Good afternoon, everybody, and thank you so much for joining us for a live Q&A with Dr. Bart L. Clark, who is the Professor of Medicine in the Division of Endocrinology and Metabolism at the Mayo Clinic in Rochester, and Dr. Vafa Tabatabi, who is also a Professor of Medicine, Endocrinology, and the Department of Orthopedic Surgery at the Montefiore Medical Center in New York. And this session is a live Q&A for Life Cycles Consideration in Hypoparathyroidism. My name is Dimpi Desai. I'm a Clinical Assistant Professor at Stanford University, and I'm going to be our moderator for today's session. Today, we'll have an opportunity to directly engage and ask questions related to the content with all the authors who are with us of the recently released educational program, which is the Life Cycles Consideration in Hypoparathyroidism, and dive a little bit deeper into the topics. So I encourage all of you to put your questions out there for our expert panel. The topics that are included in this program is hypoparathyroidism in adults, which covered the diagnosis, treatment, and complications, hypoparathyroidism in children, so the pediatric consideration in long-term care, hypoparathyroidism in pregnancy, management strategies for expectant mothers, and then hypoparathyroidism in aging, so long-term care and complication in older adults. So before we begin, please submit your questions to the chat, but I do have some questions that I will begin with. So first question is for you, Dr. Clark. What form of calcium supplement is preferred in patients with hypoparathyroidism? Okay, so this is a very good and relevant question because most of our patients will typically take a calcium carbonate tablet because that's most commonly what's recommended for other bone disease, including osteoporosis, which some of these patients have, many don't, and for the purposes of our discussion here today, we're having children transitioning to adults also. So these patients in general could do well on calcium carbonate, but I'll tell you that during the clinical trials with the particular product that we're talking about today, calcium citrate was felt to be a better version because it absorbs better, and that's largely what we do clinically here. I think a lot of other centers do it as well, and certainly in the clinical trials, that was the preferred version of calcium to take calcium citrate because it absorbs better, and then it doesn't matter if the patients are on proton pump inhibitors, H2 blockers, or other common treatments for gastroesophageal reflux. Okay, thank you so much for that answer. So calcium citrate. Dr. Tabatabi, the next question is for you. What are some of the strategies to address hyperphosphatemia in these patients with hyperparathyroidism? Yes, thank you very much for that question and for our audience for joining this webinar. I mean, we all know that hyperphosphatemia is probably one of the most common complications of treatment of patients with hyperparathyroidism, as opposed to CKD or nephrolithiasis that sometimes can happen later with longer disease duration. Hyperphosphatemia is something that we often have to encounter and find strategies for treating right away after we start patients on treatment, and that's because we have to use active form of vitamin D for improving calcium absorption and returning the serum calcium to normal, which leads to increased absorption of phosphorus from the intestine too. So the main strategy for trying to address hyperphosphatemia is to ask patients to take their calcium supplements with meals, because in that scenario, in addition to providing elemental calcium, it also acts as a phosphinder and can potentially decrease the absorption of phosphorus. The other options of phosphinders that we commonly use in patients with advanced CKD, such as develomere, have not systematically been studied in patients with hyperparathyroidism, so we don't unfortunately have good guidance about other options, but I definitely would start by taking calcium supplements with meals and potentially some dietary modifications if possible. Okay, thank you so much. Next question for you, Dr. Clark. Do all patients with hyperparathyroidism need magnesium supplements? Okay, so this is again a very good and common question, because everybody knows that these patients may be hypomagnesemic, and if they are, we're generally going to have to give them magnesium supplements. In my own experience, I would say, and based on series in the literature, I'd say probably a third of our patients with this condition may have hypomagnesemia. So one of the key teaching points about this discussion, I would say, is that don't forget when you see a patient who supposedly has hyperparathyroidism the first time, measure serum magnesium along with other things that you're going to check, because if you don't document hypomagnesemia at that point, it's easy to forget, it's easy to overlook, and you may be aware that there are disorders that cause hypomagnesemia that can mimic the biochemical appearance of hyperparathyroidism. Low serum calcium, high serum phosphorus, low serum PTH, and if you didn't check the magnesium, you can miss that, and of course, it's always embarrassing to have your nephrology colleagues correct you later and tell you that this patient doesn't in fact have hypoparathyroidism, they have hypomagnesemia. So that's why I put that question in there. I think it's useful to be aware of that. Once you rule it out, then of course, if they don't have