Thyroid Disease and Hypothyroidism in the Dog (this lecture was given in October 2000)

DR RICHARD DIXON has recently been awarded a PhD for his research into canine hypothyroidism

Please be aware that the PAWS scheme is no longer available but this information is well worth reading

The areas that Dr Dixon covered are the healthy thyroid gland; the unhealthy thyroid gland and hypothyroidism in dogs; how the immune system interacts with hypothyroidism in dogs, and where future studies in this area will take us; and he went on to say:

The thyroid gland is a bean like structure located in the neck of most mammals. It is usually just behind the larynx. The purpose of the thyroid is to produce thyroid hormones. The most important one is thyroxin - otherwise know as T4. The other main hormone is triiodothyronine abbreviated to T3. The hormone T4, from a diagnostic point of view, is the most important one.

The thyroid gland produces the hormones which enter the blood, and circulate throughout all the tissues. They essentially permeate all body cells; eg. muscles, skin and the heart, and play a very important roll in controlling the metabolism. They help maintain body temperature, a healthy skin and assist the immune system to fight off infections. They help the brain to function and maintain alertness, awareness, and energy. Essentially, thyroid hormones are needed for life. Thyroid hormones are produced from iodine, which we get from our diet.

Thyroid disease is very common in dogs, cats and humans. Dogs commonly get hypothyroidism (under active thyroid). Cats commonly get hyperthyroidism (overactive thyroid), and humans commonly get both conditions.

Hypothyroidism in the dog is when the thyroid gland slowly disintegrates. The ability of the thyroid to produce the thyroid hormones progressively diminishes and the body starts to run out of the hormones T4 and T3. When there are not sufficient hormones to keep the animal going, clinical signs appear.

Disease of the thyroid gland itself is not hypothyroidism. Hypothyroidism is clinical signs that show when the dog does not produce enough of the thyroid hormone. That is an important distinction to make. Thyroid disintegration can take months, even years, from the start of the disease process before hypothyroidism becomes apparent. Most of the thyroid tissue is destroyed and the hormone concentrations are very low before clinical signs occur. At this point, about 75% of the thyroid has been destroyed.
Once this disease is diagnosed it can be very successfully treated. For those that are affected, however, the symptoms are very tragic.

Dermatological signs and hair coat changes are the common, clinical signs of hypothyroidism. Also, metabolic signs such as hair loss down the flanks or on the tail, where the skin becomes pigmented. Dandruff is a common indication that the dog may be hypothyroid, also weight gain and lethargy. Affected dogs are prone to skin infections, intolerant to exercise, and to many owners it looks as if the dog has aged prematurely. Many have a sad or tragic look on their face. Neurological, cardiovascular and reproductive abnormalities also occur.

There are certain breeds that are predisposed to hypothyroidism such as, spaniels, retrievers, dobermans, collies, shelties and boxers, and many other breeds are commonly reported as having hypothyroidism.

Diagnosing hypothyroidism can be quite difficult. There are a variety of tests available but none are totally conclusive. The most useful tests, at present, for confirming hypothyroidism are:

Total (T4) - this is where the hormone T4 produced by the thyroid is measured in the blood. It is called Total because most of the hormone is bound to proteins in the blood, and all the hormone and the protein is measured.

Free (fT4) - is when the hormone measured is not bound to the protein. Different information is gained using the Free T4 test. In the past various methods to measure Free T4 have been very complicated but now, if the right method is used, this is a very useful test.

TSH - is the thyroid stimulating hormone. This is a hormone produced in the brain which stimulates the thyroid to produce its hormones. The concentrations change in hypothyroid dogs. This is a useful test to help diagnose hypothyroidism.

TgAb - is the thyroglobulin autoantibodies. This test does not tell anything about the thyroid function, but its presence does indicate a disease process within the thyroid gland. In conjunction with the other three tests it can be a very useful marker of thyroid pathology.

Treating hypothyroidism is relatively straight forward. The dog has to be given the thyroid hormone in tablet form, on a daily basis. ‘Soloxin’ is the registered name of the drug and costs only about 50 pence per week. The treatment is very successful.

The effect of Soloxin can be dramatic. The hair growth is rapid, often returning to near normal in 7 weeks. The prognosis, once the dog has started treatment, is excellent. Life expectancy is near normal and their quality of life is certainly adequate, although there may be subtle differences that probably only the owner would recognise. Some of the problems that are encountered relate to the immune system. The treatment helps 99% of dogs. Occasionally, skin infections may occur even when the dog is on therapy.

