Thursday 4 July 2019

IodoCats- Part 2


INTERVIEW: Pilar Xifra- Part 2

(Traduction & Transcription from the Spanish Podcast available on lagateramedicinafelina.blogspot.com/ES)



Welcome again! In this second part of the interview, Pilar Xifra speaks about her dietary recommendations before treating with radioiodine. She also describes potential therapeutic complications of treatment with I131 and talks about the studies she has in mind.             












-             Do you give any specific dietary recommendations before I131? May the diet influence the result of the treatment?
-             Yes, well, hyperthyroidism is caused by a tumour. That is something I always emphasize. When we treat it, we try to favour the uptake of radioiodine by the tumour cells. Iodine is absorbed only in the thyroid gland, which uses it to produce thyroid hormone. If it gets saturated with the dietary iodine, the I131 uptake may not be as much as we wish. Ideally the amount of radioiodine that the thyroid gland takes is between 20 and 30% of the total radioiodine that we inject. However there are cats that only take up 6 or 7%. In those cases we have to increase the dose to compensate for the radioiodine that is lost in the urine. Whilst I was at the hospital Puerta de Hierro, I watched how this topic is managed in humans and I now I do the same with cats. A few weeks before treating a person with radioiodine that person is given a leaflet with instructions about the diet for them to avoid food with a high iodine content, like fish or seafood. The problem are the commercial feline diets…

Precisely when you contacted me today I was reading a paper written in US, where iodine content was measured in different diets. A 4 kg cat needs is 87.5 micrograms of iodine. They designed a blind study and the range (of dietary content ) was between 200 and had a hundred and fifty-four thousand micrograms! A huge variation! And in a large percentage of the dietary recommendations, the daily iodine intake ended up being greater than 100 micrograms… So I talked about this with Dr Peterson. I wanted to find out more information about this!

I thought of designing a retrospective study that would involve assessing the dietary iodine intake before the therapy... However that was very complicated because there are only a few cats that only eat one type of food. The iodine content of the different diets is also very different and is really difficult to find out the iodine content of every diet. It is a very well-kept secret! Cecilia Villaverde suggested a prospective study, perhaps one where a group of cats are fed a controlled diet and a second group are fed diets has not been controlled. However I find this is also very complicated because I do not like the idea of changing the diet to geriatric cats or sick cats. I really do not want a sick hyperthyroid cat with anorexia!

I started recommending owners to avoid iodine rich food such as ham or fish or sausages… But the variety of diets, ingredients and flavours drives me crazy. However I found out that the iodine content between tins of tuna and chicken flavoured commercial diets is exactly the same as it gets injected into it.  I recommend avoiding human treats and encourage them to feed their cats commercial diets. Whether they are meat or fish flavoured does not really matter. Gourmet Gold is very popular. I tried to encourage them to feed their cats wet food, since I think hydration is very important. I am very popular amongst my patients. They all like these diets. I also feed them gourmet gold when they are in the practice with us.

-             Do you get paid by that company for the marketing you are doing right now?  

-             No but I definitely have to talk to them, you are right. I like it because its iodine content is very low. It barely reaches what they actually made need. And all cats love it! I wonder if they put something addictive in it! Cecilia Villaverde told me that it is a very balanced diet so I have no I am very happy to recommend it.

-             Well, remind Purina of that % the owe you then…

-             Aw, sorry… I am not sure about marketing being appropriate in your podcasts…

-             Haha!  It doesn't matter as long as it is very beneficial for cats. How about cats with renal disease? We know that cats in an early IRIS stage we will recommend curative treatment anyway. Do you take any extra precautions you would like to talk about?

-              It is very frequent to see hyperthyroid cats with chronic kidney disease. The chances of concurrent diseases increase with ageing.  Dr. Peterson created an amazing formula that allows to predict the likelihood of chronic kidney disease. It takes into account the creatinine value, the sdma and the urinary specific gravity.  Hyperthyroid cats have an increased glomerular filtration rate (GFR). SDMA and creatinine are the values we use to assess the GFR. We consider IRIS stage 1 when creatinine reaches 1.6mg/dl. A creatinine of 1.5 mg/dl is already suspicious in a hyperthyroid cat. We assume that the creatinine should be lower than that because of the loss of muscular mass. The urinary specific gravity (usg) is also relevant (It is also a very cheap test!  I do not understand how some vets do not measure it!) Even though is not the most specific test, it is the most sensitive. When the specific gravity is below 1035 and we observe polyuria (PU) and polydipsia (PD)… then we must suspect occult chronic kidney disease! Before discussing this with Peterson, I assumed PU/PD was a normal finding in hyperthyroidism. However he made clear that we should not assume that it is only triggered by alterations in the thyroid gland. Regardless the type of therapy (pharmacological, surgical or medical) GFR drops when euthyroidism is achieved, but CREA never increases more than one IRIS stage. You never find a cat whose creatinine goes from 1.5 up to 7 mg/dl. It may go from 1.5 to to 2.3 mg/dl. But should we treat cats with renal disease for hyperthyroidism? The answer is absolutely YES! Hyperthyroidism is perpetuating the renal disease and damaging the kidney. We treat first the hyperthyroidism and, after that, we manage the renal disease (the associated hyperphosphatemia and hypertension, etc): they become renal patients. We then have to follow the IRIS recommendations.

