Well, hello, everyone. My name is Julie Montgomery and I'm a large animal internist, and a professor and department head, at Oklahoma State University College of Veterinary Medicine. So, today, we are going to talk about equine endocrine diseases.
And as part of this presentation, I plan to share the two most common equine metabolic conditions, and that's equine metabolic syndrome and pituitary pars intermediate dysfunction, or PPID. So the term equine metabolic syndrome has been around for about 20 plus years, and it is sort of derives its term from its equivalent in human medicine, which is called human metabolic syndrome, and they do share a number of similarities, and that's kind of how this terminology developed and over the years, those similarities have also been compared. So before we delve more into the clinical condition, I would like to review a couple of clinical scoring systems that we use to assess horses that might be at risk of equine metabolic syndrome.
So we associate this condition with horses that are obese or over-conditioned in many cases. And so one of the things that we do when we assess horses is assess their body condition score. And so as part of that, we look at several areas along the horse's body, including the neck, specifically the crest, areas around the shoulder, around the hips, the back and the flank, and we look at the general condition also whether there are potentially regional fat deposits, which is something that we call regional adiposity.
And then horses body condition is scored 1 out of 9, with 1 being extremely thin, and 9 being extremely fat. We consider 5 ideal in some breeds they might have more of a. Trend more towards the 6, especially warm blood breeds.
Thoroughbreds might trend more towards the 4, but generally that's what we would consider normal condition. And then 7 we consider overconditioned and 8 and 9 we consider obese. And so when we assess these horses, some horses may have show overall obesity, but what is even more More significantly associated with a horse that might be suffering from equine metabolic syndrome is something that we call regional adiposity.
And so that would be fat deposits along some of these common areas such as the neck, the shoulder, the hips, and the flank, and these horses might have these regional fat deposits, but overall actually have a normal body condition. And so, for this reason, another scoring system has been developed that assesses one of these areas where regional adiposity is common, and that is the crest of the neck. And so this is called the cresty neck score, which goes from 0 to 5, and 5 being An extreme crest that might droop to one side, obviously in this case it's important to.
Keep breed differences in mind. So there are some breeds, specifically Spanish, the Spanish breeds, which may have a more pronounced crest as part of their breed characteristics. So equine metabolic syndrome is called syndrome because it's essentially a collection of clinical and metabolic factors that predispose these horses to a different number of problems.
The hallmark of equine metabolic syndrome or EMS is abnormal insulin metabolism, specifically insulin dysregulation. Some of the common clinical characteristics are obesity or regional adiposity, specifically fat accumulation along the crest, around the shoulder, the hips. They may also show a crease down their back, as you can see in, in this picture.
They may present for weight loss resistance, or sometimes, clients refer to those horses as easy keepers, and they may also have an abnormal fat metabolism. That being said, there is also a lean EMS phenotype, and that's important to keep in mind. So these horses may phenotypically look thin, but can still be insulin dysregulated.
And the reason why we care so much about this condition is that it's associated with the predisposition for laminitis among other health, health consequences, but the predisposition for laminitis is the most catastrophic consequence, and the one that we try really hard to prevent, which is why it's so. Important to detect these forces early. And the laminitis associated with hyperinsulinemia is now referred to as hyperinsulinemia associated laminitis.
You may also have come across the term endocrinopathic laminitis, which describes the same thing. And so when we talk about insulin, dysregulation, that is made up out of a combination of fasting hyperinsulinemia in some cases, although this may not be present in some horses, which is also why baseline insulin is not always a reliable measure of this condition. Post predial hyperinsulinemia.
And tissue insulin resistance. And the reason why this is important is because this determines the diagnostic testing that we use to diagnose metabolic syndrome. So clinically, these horses are frequently referred to as easy keepers, meaning that they don't seem to take a lot of nutrition to gain weight.
They may have a normal or an increased body condition score as previously mentioned, so not all obese horses have metabolic syndrome. Not all horses with metabolic syndrome are obese, and that's important to keep in mind. They, the regional adiposity is really considered a hallmark of this condition, and then, they may present actually for acute laminitis or they may have a history of laminitis.
