Thanks very much, Bruce, for the introduction and welcome everyone to this webinar where we're going to discuss canine parathyroid disorders. I chose this topic to present because although relatively uncommonly encountered in practise, these disorders do crop up from time to time, and I think it's important to have a a good general idea of the approach to their management. So firstly, I'm going to briefly review calcium balance in the body and the normal relationship between calcium and parathyroid hormone.
After this, we'll move on to cover the two most common parathyroid gland disorders encountered in dogs, namely primary hyperparathyroidism, where we have an overproduction of the hormone, and hypoparathyroidism characterised by deficiency of parathyroid hormone. So, calcium is the most abundant element in the body and is responsible for many diverse processes ranging from nerve conduction and neuromuscular transmission to muscle contraction to coagulation. And normally calcium concentrations are very tightly controlled in blood and when discussing calcium homeostasis, it's important to understand the different forms in which calcium exists in the body.
So when we measure calcium in biochemistry, typically it's total calcium that we're measuring. And this is made up of three fractions. So about 50% of the total calcium concentration is made up by the ionised calcium, which is the free and biologically active form of calcium.
And then of the remaining 50%, about 40% of this is a protein bound calcium, which is mainly bound to albumin. And the other 10% is complexed with various anions in the blood like bicarbonate or citrate. Now, whenever I do a total calcium reading, and find that it's above or below the normal reference interval on the biochemistry machine, the first thing I will always do is consider the possibility that this might just be an artifactual finding rather than a true hypocalcemia.
So if your biochemistry has been run on an EDTA sample by accident, you may find that the total calcium is falsely decreased because the calcium is collated by the EDTA. On the other hand, if your sample is hemolyzed or the serum is lipemic, that can lead to a false increase in your total calcium. So it's important to always check these things and make sure there's no interference with the sample.
Additionally, because of the large percentage of total calcium that is actually bound to albumin, you should always be interpreting the total calcium concentration in conjunction with your albumin concentrations. So if you, for example, find you have a mild hypercalcemia on your biochemistry, along with a hyper-albuminemia. It's very likely that that hypercalcemia is a consequence of the increased albumin rather than a primary problem in its own right.
And similarly, a mild decrease in total calcium, if you have hypoalbuminemia is likely likely attributable to the low albumin rather than a primary problem in its own right. But in general, if your total calcium is, you know, severely increased or severely decreased, then you should always be checking in an ionised calcium to determine that that's a true finding, because as I said, the ionised calcium is the biologically active form and it's the gold standard for assessing calcium balance. Unfortunately, if you want to check ionised calcium, it's not quite as straightforward as checking the total calcium, which we can usually just check on any in-house biochemistry machine.
So, some of you might be fortunate enough to have an ionised calcium analyzer on site, and this is usually if you might work at a referral centre or a busy emergency clinic. But unfortunately at the moment, most general practises won't have an in-house machine that's capable of measuring the ionised calcium. However, if this is the case, you can still send off samples to measure ionised calcium to an external lab.
So in the UK the main lab to which samples are generally sent to check ionised calcium is nationwide laboratories. And if you're sending off a sample to them to check the INS calcium, what I would always recommend is reading the instructions on their website very carefully in terms of how to collect the sample and how to process it. Because any discrepancies in how you take the sample can affect the results quite a lot.
For instance, the serum tubes need to be filled. To the absolute brim, because any exposure of serum to air can lead to a rise in the pH of the sample, and that can cause a false decrease in your ionised calcium. So it is something you can send off for externally, but you just need to read the instructions very carefully because it's a little bit more complex than most routine blood samples we will send away.
The two main factors in the body that influence your circulating calcium concentrations are parathyroid hormone made by the parathyroid glands and vitamin D. So parathyroid hormone is made by cells called chief cells in the parathyroid glands, and dogs have 4 of these parathyroid glands. So the more caudal pair of parathyroids is embedded within each thyroid lobe.
And the more cranial pair are located outside of the thyroid capsule. And the primary actions of parathyroid hormone are to increase serum calcium and to decrease serum phosphate. So that's the primary action to be aware of.
And it manages to do this by acting on three target organs, namely the bone, the gut, and the kidneys. So parathyroid hormone acts to increase the release of calcium from bone. And it increases reabsorption of calcium from the kidneys while increasing the excretion of phosphate.
It also acts to activate vitamin D into its active form, which is called vitamin D3, and this activation occurs within the kidneys, and activation of vitamin D is really important for your body to actually absorb calcium from the gastrointestinal tract. In human medicine, another hormone called calcitonin has a very important role in calcium homeostasis, but the effect of calcitonin in dogs and cats and other veterinary species is quite minor, so we tend not to focus too much on this in dogs, especially when we're talking about calcium balance due to the minimal effects it has. So the first condition I'd like to discuss is primary hyperparathyroidism, which is an uncommon condition in dogs, but one you will definitely come across in small animal practise from time to time.
It it often does go undiagnosed for some time because it often has quite non-specific clinical signs. So normally parathyroid hormone secretion is very tightly regulated, but primary hyperparathyroidism develops when One or more of the 4 parathyroid glands in the body begins to function autonomously, irrespective of the serum calcium concentrations. So it's usually only a single one of the parathyroid glands that begins to function abnormally, and the underlying disease process may be a benign tumour of the parathyroid gland.