It has already been demonstrated that treating with methimazole first is not necessary. In first place, we can predict the likelihood of renal disease using the formula we spoke about above. It has been demonstrated that both cats with and without subclinical azotemia have the same prognosis with curative treatment. If we don't treat these cats in an early stage of renal disease we contribute to the kidney dysfunction.

However cats with more advanced renal disease such as cats in an IRIS stage III or IV, need a more careful approach. These cats are going to have a short life expectancy anyway. In these cases it may be better not to consider a curative treatment. Do the owners really want to pay for the radioiodine treatment when is not the hyperthyroidism what is going to determine the life expectancy of those cats? I avoid treating cats with creatinine above 2.5 mg/dl because after treatment it usually increases up to to 3.5 or 4 mg/dl.

-             Do you then take the CREA values into account when you work out the dose of I131?

-             Yes, in those cats with CREA values just below 2.5 mg/dl you need to be cautious. The same way the same way hyperthyroidism increases the glomerular filtration rate and euthyroidism normalises it, hypothyroidism reduces the glomerular filtration rate. Hypothyroidism will cause a deficient glomerular filtration rate that is detrimental to the kidneys. And in these cases the increase in creatinine may be much greater. These cats need levothyroxine supplementation.



-             So which other factors do you take into account when you were work out the amount of radioiodine? You probably have a formula…

-             There are three different ways. You can use a fix dose as it gets done in UK: 4 millicuries per cat regardless the hyperthyroid state. In the second method considers doses between 3 and 4 millicuries based on T4 levels. There is a third method where doses are estimated according to scintigraphy results  and I131 uptake by the thyroid. Dr Peterson implemented this protocol a very long time ago. It takes into account the T4 and the TSH levels (I always say that the formula we use should have Dr Peterson's name. But he doesn't want to listen to me because he's a very humble man!) and uses human medicine as a reference. We take into account the severity of the symptoms, the hyperthyroid state, the duration of the disease... It is not the same to treat a cat that has been hyperthyroid for 3 years, as treating a cat that has just been diagnosed. Hyperthyroidism becomes more severe as time goes by. I personally also reduce the radioiodine dose when I see that occult renal disease is likely, as it is done in human medicine. On the other hand, if I consider that hyperthyroidism is the greatest contributor to the loss of quality of life, I may increase the dose

We also do scintigraphy before the treatment with the aim of measuring the volume and the function of the thyroid, by visualising the percentage of technetium uptake. This helps to estimate the initial dose. Then we monitor the uptake with a Geiger monitor 24 and 48 hours later. That way we find out the real uptake from the specific amount we inject.

-             Oh yes! I think you mentioned this earlier on, when you explained what the Geiger monitor was used for.

-             Exactly. The optimal uptake is between a 20 and a 30%. E.g if a cat has an uptake of 8% and I have calculated an initial dose of 1.8 millicuries, I will have to increase it up to 2.3 millicuries. However if there is an uptake of 45-50% (what happens in many hyperthyroid cats) I will reduce the initial estimated dose. The difference between different methods can be observed in the results. Our dose range generally varies between 1.5 and 6 millicuries. If we administer 4 to all cats, in some cases this will be too little and in some cases it will be too much. If we administer an excessive dose we will trigger iatrogenic hypothyroidism. This way we only have a 2-3% of chances of iatrogenic clinical hypothyroidism (low total T4 & high TSH), what is very good compared to the 40-50% caused with other methods. 

-             That is a significant difference!

-             Yes, it is. Regarding subclinical hypothyroidism (normal T4 & high TSH), when these cats show an unexpected increase in creatinine we also supplement with Levothyroxine. We find this issue in 20 to 30% of our patients. With other methods the total percentage of iatrogenic hypothyroidism (clinical and subclinical) is between 50 and 60% of the cats, more than half of them.

-             OK, we will have to repeat this podcast in English to help getting the message across!  When do we have to start supplementing with levothyroxine after the treatment?