hypomagnesemia acquired over time, you wouldn't normally have to give magnesium supplements. So most of our patients don't use them, but it's on the list of things that are commonly given if there is coexisting hypomagnesemia. All right, thank you so much. Dr. Tabatabi, is it important to normalize the 25-hydroxyvitamin D, given that its conversion to 125-dihydroxyvitamin D is impaired? This actually is a question that I had when I was a fellow, you know, because in patients with hypoparathyroidism, we know that they don't activate the parent vitamin D, so the 25-hydroxy to 125. So what is, you know, why should we even worry about the 25-hydroxyvitamin D? So most experts and guidelines basically try to keep the 25-hydroxyvitamin D at least close to the normal range. And by that we mean like above a level of 20. And that is mainly because of the possibility that the 25-hydroxyvitamin D might have extra skeletal effects. So there are, you know, kind of some evidence available about this here and there about potential effect of 25-hydroxy in immune mechanism and other extra skeletal manifestations. So that is the reason just to kind of be on the safe side. People try in general to keep the vitamin D somewhere near normal, so higher than 20 is generally what is recommended, which obviously adds another problem here because one of the things that we always worry about in patients with hypoparathyroidism and have to deal with is pill burden. So, you know, this is another pill on top of another pill, but generally it's best to try to keep it at least near normal. Okay, thank you. I know what to do now with my patients. For Dr. Clark, can you answer this question about whether hypoparathyroidism ever resolves spontaneously? All right. So I put this question in because I came across the answer to this question at a poster at the Endocrine Society, not looking for it, not intending to stumble across it, but sure enough, there it was. And I thought, can't be. But of course, if you have autoimmune hypoparathyroidism, theoretically, at least that could reverse or change course, as we've seen in other settings, not necessarily related to parathyroid dysfunction. And so, of course, there is a paper published, I think it is in JCNM, by the Bill Azekian Group, showing that they had four patients that they had followed for long-term for their studies in this disorder. And it found out that four of them spontaneously resolved an average of, as I recall, seven to eight years after the original diagnosis. And in this paper, they reviewed the confirmation of the diagnosis. It was not incorrect. It wasn't missed or mislabeled. It turned out, yes, they had it at the beginning. And then over time, as things developed, whatever antibody had been being produced that was driving the hypoparathyroidism either went away or was ameliorated or got better. And the assumption is that parathyroid function, parathyroid gland function came back enough that they were able to stop certainly their calcium, their vitamin D. And I believe these patients had all been given experimental drug at the time that they then didn't need it because they became hypercalcemic when they were taking their shots. And so this is a very interesting story that's, yes, a nugget and not very likely to happen in your practice or my practice. But keep this in the back of your mind because we never know when the patients show up. Certainly if they have a neck scar, we assume that it's post-surgical. But of course, even post-surgical patients may have autoimmune disorders and things can change over time. So keeping an open mind about this, I think, is important. And that's, again, one of the reasons why I thought this is something other people need to hear about, because we'll see this more commonly as time goes on, as more products become available to treat this condition. Well, thank you for that information. I didn't know that. We'll definitely keep that in mind while we monitor long-term. Dr. Tabatabi, I have a question regarding a DEXA scan. Do these patients with hypoparathyroidism need to have the DEXA bone density scans? Compared to the patients with the intact parathyroid function? So, yes, that's an interesting point about, we know that patients with hypoparathyroidism don't have a normal skeleton because of decreased bone turnover. So we know that definitely the quality of the bone might not be normal, but the density of the bone, which is what we check in DEXA, is often increased. And while we don't have a good way of measuring bone quality routinely in clinic, and basically our only routine measurement of bone strength is by doing the DEXA, does it make sense to check it in these patients? What I would say is, perhaps looking at other risk factors in these patients would be a good guidance. So, obviously if a patient is postmenopausal, especially if they develop hypoparathyroidism after menopause, so they already had the effect of parathyroid hormone the effect of parathyroid hormone on bone turnover and skeletal turnover, and could have a degree of osteoporosis or osteopenia before they develop hypoparathyroidism. So that would be a scenario that I would definitely consider doing a bone density test. And in others, maybe it would be less of a concern in younger individuals, but definitely in anybody who has any other risk factors for poor bone health, including smoking or steroid use for their other autoimmune conditions, for example. I would keep those in mind and consider them when deciding whether to do a bone