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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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