Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Beagle

Beagle

Hypothyroidism

Related terms: primary hypothyroidism, lymphocytic thyroiditis, idiopathic thyroid atrophy

Outline: Insufficient blood levels of thyroid hormone (hypothyroidism), due to disease of the thyroid glands is a common condition of Beagles. The cause is unclear, but is thought, at least partly, to have a genetic basis. The welfare consequences may be relatively mild if the disease is diagnosed and successfully treated but diagnosis (and sometimes treatment) can be difficult. Thyroid hormone insufficiency has widespread effects in the body and, in cases where the disease progresses, welfare effects can be severe and prolonged; for example due to increased susceptibility to infections and to effects on various organs including brain and kidneys.


Summary of Information

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1. Brief description

Hypothyroidism is the state of having low levels of thyroid hormone. It is diagnosed when thyroid hormone levels are abnormally low in the blood leading to signs of disease resulting from this deficit. Low thyroid hormone levels cause long-term chronic problems rather than sudden acute disease. Typically a hypothyroid dog is lethargic, reluctant to exercise, shows weight gain and has skin problems. There can also be disease consequences to the nervous system, circulation and eyes.

2. Intensity of welfare impact             

If diagnosed early, the main welfare impacts are due to inability to express normal activity levels and behaviours and these may be considered mild to moderate. In more advanced cases, the welfare consequences can be severe due to the long term effects of low levels of thyroid hormone on various tissues and organs. For example, hypothyroidism is associated with compromised wound healing and increased susceptibility to infections and so may lead to pain and malaise.

3. Duration of welfare impact

Once it has begun, hypothyroidism is a life-long problem to which there is no cure. Diagnosis of the disease is most often made in middle age. Treatment, by hormone replacements, is usually successful but permanent disease and suffering may be seen in some cases, particularly in those dogs that have developed more severe neurological problems (Panciera 1994).

4. Number of animals affected

Hypothyroidism is the most common endocrine problems of dogs (Panciera 1994) and Beagles have long been recognised as being predisposed to the condition (Nachreiner et al no date, Manning et al 1973, Hall et al 2003, Scott Moncrieff 2009). The proportion of the breed that is affected, however, is unknown.

5. Diagnosis

Blood tests are needed to diagnose hypothyroidism. Often the procedure is straightforward but it is not uncommon for multiple tests to be necessary. Simultaneous measurement of thyroxine (or T4 - the most important hormone produced by the thyroid gland) and thyroid stimulating hormone (TSH) levels is often informative and has become standard practice (Peterson et al 1997, Hall et al 2003, Scott-Moncrieff 2009). Sometimes other tests are needed, such as: assay of free T4 by equilibrium dialysis, measurement of TgAA (a specific antibody) levels, ultrasound examination of the thyroid glands and dynamic blood tests (Hall et al 2003, Brömel et al 2005, Davison 2010).

6. Genetics

The focus of research on the genetics of hypothyroidism in dogs has been on the genes that control the immune system (Graham 2008) but understanding is still at an early stage and no predictive genetic tests are currently available (Kennedy et al 2006a and 2006b, Graham 2008).

7. How do you know if an animal is a carrier or likely to become affected?

It is not known if there can be unaffected carriers of the gene(s), that is, animals that do not have the disease themselves but are able to pass it to their offspring. There is no information about the heritability of hypothyroidism in Beagles. Measuring levels of certain antibodies has been suggested as a screening test for animals that are currently normal but which might be at risk of hypothyroidism, but this is unreliable (Graham et al 2001).

8. Methods and prospects for elimination of the problem

With the current state of knowledge it is difficult to give good advice. Dogs known to be affected by hypothyroidism should not be used for breeding. Unfortunately, the condition tends to be diagnosed only after the animal has reached breeding age.