A malignant tumour of the parathyroid, or just hyperplasia of the parathyroid tissue. And one recent case series showed that about 85% of cases are caused by a benign tumour, and adenoma, about 10% by hyperplasia, and only about 5% by a more malignant process of carcinoma. So in general, we consider this to very, very commonly be a benign disease process, but there's always a small chance it could be something more sinister.
Now, primary hyperparathyroidism is typically a disease we associate with older dogs, with the mean age of affected dogs being around 11 years of age. There doesn't seem to be any sex predisposition, and out of all dog breeds, a breed disposition to developing hyperparathyroidism has only been identified in one breed, which is the quishon. But the breed disposition in this breed is quite dramatic, so they're actually about 50 times more likely to be affected by hyperparathyroidism than other dog breeds.
So if you ever see one of these, they're not particularly common breeds, always be on the lookout for hyperparathyroidism. Regarding clinical signs, unlike hypoparathyroidism, which we'll discuss in the second part of this webinar, primary hyperparathyroidism is not a very dramatic disease. So typically the signs are quite subtle and slowly progressive, and because this disease is most common in older dogs, it's quite common that owners attribute the subtle signs to normal age-related changes like osteoarthritis or just a general decrease in activity.
So it's common that patients are diagnosed when hypercalcemia is just detected as an incidental finding on biochemistry, which prompts further investigation, or that patients are diagnosed after a very long period of time displaying vague but progressive clinical signs. And the clinical signs we tend to see are a direct result of the hypercalcemia, and they can be broadly classed into three categories, renal and urinary tract signs, signs relating to the gastrointestinal tract, and neuromuscular signs. In terms of renal or urinary signs, polyuria and polydipsia are two of the more common signs we tend to see.
And the main reason PUPD is seen with primary hyperparathyroidism is that high levels of calcium directly antagonise the effects of anti-diuretic hormone in the collecting ducts of the kidneys, which leads to a polyurea and then a compensatory polydipsia. We also see that dogs with hyperparathyroidism commonly will develop euroliths, and this is primarily because of the increased amount of calcium that are filtered by the kidneys, which overwhelm the ability of the kidneys to reabsorb that calcium and lead to increased calcium loss in the urine. So the uroliths that result from this disease are typically calcium-based stones like calcium oxalate or calcium phosphate stones.
And it's not uncommon for dogs with primary hyperparathyroidism to initially present as cases who keep coming into you, forming calcium-based uroys that need to be repeatedly removed from the bladder, and they may not be found to be hypercalcemic until they've actually had to have the urulits removed 2 or 3 times. We also see that the increased circulating calcium in blood can lead to renal calcification, which could in theory lead to renal dysfunction. Thankfully, we tend to see this quite uncommonly with hyperparathyroidism, because usually for calcium to be deposited within the kidneys, we need to have very high levels of both calcium and phosphate.
And in primary hyper parathyroidism, although we have very high. Calcium levels, phosphate levels tend to be low due to the actions of parathyroid hormone. And so if we are going to develop mineralization or stones, we typically see those in the lower urinary tract rather than stones directly in the kidney parenchyma itself.
Moving on to the gastrointestinal signs, typically the signs we see are inappetent or constipation, which are related to calcium induced gut smooth muscle hypo excitability. And the neuromuscular signs we tend tend to see are also relatively vague. So these dogs may present as depressed, just have generalised stiffness or exercise intolerance, and understandably, those signs are often believed to be linked to just normal ageing in older dogs.
The physical exam findings in dogs with primary hyperparathyroidism frustratingly are also often quite vague. So the exam might be completely normal or you may just find some mild changes like muscle weakness or generalised stiffness and. Hating the neck of these dogs is typically not very helpful because the parathyroid nodules or masses that we see with this disease are usually too small to be palpable.
So it is really a condition that can very, very easily go undiagnosed. So how do we actually diagnose this condition with the signs being so vague? Well, the hallmark is obviously hypercalcemia and so generally the first indication we will get that a dog may have this disease is that we find their total calcium is high on biochemistry.
Now, as I mentioned previously, if your total calcium is found to be increased, ideally you should check an ionised calcium to confirm that you have a true hypercalcemia, because as I mentioned before, the total calcium can be affected by factors like protein concentrations, whereas the ionised calcium is not affected by these things. Total calciums. Concentrations do however somewhat parallel ionised calcium concentrations.
So if you have a very severely elevated total calcium level above the reference interval, you can usually be quite certain that that dog probably does have a true hypercalcemia, whereas if you just have a, you know, relatively mild increase in total calcium, you really always need to be checking that with an ionised calcium measurement because there is still some discrepancy between the total calcium and ionised forms. So once you've confirmed that the patient has a true hypercalcemia, ideally with ionised calcium measurement. The first thing is to consider other differential diagnoses for hypercalcemia.
