So let's get to case number two. We're going to stick with the cats for a little minute. All right. So this is Kitty. Kitty is a 12 year old female spayed domestic shorthair cat, she is previously healthy and of course, up to date on her vaccines. She has a two months, two months history of weight loss with an increased appetite. And she has been vomiting 2 to 3 times weekly. Her activity is increased and the owners also report that she's been PUPD. So here are her physical exam findings. And I just want you to take a look at the those and just kind of note the abnormalities. Just give you a second. 

Okay. So in order to further evaluate her condition, we're going to run a serum chemistry. And here are the results of our serum chemistries. And then we're also going to run a urinalysis because that always goes together with our serum chemistries. And here are the results of our urinalysis. Okay, So on the right is a summary of our serum chemistry and urinalysis findings. So we're going to note that we have an increase in our liver enzymes. We have a mild hyperglycemia with a negative urine glucose. We have a decreased urine specific gravity with a normal BUN and creatinine. Now given that we have a mild hyperglycemia and our urine glucose is negative, we can feel fairly confident in saying that diabetes mellitus has been ruled out. So if we go back to our clinical signs, you know, we don't really have an adequate explanation for why this cat came into the hospital. Right? This cat has a history of weight loss with a good appetite, agitation and increased drinking and urination, as well as vomiting. And there's not anything on this bloodwork that would explain that, yes, we have increased liver enzymes, but if the increased liver enzymes were due to primary liver disease, I wouldn't expect this kitty to have a good appetite. I would expect this cat's appetite to be decreased. And on our physical exam, if you remember, there was tachycardia with a heart murmur, tachypnea and an enlarged thyroid. So one of our top differentials in an older cat with these clinical signs is hyperthyroidism. So an overactive thyroid. 

Okay. So let's talk a little bit about how we assess thyroid hormone with our lab work. So most thyroid hormone in circulation is bound to protein, and that is what's measured as a total T4. So a total T4 measures our protein bound fraction of thyroid hormone in circulation. So our total T4 is the initial screening test that we use for feline hyperthyroidism. And the specific reference range varies according to which lab the test is run at. So I'm not going to give you a specific reference range, but if you see an increase in your total T4 above the reference range and you have clinical signs of hyperthyroidism, you can fairly feel fairly confident in diagnosing feline hyperthyroidism. Total T4 is increased in 90 to 95% of cats with feline hyperthyroidism. So in the vast majority of cases, what we may need to diagnose hyperthyroidism is a total T4 level. 

So how do we interpret our total T4? And that really comes back to why we ran the test. And so, you know, as I already mentioned, thyroid hormone level is very commonly now a part of senior screening panels. So most labs because excuse me package tests together. So in a senior screen you often have serum chemistries, CBC, urinanalysis, and then a thy, it's usually a total thyroid hormone level. So the first question when you're looking at that thyroid hormone level is why did I run the test? So was this a test that was run as part of a routine screening, once yearly evaluation that a pet came in for? Or do we have a clinical suspicion of hyperthyroidism, and that's when we run why we ran the test? So that's our first question. Our second question is what was the result? So if your thyroid hormone level is in the lower half of the reference range, and that's typically less than around about two, hyperthyroidism is very unlikely. Okay? So if it's in the lower half of the reference range, hyperthyroidism is unlikely. Now, if it's in the upper half of the reference range, this is where things get a little bit tricky because we talk about this gray zone, thyroid hormone level. And what that tells us is that that patient may have hyperthyroidism or that thyroid hormone level may be normal for that patient. So in a case that has a gray zone, thyroid hormone level, we may need to consider further investigation depending on why we ran that test. So in it, and certainly in a cat that we have a clinical suspicion of hyperthyroidism for further investigation is is warranted. 

So another way that we can look at our thyroid hormone level in circulation is by performing a free T4 measurement. Free T4 is the biologically active form of thyroid hormone, which means that it's available to cells, but it's a much lower blood concentration than total T4. So free T4 is available to cells and is biologically active. There are different ways that you can measure free T4, but the most accurate way is to perform equilibrium dialysis. And so there are sometimes different options when you look at your lab form about how to measure free T4 or how you want it measured. I would always encourage you to run it by equilibrium dialysis. This is always performed at a reference lab and generally the reference range is between 15 to 50 pikamols per liter. You're never going to look at just a free T4. A free T4 in isolation doesn't really tell us anything. We always have to look at our free T4 with our total T4. So you're going to look at these two values together. 