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1. Clinical and pathological effects

The thyroid glands are situated in the neck. They produce thyroid hormones - the most important of which is thyroxine - that are fundamental to the effective functioning of the dog and thus vital for life. The activity of the thyroid glands is under the control of the pituitary gland (at the base of the brain), which is in turn under the control of part of the brain called the hypothalamus. When increased levels of thyroid hormone are required, the hypothalamus secretes thyroid releasing hormone (TRH). This causes the pituitary gland to produce thyroid stimulating hormone (TSH), and this TSH directly causes thyroid gland cells to produce and secrete thyroid hormones. Two thyroid hormones are released from the thyroid glands – T4 (thyroxine) and T3. Much of the T4 is bound to proteins in the blood and it is inactive in this state. The T4 that is not bound to proteins is called “free T4”. When the level of circulating thyroid hormone is adequate, the hypothalamus and pituitary switch off TRH and TSH production. The latter control system is known as negative feedback (Davison 2010).

Hypothyroidism is the state of having a low level of thyroid hormone. Thyroid hormones are essential for many metabolic processes throughout the body and these processes fail to function normally when levels are too low (Thoday 1990, Hall et al 2003). This leads to signs of disease. It can be caused by low dietary intake of iodine because iodine is a component of thyroid hormones. It can also be caused by specific diseases of the hypothalamus or pituitary gland. However, the cause of the most common form – known as primary hypothyroidism - is irreversible disease and destruction of the thyroid glands. They wither and are unable to respond to TSH from the pituitary gland. Why this occurs is poorly understood, but the disease processes usually involved are lymphocytic thyroiditis or idiopathic thyroid atrophy (Graham et al 2007).

In lymphocytic thyroiditis, the immune system attacks and eventually destroys the thyroid tissue and it is replaced by non-functioning scar tissue. Antibodies are formed which are active against thyroid tissues and the gland becomes infiltrated with cells from the immune system (Graham et al 2007). Measurement of the levels of some of these antibodies (thyroglobin autoantibodies – TgAA) is possible. However, these antibodies are found in only 29% of affected Beagles, fewer than observed in some other predisposed breeds (Panciera 2009). The suggestion that routine vaccinations may be a factor in the development of the condition has not been confirmed (Scott-Moncrieff et al 2006).

In idiopathic thyroid atrophy (‘idiopathic’ means of unknown cause, ‘atrophy’ means withering away) the thyroid glands degenerate and are replaced by fat. The cause of this is unknown. It is possible that this disease is the end process, or a variation, of lymphocytic thyroiditis (Graham et al 2007).

In healthy animals, thyroid hormone levels vary considerably between individuals and with breed, sex, age, and body weight. Some other diseases can affect levels, as can some drugs, and these factors have to be taken into account when diagnosing the condition (see below) (Thoday 1990).

In dogs, hypothyroidism is most commonly diagnosed from middle-age (Dixon et al 1999).

Low thyroid levels cause chronic long-term problems rather than sudden acute disease. Typically a hypothyroid dog is lethargic, reluctant to exercise, shows weight gain, loss of fur (typically on both sides of the flanks), and scale on the skin. Wound healing may be poor. The heart rate is slow and there is a weak pulse. Dogs sometimes have an aversion to cold and seek warmth. However, other parts of the body can also be affected. Disease of nerves and of the brain may occur that, unless treated, can lead to coma and death. Eye diseases often occur in hypothyroid dogs due to the high levels of fat in the blood in these dogs and this can also cause disease elsewhere eg in the brain, heart, kidneys. The immune system may be affected leading to greater risk of infections, particularly of the skin (Nesbitt et al 1980, Panciera 2000, Hall et al 2003). The condition may also affect reproduction (Panciera 2000, Johnson 2000).

As well as finding high levels of lymphocytic thyroiditis and clinical hypothyroidism in a group of laboratory Beagles, Benjamin et al (1996) reported an association with malignant thyroid neoplasia. Over half of the dogs with hypothyroidism also had thyroid cancer of various types and the authors speculated that these cancers were induced by the long-term high levels of TSH produced by the pituitary gland in response to low blood thyroid levels.

