POTS Triggers with Dr. Cathy Pederson

[00:00:00] Jill Brook: Hello fellow POTS patients and lovely people who care about POTS patients. I'm Jill Brook, your hyper adrenergic host, and today we are discussing POTS triggers, those precipitating events that sometimes appear to bring on POTS for some of us. Our guest is Dr. Cathy Pederson, and I think you know her credentials by now, doctorate in neurobiology, tenured professor, POTS researcher, our founder, our spiritual leader. So I'll tell you something else about her today. She actually is every bit as kind and nice as she sounds. Dr. Pederson, thank you for being here. [00:00:39] Cathy Pederson: Thank you, my friend. I appreciate it. [00:00:42] Jill Brook: So I think POTS triggers is actually a slightly painful topic for some patients. I know it is for me because you can't help but feel like POTS triggers can feel just so unlucky, right? Like if it hadn't been for that one random unlucky life event, then maybe POTS wouldn't have come on, and maybe life would be easier. Of course we can't know. Maybe if one trigger didn't get us, then maybe the next one inevitably would have. But nonetheless, triggers are fascinating. Do you find yourself looking at your daughter's trigger? And just wondering what if. [00:01:21] Cathy Pederson: I don't really, but as we are prepping this, and I saw you write a little bit about that, I thought, wow, I haven't looked at it in that way. I feel like she's got so much going on that she's probably one of those that if it wasn't mono, it would've been something else. But who's to say? [00:01:41] Jill Brook: Right. And everybody's triggers can be so different. Some of us, it was a choice, right? For me it was wisdom tooth surgery. Every once in a while I'll be going to the dentist thinking, oh, I'd rather have a crowded mouth than POTS. But can't think like that. because as you said, probably something else would've come along. [00:01:58] Cathy Pederson: Well, and it's so uncommon. Think of the hundreds of thousands of teenagers and early 20 age group kids that have that surgery every. Month. It's so unlikely that this would happen, so it's probably better to just move forward. [00:02:17] Jill Brook: Yep. I agree. Okay, so with that out of the way, triggers are fascinating and there seem to be many different ones in POTS. Can you go over what are some of the main potential POTS triggers? [00:02:33] Cathy Pederson: Yeah, it's really interesting. I did some reading on this and I have to tell you, Early on in the podcast, Jill asked easier questions. And as we get deeper into things, we've covered the easy stuff physiologically, and it just gets more and more complicated. But the answer is the more physical stressors that you experience, the more likely you are to have something Go wrong. When we think about physical stressors, some of them are going after the immune system, so an infection or a vaccine. Some of them are physical trauma where you have a head injury and get a concussion, or as you were alluding to a minute ago, surgery, that may or may not have been elective, depending on what's going on there. And then a third stressor for the body are major shifts in hormones. So that can happen at puberty and at pregnancy. And so a lot of these seem to be places where a very small percentage of people go on and develop POTS as a result. [00:03:39] Jill Brook: So let's start with infection, because with COVID, I think that one's on everybody's mind. What can you tell us about that as a trigger? [00:03:48] Cathy Pederson: We knew even before COVID that infection could lead to POTS. In fact, there was a study in 2019, so again before COVID, that found that 41% of POTS patients thought that their POTS was triggered by an infection. So it could be viral like mono, or COVID. But it can also be bacterial. So Lyme disease is a bacterial disorder that can also lead to POTS or be a trigger for POTS. [00:04:21] Jill Brook: Okay. So as some people are thinking about their viral trigger and maybe, you know, shaking a fist at the sky and saying, why I will also ask how, what's going on there? [00:04:33] Cathy Pederson: Yeah, it's really interesting and I want to use COVID as the example because it is in the news. We are hopefully, hopefully at the tail end of this pandemic, but I think COVID is going to be around just like the flu is around for a long, long time. And this particular virus, the name of the virus itself is the SARS-CoV-2. So that's the name of the virus . There was a SARS outbreak in China. I don't know if you remember about 20 years ago. And SARS stands for Severe Acute Respiratory Syndrome. And so it's in this family. And we know that COVID is a Severe Acute Respiratory Syndrome for sure. And this virus though loves the central nervous system. The scientific term is neurotropic, but what it means is it has a real affinity to go into the brain and the spinal cord and cause damage to wreak havoc. Now, here's a weird thing about this brain loving virus. We