density in these patients or not. Okay, thank you. The next question is for you, Dr. Clark. Are complications worse in post-surgical or in non-surgical hypoparathyroidism? Okay, so this is a good question that has many facets to it. Of course, complications is a broad list of things that we have to be aware of. But make a long story short, based on the studies published out of the Aarhus by colleagues in that area that most of us would know or meet at the meetings, it turns out that the non-surgical patients who have longer standing hypoparathyroidism, many cases from childbirth or toddlerhood or young adult life, for longer term issues, have more serious complications. And there's a very nice table in one of the JCNM publications from 2016 that shows this, comparing those who had recent onset post-surgically as adults, most commonly, sometimes as young adults also. But the duration of follow-up in most of these studies is somewhere in the range of, say, 9 to 12 years, as opposed to the non-surgical patients who are being followed for up to 50 years. And this is the published data. Now, it kind of makes sense if you said, well, if they develop this earlier in life, of course, that might impact growth and development. If they have longer duration of disease, this would make sense that they might develop earlier complications, more severe complications, more numerous complications over time. And I think all of those play a role in this, even though there's still a question about whether these differences that are seen are really due to differences in the disease, or is this just difference in duration of disease predominantly? And up till now, there is no good answer to this question. So I put this in to sort of be a source of debate. But at the same time, what is published in the board answer question, if you got asked this on a board question, would be, say, the non-surgical patients based on the data we have. So. Thank you for that. So what do you see more in your practice? Do you more see non-surgical or more the post-surgical? Yeah. So as an adult endocrinologist, most certainly I see non-surgical, sorry, surgical patients more commonly. On the other hand, I would say maybe in my own practice, this is a filtered practice, obviously a tertiary level type practice, maybe 15% non-surgical, most commonly autoimmune, sometimes genetic causes, and a range of others. I don't think I've ever seen anybody with thalassemia who had this or with iron overload, but I know that can happen. So. Wonderful. Thank you so much. I would really encourage our audience to ask questions, more questions, and put it in the Q&A. So as you know, we have our expert faculty to answer all your questions on this topic. So feel free to ask your questions. Then I have a question for you, Dr. Rafa. Who should be referred for genetic testing? I'm happy to answer that question. I actually just wanted to tag on to Dr. Clark's comment about surgical versus non-surgical. I definitely agree. Majority of cases that we see are also post-surgical. It's interesting how sometimes we see these cases of non-surgical hypoparathyroidism that go undiagnosed for a very, very long time. Patient for some reason, let's say an admission for like an acute illness or surgery or trauma or something. And then their baseline serum calcium, which has been, you know, little low 7.98 for decades, suddenly dips a little lower than that. And, you know, when it gets to like six range, then we get called. And then you look back and you see the patient has had chronic hypocalcemia for very, very, very long time. I would imagine that they probably have a little bit of parathyroid function left in the context of autoimmunity. But I think there are cases of autoimmunity or other reasons for non-surgical hypoparathyroidism that if we look closely, we might be missing. And just come to attention for some acute reason. Now going back to who needs genetic testing. So in general, if patients are diagnosed with hypoparathyroidism at a young age, and that has been defined as less than 40, or if they have any kind of syndromic features. So for example, and other autoimmune issues that we think might fall into the APS1 autoimmune polycystic syndrome type one diagnosis. So specifically adrenal insufficiency or autoimmune hepatitis and mucocutaneous candidiasis. So anyone who has hypoparathyroidism plus any other component of what might be a syndromic feature or individuals who have a family history of hypoparathyroidism should be referred for genetic testing. And sort of going back to what happens in real life. I think having a family history of hypoparathyroidism is also one of those things that might not be very clear cut. Sometimes people don't share their history with each other, or, you know, families might know that somebody had a low calcium, but it's not one of those diagnoses that kind of sticks in your mind. Everybody knows diabetes and hypertension, but maybe not low calcium. I have a patient who has autoimmune hypoparathyroidism and her mother had a history of seizure disorder and passed away at a young age and nobody, you know, we don't know why, but I am personally having a high index of suspicion that the mother would have also had hypoparathyroidism. So sometimes family history is not very clear cut and you might need to do a little detective work to clarify it. Is it easily, is the genetic testing easily available or it has to be done at a larger center? I personally sent genetic testing for parathyroid antibodies, actually