The Immune System and Thyroid Disease in Dogs

If the thyroid gland is examined under a microscope, two pathologies are recognised. The first is lymphocytic thyroiditis (know as thyroiditis). This is caused by immune mediated cells infiltrating the thyroid gland, resulting in its destruction. This is a common disease in humans, especially females, and is known as Hashimoto’s thyroiditis. The other main type of pathology that is recognised is called idiopathic atrophy. Idiopathic is when the cause is unknown. Until two years ago idiopathic atrophy was thought to be responsible for about 50% of hypothyroidism cases. Recently, data has been released from Michigan State University, USA, where they have looked at thyroiditis dogs and idiopathic atrophy dogs, and they have come to the conclusion that there is only one disease process. It is the same disease, but at a different stage. Idiopathic atrophy is in fact dogs that have had thyroiditis two years previously.

The most commonly recognised cause of hypothyroidism is immune mediated destruction of the thyroid. In some parts of the world hypothyroidism in humans is caused by lack of iodine in the diet. This cannot be said of dogs, however, as on a world wide basis, dogs in the western world have a better diet than most humans. In the western world, autoimmune thyroid disease is the main cause of hypothyroidism in humans. It is most common in women, and it is known that there are genetic and non-genetic influences that cause it to develop.

When the thyroid is being destroyed in dogs with lymphocytic thyroiditis, the thyroid becomes damaged and exposed to the immune system in a way that it wouldn’t normally be. As a consequence, the immune system fails to recognise the thyroid as a healthy part of the dog’s own body and starts to produce anti-bodies against the thyroid. These are the thyroglobulin autoantibodies (TgAb). Recent studies involving biopsies of thyroid tissue have documented that the presence of thyroglobulin autoantibodies in the blood is now an accurate way to confirm thyroiditis.

The cause of this infiltration of immune mediated cells is unknown. There are factors known that contribute to this process but the condition is not yet fully understood. There is a hereditary component. Some breeds are over represented and develop thyroiditis more often than one would expect if it were only a chance disease. Also, certain families and lines of dogs develop thyroiditis more commonly. In all likelihood there is probably a combination of both genetic influences (some animals have a genetic predisposition to developing this disease) and trigger factors (that have yet to be identified) which if the predisposed animal is exposed to, they will develop thyroiditis. More work is needed to clarify this exactly.

A study in 1996, tried to identify trigger factors in predisposed human individuals. Some of the trigger factors that were implicated are: stress, diet, pregnancy, infectious agents, other hormones, toxins and various components of the immune system. This broad spectrum of triggers provokes numerous questions as to what causes autoimmune destruction of the thyroid in the dog. . At present the possible trigger factors that we may think are implicated cannot be supported by scientific fact.

To find out what triggers activate this disease, more genetic data is required. There is a need for dogs to be monitored from when they are perfectly healthy, following their thyroid status over a period of years, so that the dogs who ultimately become hypothyroid are fully documented. This is the sort of information needed if hypothyroidism is to be fully understood and the problem addressed.

The diagnosis of hypothyroidism is complicated, but is undoubtedly becoming more clear, and more reliable tests are available for the vets in practice. Veterinary education is improving, and the advances over the last five years have been dramatic.

Vets and researchers now have a greater understanding of the tests and interpret the results more accurately. Some of the tests for hypothyroidism that were considered reliable in the past, have now been shelved. So the veterinary profession is moving forward and vets are able to be more confident in their diagnoses.

Prevention is undoubtedly better than cure, and that now underlies the whole approach, as far as thyroid disease in the dog is concerned. It is important that an accurate diagnosis is reached when clinical signs occur, but diagnostic methods are now at a stage whereby the dogs that are about to become hypothyroid can be monitored. Ultimately there is a need to reduce the dogs that are genetically pre-disposed.

Our aims are to reduce the incidence of hypothyroidism; to rapidly achieve an accurate diagnosis when it does occur, and to accurately predict that a particular mating would increase the likelihood of producing hypothyroid offspring, so the breeder can make an informed decision on whether a mating is appropriate. It can be predicted that over the next ten years hypothyroidism will be reduced dramatically because of genetic testing.

Screening for Thyroiditis

The purpose of the PAW screening programme is to identify healthy dogs who have thyroiditis, but do not have hypothyroidism. PAWS is for dogs that appear healthy and not for those who are showing clinical signs of hypothyroidism. Clinically unwell dogs need to be taken to the vet.

PAW uses the thyroglobulin antibody method to confirm dogs that have thyroiditis.

