this situation by now and I started playing around with the dosages, but things really clicked for me when I came across Julian Stewart's research.  Things started to make sense particularly when I realized that his classification of low flow POTS included pallor.  After realizing that my hyperadrenergic pots was caused by an ACE2 deficiency, I started reading everything that I could find on the ACE2, the RAAS, the effects of Angiotensin II, and norepinephrine.  Understanding how all of these work helped me realize exactly what was happening inside my body.

About a month later, I was taking .2mg of Clonidine, 100mg of Losartan, and 3-4 grams of salt, which is when I was finally healthy enough to go back to work, even though I still wasn't in a very good state.  I was fired a few weeks later and when I got home that day, I took my blood pressure and it was 180/120.  I popped an additional .2mg of Clondine, and my blood pressure came back to reasonable levels within 30 minutes.

I continued to play around with the dosages for the next few months until I settled on 1-2 grams of salt all coming from sports drinks, 100mg of Losartan, 25mg of zoloft, testosterone supplements, and .1mg of Clonidine per night, and I also would take an additional Clonidine if I felt myself surging.  

What I really discovered though through trial and error is that I have to keep my blood volume high by consuming more salt and fluids than my kidneys process.  Losartan is a must, and Clonidine is amazing for suppressing the adrenaline storms.

It has now been nearly 2.5 years since this started for me and this condition barely affects me now as long as I stay consistent with my treatment.  I feel extremely fortunate that I was able to find a good doctor as quickly as I did that helped me understand it and learn how to treat as I did as I know that most people that become affected by this condition aren't as lucky as I have been.

Treatment Advice for Hyperadrenergic POTS from an ACE2 Deficiency / RAAS Dysfunction

Let me first start with my disclaimer that I am not a doctor and I have no medical training.  All advice I give is in the context of what I have read, what I learned from my doctor, and my own personal experiences.

It has now been about 2.5 years since I first became debilitated by this condition and I am pleased to say that after 3 months of debilitating hell, followed by another 6 months of treatment refining, that I have been very stable ever since.   Because this is such a tricky condition to get diagnosed and to treat, I am posting my advice in the hopes that it may help someone some day that is looking for answers.

First, it is important to understand the terminology:

POTS - a symptom of many different possible underlying conditions that results in a sustained elevated heart rate while standing.

Hyperadrenergic POTS - a sybtype of POTS that results in high adrenaline / norepinephrine surges that can potentially send blood pressure to very high levels.

Low Flow POTS - the name that Julian Stewart (the leading expert on this type of POTS) uses instead of Hyperadrenergic POTS, but is also more specifically focused on low blood volume / hypovolemia than the common descriptions of hyperadrenergic POTS.

RAAS disfunction - the RAAS is the complicated system of the body that is responsible for the regulation blood volume.

ACE2 deficiency - a rare, specific type of RAAS dysfunction and causes a high amount of Angiotensin II.

Before visiting a doctor, make sure that know your own symptoms and that they compare with the combined symptoms of POTS, Pheochromocytomas (since the hyperadrenergic pots adrenaline storms present in a similar manner), and frequent urination.  It would be worth doing the poor man's tilt table test before visiting your doctor.  Buy a pulse oximeter and heart rate monitor, lie down for 10 minutes, take your heart rate and blood pressure, then stand up and measure your heart rate after 1 minute, 5 minutes, and 10 minutes.  If your heart rate stays elevated by more than 30 beats per minute or if your heart rate is higher than 120, then you probably have POTS.  If your blood pressure is significantly elevated as well, then you may have hyperadrenergic POTS.  Keep in mind though that you may get somewhat different results throughout the day depending upon your recent food and fluid intake as well as your anxiety levels.  

There are very few doctors that can diagnose and have experience treating this condition.  Finding a doctor that can help will be frustrating and difficult.  There is a list of doctors on dinet.org's website that are experienced treating POTS, but also understand that there are some really good doctors that are more accessible than the experts that will appreciate the challenge of helping you figure it out.  Look for doctors that will listen to you when you show them your research, are receptive to your treatment option suggestions, that may do research on their own between appointments, and won't be in a rush to push you out the door so that they can move on to their next patient.  You may need to try out 10-20 different doctors until you find one that can genuinely help.

Second, ask your doctor to perform a tilt table test and a catecholamines blood test that compares your norepinephrine after 10 minutes of laying down vs after 10 minutes of standing up.  The tilt table test can be used to diagnose POTS and hyperadrenergic pots in some cases, and the catecholamines blood test can be used to diagnose hyperadrenergic POTS.   Specifically, if your norepinephrine is relatively normal while supine after 10 minutes but is more than 3 or 4 times higher after standing for 10 minutes. 