think it actually comes in through the nose and you might say, well, duh, right? But I mean into the brain, through the nose. And we don't see that. Think about a cold or the flu or pneumonia where it goes into the lungs. We think that's how it gets in. When I'm saying nose, I don't mean what's hanging off the front of your face. Your nose actually goes deeper into the skull between your eyes and there are little holes in the skull. It's called the cribriform plate. And little fibers from the first cranial nerve that's called the olfactory bulb, drop down through these little holes in the skull. This is the only place where neurons are in contact with the environment. So it's a weird setup, but what we think is that the virus, because it loves neurons, creeps right up those olfactory epithelium into that bulb and then moves into the brain. That's why smell is affected, [00:06:40] Jill Brook: Okay. [00:06:40] Cathy Pederson: right? because it's hitting that olfactory bulb. Okay, so we've found the virus, the SARS-CoV-2, that's again the name of the virus that causes COVID has been found in people's cerebral spinal fluid. If you remember, that's a fluid that is bathing your brain and your spinal cord. It's around the outside. It's your nervous system is hollow. And so it goes down through some holes in the inside of that as well. And there's evidence that that virus can directly harm neurons when it's in the brain. So this is really interesting. Okay, so then we add to that a receptor that this virus uses to get inside your cells, and it's called an ACE2 receptor. The way that this virus works is it has to get into your cell, your body cell, and take over the machinery in order to make new COVID virus. Okay. And then it'll make like 2000 copies of itself, and then it lyses the cell, which means it kills the host cell, your body cell. And now you've got 2000 new viral particles that are going to look for new host cells, new ACE2 receptors, right? So these ACE receptors are found on that olfactory epithelium in the nose, those smell neurons that are coming down. But they're also found on epithelium, that's a lining of something, in the lung and in the GI tract. And so we think these are the three main entry points for COVID into the body is through the nose that olfactory epithelium, through the lung, and then the lining of the GI tract. It's found in other places throughout the body. But I just wanted to point those. People are like, what is she talking about? This doesn't have anything to do with POTS. I'm getting there. Okay, here it comes. It takes a little buildup, unfortunately. So the SARS-CoV-2 virus, the virus that causes COVID down regulates the ACE2 receptor. So that's medical talk for decreasing the number, and a lot of times also decreasing the sensitivity of, in this case, those ACE2 receptors that allow the virus into your body cells. Now here's the thing. These ACE2 receptors were not made by our body just to have COVID come and hijack them, right? They have normal function, and their normal function is in a system that I know has come up in the POTScast. And I know, Jill, you and I have talked about it before, it's called the Renin angiotensin aldosterone system. it's a really long name. It's really the names of three hormones. It's a hormone cascade that's going on there. But, what they do is they help to regulate your blood volume. So if your blood volume starts to drop too low, we start releasing these hormones and they bring the blood volume back up into normal levels. They also help with blood pressure. So blood volume and blood pressure are tied together, so if your blood volume drops low, then your blood pressure often will also drop low. So I see in the group sometimes people show pictures of how low their blood pressure is. That can be a sign that their hypovolemic, that they don't have enough plasma and fluid in their blood.. So anyway, this renin angiotensin aldosterone system really is targeting the kidney and the kidney controls a lot of what we pee out versus what we keep in the body, right? So angiotensin II helps us to reabsorb sodium to keep it in the body and it moves it from the kidney tubules into the blood and where sodium goes, water always follows. When you manipulate sodium, you can manipulate how much water, how much plasma is in the blood. So the other big hormone in that system is called aldosterone, and that's the salt retaining hormone. So that's its nickname. It's not a very good nickname, but that is its nickname. And it also helps us to reabsorb sodium, move it back into the blood and where sodium goes. [00:11:26] Jill Brook: Water follows [00:11:27] Cathy Pederson: I do that in class. My students will just chime right in because I don't go on unless they participate. So normally what happens is this renin, angiotensin, aldosterone system is bringing blood volume up when it's getting down dangerously low and then it keeps our blood pressure where it should be as well. What COVID is doing is