And so several groups, including ours, have shown that when it comes to the morphometric measures, so the body condition score and the crest neck score, the cresti neck score is really the better one or the more reliable one when it comes to Detecting insulin, dysregulation or . Increased risk or odds of insulin dysregulation, and so that just highlights that this regional adiposity is, is more closely linked with the metabolic syndrome and the insulin dysregulation, rather than just over being overall overconditioned or obese. So when it comes to diagnosing and managing metabolic syndrome, one thing to keep in mind is that this is not a curable disease, it's a manageable condition, but it is something that the horse will be dealing with for its entire life.
These are a couple of really nice open access resources, so they're available for free on the web. One is, the consensus statement from the European College of Eququi Internal Medicine. Which was published in the Journal of Veterinary Internal Medicine, reviewing equine metabolic syndrome.
And then there's also the equine Endocrinology Group, which puts out free resources on both PPID and EMS and they update these every other year. They post them on their website and they're really nice resources for clinicians to review. Options for diagnostic testing, how to interpret diagnostic test results, and also how to manage these conditions.
And so when it comes to the diagnosis, one of the challenges that we have is that currently is no gold standard test, and because it's a syndrome, so a collection of clinical and metabolic abnormalities, there's also not just one clinical presentation. And so this graphic, which comes out of one of the publications from the equine Endocrinology Group from their most recent EMS summary, kind of highlights what, what, what some of our challenges are. So it's insulinous regulation specifically that's associated with a higher laminitis risk and our goal is to detect horses.
That are at higher risk before they suffer from laminitis. But the challenge is that there are obese horses that are not insulin is regulated in humans, that's called metabolically healthy obese. They're also, one of the other sort of complicating factors.
And that causes a lot of confusion amongst clients as well, is that horses with PPID or pituitary parts intermediate dysfunction, a subset of those horses can also be insulin is regulated. So they basically can have EMS and PPID concurrently. And so that is another thing that we're trying to figure out in our diagnostic testing, especially if the primary presenting complaint is laminitis.
So we wanna make sure that we also rule in or rule out PPID at the same time. So one of the challenges that we have is that many horses with equine metabolic syndrome do not not generally hyperinsulinemic all the time, and so that's why baseline insulin is frequently normal. The other thing that's different between horses and humans is that whereas in humans, metabolic syndrome is often considered a pre-diabetic state and, and the assumption is that many of these people eventually will develop type 2 diabetes.
That seems to not be the case in horses. So horses generally stay at the EMS stage, which means their baseline glucose also is generally normal. And so for this reason, we really use dynamic testing as sort of the preferred way to test and we can test sort of the two components, so the postprandial insulin response or the interinsular axis.
So that's assessed with the oral sugar test. And we can also test for tissue insulin sensitivity, and that's assessed with the insulin tolerance test. And so I put this in here just to highlight again how useful the resource is from the equine endocrinology group.
They essentially will walk you through how to do these tests, how to interpret the tests, when to take the samples, . And that is, is, really sort of easy resource to follow. The other thing that complicates interpretation of test results, and they do, do mention this in, this summary, is that depending on the actual analyzer that the lab uses, to measure insulin, the values may differ a little bit as well.
So, many labs. Now use the Emulate 2000 XPI, and that's also what a lot of the recent publications use. But when you compare different studies, it's actually important to sort of pay attention to the analyzer that's being used and also know which analyzer your lab uses when you interpret, the test results.
And then, as previously mentioned, one of our main objectives is to ideally diagnose horses and implement management strategies before they develop laminitis and detect horses at increased risk of hyperinsulinemia associated laminitis. And the reason, It has sort of switched to this terminology is because we have pretty good data that shows that it's truly the hyperinsulinemia that increases the laminitis risk. And so that also means when horses present for acute laminitis, because of hyperinsulinemia, bringing down that blood insulin as quickly as possible is a really important part of, addressing the acute laminitis episode.
So, I already mentioned that when it comes to management, this is really a condition that requires lifelong management. The most important parts of this, of the management are dietary management or nutritional management, as Well as other weight loss strategies such as exercise. The only thing that is a contraindication to exercise is when horses suffer from acute laminitis.
And in that case, those are the horses where we can, as a short-term solution to kind of accelerate their weight loss, also supplement this management with medication. But the other parts, the parts that are harder to do and the clients usually don't like to do as much, are the much, much more important part of managing this disease. So, diet and exercise is, is the hallmark of the management.