Unfortunately, there is no commonly available test that can be done to confirm that you have the dysfunctional RAAS / ACE2 deficiency subtype of hyperadrenergic POTS.  There is however a commonly available RAAS test that measures the ratio of Renin to Aldosterone that your doctor will probably perform if you suggest that your RAAS might be dysfunctional.  This test however will likely give misleading results.  The ACE2 deficiency results in a paradoxically high amount of Angoitensin II (which the test doesn't specifically measure), but a relatively normal Renin to Aldosterone ratio.  If you are male, you should also ask to have your testosterone checked since low male testosterone is common with POTS, and in my opinion is a very good indicator of the dysfunctional RAAS / ACE2 deficiency subtype when combined with the other hyperadrenergic pots symptoms and frequent urination.

If you do have a deficient ACE2, the main treatment is to prevent your RAAS from activating, which means that you can NEVER let yourself become dehydrated and you might need to supplement with additional fluids and salt.  If you are in a debilitated state due to your symptoms, then you are probably in a constant hypovolemic state with a frequently activated RAAS.  The only way to get your broken RAAS to deactivate is to get your blood volume up through fluids and salt - which I know seems somewhat counter intuitive considering that you are likely dealing with scary blood pressure surges.  The amount varies from person to person, but I would recommend that you increase fluids and salt through Gatorade, Propel, Nuun Tablets, and/or Pedialyte.  Salt sticks and/or sodium chloride tablets combined with increased water works as well.  Don't assume that you can achieve the needed salt by putting more salt on your food.  Everyone needs to play around with it until they figure out their sweet spot.  If you go too high, your blood pressure will rise from having too much blood volume, so what you're looking for is the sweet spot where your blood pressure and tachycardia stable out, but before your blood pressure starts to rise.  Because you can do real damage to your body if your blood pressure gets too high, you should go slowly, and I once again drop my disclaimer that you should consult your doctor before doing this.  My recommendation is to keep a very detailed diary of fluid and salt intake keeping in mind the sodium that you are consuming through food, and then increase by 1 gram of salt per week.  If the trend of your blood pressure immediately rises during the first week or two, then you probably aren't hypovolemic and probably don't have an ACE2 deficiency.  If the trend of your blood pressure over the week stays flat or lowers, then you could very well be hypovolemic.  Keep increasing slowly each week until the overall trend of your your blood pressure starts to rise.  When it does start to rise, then you know you've gone too far, and you should go back to the previous week's supplementation levels.  It takes some time to find that sweet spot.  I only need an additional 1-2 grams of salt per day, but I think that some people need as much as 8-10.

Appropriate medications are also extremely helpful.  Losartan is great as it suppresses the effects of the Antiotensin II, which is what ultimately causes a lot of the symptoms.  I take 100mg per day.  Lisonopril should theoretically provide the same benefits as Losartan.  Clonidine is a life saver during the adrenaline storms.  I take .1 mg every night before bed, and I'll take another .1 or .2 during the storms, but fortunately I haven't had a storm in a long time.  The clonidine pills are extremely powerful, but relatively short lasting so it can be a bit ticky to keep a leveled dosage in your body. The Clonidine patches can be used to keep you a bit more level. I haven't tried beta blockers myself, but most doctors will probably start with them because they are known to reduce tachycardia and blood pressure.  I however recommend against them because Dr. Grubb's research has shown a paradoxical effect where it can actually increase blood pressure for some of those with this condition due to unopposed alpha receptors, and I have also spoken to several of potsies that confirm this problem.  Dr Grubb has suggested that alpha-beta blockers can be an effective alternative to  beta blockers, although I have not tried them myself.  I also recommend an ssri to help prevent some of the anxiety driven adrenaline storms because even a little bit of anxiety can trigger some crazy adrenaline storms.  I recommend taking some anti-oxidant supplements because Julian Stewart has done some studies where it has shown some positive benefits since high Angiotensin II levels promote oxidative stress.  I also highly recommend getting your testosterone levels checked if you are male and supplement if you are low.  Testosterone supplements probably won't help much with this condition specifically, but will make you feel better overall.  And of course, a strong healthy heart makes a huge difference, so daily cardio exercise is crucial even though it is the last things in the world that you want to do.  Rowing machines, recumbant exercise bikes, and possibly even swimming are good ways to do cardio while minimizing POTS symptoms.

Are Beta Blockers Really a Good Treatment for Hyperadrenergic POTS?