it's downregulating the ACE2 receptor, which is involved in this system. So that throws us off physiologically. And that can lead to hypovolemia. And I think the last time you and I were together for the show anyway, we talked about the three different kinds of POTS, right? And one of them is hypovolemic POTS. We think that the virus can be directly impacting the kidney, which can lead to POTS. We think it can be causing damage in the brain, which can lead to POTS. The third way that this virus can impact and perhaps cause POTS is through inflammation. It wasn't that long ago that in the news, they were talking about cytokine storms being set off by COVID. So I think a lot of our listeners maybe remember that, And cytokines are part of our immune system and they've got a good normal role. In COVID, they get out of whack and they cause way more inflammation than we should have, and they can cause dysregulation of the brain, right? So they cause those neurons to not work the way that they're supposed to. We also know when there's a lot of inflammation, that can also increase the risk of developing autoantibodies, which are the antibodies that mistakenly attack my own body cells. So they're not supposed to do that they're trying to go after the virus, but by mistake, they're now going after my cells. And what we see often is they go after parts of the autonomic nervous system. And so they're damaging, again, that central nervous system through inflammation as well as the direct effect of that virus. So sometimes when it's infection, immunotherapy can be helpful. I know you do IVIG, you've talked about that on the show several times before, but it helps to dampen down a lot of these effects. [00:13:53] Jill Brook: Right. Okay. So that is a lot of different ways that a virus might lead to POTS. It does start to feel like if one way doesn't get you another way could. So if I'm going to summarize, it sounds like a virus or an infection could affect the brain. It could affect the kidneys, it could lead to inflammation such as autoimmunity, and I think some of the mast cell activation syndrome researchers would say that they've got some hypotheses that it might also set off some mast cell activation syndrome, and that depending on where those mast cells are set off, ie. Next to nerves for example, then that can also lead to pot. [00:14:35] Cathy Pederson: Absolutely. [00:14:37] Jill Brook: Okay. Are there other things that can trigger the immune system apart from infections? [00:14:43] Cathy Pederson: Yes. The other big one is vaccine. And so again, even before COVID, about 6% of people reported that they thought that their trigger for POTS was vaccine injury, and those folks were talking about the HPV vaccine. So the human papillomavirus vaccine, we had Dr. Reddy on the show who talked about vaccine injury with COVID. We know that that's a thing. There are case studies out there that talk about that, but the big science isn't there yet. So they haven't been able to do those big controlled studies to really figure out what percentage of folks we're talking about. I think that'll be coming really in the next year or two. So those two go together because both of them, if you think about it, the immune system is fighting. It's priming. It's trying to prevent you from having bigger issues from an infection, whether it's the virus or the bacteria itself, or it's the vaccine that's trying to gear that immune system up. [00:15:53] Jill Brook: Mm-hmm. And sometimes we talk about my favorite researcher, Dr. Datis Kharrazian and in 2020 he published a paper where he looked at the amino acids in the spike protein of cOVID and looked at how closely do they match some of the similar patterns in the human body in different kinds of tissues. And he found quite a few overlaps. And so that would be one explanation for COVID or COVID vaccine, being able to potentially trigger some immune responses against some of your own cells. That's one hypothesis. [00:16:31] Cathy Pederson: yes. A mistaken identity idea that the virus is so close to your own body cells. Absolutely. [00:16:39] Jill Brook: Okay, so let's move on to the next category of triggers. So physical trauma and POTS. What goes on there? [00:16:48] Cathy Pederson: Yeah, this is an interesting one. So I think infection is famous and it's in the forefront of people's minds because of the pandemic, and we're welcoming way too many people into the POTS community as a result of that, unfortunately. But there are a lot of people who enter the community having a trauma. It's often head trauma. And what I saw in the literature is something that they called rapid deceleration injuries. And what that says to me is, you're in a car accident where you were moving at high speed and now you've had an impact and you've stopped suddenly. And so again, the brain is floating. It's not fixed inside of our skulls. And that both of these can stimulate dysregulation of that autonomic nervous system. So the one we know the most