CANINE HYPOTHYROIDISM

Hypothyroidism in The Dog
Hypothyroidism in Dogs
What is Hypothyroidism

Hypothyroidism in the dog can be due to a number of issues associated with the production of specific thyroid hormones, with the delivery of those hormones to target tissues, with immune mediated interference with proper chemical structure the hormones and with damage to the thyroid gland itself. Hypothyroidism is the most common endocrine gland disorder in the dog.  The endocrine glands are listed below.  All of these tissues secrete chemical substances called hormones that have a profound effect on certain "target" tissues.  A hormone is a chemical that acts on or with tissues throughout the body and is carried away from the gland of production by the blood stream.  Saliva, for example, is secreted by various salivary glands but is not considered a hormone because it leaves the glands via a small duct (a small tube) and is not transported by the blood stream and does not have an effect on any body tissue physiology.

 Of all those glands and hormones, the thyroid gland is considered the Master Gland.  If the thyroid gland is malfunctioning, every cell in the body is affected.  No wonder dogs, properly diagnosed with hypothyroidism and placed on appropriate thyroid hormone supplements, will look, act and feel so much better than before treatment.

SIGNS
Most dogs show signs of hypothyroidism between 3 and 5 years of age but a diagnosis isn't made in some dogs until they are years older.  Males and females seem to be equally affected.  Routine testing of young dogs is not commonly done unless the veterinarian has a reason to suspect low thyroid function.  Some veterinarians believe that if a dog has not acquired hypothyroidism by 5 or 6 years of age, the odds are good that it will never be a problem for that individual.  (Cats rarely acquire hypothyroidism but have more trouble with hyperthyroidism, especially older cats.) 

One of the most commonly seen signs that a dog may have insufficient secretion of thyroid hormone, or issues with immune mediated thyroid dysfunction, is weight gain with apparently little food intake.  Any overweight pet should be checked for hypothyroidism.  (See this page for tips on how to get a pet to lose weight.) In long-standing cases there often is lack of proper hair coat and even hair loss.  This loss generally displays a pattern over the lumbar area on both sides, sparse hairs on the back of the rear legs and lack of hair along the abdomen.  The coat tends to lack luster and the finer hairs of the undercoat may be missing entirely.  Most dogs with hypothyroidism lack energy, prefer warm environments and have poor exercise tolerance. Of great concern to breeders is the fact that dogs with hypothyroidism may be infertile and many breeders have their dogs tested for thyroid function prior to breeding; in dogs with a poor breeding history, hypothyroidism often is the culprit.

DIAGNOSIS
If the physical exam or history indicates probable hypothyroidism, the veterinarian will take a blood sample and have one or more tests run. The most common tests for thyroid function are T4 (the main Thyroid hormone) and canine TSH (Thyroid Stimulating Hormone from the Pituitary Gland). If the screening test using the T4 analysis indicates low a value for T4, further evaluation is very important in determining the actual origin of the dysfunction causing the signs of hypothyroidism.  Some veterinary laboratories now recommend TgAA (Thyroglobin Auto-antibody) analysis be done because it identifies thyroiditis much earlier in the progression of the disease. All of these assays are relatively inexpensive, and the information they provide is very important for establishing a diagnosis.  University Veterinary Medical Colleges such as the U. of Illinois and Michigan State University have state of the art diagnostic instrumentation that have advanced the ability and accuracy of local veterinarians attempts to establish the presence of hypothyroidism in their patients.

TREATMENT
L-thyroxine (T4) tablets are generally administered twice a day.  When given twice a day, some veterinarians prescribe 0.1 mg/10 pounds twice per day as the initial dosage but each case is considered individually.  Repeat exams and occasional follow-up blood testing really helps to fine tune the proper amount of medication needed for each patient.

Is hypothyroidism inherited?  Evidence indicates some familial patterns of inheritance.  There are more than half a dozen studies reporting the familial incidence of autoimmune thyroiditis where the dog's immune system actually damages its own thyroid gland.  Much of the research on hypothyroidism is dogs has been done at Michigan State University Veterinary School.