So, as most of you are aware, there's a very wide variety of causes of hypercalcemia in dogs, and, many of you have probably learned some mnemonics for these, potentially not since vet school, but there definitely are quite a few mnemonics out there. So, the one I, tend to remember is maybe not the most catchy, but it's hard I G. So, H standing for hyperparathyroidism, A for Addison's, R for renal disease, D for vitamin D toxicity, I for iatrogenic causes, O for osteolytic diseases, N for neoplasia, S for spurious, and G for granulomatous disease, which encompasses things like lung worm infection or fungal diseases.
So it's good to remember, you know, this full list of differential diagnoses, but in practise, by far the two most common causes for hypercalcemia in the absence of other biochemical changes are either primary hyperparathyroidism or neoplasia. And you know, the other causes of hypercalcemia will usually give you some other clues on either your physical exam or your baseline blood tests. So, for example, patients with renal disease will typically be azotemic, whereas patients with Addison's disease will usually have other electrolyte changes like high potassium or low sodium.
But unless there's something in the history or the biochemistry to suggest. Any of these other differentials, if I have a hypercalcemic patient, I tend to focus my work up on screening for either neoplasia or hyperparathyroidism, because those are by far the two most likely differentials. So Focusing on neoplasia, the most common forms of neoplasia that we see causing hypercalcemia are anal sac adenocarcinomas or lymphoma, although a wide variety of other tumours less commonly can cause hypercalcemia too.
So it's really important as the first step to thoroughly palpate all of the peripheral lymph nodes of these hypercalcemic patients and also do a very thorough rectal examination to search for any anal sac mass or even anal sac thickening that may indicate neoplasia. And the second very important thing, if you have a hypercalcemic patient, is to actually send a sample of serum for measurement of parathyroid hormone and also a substance called parathyroid hormone related protein, which is a paraoplastic protein that is often increased in animals who have aparineoplastic hypercalcemia. So, again, I generally send these samples to Nationwide Labs, which is the same lab which offer an ionised calcium test.
And again, it's really important to read the instructions on their website in terms of how to submit the sample because parathyroid hormone is very, very labile, so you need to send the sample frozen. And typically if you do want to submit a sample for parathyroid hormone measurement, you can contact Nationwide labs and they'll actually send you out specialised transport packs for the samples just because this, you know, the hormone is so labile and it needs to be transported in a very particular manner. It's also worth noting that parathyroid hormone measurement is a rather expensive test at the moment, so it usually works out somewhere in the region of between 200 and 300 pounds to actually perform this test.
And what we're expecting to see in an animal with hyperparathyroidism is that the hypercalcemic dog has a parathyroid hormone concentration that is above the reference range or at the upper end of the normal range. Because the normal physiological. Of the body in a hypercalcemic dog should be to produce only very low amounts of parathyroid hormone.
So if we're documenting that, that dog has a very high level of the hormone, that's always abnormal and is consistent with the diagnosis of primary hyperparathyroidism. We usually will also measure this parathyroid hormone related protein in conjunction with parathyroid hormone. And if the parathyroid hormone itself is not found to be abnormally high, then documenting an elevation in this parathyroid hormone related protein may aid us in narrowing down the differentials to malignancies that we may not yet have.
Identified on our physical examination. So these are really helpful tests and they're not the most straightforward to measure obviously. But if you know the lab to send them to, you know, you can actually perform this test in general practise and get really helpful results back.
So if I find that the parathyroid hormone related protein is increased, which would indicate an underlying malignancy, then usually my next step will be to pursue thoracic and abdominal imaging to screen for unidentified neoplasia. So typically this will involve thoracic radiography and abdominal ultrasound, and I'm looking for any underlying type of neoplasia that I can attribute the hypercalcemia to. On the other hand, if parathyroid hormone itself has increased consistent with primary hyperparathyroidism, I will concentrate on imaging that patient's neck and I'm basically trying to see which of the parathyroid glands is affected.
Now, ultrasound. Of the ventral neck is the most sensitive means of I'm imaging the parathyroids and what we're typically looking for is a parathyroid nodule. So it will typically appear as a hypo or anechoic, spherical structure on the ultrasound.
Normal parathyroid glands are very, very small, so they typically will measure less than 3 millimetres in size. And so because of this and because the glands are very superficial. We need to use a high frequency transducer performing the ultrasound, and it's also quite technically challenging, so you generally need someone who's very experienced with imaging to actually find these.
But if you have an experienced imager, we can find these, nodules quite easily, and typically what we expect to see is this anechoic nodule that can measure up to about anywhere up to about 2 centimetres in diameter associated with one of the parathyroid glands. So, moving on to treatment, before I discuss the more definitive surgical treatment of the condition, I'd just like to touch upon the initial stabilisation that some hypercalcemic patients need. So, an immediate concern in any animal who has severe hypercalcemia should be to look for any possible acute kidney injury that could be caused by the high calcium.
As I mentioned previously, fortunately, we quite rarely see primary hyperparathyroidism resulting in acute kidney injury in comparison with other causes of hypercalcemia like neoplasia or vitamin D toxicosis. And why we don't see this acute kidney injury very commonly in primary hyperparathyroidism isn't fully understood, but again, we think it's linked to the low concentrations of phosphate these dogs have, and that helps to protect their kidneys a bit more from the detrimental effects of calcium. Now, although acute kidney injury with this condition is not common, if a dog with this problem is azotemic on presentation, then I will always place them on at least a maintenance rate of IV fluids, and the ideal fluid to place them on would be normal saline because it's free of calcium.
