Thyroid Study in Welsh Springer Spaniels
By Colleen M O'Keefe, DVM, MS
Copyright 2001, All rights reserved
What thyroid disease?
What is TGAA?
WSSCA Thyroid Study
The article in Swedish
Overview of Thyroid Disease: Hypothyroid disease, low thyroid hormone concentrations, is the most common endocrine disease in dogs. Low thyroid levels affect the metabolism of most of the cells in the body. There are many different symptoms, the most common are any combination of the following: weight gain, sluggishness, skin and hair coat problems (including hair loss), weakness, cold intolerance, and infertility. This is not a life threatening disease but it definitely impacts the overall quality of life.
The thyroid gland produces two hormones: thyroxine (T4) and triiodothyroxine (T3). The majority of hormone produced is T4 that is converted to T3 by body tissues. T3 is the active form of thyroid hormone. T4 is easily measured although using T4 levels alone, as the only method of monitoring thyroid activity, is not very accurate. The low levels of circulating T3 make it hard to measure this hormone accurately. This is why it is not commonly used for general screening. Levels of T4 will fluctuate normally and may be decreased by factors other than hypothyroid disease: i.e. stress and other systemic illnesses. The stimulus to produce thyroid hormone comes from the pituitary gland, which secretes thyroid stimulating hormone (TSH). The production of TSH is increased when there is a decrease in the levels of circulating thyroid hormone. In dogs with hypothyroid (low thyroid) disease the body produces high levels of TSH in an attempt to stimulate the production of thyroid hormone. Since the thyroid gland has been damaged or destroyed it can not produce enough thyroid hormone and there is no feedback to decrease the production of TSH. Therefore, low T4 and high TSH are findings that support a diagnosis of hypothyroidism.
Autoimmune Mediated Thyroid Disease: Thyroglobulin Autoantibodies (TGAA) are produced as an immune response to the thyroid gland. For unknown reasons the body develops these antibodies against the T3 and T4 producing cells of the thyroid gland causing the destruction of these cells. When enough of the gland has been damaged, these cells can no longer produce T3 or T4. Since the body is producing antibodies against itself, this is called an autoimmune disease. The majority of hypothyroid disease is caused by autoimmune thyroid disease, with the production of TGAA. This form of thyroid disease is strongly suspected to be genetically transmitted by a simple recessive trait.
From studies done on all breeds of dogs at Michigan State University (MSU) it was concluded that:
- Very few dogs developed TGAA antibodies under the age of 1 year, so testing should be started after 1 year.
- The majority of dogs tested for high (positive) TGAA between the ages of 2 and 6 years.
- After the age of 6 years, dogs with immune mediated thyroid disease had enough damage to the gland that there was not enough tissue present to stimulate the production of TGAA, which would cause measured levels of TGAA to fall within the normal range.
2000 WSSCA Thyroid Study: This study was done in the spring of 2000 by the WSSCA in conjunction with Michigan State University and Oxford Laboratories. The study was initiated to examine 2 areas: the incidence of TGAA in Welsh Springer Spaniels and the correlation of test results between blood spot test from Oxford laboratories and serum test from MSU. Participation in the study was voluntary.
53 Welsh Springers (19 males, 34 females) participated in the study. Only dogs between the ages of 1 and 7 years were tested. Initially, just TGAA tests were run on the samples. All the owners who participated in the thyroid study were sent copies of the results.
Five dogs (2 males, 3 females) tested positive for TGAA and 3 dogs (1 male, 2 females) tested inconclusively. The remainder of the dogs had levels of TGAA in the normal range. Since the initial study the 3 inconclusive samples have been rerun and one has tested negative, one is still inconclusive and one is probably in end stage thyroid disease causing the low TGAA reading.
After the study was completed a 3 ½-year-old female, Dog A, (with normal levels of TGAA) had a T4 level run that was low and TSH was elevated. A complete thyroid panel indicated early hypothyroid disease. A second 3 ½-year-old female, Dog B, (with normal levels of TGAA) also had a complete thyroid profile run and she also had extremely low thyroid levels. Her thyroid gland was biopsied and showed severe lymphocytic inflammatory thyroiditis with near total follicular atrophy. This means that immune disease had almost completely destroyed the thyroid gland that produces thyroid hormone. Because of this there was too little tissue remaining to produce high amounts of TGAA. This dog also had clinical signs compatible with thyroid disease: thinning hair coat and thickened pigmented skin over the shoulders and chronic low grade yeast otitis (ear infection).
A thyroid biopsy was also done on a clinically normal 17 month old female, Dog C, with a very strong positive TGAA (2311, normal is less than 200). The biopsy was done 4 months after the initial testing and the TGAA was now 1426, the TSH was elevated (92, normal less than 30 mU/L) and the T4 was normal. The thyroid gland showed diffuse and severe lymphocytic inflammation, which was compatible with lymphocytic thyroiditis of an immune origin (early thyroid disease caused by autoimmune disease). This dog was from a litter of 8. 8 siblings have been tested. Four are strong positive, 2 are normal and 2 are inconclusive. The mother of this litter is Dog A and the father has normal thyroid function at the age of 10 ½ years. However the father has one other offspring, Dog B, with autoimmune lymphocytic thyroiditis which would make him a carrier of the disease. If this is a simple recessive trait and the mother is affected and the father is carrier then approximately 50% would be affected and 50% would be carriers. This appears to be the case in this litter even with the small numbers available.
After it became apparent that WSS in this study developed TGAA levels earlier than expected and immune mediated thyroid disease progressed more rapidly than expected, all the dogs in the study had serum T4 and TSH levels run. Owners whose dogs exhibited abnormal T4 and/or TSH levels were then notified. From this testing there were 2 dogs that were suspected as having hypothyroidism with normal TGAA levels due to end stage thyroid disease. One of these dogs upon retesting has low normal levels and it was recommended to retest in 6 months. The second dog had low T4, T3 and slightly elevated TSH and this dog has clinical signs of hypothyroid disease.
Conclusions: The Blood Spot procedure is highly correlated with serum results and, therefore, valid for checking TgAA in dogs (correlation = 0.99). Although only a small sampling was done it appears that overall incidence of immune mediated thyroid disease in WSS was low. However Welsh Springers started developing TGAA at an early age, possibly earlier than 1 year. Affected dogs were strongly positive by 2 years and damage to thyroid tissue occurred rapidly. Enough of the gland was destroyed by the age of 3 ½ years that the TGAA levels became near or below normal and the TSH started to elevate. Eventually the T4 levels decreased.
- All breeding stock can be tested for early autoimmune thyroid disease by measuring TGAA only between the ages of 12 and 30 months.
- Between 30 months and 6 years a TGAA along with a T4 and TSH levels should be measured to rule out immune mediated thyroid disease and early hypothyroidism.
- If the dog is negative for TGAA after 6 years and there is no elevation of the T4 and TSH, the dog will probably not develop autoimmune thyroid disease.
- Dogs positive for TGAA should have a T4 and TSH run annually to monitor thyroid function. When clinical signs develop the dog should be put on thyroid supplementation.
- Carefully consider whether the dog should be used in a breeding program. If dogs with high TGAA are bred it should be to dogs that are negative for TGAA and/or tested clear (normal T4 and TSH levels) for thyroid disease as older dogs.
Treatment: When the dog starts to show symptoms of hypothyroid disease, supplementation with T4 (thyroxine) should be started. The dose is given by weight and is given once or twice daily. After therapy has started it is important to check the blood levels occasionally to make sure that the dose is correct. Therapy is life long.