Not all cases of hypothyroidism are due to autoimmune lymphocytic infiltration of the gland.  There can be other "inducers" of the disease such as consumption of too much Iodine.  These inducers can be very difficult to identify.  Humans may acquire what is called Hashimoto's Disease, a genetically transmitted form of hypothyroidism but this disease is not the same as autoimmune thyroiditis in dogs.  In Hashimoto's Disease females are five times more likely to get the disease than males.  There are other differences, as well.

The following case represents a fairly atypical case of hypothyroidism in that most cases are identified prior to such advanced skin and coat signs.  The dog had been treated for non-specific allergies, and in fact does some allergic problems and skin scarring due to chronic inflammation of the skin.  However, once the Hypothyroidism was discovered and proper treatment instituted, the allergic conditions were less severe simply because the skin became much healthier and more resistant to infections, irritants and allergens.

This is how a dog recently looked when presented...  Hypothyroidism was suspected and the blood values of thyroid hormone supported the presumptive diagnosis.   The dog was placed on Soloxine in early June, 2001 and the photos in the second row show the improvement in her after six weeks on medication. You can see what a change can occur when a diagnosis of Hypothyroidism is made and proper therapy instituted. The dog's owners report excellent new growth of hair, renewed vigor and weight loss... all improvements!

Click on the image to see a close-up view.
Above... Before Treatment                      Below... After Treatment  Click to enlarge the photos
	click to enlarge photos

This dog will need to be on thyroid supplementation for life but the medication is not expensive and the patient has resumed a more normal attitude and looks much improved.  Be sure to ask your veterinarian to check for hypothyroidism if your dog displays a poor coat, weight gain, poor exercise tolerance and seeks warm areas in which to spend time.

(See this page for tips on how to get a pet to lose weight.)

The study of Greyhounds and Thyroid Testing has been competed and the results reported in an article written by Dr. Marcus Rick and published in the GCA Fall 2005 Newsletter.  Of one hundred samples that were collected, 98 were analyzed statistically to establish a reference range of thyroid test results in the Greyhound.  The majority of the samples were from AKC registered Greyhounds, seven were from NGA dogs.  The results were then compared graphically with the reference range for the general dog population used at Michigan State University and the result ranges from three previous studies by other researchers.

Dr. Rick states “Overall it can be seen that the reference range of Greyhounds is considerably less than that of the general canine reference range.”  In very short summary he concludes:

1.)  Overall, hypothyroidism is very unlikely in the Greyhound, however well documented cases exist.

2.)  If either total T4 of free T4 by dialysis are detectable with the currently available assays (GT 6nmol/L, GT 2pmol/L, respectively) it is very likely that your Greyhound is NOT hypothyroid.

3.)  Lymphocytic thyroiditis is unlikely as well.  Of 1,409 Greyhound samples received at Michigan State University, 2 % were TgAA positive compared with 10 % of 143,800 dogs of the general dog population.  Of these 1,409, only 43 (3%) had thyroid results including elevated TSH consistent with hypothyroidism compared to 8 % of the general 143,800 samples.

4.)  Diagnosing hypothyroidism might be difficult due to decreased reference values that, in many cases, are below the detection limit of currently available assays.

5.)  Greyhound-specific complaints, including bald thigh syndrome, poor racing performance, and infertility do not have an association to thyroid hormone concentrations.  Supplementing these animals with thyroxine is not recommended.

THE PET HEALTH LIBRARY

Hypothyroidism in Dogs

Hypothyroidism is the most common hormone imbalance of dogs. It seems like it would be a straight forward problem: the body does not produce enough thyroid hormone, problems result, a test shows thyroid hormone level is low, the hormone replaced given in pill form, problem solved. Unfortunately, it is not quite so straight-forward in real life. This article attempts to review the issues relevant to this condition and the pitfalls that keep it from being a simple problem. 
  
WHAT IS THE THYROID GLAND AND WHAT DOES IT DO?
The thyroid gland is an H-shape in one's throat. It produces two forms of thyroid hormone: T3 is the active form of the hormone, and T4 is the inactive form created to circulate in the bloodstream. When T4 is absorbed out the bloodstream and into tissue cells, it is converted into T3. Most of the circulating T4 is carried by blood proteins and is not available for tissue absorption; the portion that is not carried by proteins (the so-called "free T4") is the portion that is able to enter tissues for activation.