But if you don't have this available, it is acceptable to use something like lactated ringers, because although this does contain a small amount of calcium, the amount of calcium is really quite tiny, and I think the diuresis that placing the fluid patient on fluids will induce should help lower your serum calcium even if the fluid type contains a small amount of calcium. Other options you could consider in severely hypercalcemic patients would be to give a small dose of dexamethasone, or a low dose of furosemide, both of which, can help to increase calcium excretion from the kidneys and thereby lower your serum calcium. Some of you may have also heard of, the use of bisphosphonate medications like permidronate for treatment of severe hypercalcemia.
So these medications inhibit osteoclast activity in bones, which helps to drop serum calcium. And these drugs are, are definitely something we use in certain cases that are hypercalcemic. But if the hypercalcemia is caused by primary hyperparathyroidism, I tend to avoid using bisphosphonates, and this is because they're quite long lasting medications.
So something like permidronate will exert an effect for about 3 weeks after we administer it. And because we'll ultimately be wanting to surgically remove the abnormal parathyroid nodule in these patients in the near future, giving that patient a bisphosphonate before surgery or a week or two later might complicate the control of your serum calcium levels in the postoperative period, because the bisphosphonates will still be exerting an effect even when you've removed the parathyroid nodule surgically. So Although sometimes we will need to initially stabilise the patient and get the calcium levels down, most commonly we can go straight for surgery, and surgical removal of the parathyroid nodule is the recommended treatment.
So, it's very helpful to have identified the affected parathyroid gland preoperatively via ultrasound, so that can aid our surgical approach. And we can access the parathyroid nodule from a ventral midline surgical approach. Usually the abnormal parathyroid gland obviously looks abnormal grossly compared to the rest of the parathyroid glands.
So typically it's discoloured, it's darker in colour and larger than the other parathyroid glands. So typically the surgeons just need to remove the affected gland. The other three parathyroid glands are left in situ, and it's a relatively routine surgery, but, you know, it does have similar risks to those of a thyroidectomy, which includes haemorrhage or potential damage to some of the local nerves in the neck area.
. And an additional concern in especially in dogs who have very elevated calcium levels preoperatively, is that those dogs are at risk of an acute hypocalcemic crisis after the affected parathyroid nodule has been removed. Because what we see is that parathyroid hormone production by the other three glands has been suppressed because of the very high calcium levels that have resulted from the abnormal. Thyroid gland.
And I generally would class patients as having a severe hypercalcemia if their total calcium is over 3.5 millimoles per litre or if their ionised calcium is greater than 1.8 millimoles per litre.
So if a patient has a calcium level above these cutoffs, we need to monitor their calcium extra closely, at least twice a day, for the first few days after removing the parathyroid nodule. And as an additional precaution, most surgeons will routinely supplement vitamin D to patients with these severely high calcium levels starting from the day of surgery, and they'll continue giving that patient vitamin D to help them absorb calcium for. Up to 2 to 3 weeks postoperatively until the remaining parathyroid glands have regained their normal function.
And I'll be discussing this vitamin D supplementation a little bit more in the next section of the webinar. So, hold on and I'll get to that shortly. Now, the prognosis of dogs after surgery with this condition is excellent.
So surgery is generally curative and even if the root cause of the hyperparathyroidism is found to be a carcinoma instead of the more common benign causes, the prognosis is usually still excellent as long as the tumour has been fully removed. But unfortunately, the prognosis is different for quions because in this breed it's very common that the hyperparathyroidism recurs in a different parathyroid gland in the future. So if you ever have a quion with primary hyperparathyroidism, you need to make the owners aware that recurrence is highly likely and that dog may need further surgery in the future if there is a recurrence of the disease.
But that really is an exception to the rule. Every other breeds, the general rule is that these dogs do very, very well. So, for the remainder of the webinar, I'm going to discuss the pretty much the opposite condition, which, we also see relatively commonly, which is hypoparathyroidism, the other main disorder of the parathyroid glands.
And what we tend to see in these patients is that the lack of parathyroid hormone results in clinically relevant hypocalcemia through a number of different mechanisms. So if we think back to the normal function of parathyroid hormone, which is to increase calcium release from bone and to increase intestinal absorption of calcium via activation of vitamin D. In a state of hypoparathyroidism, these functions are going to be lacking, leading to low calcium levels, and typically we'll see increased phosphate levels.
So basically the complete opposite pattern to hyperparathyroidism, which would make sense. In normal animals, calcium is really important to help stabilise the cell membranes of your neurons. So if we have a patient with severe hypocalcemia, what we see is that the neurons of both the peripheral and central nervous systems become hyper excitable, which leads to some of the more common clinical signs we see in dogs with hypoparathyroidism, which can include things like seizures, severe muscle tremoring, or muscle cramping.
We still widely consider this condition as an idiopathic disease, so we don't yet fully understand exactly why production of parathyroid hormone appears to decrease dramatically. But as with many other endocrine diseases, we do suspect an immune mediated aetiology. And this theory is backed up by some of the changes that are observed on postmortem examination of affected dogs.