-             We have to supplement all the cats that show clinical hypothyroidism (low T4 & high TSH). In subclinical hypothyroidism (normal T4 & high TSH) we only treat when creatinine is above 2. It has been demonstrated that it helps reducing the creatinine and is beneficial to the kidney function.

Iatrogenic hypothyroidism barely causes any symptoms. It is very difficult for the owners to recognise it. Hyperthyroid cats show polyphagia and hyperactivity. After euthyroidism, the put on weight, stop showing PF and are calmer. This is the same process they pass through when they become hypothyroid. So it is very difficult for the owners to recognise it. However we want to preserve the renal blood flow, since hypoperfusion can cause kidney injury.

-             Thank you so much. I find this information very valuable. Going back to the dose of radioiodine, I guess that underestimating the initial dose of I131 necessarily causes a need for a second injection?

-             Yes, we call it persistent hyperthyroidism. There's about a 5% of cats that need a second treatment. 

-             ... which is administered in injectable form.

-             Yes we administer it subcutaneously. In human medicine, it can be administered orally. However giving a capsule to cat is much more complicated and becomes a health and safety issue.

-             Which other complications do you see more frequently after I131 treatment apart from iatrogenic hypothyroidism?

-             There is a difference between treating a benign tumour, such as an adenoma, and treating a malignant tumour, such as an adenocarcinoma.

We may make a presumptive diagnosis adenocarcinoma based on scintigraphy. We do not do biopsies. Some tumours are multifocal, and even resistant to methimazole, because of the massive production of thyroid hormones. Sometimes these tumours need up to 30 millicuries of I131! Our main goal when we treat adenomas is to destroy the tumour cells, whilst leaving the healthy tissue intact. However when we treat adenocarcinomas our main goal is to destroy the whole thyroid gland. Low doses (1-7 millicuries) do not have a lot of adverse effects. Sometimes they may show temporary or permanent hoarseness. But that's not that important…

-             Somebody should steal your voice for a few days…  then you let us see what you think!

-             J The main problem with high doses of I131 is thyroiditis. We are talking here about really large tumours, sometimes even greater than 10 cm3. They may even invade the thorax. I imagine it as a huge incandescent mass that must burn once you treat it! They may show with fever and anorexia. These cats have to stay with us for a couple of weeks. In cases of benign adenomas usually three or four days is enough. Some of our patients have had a bad time, but it does not happen frequently. We opened our practice in 2016- by the way on Monday we will treat our cat number 100!- and we only have seen 4 adenocarcinomas. Two of them did not have any problem at all and went home without further complications. A third cat showed a bit of fever and mild hyporexia but responded well to NSAIDs. However the fourth cat… she came from Israel... I have now more grey hairs thanks to that kitty! Everything went fine but the anorexia was terrible. She even needed an oesophagostomy tube because she did not want to eat at all. However she is perfectly fine now.

-             What a great success! 100 successfully treated hyperthyroid cats!

-             Yes, indeed. We are actually writing a paper for the Journal of Feline Medicine and Surgery.

-              I guess that will not be the last one. I guess you are collecting a lot of interesting data. 100 cats is quite a large sample when it comes to feline medicine. Our studies always seem to be based on small samples.

-             Yes, indeed! We are now measuring the blood pressure and the proteinuria. We measure these parameters before the treatment, on the day of admission and 6 months after the treatment, when they come back for the follow-up scintigraphy. Dr. Peterson also got me involved in a new study about ultrasound measurements of muscles. This is a very important parameter because some hyperthyroid cats have a normal body condition score but a very poor muscle condition score. I am very happy that many practitioners have now the habit of measuring the body condition score. And as well as the urinary specific gravity it is very cheap! Measuring muscle condition score is the third cheap thing that we can measure and it may have prognostic value. We are studying how cats get their normal muscle condition back after achieving euthyroidism. There is a study from the University of Tufts showing normal muscular conditions scores in cats and dogs. We use that study as a reference.

- And how do you manage to keep your family life going at the same time as all these things that you are telling me about??

- Haha! I think one of these days they are going to tell me to go away and possibly change the door keys!

- You told me not long ago this was an initiative you had much later after graduation, when you already had family.

- It is true that sometimes I envy young people without commitments, who can start a residence or just spend more time abroad! Every time I go to New York I can only stay there for a week! Very “New Yorkish”… Everything seems to happen fast over there! I try to go at least once or twice a year. I love these opportunities of brainstorming and talking about new projects.

- How lucky are Spanish cats! And how lucky are their owners and also the vets who can listen to you! I feel really lucky to have been able to talk to you for a whole hour. I have learnt loads. I really, really appreciate your contribution to my blog.

- It has been good and I also wonder where do you get your time from, now that you have embarked in La Gatera! I find it is a very nice project!

- It is fun! I am learning a lot. That is basically why I do i!







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