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2. Intensity of welfare impact

Because signs of hypothyroidism are those of reduced metabolic rate and because the hormone levels decline slowly, many owners do not notice signs of disease in the early stages, and the condition is only diagnosed when signs become more severe. At this stage the dogs may have had the disease for months. The signs may be missed because the disease is misinterpreted as normal ageing (Panciera 2009). If diagnosed early, the welfare impact - inability to express normal activity levels and behaviours - may be considered to be mild to moderate. In more advanced cases, welfare is affected by the effects of the disease on various tissues and organs as outlined above – and the consequences can be quite severe (eg leading to pain and malaise due to poor wound healing or increased susceptibility to infections as a result of compromised immune system). Welfare may also be adversely affected by the veterinary diagnostic investigations and life-long monitoring of the treatments necessary for adequate control of the condition.

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3. Duration of welfare impact

Hypothyroidism is a life-long problem once clinical signs have started, and there is no cure. The diagnosis is most often made in middle age. The disease can usually be managed by administering thyroid hormone supplements by mouth, once or twice daily, but permanent disease and suffering may be seen in some cases, particularly in those dogs that have developed more severe neurological problems (Panciera 1994).Return to top

4. Number of animals affected

Hypothyroidism is the most common endocrine problem of dogs (Panciera 1994, Chastain & Panciera 1995) and Beagles have long been recognised as being predisposed to the condition (Nachreiner et al no date, Musser & Graham 1968, Fritz et al 1970, Manning et al 1973, Benjamin et al 1996, Scott Moncrieff 2009). Benjamin et al (1996) found clinical hypothyroidism in 16% of the animals in one group of Beagles and lymphocytic thyroiditis in 26%.

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5. Diagnosis

The clinical presentation of hypothyroidism is very variable. In more than half of the dogs affected with hypothyroidism, none of the clinical signs that can occur are found. The most common sign is obesity and this is found in 41% of affected dogs (Panciera 1994).

Blood tests are needed to diagnose hypothyroidism. Often this is straightforward but it is not uncommon for multiple tests to be necessary. The laboratory test results are also often vague and the results of specific hormone assays can be affected by other diseases and some drugs (Kantrowitz et al 2001, Frank et al 2005, Davison 2010).

Affected dogs often have mild anaemia and high levels of fats in the blood. It might be expected that measuring the level of thyroid hormone (T4) in the blood would be useful in diagnosis but, as outlined above, this varies with many factors. Measuring both T4 and TSH levels at the same time is often informative and has become standard practice (Peterson et al 1997). In a dog with typical clinical signs and for which the results of blood tests are typical of hypothyroidism, this combination of tests may be provide sufficient evidence for the diagnosis to be confirmed (Hall et al 2003, Scott-Moncrieff 2009).

Sometimes other tests are needed, including: measuring the non-protein-bound form of T4 (called free T4) by equilibrium dialysis; measuring levels of thyroglobin antibodies (high in some dogs with lymphocytic thyroiditis); ultrasound examination of the thyroid glands; and dynamic blood tests (Hall et al 2003, Brömel et al 2005, Davison 2010). Dynamic tests involve measuring T4 levels before and after injection with TSH or TRH. Trial treatment for a number of months is sometimes advised as a diagnostic method but this can often be unsatisfactory as many non-thyroidal diseases can appear to improve with thyroid hormone supplementation and this approach often leads to misdiagnosis and incorrect treatment, possibly for years (Peterson et al 1997, Scott-Moncrieff 2009).

The potential involvement of lymphocytic thyroiditis can be tested for by measuring the level of one of the anti-thyroid antibodies. Antibody levels may be high in some dogs prior to developing any other signs of hypothyroidism but high levels are absent in many dogs with hypothyroidism – perhaps because levels have declined after the thyroid tissue has been destroyed or has atrophied (Graham et al 2001).