Where histopathology of their parathyroid glands reveals that they have very decreased numbers of parentchimal cells or the chief cells that should normally produce the hormone, and also we have infiltration of inflammatory cells into the parathyroids. And unlike primary hyperparathyroidism, which is, as I said, typically a disease of older dogs, with primary hypoparathyroidism, we can see that the, any basically any age of dog can be affected. The age distribution is a lot more variable, but we do see that females, miniature schnauzers and standard poodles are.
I overrepresented in terms of case numbers. So, my experience, I definitely have seen this disproportionately in miniature schnauzers in the UK, and so if I had to name one dog breed where I would be extra suspicious of this condition, especially if you have a a tremoring or seizure in schnauzer, it would be the the miniature schnauzer. Regarding the clinical signs, again, unlike hyperparathyroidism, which I said is associated with very kind of mild or vague signs.
Signs of hypoparathyroidism are usually very dramatic, so this is a dramatic disease, and the signs are generally related to the neuromuscular hyper accessibility that we see. So in some dogs, the signs might initially be mild and might just be things like muscle cramping or they may have an abnormal tingling sensation in their muscles, and these. Feelings can induce some signs like facial rubbing, that the dogs might be biting at their paws, or the owners might notice some behaviour changes like restlessness or aggression, because the dogs are having these abnormal tingling or cramping sensations.
But what we see is that even if the signs start mild, they tend to progress quite quickly, often over a matter of days, to become more severe. And in these cases, they can present with generalised muscle tremoring, often this kind of jaw chomping behaviour and generalised seizure activity. So, hypocalcemia should always be on your list of extracranial causes of seizures, and always especially bear in mind if you have a miniature schnauzer who's started seizuring.
We also see that sometimes the signs of tremoring are episodic in nature, and they do seem to be exacerbated by exercise or excitement in some cases too. On your physical examination, although the signs can wax and wane, generally you will see abnormalities on the examination in these cases. So even if the dogs aren't displaying generalised tremors, they will usually be hypersensitive to touch, especially.
In the face area, they may growl or snap when palpated because of the muscle cramping. And other signs are a little bit more variable. So some patients will be hypothermic because of the prolonged, muscle contractions they have with cramping.
And occasionally we'll see dogs presenting with tacky arrhythmias due to the effects of hypocalcemia on the function of cardiac muscle as well. But most commonly the signs are severe trembling, tremoring or seizures. So, a high suspicion for primary hypoparathyroidism should be present whenever you find total calcium is low in a dog with compatible clinical signs like tremors or seizures.
And again, because ionised calcium is the active, biologically active form of calcium, checking ionised calcium is the most accurate way to confirm true hypocalcemia. But unless you have an on-site machine that is capable of checking the ionised calcium levels, you may not be able to wait on an ionised calcium result to come back from an external lab before you start treating the hypocalcemia, especially if the dog presents to you with severe clinical signs like tremors or seizures. So in such cases where dogs are displaying severe signs and you're not able to check an ionised calcium straight away, it is acceptable to use the total calcium as a general gauge of the calcium status because the decrease in total calcium and ionised calcium tend to be quite similar in severity.
So, again, if you're going to be using total calcium as your indicator of calcium status rather than ionised calcium. Again, you need to check the patient's albumin level, first of all, to make sure the hypocalcemia isn't just an artefact of low albumin. And again, you need to make sure that a sampling error didn't occur.
So make sure you haven't used an EDTA tube by mistake to run the biochemistry, or even contaminated the needle with EDTA before you injected the blood into a serum tube. And either of these scenarios could cause a false decrease in serum calcium. And lastly, because a severe hypocalcemia is quite an uncommon finding, I'd always advise to recheck the finding at least once, just in case there was a sample error or a machine error, because, you know, it, it's something that, you know, if you think about it, we don't tend to come across hypocalcemia very commonly.
So when you have these unusual findings, I think it's always good to just try and recheck the sample at least once. In general, hypocalcemia has to be very severe to cause clinical signs. So, a patient with primary hypoparathyroidism should have a severely decreased total and ionised calcium, and more specifically I mean here, a total calcium of less than 0.4 millimoles per litre or an ionised calcium of less than 0.8 millimoles per litre.
So these are the dogs where you should be really suspicious, of primary hypoparathyroidism. You should consider differential diagnosis for severe hypocalcemia because there are really only a very small number of other conditions that can cause severe hypocalcemia. So, iatrogenic hypocalcemia is an uncommon complication after surgical removal of the parathyroid glands.
So this might be unintentional if a patient is having a thyroidectomy and the parathyroids have been removed by accident, or it could be an intentional surgery where you've been taking out a parathyroid mass in a patient with hyperparathyroidism. Another iatrogenic cause of low calcium would be a patient who's had a phosphate-containing enema administered, whereby a sudden absorption of large amounts of phosphate from the colon leads to a sudden decrease in serum calcium. And other potential causes of severe hypocalcemia would include a severe acute kidney injury or severe chronic kidney disease, or a severe pancreatitis whereby massive release of pancreatic enzymes causes what we call suponification and calcification of the fat around the pancreas.