about is concussion. So let me start there. And about 4% of adults said that their trigger for POTS was concussion. But if you look at pediatric studies, it's higher than that. It's 11%. And that might make sense when you think about, kids at recess or in organized sports in middle school and high school. A lot of activity that's going on there where. their developing, brains are at risk. What's going on if you get a concussion? Well, it's a little bit of an oversimplification, but you are bruising the brain, so you've had a hit, either you are moving fast and now you've stopped, or something's coming at you with some force. Either way , it causes this bruising of the brain so you can have breaking of blood vessels and a literal bruise like you would have in your skin. It can decrease the blood flow to the brain. It can trigger inflammation just like you would with other kinds of bruising. But in the brain, what we really worry about is a s the brain is shaken, if you will, with this stimulation that you are tugging on axons, you're tugging on neurons, and that we might disrupt the communication because your brain has a consistency of a jello right? And so it's swishing around in there, and that's the big concern. [00:19:15] Jill Brook: So that's interesting. So you're saying that in a concussion or an accident or a hit to the head, your brain bounces around like jello, it could get bruised or inflamed, but also just the axons, the long kind of tail of the neuron. Is that correct? That they just might get stretched and stress? [00:19:36] Cathy Pederson: Exactly. And they have a name for it. They call it diffuse axonal injury. So a neuron has several parts, the cell body is where it does what a normal cell would do. And then the axons really long. Sometimes it's really, really small, a millimeter or less. But like the neurons that go from your spinal cord to your big toe, so you can wiggle your toe, it's axons going through your hip, through your leg. All the way across the foot to that big toe. So think about a basketball player in the NBA who's seven feet tall. These axons can be a meter long, easily. [00:20:17] Jill Brook: and are they fragile? So then what happens? [00:20:20] Cathy Pederson: They're very thin and they're fragile. So let's bring us back to the brain and the spinal cord. When we have that kind of impact, it can cause injury to these axons and it can be in a variety of places. So it matters where you got hit. how much force was involved in that impact, but it can affect what's called cortical structures. That's the outside of your brain. That's the part that makes you, you, your personality, your intellect, all of that stuff is there. And then also subcortical structures. So structures that are deep in your brain that you wouldn't see from the outside. The one of those that I want to pull out that's relevant to POTS is the hypothalamus. So if with concussion, We have damage that's coming from swelling from the impact itself or from this diffuse axonal injury. The home of the autonomic nervous system is actually in the hypothalamus in your brain, and so that can lead to dysregulation of things like body temperature, sleep cycles. We know that most with POTS don't sleep very well. Digestion and other autonomic functions. So damage to the hypothalamus is really important and can be an important trigger. Then as far as linking concussion to POTS, so they've done some other studies where they really are looking at people. Got their concussion from either sports injury, think like football or a blast injury. So that might be a soldier who has a bomb blow up, and their truck gets thrown or something like that. Those kinds of injuries are linked with a temporary autonomic dysfunction that affects your cardiovascular system, your heart rate, and your blood vessel function. So again, sounding very potsy here. Right? [00:22:21] Jill Brook: So you're saying in those situations it tends to be temporary, like somehow the system heals again. [00:22:28] Cathy Pederson: In lots of people that have concussion, that's exactly right. They are really bad. They really need to go into the dark, pretty literally for a week or two to let their brain rest. and heal, and then they can come back to full function. But again, we know a small percentage of folks that get concussion are not that lucky. Just like you were with your wisdom teeth unlucky, my daughter was unlucky with the virus. Some people are unlucky with these concussions. So in a lot of people it's temporary. And in the POTS population, it may be permanent.. So there's another study that really focused on athletes who had gotten a concussion during the course of their sporting event, whatever that was, and they didn't bounce back. So they're on protocols where they're trying to gradually get them back up to maximal exercise and they can't do it. Their symptoms go out of control, sound familiar to anybody out there? And so when that happens, they call it here's a air quotes, "likely