to Mayo Clinic for this patient. And I think it's commercially available at Quest as well. And it actually came back positive. And so I think the next step for this scenario, in this patient, she also has vitiligo and also has Hashimoto's. So the next step would be to test her for the AR gene and APS1. And there are gene panels that can be ordered commercially, like you've said, both for hyper and hypoparathyroidism. There's also investigative labs around the country and around the world, actually, that you can request. And of course, if you think you have a new mutation, because it's not the common ones that we would think about, they're very interested in this. And so, for example, Michael Manstadt at Harvard has an interest in this. Raj Thakkar at Oxford, who's published on this a lot, has an interest in this. And communication and sending serum can be done both sort of at an experimental level, where, of course, the patient wouldn't be charged. I don't know what the billing is for, say done at Invitae or other groups that offer these, but these are options that increasingly we're going to have. And of course, with these family histories or weird features and syndromic features, perhaps, as long as we recognize them, of course, they wouldn't be missed. But a lot of these, you realize the syndromic versions of this tend to be, you know, found in one or two or three or four families around the world in the last 30 years. So these are not common mutations, but some of these are. And of course, the ADH1 is a common mutation that is thought to be fairly common genetically, and that we might find in a fair number of patients were we to screen for it, but you have to use judgment. So. Thank you so much for all that insights about genetic testing. I'm sure very helpful to the audience. There's a question from the audience asking if there's any connection between hypoparathyroidism and pseudohypoparathyroidism. Yeah, I'll just give my version of this. In the adult world, I don't see that like hardly ever. We have patients with pseudohypoparathyroidism that are recognized and being appropriately cared for, sometimes referred in from the outside, sometimes managed internally. And I would say most of those people have no common denominators, at least, that would make you think about a commonality between hypoparathyroidism and pseudohypoparathyroidism, almost by definition, because what's required to make the diagnosis excludes the other. And whether that's always true or if they have a borderline level that you potentially could argue might have features of both, it gets complicated. And because a lot of the people with great expertise in both pseudohypoparathyroidism and pseudosuedohypoparathyroidism tend to be in the pediatric world, oftentimes I will send questions to my colleagues who deal with calcium disorders in the pediatric world and see what they think. I've never seen a patient who had both or that was said to have both, so. All right, thank you for that. Thank you for sharing so much lovely information about hypoparathyroidism with our audience. I don't have any further questions. Any closing points from our expert panelists, anything you would like to teach, last learning points that you would like to give our learners? I actually wanted to ask a question. Yeah, let us ask questions. Let's have some discussions here. I was wondering if anyone on the panel has any preference for use of a thiazide diuretic in a patient who has hypercalciuria. So I'll tell you my approach to this, which more or less reflects the approach here, but I think it reflects the approach taken elsewhere as well. If you have hypercalciuria that you cannot control through dietary manipulation, changing in supplements and the patient, certainly if they develop kidney stones, whether by imaging only or by symptoms and passage, where it's very obvious they are, I think most of us would have a low threshold for starting a thiazide diuretic and trying to manage that to get the 24-hour urine calcium less than nowadays, the guidelines would say less than 200 milligrams is the optimal goal. In the old days, before the most recent guidelines came out in December, 2022, it was said 400 milligrams was the target. And so I'd say, well, for kidney stone prevention, I think even if you get the numbers under 400 or ideally under 300, if you can accomplish it to 200, sometimes the limiting factor is the blood pressure of the patient who tends to drop more than they can tolerate. They get lightheaded, they get dizzy, they get hypokalemic. I mean, all these things are fairly common limiters. And so I've taken an approach where I just use the dose that they can tolerate. And even if I can't make it better, I'm happy with that. I try to do the best I can, but some of these people I think are going to be stuck with some degree of kidney stone risk that you can't really fully ameliorate, more or less like we see in other patients who have idiopathic hypercalciuria or other causes for hypercalciurian stones. This is a case in point, I think that hypoparathyroidism does this. Now, maybe a bigger mystery is why not more patients with hypoparathyroidism develop hypercalciuria because most of them starting out have decent upper normal levels. It's only when they start the calcium supplements, the vitamin D supplements, that this becomes a bigger issue, at least in my experience anyway. So. That's great, thank you. Okay, maybe I'll ask you a question because one of the topics you had was whether people need vitamin