And so that also means one of the, important things when it comes to Client communication is really sort of outlining to the client why this is so important and this is kind of a long game, and this is really, really important for the animal's quality of life. And client compliance is probably one of the biggest factor when it comes to treatment success. So I took this information also out of the summary from the equine endocrinology group and they kind of break down the dietary management between the overconditioned and obese metabolic syndrome horses and then what we call the lean phenotypes, so those with a normal body condition score that will still, however, require specific dietary management because they do have insulin dysregulation even though they are not overconditioned.
And so some of the things that are really important, and that can be challenging again when it comes to sort of the, the managing client expectations and client communication is that many of these horses will require complete elimination of grazing, or, or at least restricting grazing, grazing on a Graze down pasture or wearing a grazing muzzle, as you can see in this picture, ideally avoid grain and then feed hay with a low non-structural carbohydrate content. And so in an ideal world that means that hay analysis should be should be should be done in these cases, and then based on that select hay with a non-structural structural carbohydrate content of less than 10%. There are some other strategies that are out there that can kind of help get rid of some of the water-soluble carbohydrates.
So depending on the management set up and also the climate, soaking the hay may be an option. To sort of help still support the horse's behavioural needs and avoid prolonged or longer periods of fasting. It, it might help to incorporate slow feed or hay nets to slow them down, .
Because we are feeding them kind of lower quality hay and we're eliminating grain, it's still important that they receive a mineral, vitamin and protein ration balancer, but it is also important to pay attention to the content of those balancers and make sure to choose one with a low sugar content. And then when it comes to the lean EMS phenotypes of those that have a normal or low body condition score, but are still insulin is regulated, the management is essentially the same when it comes to paying attention to the Non-structural carbohydrate content of the feed, but because they may have still higher caloric needs, those calories that are subtracted need to then be replaced with adding higher fat feed to the diet. And what is then important to keep in mind is that as the fat content of the diet goes up, the vitamin E requirement of the horses will also increase, so potentially they may have to receive additional vitamin E supplementation, especially if we're restricting grazing since grass is the number one source of vitamin E for horses.
So this graph from the equine endocrinology group kind of basically summarises the approach to the diagnostic testing and which horses, ponies, or donkeys would be tested. One of the things that I haven't mentioned yet, but it's kind of mentioned in here, which is important to keep in mind that one consider consideration actually for testing other than suspicion based on, say, the phenotype, or a history of laminitis is if you consider giving steroids to these horses. So horses, insulin is regulated, are at higher risk of developing laminitis, when administered glucocorticoids, and so that is potentially something to keep in mind, in these cases.
And then, as this, also summarises basically the slight difference in management between the obese insulin, dysregulated and the lean insulin dysregulated horses. And then the other thing that it highlights is that more and more we recommend to actually consider testing horses that we consider at risk maybe based on their, breed that they belong to, or the fact that they're easy keepers, is to consider testing them annually as part of their wellness exam or potentially even as part of a pre-purchase exam. And then this sort of graphic summarises some of the potential management challenges that we may encounter along the way as we help these horses.
So one, would be that the diet and weight loss strategy alone is not sufficient, and so these would be the horses where we would consider adding medical therapy. And I'll get into that a little bit more in a couple of slides. As I already mentioned, compliance by the client can be an issue, and so that is something to just continue client education.
They may also suffer from PPID concurrently and then will have to also be managed for PPID and then if hyperinsulinemia persists, they are at higher laminitis risk, so they may suffer repeated laminitis episodes which would potentially require additional management. And because of the fact that it's sort of a collection of syndromes, there are a number of health consequences, potentially the most severe and devastating one being laminitis, is really the reason why we, we emphasise prevention so much. So as much as possible, we want to detect.
Horses early, want to diagnose them early, and then implement strategies that in an ideal world, prevent laminitis from ever recurring. And so early recognition includes recognising their physical characteristics, being part of certain breeds, pony breeds, hardy breeds. Such as Arabian, Spanish breeds, Morgans, implement dietary management, that is evidenced based and, .
Encourage physical activity, as long as they don't suffer from acute laminitis, and all of these help then reduce the laminitis risk by managing their blood insulin levels. And so I wanted to just comment a little bit specifically on horses with acute laminitis because unfortunately still, this is probably one of the Main presenting complaints, at what point the diagnosis is reached, so the horse will present for signs associated with laminitis and then we'll get diagnosed with equine metabolic syndrome. And so, in general, about a third of horses will have laminitis in their lifetime, and the most, most clinical laminitis cases are a result of hyperinsulinemia associated laminitis.