And a final differential is in bitches in the few weeks after wealthing you should think about eclampsia as a differential, especially in bitches who have a large litters and are producing very large amounts of milk. Now, fortunately, even though there's only a short list of differentials, the differentials that are on the list are all quite easy to rule out in most cases. So obviously, if a dog doesn't have a recent history of parathyroid or thyroid surgery or having got a phosphate enema recently, you can rule out an iatrogenic hypocalcemia.
Kidney dysfunction usually needs to be very severe to cause a severe hypocalcemia. So you would expect. These patients to be really aotemic and unwell, if, that's the cause.
And, and similarly, pancreatitis needs to be very severe to cause hypocalcemia. So you would expect the patients will be showing signs like abdominal pain and vomiting if that were the cause. And obviously then male dogs or female dogs who have not recently helped and are not going to have eclampsia.
So typically, if you have a very hypocalcemic dog that is tremoring or seizuring. By far the most common cause is primary hypoparathyroidism and usually you could be quite confident confident of this as a diagnosis even before you measure the parathyroid hormone level. So obviously to definitively diagnose it, we would always recommend to measure the parathyroid hormone, and again you can measure this at nationwide labs, as I mentioned previously, and a a normal patient who is hypocalcemic would be expected to have high levels of parathyroid hormone as the body tries to raise calcium back up to a normal level.
But animals with primary hypoparathyroidism. Are expected to have parathyroid hormones that are low or at the low end of normal, despite being hypocalcemic because they're just not able to make the parathyroid hormone like a normal dog would. So moving on to treatment, this is something that it's, it's quite important to know how to treat this in the acute setting because the, the signs can be so dramatic.
So if you have a very severely hypocalcemic patient who is displaying signs like tremoring or seizuring. You should initiate treatment of that hypocalcemia immediately. You shouldn't be waiting on an ionised calcium to come back from the lab or for your parathyroid hormone assay to come back.
You, you know, should go off the total calcium if it's very low, and if the clinical signs are compatible with hypoparathyroidism, you should start calcium supplementation without delay. So, initially I treat patients with an intravenous slow bolus of calcium gluconate. So, typically I will give a dose of 1 millilitre per kilogramme of a 10% solution of calcium gluconate over about 15 to 20 minutes.
We don't give it any faster than that because calcium, if given too quickly, is going to cause severe arrhythmias or could even stop the heart. So it's not really a bolus, it's more like a, infusion over 15 to 20 minutes. Now, when giving this infusion, there are a couple of really important precautions that you need to take.
So, firstly, it's important to be aware that IV calcium formulations can be very, very caustic if they extravasate and so they can cause very severe. Sloughing. So no, whenever I'm giving IV calcium, I will always only give it through an IV catheter rather than off the needle.
I have seen some animals develop extensive open wounds and in one case even require limb amputation due to the extraversation of IV calcium. So it's something I feel really strongly about having seen some patients having had those really bad effects of extrovisation. Additionally, while most practises will have calcium gluconatese in stock, some practises will only stock calcium carbonate, which is a slightly different formulation, and this is much more caustic than calcium gluconate.
So it's quite risky. To give if there's, you know, even any small leakage of the calcium solution outside of the vein, it could cause a lot of problems. So I will usually only give calcium carbonate IV if it's an emergency and I don't have any other formulation of IV calcium available.
And a final precaution is that because, as I mentioned, IV calcium can cause severe arrhythmias, placing an ECG on the patient during the calcium infusion is always recommended. Things you're going to want to monitor for is mainly the development of, A sinus bradycardia. Sometimes we can also see ventricular premature complexes or shortening of the QT interval.
But if you see any of these signs, particularly bradycardia, I would advise stopping the trans the infusion temporarily and then reinitiating it at a slower rate once the ECG abnormalities have gone back to normal. Typically, once you finish this 20 minute infusion, I think it's a good idea to recheck the ionised or total calcium to, to see where you're at. And fortunately, the clinical signs tend to improve rapidly after getting even a small amount of calcium.
So with this infusion or this slow bolus, we're not trying to completely normalise the calcium concentrations. We're just trying to give them enough calcium to get them out of this acute crisis. And once you've stabilised the patients with this slow bolus, I will generally add 10%.
Calcium gluconate to maintenance IV fluids at a dose of 0.3 mL per kg per hour. And I will only give repeated boluss if the patient has acute signs like a recurrence of tremors or seizures, because the bolus is not without risk.
The main thing I worry about is inducing arrhythmias. So we'll only give a bolus if the signs are very dramatic and we need to treat them straight away. Once I have the patient on maintenance fluids that contain a small amount of calcium gluconate, usually I'll keep the patient hospitalised for a few days, and I'll recheck their total or ionised calcium once or twice a day, and I will adjust the rate of the infusion accordingly based on the overall trend of calcium.
So in the short term, again, I'm not trying to get The calcium completely back to normal. I just want to avoid it dropping, and I want to, ideally, you know, get it back up to a near normal level or, or even the lower end of the normal reference range. But, complete normalisation of calcium in the short term shouldn't be the goal.
