COMMENTS ON THYROID DISEASE

BY DR. THOMAS, DVM, Dipl.ACVIM(Neurology)

One of the simplest and least expensive tests to have done, which could possibly reduce or stop seizures, is a test for low thyroid function or hypothyroidism. I have found from experience that thyroid testing is very important in every case of canine epilepsy.

Dr. William Thomas, a board-certified neurologist, had this to say about thyroid testing:

1. Thyroid testing should be considered in any dog with recurrent seizures. Although the relationship between hypothyroidism and recurrent seizures is unclear, thyroid testing is relatively inexpensive and carries little risk to the patient.

2. In general, any dog that is diagnosed with hypothyroidism by appropriate testing should be treated with thyroid replacement therapy. This applies to all dogs, whether or not they suffer seizures. If the seizures improve with thyroid therapy, then great! If not, the patient should still be treated because hypothyroidism can cause many other health problems.

3. Thyroid replacement therapy is not indicated in dogs with seizures if the patient has *not* been diagnosed with hypothyroidism. There are potential risks associated with any therapy, so subjecting the patient to unnecessary treatment is rarely a good idea. On the other hand, appropriate use of thyroid medication is one of the more safe and effective treatments available in veterinary medicine.

4. Many illnesses as well as some drugs, including Phenobarbital, will lower the level of certain thyroid hormones (for example, T4) without causing clinically significant hypothyroidism. Thyroid replacement therapy is not indicated in these instances. Measurement of a T4 concentration alone does not allow discrimination between true hypothyroidism and the effects of drugs and illnesses. In these patients diagnosis of hypothyroidism requires measurement of several different parameters of thyroid function ("thyroid panel").

Sincerely,

WB Thomas DVM
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN

INTERVIEW WITH DR. DODDS, DVM

Based on Dr. Thomas' recommendations, I sat down with Dr. Jean Dodds for an overview on hypothyroidism which follows.

W. Jean Dodds, DVM, is a nationally and internationally recognized authority on blood and immune disorders, thyroid disease and nutrition. Dr. Dodds is the president of Hemopet/Pet Lifeline, the first national nonprofit animal blood bank and greyhound rescue/adoption program serving North America. Hemopet also conducts nonprofit clinical research studies. Dr. Dodds has always been available to those with questions about hypothyroidism, blood and immune disorders, and nutrition.

I hope all of this is helpful...
Joanne and Asia
Joanne Carson, Ph.D.


Dr. Joanne Carson: Dr. Dodds, why should a dog with seizures have a thyroid panel done to test for low thyroid function or hypothyroidism?

Dr. Jean Dodds: Because thyroid dysfunction can precipitate or aggravate existing seizure disorders. The mechanism is unknown, but may relate to the vital role of thyroid hormones in cellular metabolism of the central nervous system.  In some cases the seizures are related to thyroid dysfunction and when placed on appropriate thyroid medication the seizures may no longer occur or are reduced in severity or frequency.

Dr. Carson: What are some of the classic symptoms of hypothyroidism?

Dr. Dodds: There are more than 50 different symptoms of hypothyroidism. Classical signs include chronic skin disease, hair loss, weight gain, lethargy and slow  metabolism, although behavioral changes (aggression, hyperactivity, poor  concentration, passivity, phobias, anxiety or neuromuscular events such as seizures), and many other signs of metabolic imbalances also can occur. This condition can mimic other disorders.

Dr. Carson: How many symptoms would a dog need to have to suspect hypothyroidism and have a thyroid panel done?

Dr. Dodds: Only one symptom may be present to suspect low thyroid function. Seizures can be a symptom of thyroid imbalance, which warrants performing a full thyroid panel.
Thyroid dysfunction in dogs is nearly always caused by low levels of thyroid hormones. (i.e., HYPOthyroidism). The rare exception would be in thyroid cancer which may, but not always, produce signs of HYPERthyroidism. As the thyroid gland controls all metabolic functions, symptoms of hypothyroidism are many and can mimic a variety of other conditions. Affected dogs can show only one, or several or even many classical symptoms, which begin in subtle ways and then usually progress to more obvious signs as the disease process that destroys thyroid tissue becomes more advanced. This can take months to years. Occasionally symptoms disappear without treatment and the gland recovers.