physiological post-concussion disorder." And what they mean by that is that what most people heal from in, let's say, two to four weeks, some folks don't. So that blood flow to the brain continues to be too low. It's ongoing. It doesn't heal after a week or two weeks. There's also something called a metabolic energy crisis that many people have with concussion. That heals and after a few days or a week or two, it dissipates, it goes away, but in some folks it doesn't. So let me tell you what, this is a metabolic energy crisis. . It does not sound good, right? This means that the brain in this case needs more energy to heal than it has. So anytime your body is injured or you've got an infection, or in this case concussion and there's damage to that brain, you need to spend energy to clean up the damage and then to do as much repair as you can to restore function. Okay. We've got two things against us in concussion for this brain to heal. One is a decreased blood flow, so I said that in these people that have this likely physiological post-concussive disorder, that their blood supply to the brain remains low. Okay. they need a ton of energy. Well, where does the brain get energy from? Blood flow. It needs oxygen, and it needs sugar. It needs glucose, right? Our brain is a huge baby. It doesn't store it. It doesn't store lipids like other parts of the body. In fact, it doesn't burn lipids well, right? Like the rest of the body can, and it doesn't have a big store of glucose, which it needs, so it needs blood flow. So now I need more energy to heal, and I'm not getting it because I have less than normal blood flow to the brain. So they think that can be part of it. And then we can have, again, maybe that hypothalamus was impacted in a way that doesn't heal. So we get this autonomic dysfunction, which again, many of us recognize that Orthostatic intolerance, that exercise intolerance. And remember, this study was done in athletes who developed this largely when they were in season and it just knocked them for a loop. [00:26:18] Jill Brook: Wow. So it would be interesting for future research to look at what kinds of people don't heal. From those athletic injuries, which I'm guessing are a fairly standard common part of growing up and doing sports. [00:26:34] Cathy Pederson: Absolutely, and it's huge. And I have to say that we pay a lot more attention to concussion now than we did 10 or 15 years ago. And so I've been teaching at Wittenberg for almost 30 years. And when I started, I didn't have kids on concussion protocols and I had cheerleaders. I had football players, I had soccer players. But I see so many kids now that are on those protocols, we are identifying it better. Hopefully we're treating it better. We're really sending those kids into the dark and the quiet. But we're also realizing because we're recognizing concussions more that it is leading to some of these long-term health effects that maybe we didn't link it to when we weren't paying so much attention. [00:27:24] Jill Brook: Okay, I know that I'm going to be driving a little bit more defensively here in the next few weeks, and taking care of that head that's so fragile. Okay, so what about traumas to other parts of the body, or aside from just concussions, what do those look like? [00:27:44] Cathy Pederson: Yeah, this is really, I think scary. So the other major trauma that people have identified as their trigger for when POTS started was surgery. So, Jill, your wisdom tooth surgery, but it could really be any kind of surgery. About 12% of POTS patients identified surgery as the trigger. I have to say that the data is not out there. I looked. Okay, so what's out there in the publications, the scientific literature that I look at for these podcasts are mainly case studies, and what that means, folks, is that a doctor is doing a write up based on one case. Sometimes they'll do two or three cases, but it's not a good study. Where you're trying to control lots of things, it's really describing something that they haven't seen before typically. And so nothing that I saw said why? Why a surgery would trigger POTS. So I don't have an answer for that. Thinking back to what we just said about the trauma with concussion, needing that energy to heal. So maybe if the surgery is really invasive, which frankly wisdom teeth is not really, you're not bedbound for weeks like you might be for a heart transplant or some other really major surgeries. The other thing is that, again, if people are bedbound, For some time as a result of that surgery. Perhaps there are physiological adaptations that happen during that, where it just gets used to that laying down position and loses the ability to change position to being upright. We don't know. The studies aren't there. It's interesting. I think it's very interesting, and again, if you need surgery, you need surgery, but it's interesting that it could be a trigger for POTS. [00:29:44] Jill Brook: Okay. Our next trigger on the list is really