The main thing you just want to do is to prevent them having severe clinical signs. What we're going to be doing at the same time as keeping these patients on calcium spiked fluids is we're going to begin the more chronic management of hypoparathyroidism, which involves oral calcium and oral vitamin D supplementation. And what we'll then aim to do is try to slowly wean the patient off the IV calcium over the course of a few days, as long as their calcium remains stable, we can usually get these patients home on oral medications after probably an average of 5 to 7 days.
In a small number of cases, I see that, you know, despite giving these patients oral calcium and vitamin D and even IV calcium, the the hypocalcemia seems to be refractory to management and the dogs have ongoing severe signs. And in these dogs, we should we would always recommend checking serum magnesium, because, magnesium, although, you know, most dogs with primary hypo. Thyroidism have normal magnesium levels.
A small number have low magnesium, and this can actually make the hypocalcemia worse. So if the, if the calcium levels are not coming up as expected, I'll always check magnesium. Usually it's not on routine biochemistry panels, so you usually need to request this as a separate test from a lab, but it is worth considering testing in those minority of cases who don't respond as expected.
So, in an ideal world, to chronically manage patients with hypoparathyroidism, we would give them a synthetic parathyroid hormone supplement and just replace the hormone that they're lacking. But unfortunately, parathyroid hormone supplements aren't commercially available. So what we tend to do is give these patients oral vitamin D analogues long term, and that can control their signs very, very well.
So if we think back to the physiology of calcium homeostasis in dogs. Parathyroid hormone is needed to convert vitamin D to its active form, which is called vitamin D3, or calcitriol in the kidney. And this activated vitamin D is necessary to help you absorb calcium from your gut.
So if we supplement these patients with activated vitamin D lifelong, they should be able to maintain normal calcium levels and have a normal quantity and quality of life, even if they don't have parathyroid hormone. We do need to also give these patients oral calcium initially, but we can usually taper patients off oral calcium supplements after 2 to 3 weeks and keep them just on activated vitamin D long term. So, what I tend to do is start patients initially on a.
Daily dose of 1 to 4 grammes of calcium per day. That's a total dose, so 1 to 4 grammes per dog. And the range in dosing there is basically just depends on the size of dogs.
So, a Chihuahua, I'll probably just give 1 gramme of calcium per day, a great day and I'll go for the 4 grammes. And the most common form of oral calcium that's commercially available or you can get in the health food shops is calcium carbonate. But it's important that when you're actually calculating the grammes of calcium to give the dog, it's important to note that calcium carbonate itself isn't 100% made up of calcium.
So 1 gramme of calcium carbonate only contains 400 milligrammes of actual calcium. So you need to take that into account when you're actually calculating how much calcium to give these dogs. But again, this is usually just something we need to give in the short term.
We give it for at least a few weeks until we're happy the calcium levels are staying stable, and then we should be able to taper the patient off that and maintain them on just vitamin D. So, with vitamin D supplementation, it's really important to recognise that multiple different vitamin D supplements are available, but only some of these are appropriate to give to dogs with primary hypoparathyroidism. So it needs to be an activated form of vitamin D that we give these dogs because they're unable to activate vitamin D themselves because they don't have the necessary hormone.
So the gold standard form of vitamin D to supplement would be to just give them calcitriol, which is the activated form of vitamin D. And this is also ideal because it has a very short time to its maximal effect. It kicks in really quickly.
But unfortunately, the downside of Calcitriol is that although it's widely available and you can get it in human health food stores, there aren't any veterinary formulations available, and the human doses are far in excess of what we need to use in dogs. So it's near on impossible to actually split vitamin calcitriol capsules or tablets into doses that are appropriate for dogs. And for that reason, practically, we have traditionally tend to use one of two alternative options for vitamin D supplementation.
Either one called dihydrottaisterol, or one called alpha calcidiol. Now dihydrottaysterol, is a synthetic analogue of vitamin D that doesn't need to be activated by the kidneys. By by parathyroid hormone in the kidneys, and it used to be used very commonly, but unfortunately, it's been discontinued.
So some of you may have come across that in practise, but it hasn't been widely available for the last 1 to 2 years and probably won't be again in the near future. So because of this, most of us now have moved on to using alpha-calcidiol, which is another tongue twister medication. And this is really now the go to means of supplementing vitamin D.
. The doses for this, there isn't a lot published on it because, you know, traditionally we have used dihydro taosterol a lot more, but I typically start patients on a dose of 0.06 mcg per kilogramme twice daily for the first few days. And then when I recheck their ionised or total calcium, I assess the dose to give them longer term based on what the calcium levels are doing.
So if the patient is still hypocalcemic, I will very, very slowly increase the dose. If I'm actually overshooting and the patient has become hypercalcemic. I'll reduce the dose slightly.
And I think at the moment that's as good as we can recommend for a dosing regime because it's quite new that we're starting to use this form of vitamin D, and every dog does seem to respond a little bit differently to the more standard doses that we give. And so the, the long term goal of treatment is to be able to maintain the patient's serum calcium levels at the lower end of the normal reference range. So we want, a level that's high enough to prevent the patient having clinical signs, but we don't want the calcium levels to go too high and actually get vitamin D toxicosis.
And giving too high a dose of vitamin D is dangerous because not only will it induce hypercalcemia, but it will also cause the phosphate to become high. And when we have both of these minerals increased, it puts patients at a very high risk of, having an acute kidney injury due to calcification of the kidneys. So in the short term.