Production of T4 is regulated by the pituitary gland at the base of one's brain. (This gland is called the master gland as it regulates hormone production in the adrenal system, the thyroid system, the reproductive system and more). The pituitary produces a substance called TSH, which stands for thyroid stimulating hormone. When T4 levels are dropping, the pituitary gland stimulates the thyroid gland to make and release more T4.

Active thyroid hormone serves as a sort of a volume dial for metabolism. Since virtually every cell in the body can be affected by reduced levels of thyroid hormone it is not surprising that reduced levels of thyroid hormone lead to symptoms in multiple body systems.

WHAT IS HYPOTHYROIDISM?
In short, hypothyroidism is the natural deficiency of thyroid hormone. This deficiency is produced by immune-mediated destruction of the thyroid gland, by natural atrophy of the gland, by dietary iodine deficiency, or as a congenital problem. In the dog, the first two causes listed account for almost all cases.

Hypothyroidim generally develops in middle aged or elderly dogs. Breeds with definite predisposition to develop hypothyroidism include: the Doberman pinscher, the Golden retriever, the Irish Setter, the Great Dane, the Dachshund, and the Boxer.

MANIFESTATIONS OF HYPOTHYROIDISM
Hypothyroidism is a classical disease with a classical collection of clinical signs. One particularly well published survey of 162 confirmed hypothyroid dogs showed the following common findings:

88% had some kind of skin abnormality 

40% had hair loss (often this starts on the tail leading to a "rat tail" appearance or a bald area around the collar is created) 

22% had skin infection (often dogs are scaly and smelly due to an excessively oily coat) 

14% had brittle or dry coats (often the outer hairs break off leaving a short, softer under coat, classically described as a "puppy-like coat") 

49% were obese 

48% were described as lethargic or listless at home 

36% were anemic (had a reduced number of red blood cells  due to slowed red blood cell production in the bone marrow.) 
  
One classical finding in hypothyroid dogs is a thickening of some tissues, especially of the face and head. The skin in particular thickens leading to more skin folds and what is classically referred to as a tragic face. This thickening is called myxedema and can occur in some other tissues as well (such as facial nerves - see later).

Cardiovascular Signs - Hypothyroidism interferes with the electrical fibers that more or less provide the wiring for the heart. The rhythmic contractions of heart muscle as normally stimulated by these electrochemical fibers. Abnormal rhythms or slow heart rate occur in as many as 26% of hypothyroid dogs; still, the significance of this in terms of overall lifestyle is not clear.  Many specialists feel thyroid supplementation should be started at a lower dose for patients with obvious heart disease.

Neurologic Signs - According to surveys of confirmed hypothyroid dogs, only about 2% to 4% have nerve problems. There are several syndromes reported.

Polyneuropathy - In hypothyroidism, nerves simply do not conduct electrical impulses normally. This may account for some of the general weakness and listlessness seen in hypothyroidism. Response to thyroid hormone therapy is rapid (improvement within the first week of treatment). 

Focal Neuropathy - Single nerves can get entrapped as they exit the skull or spinal cord as they (like other tissues) swell with myxedema. Pressure on these nerves can lead to paralysis of the facial muscles and/or head tilt, bizarre eye motions and balance disruption (vestibular disease). 

Central Nervous System - may represent abnormal electrical conduction within nerves; however, vascular disease has been found in hypothyroid dogs with central nervous system signs. Clinical signs have involved ataxia (drunken gait), hemiparesis (weakness in front and back legs on the same side of the body), hypermetria (inappropriate measurement of steps), head tilt, circling and cranial nerve abnormalities. It may take several months of therapy to see a response. Coma from myxedema in the brain's tissues is a rare possibility but has been known to occur. 