Although it can be predicted that TgAb positive dogs will become hypothyroid the disease process cannot be stopped. An abnormal thyroid cannot be turned back into a normal thyroid. The purpose is to be able to identify these dogs before they develop clinical signs of hypothyroidism. This allows the dog to be monitored closely so that treatment can commence as soon as clinical signs show. This will alleviate much of the prolonged suffering that is usual before a diagnosis is made, and also gives the breeder the opportunity to make informed decisions with regard to their breeding programme.

Particularly in numerically smaller breeds, it may be necessary to perform a mating even if there is an increased risk in passing on thyroid disease. Hopefully that is a rare situation. The breed should be looked at as a whole, taking into consideration what problems there are within that breed, and where the priorities for that breed lie.

With regard to thyroid disease alone, the TgAb test gives the breeder the opportunity to remove affected dogs from the breeding pool, if this is appropriate. This is starting to address the problem using the latest science. We are now following the example that has been set and the in the USA, where the Society of Comparative Endocrinology are running a widespread screening programme for multiple breeds and logging the results for the purpose of DNA technology.

The scheme is based at Glasgow Veterinary School and the results are confidential between PAW and yourself. Your vet will be informed of the result, at your request.

The test is run in association with your vet and can be performed routinely, either every couple of years or as a pre mating test, a few months before you mate your dog. Also, the dog, which you are planning to mate your dog to, should be tested. After your dog’s blood sample has been taken it will be sent off to PAW. The test will be carried out at Glasgow Veterinary School. You will be informed of the result within a couple of weeks and will receive a certificate if your dog is clear of thyroiditis.


Thyroiditis can develop at anytime. PAW recommends that a one off blood sample that shows ‘clear’ is of value at that time, but there are no guarantees that thyroiditis will not develop at a later date. It is suggested therefore, that dogs which are used for breeding should be tested every two years. Even if your dog is not used for breeding, monitoring its thyroid status is still important for that dog.

Ultimately, it is hoped that a genetic marker will be found for thyroiditis. This will eliminate the problem of breeding apparently clear dogs that may go on to develop this disease. It is inevitable that, although this screening will limit the number of affected matings that occur, some will slip through. A DNA test is the only way of being 100% accurate.

One of the ways forward is to have educational seminars where people can become more informed, and some of the rumours about thyroid disease can be dispelled and the genuine problems outlined. Also, veterinary education is very important. Increase in openness and awareness within the breeding community is essential if this is going to move forward and develop, and the fact that there are over 180 people in attendance at this seminar speaks for itself. It makes it quite clear that people are genuinely interested and want to move things forward and put the welfare of their breed first.

It is important that what is done is based on science and reliable research. It can’t be based on something that somebody found on the Web. There is a lot of misinformation and confusion and although much of this information may be right, unless someone has demonstrated it in a reliable manner, there is no point in taking it further. We have to go forward in a co-ordinated, scientific, and structured fashion.

Without the involvement of the breeders and the breed clubs, health issues will not move forward. It has to be led by the clubs and the individuals within the clubs. If the owners and breeders want to do something in their breed, they can undoubtedly do it.
Questions from the floor
Q What is the cost of PAW screening test.
A The cost of PAW scheme for an individual is £23.50. If the breed clubs or an individual want to buy a batch, 12 kits can be bought for the price of 10.
Q Is there an age after which thyroiditis is less likely?
A Yes. There is no age at which thyroiditis cannot develop, but it is less likely after about 7 years.
Q Given that knowledge has advanced quite considerably over the last few years with regard to diagnosing thyroiditis specifically, should we be involved in diagnosing other similar immune mediated conditions at an earlier stage?
A Yes. There is a lot of activity within many of these immune conditions. Much work is being done in the area of measuring antibodies in dogs that are going to develop Addison’s disease. It is the same concept as the TgAb test. We are trying to identify dogs before clinical signs show. This enables the dog to be monitored, and pick up early signs of the disease. This knowledge can assist the breeder to make informed breeding decisions.
Q If an animal is predisposed to thyroiditis and hypothyroidism, is it more likely to develop some of the other immune mediated diseases?
A Sadly, yes. Certainly it is the case in humans. We do recognise polyglandula syndromes in dogs, whereby the immune mediated destruction which is damaging the thyroid tissue, can damage other tissues. The most common combination, found at Glasgow Veterinary School, was dogs that had destruction of pancreatic tissue, also became diabetic. In the USA, the most commonly recognised combination is, dogs that have thyroiditis and an immune mediated destruction of the adrenal gland, which makes them become Addisonian. There are some reports of dogs that have three or four different conditions, which is confusing to confirm, and is very bad news for the individuals concerned. There is a cross over between multiple systems.
Q If a dog is tested by PAW and gets a certificate to indicate that it doesn’t have thyroiditis, does that cause a false sense of security since some of those dogs may potentially develop thyroiditis at an older age?
A A PAW certificate means that when the dog was tested it didn’t have thyroiditis. With the current state of science and knowledge it is unfortunately, the best we can do, because we don’t have a genetic test. If they are going to continue breeding with the dog, they should retest at intervals to make sure it hasn’t developed in the meantime.
Q If a dog is tested and pronounced clear of thyroiditis and is bred from, and four years later is found to have thyroiditis, what about the puppies produced by that dog?
A This is a major problem, but it is not one that would make me think that we shouldn’t use the test. Running the TgAb test will identify a high percentage of affected dogs, which could be eliminated from the breeding community. In the early stages, a number of individuals will be missed, which is why ultimately a genetic test is needed. So, just because we do not have a genetic test at the moment, doesn’t mean to say that it should be ignored and that nothing should be done about it. Until there is a genetic test, we have to use what is available and the best test at this time to predict if a dog will become hypothyroid is the thyrogobulin antibody test. Science is changing all the time and this is a way forward and the TgAb test certainly limits this disease at present.
Q Once a hypothyroid dog is on treatment does it have to be monitored to ensure that the level of medication is correct?