Dr. Carson: What kind of thyroid tests are important and why?

Dr. Dodds: Because the diagnosis of hypothyroidism is often complicated, we need to run complete thyroid profiles (i.e., T3, T4, free T3, free T4, T3 and T4 auto antibodies, plus thyroglobulin auto antibody and TSH where indicated) rather than just one or two analytes (e.g., T4, TSH, free T4) We need to look at the whole picture along with the clinical history of the seizing animal, breed and family history for likelihood of seizure disorder and thyroid disease. When I interpret profiles and make recommendations, I take all these factors, including drugs being given, into consideration.

Dr. Carson: If a dog is diagnosed with low thyroid function, how soon after starting on thyroid medication should thyroid re-testing be done and why?

Dr. Dodds: After 6 to 8 weeks on thyroid supplementation given twice daily, at the appropriate dose for the dog's age, breed and weight, the thyroid levels should be retested to determine whether the current dose is correct This sample needs to be drawn 4 to 6 hours after the morning pill was given. IMPORTANT: Correct therapeutic ranges at that time should be at the upper 1/3 to 25% above the upper limits of the lab reference ranges (except for geriatric dogs or sight hounds where mid-range is adequate).

Dr. Carson: If thyroid medication raises the metabolism, is it possible that Phenobarbital and potassium bromide levels could change? If so, when should these levels be tested after starting on thyroid supplementation?

Dr. Dodds: Yes, drug metabolism and drug clearance from blood and tissues can be altered when body metabolic function is raised, such as with thyroid supplement. This could result in raising or lowering Phenobarbital and potassium bromide levels in individual dogs, depending upon their liver function and effectiveness of drug binding/clearance mechanisms. Other drugs, chemical and toxic exposures, or stress situations present in these dogs could also alter metabolism of thyroid and anticonvulsant medications.


Dr. Carson: I've heard that Phenobarbital can cause a low thyroid reading. Is this true hypothyroidism and should a thyroid medication be used?

Dr. Dodds: Drug effects on thyroid binding proteins and thyroid levels do not produce true hypothyroidism, and so treatment with thyroid supplement is unadvisable. However, many dogs with seizure disorders have thyroid dysfunction independent of Phenobarbital use, and so significantly lowered thyroid levels---especially of free T4---indicate the likely benefits of thyroid treatment for assisting in seizure control and any other metabolic symptoms of hypothyroidism that also may be present (e.g., chronic skin disease, weight gain, lethargy).

It is well known that Phenobarbital and some other drugs, such as potentiated sulfonamides can affect blood levels of thyroid hormones. With the sulfonamides, after long-term use, a clinically hypothyroid state can be produced. Regardless, it is typically the total T4 level that is most affected, with the free T4 being affected much less and temporarily, depending to some extent on how it was measured.

Dr. Carson: Quite a few vets use only a TSH test to test for low thyroid function on epi's taking Phenobarbital. Is this an accurate test?

Dr. Dodds: TSH is NOT a reliable assay when used by itself in the dog, and generally has poor sensitivity and predictive value in the dog. This is in contrast to the use of endogenous TSH assays in people which work very well.

Here are four very recent studies that support the fact that using endogenous canine TSH as the sole assay is unreliable for diagnosing canine hypothyroidism.

JAVMA, Vol 212 1998 - Effect of time of sample collection on serum thyroid-stimulating hormone concentrations in euthyroid and hypothyroid dogs. - Bruner, Scott-Moncrieff, Williams.