Ocular Signs - Ocular changes are not common in hypothyroidism but the high levels of blood cholesterol and circulating fat can sometimes lead to eye changes. When these changes are seen, often thyroid testing is recommended. Corneal dystrophy, an abnormal change in the clear covering of the eye, is such an eye sign. This finding is usually represented as a small white spot (sometimes a white circle) on the eye surface. At this degree it is only a cosmetic problem and does not interfere with vision. In more severe forms, painful bubbles can erupt on the corneal surface leading to ulceration. Obviously, this form would require treatment.

Conditions not proven (but previously suspected) to be associated with hypothyroidism: megaesophagus, laryngeal paralysis, infertility, and behavioral aggression.

VON WILLEBRAND'S DISEASE
For a long time, von Willebrand's disease, a hereditary blood clotting disease, was felt to have an association with hypothyroidism (when a dog borderline for von Willebrand's factor levels became hypothyroid later in life, the abnormal clotting ability would become evident). This theory has largely been abandoned but there does seem to be a positive effect when a von Willebrand's dog is treated with thyroid hormone.

TESTING FOR HYPOTHYROIDISM
One would think testing for hypothyroidism would be simple: a blood test of the T3 or T4 level could be checked and if it is low, the patient is hypothyroid. Unfortunately, the situation is rarely so simple.

Measurement of T4: The T4 level (also called the total T4 level) is measured commonly and is included in most routine blood panels. It would seem that a low T4 would indicate hypothyroidism and a normal T4 would indicate normal thyroid function. Unfortunately, it isn't that simple. Dogs on certain drugs (most notably phenobarbital, prednisoneor other corticosteroids, or trimethoprim sulfaor with illnesses other than thyroid disease often have depressed T4 secretion. These dogs will have low T4's but are not hypothyroid. This means a normal T4 indicates normal thyroid function but a low T4 may or may not indicate hypothyroidism.

Measurement of T3: If T3 is the active hormone, why can't we just test blood levels of T3? Due to assorted compensatory mechanisms, T3 levels often fluctuate into the normal range in even truly hypothyroid dogs. This means that T3 values are virtually useless in diagnosing hypothyroidism.

Free T4 - T4 is the precursor hormone that is not active but is converted by body tissues into T3, which is active. T4 exists in two forms: the form that is carried around bonded to a blood protein (this is called bound T4) and T4 floating around loose in the bloodstream (called free T4). Only free T4 can enter cells and be converted to T3 and the concentration of free T4 corresponds to thyroid hormone activity where it counts (i.e., at the tissue level). Free T4 levels are less subject to fluctuate into a falsely low range in response to non-thyroidal diseases or drugs than is a total T4 level.

Because free T4 levels are typically 1000 times smaller than total T4 levels and tests for free T4 have to work in such a way so as not to convert bound T4 into free T4 and thus interfere with results. It is somewhat difficult to test for free T4 and the only acceptable way to do this is by a method called Equilibrium dialysis. At this time most labs offer equilibrium dialysis free T4 but it is important to realize that a free T4 level on a lab report is not an equilibrium dialysis free T4 unless it specifically says so. (Equilibrium dialysis free T4 is sometimes notated fT4(ED)).

TSH Stimulation and Endogenous TSH levels - Before there was readily available equilibrium dialysis free T4, the test that was felt to be the gold standard of reliability was called the TSH stimulation test. In this test, a T4 was measured and then compared with a value drawn 8 hours after administration of an injection of thyroid stimulating hormone. Inability to respond to TSH was considered indicative of hypothyroidism. The problem was expense, the need for 8 hours of hospitalization, and the fact that injectable TSH was frequently off the market.  This test is rarely performed nowadays.

But TSH can be directly measured in a patient's bloodstream. The idea is that the pituitary gland should be secreting high levels of TSH in a futile attempt to stimulate a diseased thyroid gland. Measurement of TSH level is apparently a very important means of diagnosing hypothyroidism in humans and a canine version of the test was long sought. Unfortunately, when it finally became available, it was found that many dogs with true hypothyroidism did not have elevated TSH levels as one would expect; still, this test is often helpful in making the diagnosis of hypothyroidism.

Testing with a Trial of Medication - Sometimes the only way to test for hypothyroidism is to simply administer the medication for several months and see what happens. Often an improvement in attitude and energy level is seen within the first week. Hair re-growth takes substantially longer (typically 4 months minimum) as the follicles must "reawaken" and then grow a hair long enough to create a visible coat change.