A Yes. There is a lot of variation in how much Soloxin a dog needs but once the correct dose has be achieved, the level tends to be relatively stable throughout the dog’s life. There may be a small increase in requirement with time. Regular monitoring, about every six months or so, is advised.
Q If a dog’s thyroid had disintegrated and is hypothyroid can it eventually become cancerous?
A At this time, we know of no link between the development of thyroid cancer in dogs and hypothyroidism, other than some dogs that develop thyroid cancer can become hypothyroid. This is caused by the cancer destroying the thyroid tissue and is not connected to autoimmune destruction of the thyroid.
Q What work is being done to identify trigger factors in predisposed dogs?
A There is not much co-ordinated work being done. There are a small number of groups around the world, mostly American, that are doing epidemiological evaluation. This work looks at when dogs develop particular problems and studies systematic characterisation and possible explanation of patterns for a disease. One of the problems is that there are so many potential triggers and there is so much to be learned about the genetics. The only study that has been conducted demonstrated that hypothyroidism was most likely to be an autosomal recessive problem. A lot more work is needed to be done.
Q After a PAW certificate has been granted, should it become invalid after a certain period of time?
A It is recommended that dogs should be tested every two years, so when people are looking for certified dogs then the date of the certificate should be asked. In the USA they are testing every year, and the more tests you do the better grip you have on the thyroid status, but that has to be balanced against the finances of testing, therefore a two yearly compromise has been reached. The test can be performed more often if you chose.
Q When people start to be open about problems within the breed there is scare mongering.
A I have heard this so often, but I have no doubt that that culture is slowly becoming a thing of the past, but it is still very much present. The way forward is to discuss the problems and the people who are here today are the ones who are going to make that move. It is not something that vets or researchers can do. It is the grass roots people involved in breeding that are the ones who are going to move this forward. If people discuss the health matters they are experiencing in their breed, for a time it may cause some problems, but if they genuinely have the welfare of their breed at heart, and I believe that that is most important to most breeders, then I don’t think that the politics or personalities will stand in the way, but it does require for people to stand up and get together to discuss these problems. It is not easy, but it is the only way to move forward.
Q Vets are suggesting that breeders should be open to move health matters forward and yet vets seem quite the opposite and are very closed to the issue of whether vaccination is implicated in these diseases.
A I know exactly what you mean. I don’t think it is an area that any vets have discounted. It is very important to differentiate between saying that something might be relevant, such as vaccination, and saying that is relevant, or it is not. The people who are involved in the research of links between say, vaccination and thyroid disease are objective and have no vested interest in wanting vaccines to be used on an annual basis, for example. There is no well conducted, scientific data at this present time, that links vaccination to the development of say, thyroiditis. Numerous trigger areas could be identified but until the vets have the science, and the education is at a point whereby the breeding and veterinary communities can make truly, informed decisions then it would not be appropriate to make sweeping changes. You may well be right, and if future data shows that there is a cause and effect relationship between vaccination and autoimmune diseases then no vet will continue using them in the same way.
 

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Updated 15-07-05