D supplements in addition to the calcitriol supplements. It turns out in the clinical trials, and I've been part of most of them up until the current time, everybody agrees that taking the 25-hydroxyvitamin D supplement in addition to calcitriol and trying to maintain both 25 and 125-dihydroxyvitamin D in the normal range makes sense because it's known that many tissues depend on 125-D, but other tissues depend on 25-hydroxy-D, not just the kidneys, and they'll one-hydroxylate the tissue. They have the enzyme machinery to do this in these tissues. And if they're maintained at a 25-hydroxy-D deficiency state, they will not have in tissue 125-D levels that you might want otherwise, even if it's not directly related to calcium or phosphorus or parathyroid over secretion. So I think for general health, that's kind of been the consensus pretty much of all the investigators I've worked with, and everybody has no debate about that anymore. Although at the beginning, I would say 10 years ago when these clinical trials got started, there was debate because people didn't know. They weren't convinced they had to have both. I think most of the evidence accumulating since then says they do better if they get both 25 and 125-D levels close to normal, so. Yeah. Yeah, that's an excellent point. It's sort of, I think the journey of endocrinology for a lot of us starts by thinking about the mechanism, which I personally always encourage in our trainees. And then kind of you make your way through there, and we're lucky that we're accumulating more and more data to support the kind of physiological mechanism that we kind of think our way through. Yeah, yeah. And one of your earlier points about the phosphorus, if you said, what is the most effective method for lowering phosphorus in these patients? I would have to say based on the clinical trial experience, but also based on my own clinical experience, it seems to be that parathyroid hormone analogs are more effective at lowering serum phosphorus than any other version of what we can try. We always try those other things, but there's still a fair number of patients who are left with more significant hyperphosphatemia than we want, and of course that contributes to urine phosphorus and other things, and it complicates other matters. And so if we can get the serum phosphorus as close to the upper limit of the normal range, most of us would aim for something close to 2.5 milligram per deciliter as a, sorry, 4.5 milligram per deciliter as a target. You can sometimes get there, but sometimes you can't, and then you're stuck with a phosphorus of 5.3, and in some cases, much higher levels of phosphorus that you just cannot bring down until they get parathyroid hormone analog therapy. And so that's been one of the early things. The improvements in serum calcium, at least with the first product that was on the market, were less than the improvements in serum phosphorus, and yet that's not a highlight or what we think of as to when we think about giving patients parathyroid hormone analogs, but that was the data. So it's been a very interesting experience to see how these things develop. I am so glad you mentioned that. I think we are kind of mainly, that this are centering our discussion around conventional therapy, but it's great to know that now we have an approved product for PTH replacement, palopectary paratide, which was approved as of August, 2024. So it's, when we started kind of creating this educational activity, it was not approved, and then sort of in the middle of it, it got approved, and it's really good to know that that option is now available to our patients, and especially those who have challenges with the conventional therapy because of all of the reasons that was mentioned, hypercalciuria, pill burden, quality of life issues. I have a question about that. How was your experience with that drug in terms of insurance coverage and efficacy? Yeah, so those will become more evident here in the next few months, because up until now, it's only been investigational, and of course, there was no difficulty getting it for the people in the trial. On the other hand, as you know, there's an expanded access use program going on sponsored by the company, Ascendus that makes it, and of course, you can get it even till now, even though the commercial supply is apparently not gonna be available till mid first quarter 2025. We hope sooner, there may be reasons why it does become sooner, but right now, all of my patients who are waiting for it were anticipating somewhere in February 2025 is when we're gonna find out. I don't know the cost yet. I don't know the logistics of that. That'll become evident too as we hear more, but the drugs are, as they become available, and other products that are under development currently will likely become available eventually. This has made managing this condition that used to be a very large challenge for the endocrinologist because we just don't have anything we can give that improves some of these things if they don't tolerate the options we have, and this has really limited what we could do in a lot of those patients. I think going forward, this will be quite a bit easier to manage as long as the cost is reasonable and patients can get the drug, so yeah. I also wanted to encourage everyone, you know, while we're kind of navigating this emerging market of PTH replacement to keep an eye on ongoing clinical trials, maybe in your vicinity, so that might be also an option for referring patients if they