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6. Genetics

It has been shown that there are significant genetic influences on hypothyroidism in Beagles (Musser & Graham 1968, Fritz et al 1970, Benjamin et al 1996) but the exact mechanisms are not yet known. They have been investigated in other breeds where the focus has been on the genetics of control of the immune system (Graham 2008) but understanding is still at an early stage and no predictive genetic tests are currently available (Kennedy et al 2006a and 2006b, Graham 2008).

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7. How do you know if an animal is a carrier or likely to become affected?

Although evidence suggests that Beagles have a predisposition for developing hypothyroidism, there is no specific information on their carrier status, ie the possibility that animals may be able to pass on the disease to offspring without developing it themselves. Nor is any information available about the heritability of hypothyroidism in Beagles.

Measuring levels of anti-thyroid antibodies has been suggested as a screening test for animals that might be at risk of hypothyroidism but which are currently normal (Nachreiner et al no date). However, this has proved to be too unreliable (Graham et al 2001).

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8. Methods and prospects for elimination of the problem

The mode of inheritance of the disease is unknown and it is likely that both genetic and environmental factors influence its development (Graham 2008). With the current state of knowledge on the causal factors of hypothyroidism, the best advice that can be offered to prospective breeders is to avoid breeding from animals with affected relatives (or which have more than a very few affected relatives) including siblings and siblings of parents (Bell 2010).

Affected dogs should not be bred from, but unfortunately the condition is unlikely to show until after breeding age has been reached, and often it only occurs after the dog has been retired from breeding. This makes it particularly important that the genetics of the disease are elucidated and a predictive test developed.

Bell (2010) has suggested that dogs at risk of hypothyroidism (which would include all Beagles) should be tested for susceptibility to hypothyroidism based on the presence of TgAA (anti-thyroid antibody), and that a dog found to have normal TgAA levels on two test occasions, at least two years apart, and that is between two and six years of age could be considered to be suitable for breeding (Bell 2010). However, the validity of this approach has been questioned (Panciera 2009) due to the limitations of the test as there is not a strong correlation between TgAA levels and the risk, or presence, of the disease.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section

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10. References

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. 35th World Small Animal Veterinary Association World Congress Proceedings. 2-5th June 2010, Geneva, Switzerland. http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2010&PID=pr56159&O=VIN accessed 19.8.2011

Benjamin SA, Stephens LC, Hamilton BF, Saunders WJ, Lee AC, Angleton GM and Mallinckrod CH (1996) Associations between Lymphocytic Thyroiditis, Hypothyroidism, and Thyroid Neoplasia in Beagles. Veterinary Pathology 33: 486-496

Brömel C, Pollard RE, Kass PH, Samii VF, Davidson AP and Nelson RW (2005) Ultrasonographic evaluation of the thyroid gland in healthy, hypothyroid, and euthyroid Golden Retrievers with nonthyroidal illness. Journal of Veterinary Internal Medicine 19: 499-506

Chastain CB and Panciera DL (1995) Hypothyroid diseases. In: Textbook of Veterinary Internal Medicine editors SJ Ettinger & EC Edwards. WB Saunders, Philadelphia. pp 1487

Davison LJ (2010) Thyroid Testing: When, How and What It Tells Us. Proceedings of British Small Animal Veterinary Congress, Birmingham, UK http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=bsava2010&PID=pr54183&O=VIN accessed 19.8.2011

Dixon RM, Reid SWJ and Mooney CT (1999) Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism. Veterinary Record 145: 481-487

Frank LA, Hnilica KA, May ER, Sargent SJ and Davis JA (2005) Effects of sulfamethoxazole-trimethoprim on thyroid function in dogs. American Journal of Veterinary Research 6: 256-9

Fritz, TE, Zeman RC and Zelle MR (1970) Pathology and familial incidence of thyroiditis in a closed Beagle colony. Experimental and Molecular Pathology 12: 14-30

Graham PA (2008) Etiopathogenesis of Canine Hypothyroidism. Proceeding of the American College of Veterinary Internal Medicine June 4-7th 2008 San Antonio,Texas http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2008&PID=pr22952&O=VIN accessed 19.8.2011