fascinating to me. it's puberty because everybody has to go through puberty. You would think that humans would be well adopted to go through puberty just fine. What on earth do we think might be happening there? How in the world could just puberty trigger POTS? [00:30:07] Cathy Pederson: Yeah, it's crazy to think about, but many of us had a child. Or developed POTS as as a teenager. We see this very often in teens, within two years of beginning puberty, that they develop POTS. Well, let me start off by saying that about 5% of POTS patients identified puberty as the trigger. They don't remember a concussion or a significant trauma, they don't remember an infection. They think it's puberty. I will say in general that kids between the ages of 10 and 15, which is usually when puberty is starting, or the body is developing, have have much higher syncope and pre-syncope incidents than they did before that. So syncope of course, is fainting. Pre-syncope is when you feel like you're going to faint. Your vision goes gray. Maybe your head starts to spin a little bit, but you sit down before you actually faint. So that's pre-syncope. We see increased numbers of that as kids start going through puberty, both for males and females. The hypothesis is that it's related maybe to impaired autonomic function. Start seeing all the things that we talk about that fatigue, headache, dizziness, nausea, etc. etc. I read a really interesting paper. It's very complicated, so I pulled out the parts of it, frankly, that I could explain in a podcast, to be honest with you, when you can't see all of the interactions with things, but I also think they're the most important parts, and the paper was focusing on females. There's a higher preponderance, particularly at puberty of females developing POTS than males, and I can hear the guys groaning. I think that in the United States, what we are saying is percentages of men versus women is grossly over exaggerated towards females, other countries. That's much closer to 50 50. It's where we are right now. But anyway, this study was on women's, sorry fellas. Okay. But it's interesting to think about. In female puberty, the ovaries essentially are turning on ? They've been dormant during childhood and they start making that egg of the month that's going to be ovulated. But as part of that normal womanly cycle that we love O so much, we get big increases of estrogen and progesterone, which are the main female hormone. What people may not know is that both of these hormones promote vasodilation. Vaso means blood vessel dilation means that you're dilating it, you're making the diameter bigger. What that does when you're doing that in the blood vessels is it decreases blood pressure. So this is going to allow for blood pooling. It decreases that blood pressure as we're increasing the estrogen and progesterone. So that's really interesting. What I thought was even more interesting is that they talked about, and so here guys, you can come back in. Okay? Quit rolling your eyes at me. Because all kids, as they go through puberty, have other hormones that are not involved in the female cycle that are increasing. I'm going to pull out just a couple of these that I thought were the most important and it's insulin, which is probably your best friend, Jill is a nutritionist. And so that's really important in maintaining a good blood sugar. And then the second one is a group of hormones that are the thyroid hormones, which help to set metabolic rate in all of the tissues of the body. So if you think about it kids grow through a growth spurt at puberty. Growth hormone was in the paper. But both insulin and thyroid hormones also promote vasodilation. They're opening up these blood vessels, right? And. They also decrease or favor the decrease in blood volume. Remember that blood volume and blood pressure are tied. So now I'm opening up these blood vessels and I'm decreasing the blood volume, which means I'm decreasing my blood pressure. In addition, insulin and thyroid hormones also kick up. They increase our heart rate. So this is feeling very potsy. Now we're talking about normal, but in this paper they were talking about how if you went a little too far, that these hormones could be related to the development of POTS at puberty. It's an exceedingly complicated paper. And it's absolutely fascinating. So the other thing that they saw was that the insulin and thyroid hormones, so again, the one that's helping us with our blood sugar and then the thyroid hormones that are helping us with metabolic rate increased sympathetic tone. And the sympathetic nervous system is in overdrive in POTS, high sympathetic tone. They also found that insulin and thyroid hormones can increase the release of catecholamines, including norepinephrine. And norepinephrine is the neurotransmitter of that sympathetic nervous system. So it's really fascinating to think about all of the things that are going on in puberty, much more than the ovaries or the testes, waking up