And so our goal really is to continue to raise awareness among clients and, and really emphasise this early detection of EMS. And so in, in horses that do suffer from acute laminitis, we add additional management strategy. So obviously exercise in these horses is contraindicated.
So to accelerate weight loss, we do add pharmacological interventions. So one of the drugs that has been around for quite some time to manage EMS is levothyroxine. Which is indicated either in weight loss resistance or in acute laminitis cases.
And then more recently over the last few years, different groups have studied the use of SGLT2 inhibitors in the use of these horses as well, with the main sort of intent is to lower their blood insulin levels and get the laminitis episode under control. And then the other thing that has been studied as well as cryotherapy, and to me this is really the main reason why, if possible, these are cases, if they present for acute laminitis, these are the cases that in a perfect world should be hospitalised, mostly so that they can be received. Effective cryotherapy because it has been shown to be helpful even in horses already suffering from laminitis secondary to hyperinsulinemia.
And then another common question that clients will ask, because obviously it's, it's, it can be quite involved, managing a horse with acute laminitis, especially if it has to get hospitalised, it can be costly as well. It, it requires a lot from the clients sometimes to change their management approach. So one of the common questions will be how long until they are sound again.
And so, . There's some data out there that kind of helps us answer that question, although there's always a little bit of an unknown still, and it is certainly a bit of a wait and see scenario, but the general rule of thumb is that we recommend one week of rest for each day of lameness, and that is something that the clients should be prepared for. So this is a lengthy process to rehabilitate a horse that has suffered acute laminitis, and especially if they have also suffered structural changes to their foot.
So the second condition that I'm going to talk about today that is common in horses is pituitary parts, intermediate dysfunction or abbreviated as PPID. And similar to equine metabolic syndrome, really our goal here is to detect horses that are suffering from this condition early before they look like the horse in this picture, which is sort of the, the. The poster child for PPID.
So, with the long curly hair coat hair coat, and the one that I kind of call, the one you can diagnose from across the pasture without doing any further diagnostic testing. So we want to try and identify these horses early so that we can. Intervene early.
Similar to EMS, it is, a disease that will not be cured, but that can be managed. There's a specific treatment that we can use and then the other thing we wanna make sure is they don't suffer from insulin dysregulation concurrently because that is something that can also put these horses at a higher laminitis risk. So the objective is diagnose them early.
Prevent more severe health consequences for as long as possible and really improve their quality of life or maintain good quality of life as long as possible. So the hallmark of PPID is this long hair coat, so what we call hypertrichosis, that will often initially present as a failure to shed the winter hair code in the spring normally. They can also present with skeletal muscle atrophy, which is something that clients often will notice as Weight loss or may described as weight loss.
They can also have hiuria polydipsia and as I already mentioned, they can suffer from laminitis if they also have insulin dysregulation. The part about the abnormal shedding, one of the things to keep in mind is that before they look kind of like more the poster child, like the picture here on the left, sort of the overall long hair coat or hypertrichosis, initially one of the earlier signs may be abnormal shedding just in certain parts of the body, specifically under the abdomen, or under their jaw. And so having sort of a horse that sheds out.
Most of its winter hair coat, but then retains some long hair, might be a horse that is sort of early PPID and that would be a good time to consider start testing those horses so that we can intervene early before they suffer more severe health consequences. And so when we think about the typical PPID, we think about the, the, the woolly or curly pony with the general hypertrichosis. And the muscle wasting.
So this is basically, the, listed here, on the table on the right. This also comes from the equine endocrinology group and their sort of summary on PPID and the most recent one was published a couple of years ago. So this will get updated at some point this year.
And so what, what we're aiming to do is kind of recognise these horses earlier when they might have the more subtle signs so that what I described as the regional hypertrichosis, just some delayed shedding or incomplete shedding, and diagnose them early on so that we can start treating them earlier and that we can prevent more severe health consequences. So when it comes to risk factors for PPAD, the number one risk factor is advancing age. So we think of this as a condition of middle aged or older horses.