I personally think that beta blockers are over-prescribed as a treatment option for hyperadrenergic POTS.  They are known to slow heart rate and reduce blood pressure, which on the surface sounds exactly like what we would want.  There are many people however that report worsening symptoms while on beta blockers.  Some with hyperadrenergic pots even report an increase in blood pressure while on beta blockers.  Dr Grubb (one of the leading POTS specialists) has reported this as well. 

To understand the paradoxical effect of beta blockers on some POTS patients, some background on the sympathetic nervous system is helpful.  The sympathetic nervous system is typically activated by the brain in times of stress.  This is the fight or flight response.  The brain signals to the adrenal glands to release adrenaline, which causes your heart rate to increase and your blood pressure to rise in order to increase oxygen temporarily to the vital parts of your body that are needed for survival.  More specifically, the heart has beta receptors that when activated by adrenaline will increase heart rate and has the side effect of increasing blood pressure because the heart is beating harder and faster.  The arteries have alpha receptors that when activated by adrenaline will cause the arteries to constrict in order to increase blood pressure.  In addition of anxiety, the sympathetic nervous system can also be activated by a lack of blood flow to the brain.  Hyperadrenergic POTS is when the sympathetic nervous system is significantly activated while standing, which is usually caused by to a lack of blood flow to the brain.

Beta blockers work by blocking the beta receptors in the heart.  In most people, this causes a drop in heart rate and blood pressure because the heart beats less often which has the side effect of lowering blood pressure.  With the beta receptors blocked though, the adrenaline will interact with the alpha receptors in the arteries to raise blood pressure, but not typically as much as it would have been raised by the faster and harder beating heart for the same amount of adrenaline.

For those with hyperadrenergic POTS that report an increase of blood pressure while on beta blockers, I believe that the reason is because more adrenaline ends up being released than would normally be necessary to keep a healthy amount of blood flow to the brain.  With the beta receptors blocked, the adrenaline binds to the alpha receptors to raise blood pressure, and the brain will continue to release more and more adrenaline until it gets enough blood.

In this scenario, beta blockers end up having the opposite effect of what you would typically expect.

Hyperadrenergic POTS from an ACE2 Deficiency / RAAS Dysfunction

About a year ago, I became debilitated for a few months due to a condition that is known as Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (Hyper POTS).  The definition of POTS is an increase in heart rate of more than 30 beats per minute when standing up versus lying down - typically resulting from a lack of blood flow to the brain.  The hyperadrenergic subtype indicates that the tachycardia corresponds to high levels of adrenaline (norepinephrine to be specific).  There are many different underlying conditions that can cause POTS, but this post is going to focus on the one that has affected me.

I am nearly positive that the underlying cause of my POTS is from an ACE2 deficiency.  For some background, the system that regulates blood volume is called the renin-angiotensin-aldosterone system (RAAS).  When the kidneys detect low blood flow (for example, when you are dehydrated), the kidneys release renin into the bloodstream.  Renin causes the release of a hormone called angiotensin I.  Angiotensin I then gets converted to Angiotensin II through an enzyme called the Angiotensin Converting Enzyme (ACE).  Angiotensin II then triggers a variety of activity in the body.  It is a very potent vasoconstrictor that causes your blood pressure to rise.  It also triggers the release of aldosterone from the adrenal glands, and the aldosterone is responsible for making you feel thirsty and it also causes the kidneys to retain sodium, thereby increasing blood volume.  Most of the angiotensin II in your system gets catabolized to lesser forms of angiotensin (angiotensin 1-7) through another enzyme called the ACE2.  The other interesting thing about this system is that when the kidneys detect a certain level of angiotensin II in the blood stream, it will stop producing any more renin even if the blood flow is low.  It does this because if it didn't, your body could kill itself by overproducing angiotensin II thereby raising your blood pressure too high.  Wikipedia's article on RAAS is very informative (https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system)