CONCLUSIONS:
This study demonstrates the limitations of the current c-TSH assay. In the present study, serum c-TSH was supportive of hypothyroidism in only 37% of the samples obtained from spontaneously hypothyroid dogs. A normal serum
c-TSH concentration does not exclude hypothyroidism as a diagnosis. Current c-TSH assays are often unnecessary for the diagnosis of hypothyroidism. (J Am Vet Assoc 1998,- 212:1572-1575)

Vet Clin Pathol 1999 28:16-19 - Biological Variation of Canine Serum Thyrotropin (TSH) Concentration - Iversen, Lundord-Jensen, Holer, Aaes

CONCLUSIONS:
The present study was to estimate the between-dog, within-dog and analytical components of variance for serum thyrotropin (TSH) in healthy dogs. The number of samples required to determine the true mean value in a single dog
was 40. Comparing a single serum TSH measurement from an individual dog to the conventional population-based reference range may be too insensitive to detect small but important changes in the serum TSH level of that particular dog. (Vet Clin Pathol 28:16-19 1999)

JAVMA, Vol 211 No. 11 December 1, 1997- Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. - Peterson, Melian, and Nichols.
CONCLUSIONS:

 Results indicate that measurement of serum free 1 and TSH concentrations is useful for diagnosis of hypothyroidism in dogs. About a quarter of the dogs with confirmed hypothyroidism, however, will have serum
TSH concentrations within reference limits (J Am Vet Med Assoc 1997:211;1396-1402)

JAMVA, Vol 212. No. 3, February 1, 1998 - Comparison of serum concentrations of thyroid-stimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease - Scott-Moncrieff, Nelson, Bruner, and Williams
CONCLUSION:

cTSH assay had good specificity for use in the diagnosis of hypothyroidism in dogs. Because this assay had low sensitivity, a diagnosis of hypothyroidism could not be excluded on the basis of a serum cTSH concentration that was within the reference range. ( J Am Vet Med Assoc l998:212:387-391)

Dr. Carson: Thank you Dr. Dodds. You have always been a wealth of information and always accessible for questions.

W. Jean Dodds, DVM resume'

Dr. Dodds was born on January 4, 1941. She received her D.M.V. in 1964 from the Ontario Veterinary College. In 1965 she moved to the New York State Health Department is Albany and began comparative studies of animals with inherited and acquired bleeding diseases. This work continued full time until 1986 when she moved to Southern California to establish Hemopet, the first nonprofit national blood bank program for animals.

From l965 to l986, she was a member of many national and international committees on hematology, animal models of human disease, veterinary medicine, and laboratory animal science. Dr. Dodds was a grantee of the National Heart, Lung, and Blood Institute (NIH) and has over 150 research publications. She was formerly President of the Scientist's Center for Animal Welfare, and Chairman of the Committee on Veterinary Medical Sciences and Vice Chairman of the Institute of Laboratory Animal Resources, National Academy of Sciences. In 1974 Dr. Dodds was selected as Outstanding Woman
Veterinarian of the Year, AVMA Annual Meeting, Denver, Colorado; in 1977 received the Region I Award for Outstanding Service to the Veterinary Profession from the American Animal Hospital Association, Cherry Hill, New Jersey; in 1978 and 1990 received the Gaines Fido Award as Dogdom's Woman of the Year; and the Award of Merit in 1978 in Recognition of Special Contributions to the Veterinary Profession from the American Animal Hospital Association, Salt Lake City, Utah. In 1984 she was awarded the Centennial Medal from the University of Pennsylvania School of Veterinary Medicine. In 1987 she was elected a distinguished Practitioner of the National Academy of Practice in Veterinary Medicine. In 1994 she was given the Holistic Veterinarian of the Year Award from the American Holistic Veterinary Medical Association, Orlando, Florida. She is a member of numerous professional societies.

Today, Dr Dodds is actively expanding Hemopet's range of nonprofit services and educational activities. On behalf of Hemopet, she consults in clinical pathology nationally and internationally and regularly travels to teach animal health care professionals, companion animal fanciers, and pet owners on hematology and blood banking, immunology, endocrinology, (including thyroid) nutrition and holistic medicine. She is also the editor of "Advances in Veterinary Sciences and Comparative Medicine" for Academic Press.