Studies have shown, it increases in prevalence sort of in horses older than 14 years of age, and so that is by far, . The number one risk factor, and it's, it's really almost as horses age, if they live long enough, it's more a question of when will they develop PPID rather than if they will develop PPID. And so, back in the day, before we sort of introduced this PPAD, terminology, this was referred to as equine Cushing's disease, and it's probably still a phrase that many horse owners might be familiar with or what they might still be referring to this too.
The reason we changed the name is that it's a different path of physiology than Cushing's disease in humans or dogs, and so. The underlying pathophysiology of this disease is loss of dopaminergic inhibition to neurons that innervate the parts and the media of the pituitary, that's why it's called pituitary pars intermediate dysfunction, and the result of the loss of this dopanergic inhibition is that now the pars intermedia releases . More peptides, including ACTH, and this is the, the biomarker that we measure, when we diagnose PPID.
And because it is a released from the pars intermedia, it does not respond to the normal, ACTH. Negative feedback loop. So over the years, there have been different diagnostic tests to diagnose PPAD or equine Cushing's disease, the The most commonly used test, initially was the dexamethasone suppression test, and more recently, as the pathogenesis of this disease has been more studied and we now have an understanding of, The underlying principles of the loss of dopaminergic inhibition and this increase of release of the Palm C peptides, which includes ACTH but a number of other peptides, we have sort of switched to measuring ACTH either as a baseline or in a dynamic testing.
Technically, the gold standard test is postmortem exam, which obviously is not a useful diagnostic test, but when you look at, experimental studies, that is often what other tests will be compared to, and there are also some studies that have looked at imaging, so that would be to look at actual changes in size, of the pituitary, so often that might be later on in the disease, process. So basically, the two diagnostic tests that we use now is baseline ACTH or TRH stimulation tests. So that's a dynamic test measuring ACTH response.
The TRH stimulation test is much more sensitive, especially in picking up. Earlier in the disease process, the biggest challenge can be, the availability of TRH, so depending on where you're practising, it may or may not be available. It's frequently, if it's available, it's compounded, so that is something to just, That might require a little bit of research to figure out where to get the TRH from, but, so once sort of that challenge has been addressed, this is definitely the more sensitive test and the recommended test in those animals, earlier on in the disease process.
And since the intent is to catch them early, that would be the recommended test. Since it may not always Be available that you may have no choice and sort of are left with the baseline ACTH test. And so what that just might mean is if a horse is early on in the disease process, it's baseline ACTH may still be normal, or in what we call the interpretive zone, and I will get into that here in the next slide, .
And it may just require reevaluating them every 3 to 6 months, and to see if if ACTH will start to go up. To add a little bit more complexity to the diagnostic side, it's pretty well established now that there is a normal seasonality to ACTH levels, and in general, ACTH, rises in the autumn or in the fall. And so there are a number of studies that have, Established seasonal reference values, both for baseline ACTH, as well as for ACTH after TRH stimulation.
So that is something to keep in mind and, and, another example of where the equine endocrinology group resource is really useful because they have sort of a table in there that kind of breaks down, . The, the, the interpretation of the diagnostic test results by time of the year. And so this would be, the month would be for the northern hemisphere.
The, the seasonality is seen in the southern hemisphere as well. It's just obviously, the months would be reversed. But it generally rises in the fall months.
And then the added challenge when it comes to interpreting test results is there is a sort of The span of of results where PPID may be present, but may also not be present. And so it used to be called the equivocal zone. Which caused a lot of confusion, so the endocrinology group has changed that terminology to interpretive zone, which essentially means interpret the number that is the result of the diagnostic test in context of the history, the clinical presentation.
And the age of the horse, and then potentially consider retesting, or if possible, if you do baseline ACTH, you have a horse that falls into the interpretive zone, and you have availability of TRH, then do the TRH, stimulation test. So when it comes to the treatment, there is, in this case, which is different to equine metabolic syndrome, pharmacological intervention is an important part of the treatment. So this again is a disease that cannot be cured, but it will require lifelong management.
And the drug of choice, . To treat these horses is a drug called Pergolide, because the underlying pathophysiology is a loss of dopaminergic inhibition. It is a dopamine agonist, it is, it used to be, used as a, a drug to treat Parkinson's, disease in people.
But it is now formulated and marketed, and labelled for use in horses under, the brand name percent. And That would be the drug of choice. There are some other studies out there that have looked at other drugs.