are willing to participate. Yeah, and there's at least two other products that are under clinical trial application now, so I don't know that those trials have closed yet for recruiting of new patients, so you could ask around and find out. I'm not sure where those centers are, but the sponsors of those trials, of course, would be happy to let you know where the nearest center is to you, even if you don't know somebody there and put you in connection. Patients find this information out all the time going on the website and looking, but that's an option that you have even till now, so. Such a wonderful, exciting time for our patients with long-term hypoparathy autism and the spill burden to get these medications. I have an interesting question from the audience about nephrology specialty. So how often do nephrologists manage hypoparathy autism patients? I know it's all institutional, but what is your experience for nephrology? For most of the nephrologists that we have here, it's an immediate cause for referral to endocrinology if they're diagnosed, because it's not something that they're familiar with, and the therapeutics of this as it's developing is not something that has really included nephrology in the development process. I think some of the newer clinical trials will do that more, but early on it was endocrine only. And so, of course, I think eventually they will probably have interest in this. On the other hand, it's almost easier to send the patients to your endocrine colleagues than to have to deal with that too on top of all the other issues related to the renal function, so. I absolutely agree with that. I am not aware of our institution in nephrology department to have any interest in managing hypoparathyroidism. And in fact, this is one of those areas where I think nephrology is very used to seeing low serum calcium levels in patients who have advanced CKD. And obviously, if you check your PTH, it will become clear, but this might be one of those situations where your eyes are used to seeing low calcium and might not necessarily kind of trigger the question of what the etiology is. So yes, there's definitely a role for endocrinologists to come in and help with diagnosis and definitely management. Yeah. I think they manage the second G and the tertiary hypoparathyroidism. Yeah, exactly. Not the hypoparathyroidism. Not hypoparathyroidism, exactly. Yeah. So another question that comes up sometimes is what about the patient who presents with acute onset of hypoparathyroidism after their anterior neck exploration for whatever reason, be it thyroid, thyroid cancer, other head and neck tumors, or even sometimes hypoparathyroidism or primary hyperparathyroidism, the initial surgery. This medication that's currently coming and none of the medications thus far has been approved for use in the treatment of acute onset hypoparathyroidism, even though it's the only drug we have that could be used for that indication. Right now, you still have teriparatide, but now there's the new palopeg teriparatide. Somebody could do a clinical trial in this setting in the hospital setting, post-surgical, and hopefully show benefit that would eventually get FDA approval for this. But to my knowledge, there's no actively planned investigations going on to that effect, but yet that would be another reason. And yet we'd have to tell all of our colleagues who now have a patient who's post-surgical, usually a day or two out, they're severely hypoparathyroid. And why can't we use the new drug? Because the FDA didn't approve that. And because it was not investigated for that reason. And of course, this would be off-label use, which means usually the patient has to pay out of pocket. And if the cost is more expensive than they want, of course, this will not be used very commonly, but it's an option to consider, so. That's a great idea for a clinical trial. Yeah, and there's enough post-surgical hypoparathyroidism out there that it wouldn't take very long to recruit those patients. Exactly. Even a single institution might be enough to document that. And of course, the company that makes the product, of course, might take that to FDA and all that. It's not an FDA-regulated trial, so of course the company would have to be convinced that this is an important thing, that this would expand the use of their product and all that and take the time and effort to do it. As you know, these days, cost of clinical trials is substantial and smaller companies have less resources to do this and all that, so. Thank you. There's another question regarding diet from the audience. How often do you involve a dietician to co-manage the patient? I have not routinely done that. I think between management of hypoparathyroidism and management of osteoporosis, we have all kind of developed lists of food items that have calcium in them. And especially if, you know, it's gonna be more challenging in patients with hypoparathyroidism because they are so dependent on like a specific prescribed amount of daily calcium intake. But there are a lot of online resources for looking at the content of calcium in different food products. So I have not routinely referred patients to dietician, but it's definitely a part of my personal consultation with the patient to go over the list of food products that have calcium in them in an attempt to decrease pill burden both here and also in osteoporosis more commonly. Yeah, I would agree. I think our dieticians developed a pamphlet that talks about food sources of calcium, which we