Graham PA, Lundquist RB, Refsal KR, Nachreiner RF and Provencher AL (2001) 12-month prospective study of 234 thyroglobulin antibody positive dogs which had no laboratory evidence of thyroid dysfunction (Abstr). Journal of Veterinary Internal Medicine 14: 298

Graham PA, Refsal KR and Nachreiner RF (2007) Etiopathologic findings of canine hypothyroidism. Veterinary Clinics of North America 37: 617-631

Hall E, Murphy K and Darke P (2003) Hypothyroidism. In: Notes on Canine Internal Medicine. Blackwell, Oxford. pp 242

Johnson CA (2000) Effects of hypothyroidism on canine male infertility. Current Veterinary Therapy XIII Small Animal Practice. Editor WB Saunders, Philadelphia. pp 940

Kantrowitz LB, Peterson ME, Melián C and Nichols R (2001) Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. Journal of the American Veterinary Medical Association 219: 765-769

Kennedy LJ, Quarmby S, Happ GM, Barnes A, Ramsey IK, Dixon RM, Catchpole B, Rusbridge C, Graham PA, Hillbertz NS, Roethel C, Dodds WJ, Carmichael NG and Ollier WER (2006a) Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele. Tissue Antigens 68: 82–86

Kennedy LJ, Huson HJ, Leonard J, Angles JM, Fox LE, Wojciechowski JW, Yuncker C and Happ GM (2006b) Association of hypothyroid disease in Doberman Pinscher dogs with a rare major histocompatibility complex DLA class II haplotype. Tissue Antigens 67: 53–56

Manning PJ, Corwin LA Jr and Middleton CC (1973) Familial hyperlipoproteinemia and thyroid dysfunction of Beagles. Experimental and Molecular Pathology 19: 378-388

Musser E and Graham WR (1968) Familial occurrence of thyroiditis in purebred Beagles. Laboratory Animal Care 18: 58-68

Nachreiner RF, Bowman M, Refsal KR, Graham PA and Provencher Bolliger A (no date) Canine  Hypothyroidism: prevalence of positive TgAA in 7237 laboratory samples from Beagles Http://oxfordlabs.com/Beagle.pdf accessed 19.8.2011

Nesbitt GH, Izzo J, Peterson L and Wilkins RJ (1980) Canine hypothyroidism: a retrospective study of 108 cases. Journal of the American Veterinary Medical Association. 177: 1117-22

Panciera DL (1994) Hypothyroidism in dogs: 66 cases (1987-1992). Journal of the American Veterinary Medical Association 204: 761-7

Panciera DL (2000) Complications and concurrent conditions associated with hypothyroidism in dogs. In: Kirk’s Current Veterinary Therapy XIII Small Animal Practice. WB Saunders, Philadelphia. pp 327

Panciera DL (2009) Clinical Manifestations of Canine Hypothyroidism: When Should I Test? Atlantic Coast Veterinary Conference Proceedings. October 12-15th 2009 http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvc2009&PID=pr53386&O=VIN accessed 19.8.2011

Peterson ME, Melián C and Nichols R (1997) Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. Journal of the American Veterinary Medicine Association 211: 1396-402

Scott-Moncrieff JC, Glickman NW, Glickman LT and HogenEsch H (2006) Lack of Association between Repeated Vaccination and Thyroiditis in Laboratory Beagles. Journal of Veterinary Internal Medicine 20: 818–821

Scott-Moncrieff JC (2009) Canine Hypothyroidism. Western Veterinary Conference 2009 15-19th February 2009, Las Vegas, Nevada http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wvc2009&PID=pr50771&O=VIN accessed 19.8.2011

Thoday KL (1990) The thyroid gland. In: Manual of Small Animal Endocrinology. British Small Animal Veterinary Association, Cheltenham. Editor M Hutchinson.  pp 25

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