We have to keep a very close eye on these patients. When I send them home, I'll typically get them back in once a week for the first month or so to check their calcium levels and make sure we're keeping it at the low end of normal. And then longer term, I'll try to space that out to make it more practical for the owners, but they typically will need to have it checked every 2 to 3 months lifelong.
Fortunately, the prognosis of hypoparathyroidism is very, very good. Assuming the owners of affected dogs are committed to the long-term management and the rechecks that are needed, patients should be able to have a normal quality and quantity of life. But the main causes of morbidity or mortality, would be that, you know, either this isn't diagnosed quickly enough when the dog is seizure.
And patients miss out on the calcium supplementation they need when they're having the acute crisis. Or the other main problem is that some owners may not show up for rechecks as frequently as they need to. Patients will actually get vitamin D toxicosis and end up having long-term kidney dysfunction because of that.
So as long as you monitor them very carefully, patients do very well, but you need to keep a very close eye on these dogs. And finally, the last question is, you know, are these cases that you can manage in general practise or should you be referring them? With primary hyperparathyroidism, you know, this is definitely a condition that you should be able to diagnose in general practise.
You can submit the tests to measure parathyroid hormone related protein, and so you can usually get your diagnosis very well in general practise. As to whether or not performing the surgery for this condition is something you can do in general practise, I think that depends a little bit on the setup. So you would need to have an experienced surgeon, ideally someone who's confident with ultrasound, who can find the nodule in the neck, and definitely you need to have a 24 hour hospital because these patients need their calcium checked very, very frequently, and it would be perfect to have an on-site ionised calcium machine.
Although if you don't have that, you could check total calcium. With primary hypoparathyroidism, again this is something you should be able to diagnose and treat in general practise, as long as you have a 24 hour hospital because these patients do need to be hospitalised for at least a few days. They need to have the calcium levels checked at least once or twice a day.
And therefore, you know, having a 24 hour facility is really important. And ideally it helps if you have the on-site ionised calcium machine, but as I mentioned, the next best option is just to keep tracking the total calcium. But obviously, at any point, if you weren't comfortable or you don't have these facilities, referral is always an option.
So, that concludes the webinar, and I hope you have found it helpful and I'd be very happy to answer any questions. Miles, that was absolutely fascinating. And as always, with the good speakers and, and good clinicians, you make it all sound so easy.
When we get back into our clinics again, we go, what was it that Miles was saying again? So thank you very much for that. That's really fantastic.
No problem. The, the surgery for removing these tumours and that sort of thing is obviously going to be quite a delicate surgery. Why would you think that we would get as much bleeding with, the parathyroid removal as we do with, with some cases of thyroid.
Yeah, I think it depends a little bit. I, I think obviously, you know, I think what I meant by haemorrhage as a risk would mainly be just the other structures in the neck, obviously, like some of the, the big, big blood vessels like jugular vein and carotid, for example, which hopefully you wouldn't hit. But, yeah, typically, you know, as long as you're confident with the surgical approach, I would imagine that you're going to encounter less haemorrhage than with a thyroidectomy.
Although, you know, thankfully I'm, I'm quite happy I don't have to perform the surgeries anymore. I say that it's quite a routine surgery, but if someone asked me to do it, then that would be another story, I imagine. Yeah.
something else, when you were talking about the hypercalcemia and that initial treatment to stabilise the patients, you were talking about using dexamethasone or furozamide. I guess the question is, you know, which one would you go for first and, and could you use both together in extreme cases? Yeah.
And you can use both together. And I think which one you use first, I think it, it, it depends a little bit on the situation. So, you know, just say I'm really suspicious that a patient might have lymphoma and that's the cause of the hypercalcemia.
I might want to try and hold off in giving that dog dexamethasone until I've done a bit more work up and taken some samples so that I don't miss out on the diagnosis. So in that case, I might try furosemide first. But you know, at the same time, if the hypercalcemia is remaining, you know, really severe and I have to give that patient a once off, once off dose of Dex, it's, you know, not the end of the world.
You can maybe still get the, the diagnosis of lymphoma. But yeah, typically, unless I, I'm worried a patient might have something like lymphoma, there, you know, there's not really a consensus on which one you should use first. You can kind of take your pick, and it is OK to use both of them at the same time.
Yeah, excellent. And I suppose the, the furosemide is always going to benefit the kidneys as well if we're starting to get renal involvement in azotemis and all sorts of things. Yeah, I guess if if you're worried that, you know, the patient has severe kidney insufficiency and the urine output is, you know, decreased there, you know, it's kind of you know, there there is an opinion that yeah, diuretics can help with that certainly so and that might be an additional benefit.
Yeah, fantastic. Miles, we've got no more questions for you, so it is just my, my absolute honour to be able to say thank you so much for your time tonight and thank you for making this such an amazing presentation and so easy and logical to understand. So thank you for your time.
You're very welcome. Thank you. To everybody that attended tonight, folks, thank you very much for your time.
To Amy, my controller in the background who made everything happen seamlessly. Thank you very much. And from myself, Bruce Stevenson, it's good night until the next time.