TREATMENT OF HYPOTHYROIDISM
At least treatment of hypothyroidism is relatively straight-forward. Hypothyroidism is treated with oral administration of thyroid hormone (T4). Even hypothyroid dogs are perfectly capable of converting T4 to T3. Pills are given usually twice daily to start but may be dropped to once a day after good thyroid control has been achieved.

There are many brands of thyroid supplementation available and prices are somewhat variable depending on the manufacturer.

TREATMENT IS FOR THE LIFE OF THE DOG
Occasionally we are asked if it is reasonable to use dried or powdered thyroid glands of hogs or cattle as a more natural form of treatment. The answer is simply no. These products are not produced with adequate quality control to insure that they contain a reliable amount of thyroid hormone. Each dose may be completely different when such a product is used.

Re-testing later on?
Whenever an animal goes on a medication long term, periodic blood testing is a good idea. In the case of hypothyroidism treatment, it is important to know if the medication dose is too low or too high. Thyroxine (T4) is a very safe medication but if it is not given in adequate doses, obviously the patient will not be adequately treated. If the dose is too high and given for too long a time, excessive water consumption, weight loss, and restlessness can result.

Monitoring with T4
The lowest thyroid level of the day is found by taking the blood sample right before a tablet would normally be given. The highest level of the day is found by taking the blood sample 4-6 hours after it is given. Expect one or both such tests to be periodically recommended. Our hospital recommends some type of blood test monitoring annually.

Monitoring with TSH level
The canine thyroid stimulating hormone level (abbreviated cTSH) does not seem to require any particular timing issues and can be run on a blood sample taken any time of the day. The cTSH level will not indicate whether or not the thyroid dose is too high but is quite accurate at determining if the level is too low. (Inadequate treatment is associated with high TSH levels indicating that the pituitary gland is vainly trying to stimulate the thyroid gland with high levels of stimulating hormone.) This test may be run instead of or in addition to a T4 level when it comes time to monitor thyroid hormone treatment.

IS THE DIAGNOSIS CORRECT?
Because of difficulties in diagnostic testing methods (especially before 1995), many dogs have been erroneously diagnosed with hypothyroidism and have been on medication for years. If there is any question about a patient and one wishes to re-test now that newer testing methodologies are available, thyroid hormone supplementation must be discontinued at least 2 months for blood testing to be valid. If possible, medications known to interfere with testing should be discontinued for testing (though this is obviously not always possible).

OTHER HYPOTHYROIDISM RESOURCES

http://www.soloxine.com  (Soloxine is one of the more prominent brands of canine thyroid supplements.)

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What is  hypothyroidism? http://www.upei.ca/cidd related terms: familial thyroiditis, lymphocytic thyroiditis, congenital hypothyroid dwarfism

The clinical signs of hypothyroidism are caused by a decrease in normal thyroid hormone activity. The disorder may be acquired (a progressive deficiency of thyroid hormone) or congenital (meaning the animal is born with the disorder). The acquired form is the most common disorder of the endocrine system in dogs. It occurs as a result of gradual atrophy of the thyroid gland or of gradual infiltration and replacement of the thyroid gland with lymphocytes due to an autoimmune process (lymphocytic thyroiditis).

Acquired hypothyroidism is generally seen in middle-aged (4 to 10 years) mid - to large breed dogs. Congenital hypothyroidism  is very rare.

How is hypothyroidism inherited?
unknown

What breeds are affected by hypothyroidism?
The following breeds have an increased risk of developing hypothyroidism: Afghan hound, Airedale terrier, boxer, Chinese shar pei, chow chow, cocker spaniel, dachshund, Doberman pinscher, English bulldog, golden retriever, Great Dane, Irish setter, and miniature schnauzer.