and starting to make those hormones. Fascinating. [00:36:11] Jill Brook: Yes, and thank you for sifting through all of that complex stuff for us. And what is coming to my mind is Dr. Shibao's lab at Vanderbilt has shown that POTS patients, even when they're young and lean, have twice the insulin response a couple hours after a glucose challenge. And so now, you know, just gets the wheels turning about are these connections. [00:36:35] Cathy Pederson: Right. It's so interesting and it's so complicated. That's the problem with all of this, right? In this episode, we're talking about all of these different ways that POTS might be triggered, and the way that it might be triggered from concussion is really different from infection, which is different from the hormones that we're talking about right now. And so when you really try to sit and think about and get your head around all of this, it's exceedingly complicated. [00:37:03] Jill Brook: So let's throw one more complicated scenario at you pregnancy. Talk about that as a trigger. [00:37:11] Cathy Pederson: Yeah, this is something I'm really interested in. People write into the show frequently, and you and I have talked about off the podcast trying to get an expert to come in and really talk about POTS and pregnancy and medications. If we've got any practitioners we would love to have that because there are many women of childbearing age who already have POTS, but 9% of women with POTS said that they think that pregnancy triggered the onset of their POTS. So when I looked and I actually texted Jill and said, I'm in trouble here, my friend , can you find anything? I'm not finding a doggone thing. And there's not much out there. So again, if we're hypothesizing a little bit based on what we just said in puberty, what we know in pregnancy is that the corpus luteum and then later the placenta. Have huge release of estrogen and progesterone. Progesterone helps us to maintain that pregnancy. We need it to maintain that pregnancy. But again, those are vasodilators. There are other studies, they didn't say very much. What they said was that they found physiological cardiovascular changes in women who are pregnant that they thought could lead to the development of POTS, but no explanation of what that was or what might be driving it. Most of the articles that I found, and I think you also, Jill, were case studies, but not about developing POTS from pregnancy, but rather is it safe? What medications are safe to stay on while you're pregnant? Or does it make your POTS worse or better? or do your symptoms stay about the same during pregnancy? So there were a lot of case studies on that. Again, I didn't see even big studies on that topic. So let's put out a call right here that we need people to work on this. There are so many young women who may want to start a family that need these answers. So please, practitioners call in, write in, and let's get you on the show to talk about that. [00:39:32] Jill Brook: Yes, more answers. That's what we are all about here at Standing Up to POTS. Okay, is there anything left for us to talk about triggers? I'm sure there's a world of more information to yet be learned. We have not even begun to scratch the surface of understanding triggers, but is there anything else out there? I know you really dug hard to find the best literature. [00:39:55] Cathy Pederson: Yeah. You're working me hard now. Like I said, those early episodes were pretty easy, but you're working me hard here, Jill. No, I think I would say that circling back to where we started that every POTS case probably has something trigger. We may not understand what all those triggers are. We don't understand the physiology of how that sets off this cascade of events that becomes what we call POTS, but we're working on it and I think that the more we understand some of the basic physiology, the better we're going to get at differentiating the subtypes of POTS and hopefully leading to treatments. But if we know that it's hormone related, we do this. If it's trauma related, if it's surgery or concussion, we do that. Or if it's autoimmune or from infection or vaccine. We use these other things. I do think that while it might be frustrating and sad to think about and hear about these triggers, I do think that the more that we understand about this, the better we're going to get at treating folks for their own personal version of POTS. At least that's what I hope. [00:41:16] Jill Brook: Amen. Well, thank you so much Dr. Pederson. We so appreciate all your hard work finding answers for us here on the podcast, and when you're working for the organization working to raise money to support research that's going to find answers. We really appreciate you. Thank you. [00:41:35] Cathy Pederson: It's a pleasure as always. Thank you, Jill. [00:41:38] Jill Brook: Hey, listeners, that's all for today. We'll be back next week, but until then, thank you for listening. Remember, you're not alone, and please join us again soon.