Julian Stewart has published some articles on a version of POTS that he calls "low flow pots" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511483).  He found a defect in the ACE2 that results in elevated levels of angiotensin II.  The high levels of angiotensin II cause havoc on your system.  One affect is low blood volume (aka hypovolemia) since your kidneys aren't releasing enough renin due to the inhibitory feedback loop of the high angiotensin II levels.  Low blood volume makes it so that you aren't getting enough blood flow to your brain when you are upright.  Julian Stewart states that angiotensin II can exaccerbate the release of norepinephrine as well.  Norepinephrine is typically released as part of the fight or flight system (sympathetic nervous system) in order to provide blood and oxygen to the parts of your body that are required for immediate survival by inhibiting to the areas that are less important.  Since a sufficient supply of blood to the brain is critical, the brain activates the sympathetic nervous system for the same survival reasons.  My experience is that a relatively low amount of anxiety when blood volume is low can trigger a vicious norepinephrine attack that when combined with the already high levels of angiotensin II can lead to dangerously high blood pressure - even while lying down.  Basically, I think that my body was releasing way more norepinephrine than it normally would have for the amount of anxiety that I was experiencing.  Another problem that high levels of angiotensin II can cause is oxidative stress which can also lead to fatigue, brain fog, vision problems, etc.  There is also research to suggest that high levels of angiotensin II can cause low levels of testosterone in males (http://www.sciencedirect.com/science/article/pii/S0018506X12001377). Basically, the leydig cells in the testes have angiotensin II receptors that when activated stops the production of testosterone. 

The symptoms that I personally have experienced are a dizzy-like feeling that felt like I was on the verge of passing out when upright, constant brain fog, tachycardia when standing or when anxious, chest pressure, high blood pressure when standing or when anxious, skin that turned noticeably pale, cold / tingly feet hands and face, pressure in the back of my eyes, slightly blurry vision, low testosterone, high norepinephrine levels when standing vs lying down, severe fear and anxiety (presumably from the activation of the sympathetic nervous system), frequent urination, and occasional flushing of my ears when especially symptomatic.  The symptoms were so intense that I was practically bed ridden for 10 weeks.  Before I understood what was happening to me, I spent nearly every day feeling fear that I was about to die at any moment.  I visited about 10 different doctors including a couple of trips to the ER, had an MRI, 2 echocardiograms, 2 cardio stress tests, wore a 2 week event monitor, had a renal ultrasound, and had tons of lab work done.  I was even told multiple times that it was probably just anxiety, which I knew couldn't be true because I had never had a problem with anxiety previously.  The key to unlocking the mystery though was that I got lucky and happened to visit a doctor who was experienced treating POTS.  He ran a test where he drew my blood after lying down for 10 minutes, then again after standing for 10 mintues to check my catecholamines in both positions.  My lying down norepinephrine was 225, but was 849 when standing.  This large difference between the two positions indicated that I had the hyperadrenergic subtype of POTS.

There are a few things that I do to keep myself functional.  The most important thing is to prevent my body from being in a dehydrated state.  This helps prevent the release of renin and the subsequent conversion to angiotensin II.  I take one or two 1 gram sodium chloride tablets a day and I drink 3-6 Propels a day in addition to a few glasses of water to keep my blood volume high enough to keep a sufficient supply of blood flowing to the brain.  Those with the hyperadrenergic subtype like myself have to be extremely careful with the intake of sodium though because an increase of blood volume can lead to dangerously high blood pressure if a norepinephrine attack happens.  Manually balancing blood volume and blood pressure is a delicate task.  When my anxiety is higher, I will consume  less sodium to keep my blood pressure in check.  The most important medication that I take is Losartan.  Losartan is an angiotensin II receptor blocker (ARB) which lessens its effects.  Second, I take Clondidine because it suppresses the release of norepinephrine.  I actually carry with me Clonidine everywhere I go just in case I get another norepinephrine attack where my blood pressure nears 180/120.  Third, I take a low dosage of Zoloft (SSRI) to help keep my anxiety in check since like I mentioned above, anxiety with high levels of angiotensin II have the potential to trigger norepinephrine attacks that exceeds what my dosage of Clonidine suppresses.  I actually tried an SNRI for a week or two before switching to an Zoloft, but that made things much worse for me since SNRIs increase norepinephrine.  I also take a daily multivitamin primarily for the antioxidant effects from the vitamin C.  Since the angiotensin II leads to oxidative stress, antioxidants like vitamin C are extremely important (http://www.prohealth.com/library/showarticle.cfm?libid=17890)

Unfortunately for those that suffer with this condition, the medical world struggles understanding and treating POTS.  There just aren't many doctors that are familiar with it or have experience treating it.  POTS is often misdiagnosed as anxiety because both can activate the sympathetic nervous system.  POTS should really be thought of as more of a symptom of an underlying cause instead of a stand alone condition in the same way a cough is a symptom of a cold, influenza, asthma, etc.  Another common point of confusion is that the underlying condition that is causing the symptoms of POTS has the possibility to lead to other symptoms even while supine.  Sometimes doctors will discount a diagnosis of POTS because all symptoms are not isolated to standing up.

Please note that I am not a doctor so it is possible that some of this information is incorrect.  Please take it with a grain of salt and do not view it as authoritative.  My hope though is that this information may help someone that is struggling to find answers to this same condition.