All right. So what's really important now that we're talking about these hyperthyroid cats is that to have a total T4 in the gray zone with true feline hyperthyroidism is actually pretty uncommon. It happens in less than 10% of cases. And I can tell you that all of the cats that I've seen over the years that have a gray zone total T4 that are presented to me for evaluation of hyperthyroidism, the vast majority of those cats have other diseases that are causing the clinical signs. So why, though, could it be that we do have hyperthyroidism and our total T4 is in the gray zone? So it may be just that there's a daily fluctuation in our thyroid hormone level. So thyroid hormone levels change during the day. And so depending on when we draw that blood sample, that may affect our T4 level. That also may be non thyroidal disease that's affecting our total T4, and we'll talk a little bit more about that coming up. But this would be something like a sick euthyroid syndrome. So if we want to investigate our thyroid hormone because we really think a patient is hyperthyroid and his total T4 is in the gray zone, we can measure these two together. So the total T4 and then the free T4 by equilibrium dialysis. And the reason that free T4 is useful is because it's less affected by non thyroidal illness than our total T4. 

So what about measuring TSH? So this is something which in the literature is being talked more about in the assessment of hyperthyroidism in cats, we would expect based on our negative feedback loop. So going back to hormone physiology, we would expect that as our T4 and T3 increase, this is going to decrease production of TRH by the hypothalamus and decrease TSH production by the ad, by the pituitary. So we would expect that our thyroid stimulating hormone level would decrease in hyperthyroidism due to that negative feedback look, loop. Now, the problem is that in cats, the lower end of the reference range is zero. So it's kind of hard to interpret if it's low because you can't have less than zero. So, you know, this is something I don't want to spend a lot of time on in cats, but you may see comments about this coming up in the literature. But essentially what's important to remember is that your TSH is going to decrease. We do look at TSH more in the diagnosis of canine hypothyroidism. And so we're going to talk about that more coming up. Primary hypothyroidism is incredibly uncommon in cats. The only cases that I've seen have been congenital. I haven't seen it ever in an adult cat, but hypothyroidism can occur because of things we do. So radioactive iodine therapy or giving methimazole all can result in a low circulating thyroid hormone level. So that may be a situation where evaluation of TSH is helpful, particularly post radioactive iodine. 

All right. So this is a little flowchart that's going to help figure out what we're going to do with these results that we have. Okay. So we've got three possible scenarios. We have our hyperthyroidism is suspected, and then we have a low total T4, a normal total T4, and an elevated total T4. In the most straightforward situation is when our total T4 is increased because that makes hyperthyroidism very likely and we can move forward with further treatment. It's in it's kind of middle gray zone that we get a little bit more complicated. But remember that if your total T4 is in the lower end of the reference range, hyperthyroidism is very unlikely. And I think we need to go back to the drawing board in those cases to figure out what else might be going on. If your total T4 is in the gray zone with then going to run our free T4 by equilibrium dialysis. If your free T4 is high, that puts hyperthyroidism higher on our list. But if our free T4 is normal, that pretty much rules out hyperthyroidism. And it's going to make me think that something like non-thyroidal illness is affecting my total T4 being in the gray zone. Or that may just be normal for that pet. That pet may just have a thyroid hormone level of three and that might be normal. 

All right, so what else might we see in cats with hyperthyroidism? Liver enzymes are fairly consistently increased in hyperthyroidism, so more than 80% of cats with hyperthyroidism will have an increase in their ALT. More than 50% will have an increase in that alkaline phosphatase. We may also see and this is just an example of a CBC here, we may also see a mild erythrocytosis. So remember that these are older cats and often older cats have a lower red blood cell count or red blood cell count that's towards the lower end of the reference range. And these cats will often have a very robust hematocrit. They may also show a stress leukogram. And they may have isosthenuria or an inappropriate urine specific gravity due to PUPD, which is caused by the hyperthyroidism, even though their renal function is normal. 

So let's look at Kitty. This is a summary and I did include those CBC reference points for her as well. So in Kitty, we did have an increase in liver enzymes. We did have a stress leukogram and we had a stress hyperglycemia, even though urine glucose was negative. So that rules out hyper, sorry that rules out diabetes mellitus. Our urine specific gravity is decreased but if you remember back our BUN and creatinine were normal, so that can help us rule out renal dysfunction and total thyroid hormone concentration when we were on it was at 8.9. Normal end of the reference range being up to 4.7. So this is a very clear case of hyperthyroidism. So we can feel confident in Kitty diagnosing her with hyperthyroidism and then starting her on appropriate treatment. Remember that hyperthyroidism in dogs is rare. There are two situations where they can have an increase in their thyroid hormone. One would be a thyroid carcinoma, that secreting secreting thyroid hormone. Another would be dietary exposure to thyroid tissue in raw products. So there's definitely a trend or a fad going towards feeding raw meat in dogs. And certainly I've seen like raw trachea treats and things like that still have thyroid attached, and that can cause an increase in your thyroid hormone levels. Of course, the other thing would be if a patient is on levothyroxine supplementation for hypothyroidism, if we're overdoing that, then our T4 could also be increased. But true primary hyperthyroidism in dogs is, I would say, doesn't occur. All right.