For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a general consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does hypothyroidism mean to your dog & you?
The changes due to gradually decreasing levels of circulating thyroid hormone are slow and insidious. Early signs (which are usually not recognized as being related to hypothyroidism) include lower energy levels and increased susceptibility to infections. As the disease progresses, you will likely notice changes in your dog's hair coat - symmetrical hair loss with or without darkening of the skin, and dry or greasy hair. Other signs of hypothyroidism include a slow heart rate, lethargy, mental dullness, intolerance to cold, infertility in males and females, constipation, and weight gain. Less commonly, a dog with hypothyroidism may experience heart disease, a bleeding disorder, profound muscular weakness associated with abnormalities in the muscles or nerves, or another endocrine disorder such as diabetes mellitus.

Congenital hypothyroidism
Thyroid hormones are essential for normal growth and maturation of the nervous and skeletal systems. Puppies with congenital hypothyroidism will have stunted growth as well as many other abnormalities. Severely affected puppies most likely die before weaning.

How is hypothyroidism diagnosed?
Because there is such a broad range of possible clinical signs, hypothyroidism can be quite difficult to diagnose. Blood tests may show certain suggestive (but non-specific) abnormalities. If your veterinarian suspects this condition, s/he will perform laboratory tests to assess thyroid function.

FOR THE VETERINARIAN:
CLINICAL PATHOLOGY: Suggestive findings include hypercholesteremia, mild nonregenerative anemia, elevated serum creatine kinase (CK), and hypoglycemia

CONFIRMATION: Measurement of free T4 (FT4) and canine thyroid-stimulating hormone (cTSH) are the tests of choice to diagnose hypothyroidism, and to differentiate the primary from the secondary form.

 [Secondary hypothyroidism is much less common.] Some laboratories can also test for thyroid autoantibody levels (TgAA) which is helpful in the early diagnosis of autoimmune thyroiditis. This may provide useful information for breeders. [See reference 2 for a good discussion of tests.]

RADIOGRAPHS: In congenital hypothyroidism, there are typical radiographic changes including epiphyseal closure, shortened vertebral bodies, kyphosis, and arthritis. Epiphyseal dysgenesis (ragged epiphyses with a few foci of calcification) is pathognomonic for congenital hypothyroidism.

How is hypothyroidism treated?
The standard treatment is levo-thyroxine given once a day. This must be continued for life. Within a week of starting treatment, your dog's attitude and activity levels should improve. It can take up to 6 weeks before there is noticeable improvement in the skin and haircoat, but eventually all abnormalities should completely resolve.

Dogs on thyroid replacement can live a normal life. Your veterinarian will monitor thyroid hormone levels periodically and adjust the dose if required. Certain other illnesses may also necessitate dosage adjustment.

Congenital hypothyroidism is treated the same way. Clinical signs are usually completely reversed with subsequent normal physical and mental growth and development, as long as the condition is recognized and treatment started very early (3 to 4 months of age).

Genetic counselling
Although inheritance of this disorder has not been determined, it is advisable not to breed affected dogs. The OFA (Orthopedic Foundation for Animals) maintains a thyroid registry based on assessment of FT4, cTSH, and TgAA, which is useful for breeders attempting to choose dogs free of hypothyroidism for a breeding programme.

FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources
Chastain, C.B., Panciera, D.L. 1995. Hypothyroid diseases. In S.J. Ettinger and E.C. Feldman (eds.) Textbook of veterinary Internal medicine. p. 1487-1501. W.B. Saunders Co., Toronto.
Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. JAVMA  1997; 211(11):1396-1402. This reference clearly explains the different tests available, and the significance and interpretation of the results.
Orthopedic Foundation for Animals: www.offa.org

Copyright © 1998 Canine Inherited Disorders Database. All rights reserved.Revised: October 30, 2001.
reprinted with kind permission from:- Alice Crook, DVM,Coordinator,
 Sir James Dunn Animal Welfare Centre, Atlantic Veterinary College,University of Prince Edward Island, 550 University Ave.Charlottetown, PEI C1A 4P3

http://www.upei.ca/cidd

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Thyroid Testing in Dogs	Phenobarbitol and Thyroid Testing	Hypothyroidism Supplements	Diagnostic Evaluation of The Hypothalamic-Pituitary-Thyroid Axis
T4 Diagnostic Protocol for Dogs	Behavioural Changes Associated with Thyroid Dysfunction in Dogs