very readily hand out because it has a lot of information in there that even I wouldn't know off the top of my head usually. So that's one source. On the other hand, if you said the situation where I tend to use dieticians more is when they're hyperphosphatemic and I can't bring them down. And I'm trying to think, I don't wanna put them on a renal diet like we would with renal failure. But on the other hand, if they're eating, virtually everything has phosphorus in it, is there any way they could have a modified diet that's not as strict as a renal diet and yet would be helpful? Because otherwise, again, we don't have a lot of experience using the late stage chronic kidney disease, phosphate binders, they're out there. We could try them, but again, there's no clinical trial data with them. And of course this would be off-label use. And so it brings up a number of issues. But the dieticians I think are particularly used to giving the renal diets to the renal patients and they would be able to figure out a low phosphate diet that maybe is not as restricted as the renal diet but would help us because otherwise, like I said, the most difficult patients I've ever taken care of with this condition have not got low calcium that I can't fix. It's the hyperphosphatemia I can't bring down. And that's particularly true before the parathyroid hormone analogs became available. So big issue. Thank you so much. All right. Can I bring up another question? Are we, we're not out of time yet. So I'll just ask another question or two. Couple of things, postmenopausal women, I have a number of women with hypoparathyroidism in my practice that went through menopause after they had been diagnosed. I'm amazed at how fast those people can lose bone density because they lose it as fast as it seems the normal people do who are just postmenopausal without hypoparathyroidism. The protective effect of lack of parathyroid hormone against bone loss, I think definitely is real but in other settings, you know, you have other conditions that may cause bone loss independently of the parathyroid function and status. You have to look at those patients I think a little bit more carefully and maybe check them more often or certainly closer to menopause. So I tend to check those women that are losing bone density that I know of it already because it's been checked. I continue to monitor usually every two years. Otherwise I normally would check people maybe initially at the baseline and then maybe five years later if they have normal bone density and they don't have other factors. But, you know, the other factors are not just postmenopause it's other things. I had a lady today with mastocytosis and this is a known factor for causing bone loss. She's not got hypoparathyroidism but if she did, I'd predict maybe the histamine excess and all that might be a factor driving bone loss. So I think you have to think with an open mind about this. I generally tell my patients with hypopara who don't have other known diseases that cause bone loss they're probably largely protected and they're better protected than if we gave them antiresorptive drugs that prevent bone loss. So they're happy to hear that even among all the pain and suffering they have for the hypocalcemia and hyperphosphatemia. But at least that part of it, I am more suspicious with women approaching menopause or who have other factors independent of the hypoparathyroidism that should protect them because sometimes even that is not effective, so. Wonderful, that's a great point. I think I've learned so much in this conference myself by just listening to the two of you and I'm sure our audience has even learned a lot. Any final questions from the audience? You know, we're happy to answer here. Or any final closing points from the panelists? I don't know if our emails are given as part of the package for the program. If it is, feel free to ask later because lots of other people do anyway and you're certainly, you know, not paying good money for it but at the same time, we can answer things as best we can, so. Yeah, we have one question. Since low alkaline phosphatase can be seen, have you ever had any secondary diagnosis of hypophosphatasia? Yeah. Vafa? I have not and I would imagine, I mean, what an unlucky situation that will be for someone to have two relatively real conditions at the same time. Fortunately, I have not come across that scenario yet. Yeah, and I haven't either and I see a fair number of newly diagnosed hypoparapatients but not anybody who's had coexisting proven hypophosphatasia and hypoparathyroidism. If you come across one, that certainly should be a JCNM case report because they're taking case reports now and I think that would be a very high likelihood of acceptance and let the rest of us know. Exactly, would be helpful for us to know such a entity exists as well. Yeah, yeah. Yeah, very rare. All right then, I think we had a really great session with so many interesting questions and so much. I think both questions can definitely be answered on this topic just by attending this webinar. And thank you both of you for your time and your patience and for answering all the questions and thank you to the audience for attending and I wish everybody a really good evening. Thank you. Thanks very much for having us. Have a good evening. Thank you now, good luck. Bye-bye. Bye.

hypoparathyroidism

calcium citrate

hyperphosphatemia

magnesium supplementation

25-hydroxyvitamin D

genetic testing

parathyroid hormone analogs

bone density