One potential, alternative is ciproheptadine, which is a drug that some people will use, and horses that, develop really the, the one commonly reported side effect of which is loss of appetite. So some horses, when started1%, will stop eating. Most, most of the time that is transient, but in the few cases where that might remain a challenge for the owner, that is, those are really the cases where sometimes clinician will choose to try ciproheptadine.
And then the other management really is management of comorbidities, . And if they are insulin is regulated, also management of insulin dysregulation. Another thing that can be quite common in these horses, because they, the PPAD results in immunosuppression is that they might have recurring infections, such as recurring sinusitis, recurring corneal ulcers.
So those are some potential other comorbidities that may have to be managed, but should improve, the reoccurrence should improve once they're started. On Pergoli. And so similarly to sort of the EMS management, the equine endocrinology group has a really nice breakdown on how to sort of initially treat, but then also how to reassess horses suffering from PPID once they've been started on Pergola.
And it depends a little bit on, so if they've broken it down on how well they respond to the treatment, both clinically, but then also as far as their laboratory response, so that means like how does their blood ACTH respond to the treatment. And so, Generally, the recommendation is to start them on the lower end of the dose and see how they respond. And then, then one of the potential interventions can be, if there's some response, but not ideal response, that that dose of proboli, can be increased and it, the sort of As part of managing client expectations, part of the conversation with the client should be that eventually, because this is a progressive disease, that is something to be assumed that at some point, the dose will have to be increased.
And even though the treatment and the management will prolong their life and improve their quality of life, it, it will continue, the, the disease will continue to progress, and There will be a time point where quality of life may be impacted to such an extent that the client will have to sort of make a decision on how long they want to continue, but it certainly will slow that process down and significantly improve quality of life for a time, and the sooner, the earlier they're diagnosed, the better. And as I already mentioned briefly, at the beginning, there, there is a subset of horses that will suffer from both PPID and EMS concurrently. So that is one of the things that can be very confusing to the clients.
It's also something that makes it. Can make it challenging to sort of teach about these diseases to to the vet students because it can cause confusion there as well and so. And that is sort of an important conversation to have with clients because this is a question that very frequently will come up.
So our EMS and PPID the same? And the answer to that is no. But like everything in internal medicine, it's not black and white, it's shades of grey, so it's no but.
So basically, they're not the same, but they can exist in the same horse at the same time. And so the, the The, the subset that we're really talking about here, are the horses and this graphic where the pituitary parts intermediate dysfunction and the insulin dysregulation overlap. So horses have PPID, but they also have insulin dysregulation, .
That's why horses with PPID that present with laminitis, with the history of laminitis or physical exam findings that suggest that they may have suffered from laminitis before, such as rings on their hooves, should really also be tested for insulin dysregulation. So, just one more time, to highlight that laminitis risk, will increase with high blood insulin levels, so hyperinsulinemia associated laminitis, and that is something that can, Exist concurrently with PPID. And so just sort of to, to, to recap and finish up comparing some of the sort of main parts of those two conditions, so both of them are fairly prevalent in our horse populations.
The number one risk factor in horses for PPID or for suffering from PPD is advancing age, so it's common in middle age to older horses, . Hyperinsulinemia has been. Shown to be present in almost up to 30% of horses in some studies, the, the rates of obesity, can be quite varied depending on the studies, but certainly similar to our small animals, dogs and cats, it's on the rise.
PPID is a result of loss of dopaminergic inhibition over the past intermediate of the pituitary. And EMS, insulin dysregulation is sort of the underlying. Problem and horses with PPID, a subset of horses with PPAD can also have EMS and be insulin is regulated.
. Both of them, we, we really are concerned. Both conditions we are concerned about the effects on quality of life and the main thing we worry about is laminitis because it's such a painful and debilitating disease. And once it's happened, rehabilitation can be quite prolonged, especially if structural changes in the foot occur.
Both are conditions that require lifelong management after diagnosis. And PPID part of that management includes pharmacological intervention, through perlite or treatment, and EMS, the dietary management and exercise, weight loss management. Is the most important part of the management, but if they are sort of resistant to weight loss interventions, and especially if they have acute laminitis, so that exercise is contraindicated, that's when we can use pharmacological intervention short term to accelerate the weight loss, but then they do need to continue to be managed appropriately for the rest of their life.
So that brings us to the end of the today's presentation. I've included my email address here, so if you have any follow-up questions, you are more than welcome to reach out and send me an email.
