Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Doberman Pinscher

Doberman Pinscher

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 Doberman pinschers. 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 disease 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 problems (chronic) 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 in the nervous system, circulation and eyes.

2. Intensity of welfare impact    

If diagnosed early the main welfare impacts are due to an inability to express normal activity levels and behaviours and may be considered mild to moderate. In more advanced cases,  the welfare consequences can be severe  due to the long term effect of low levels of thyroid hormone on various tissues and organs; for example it is associated with compromised wound healing and increased susceptibility to infections.

3. Duration of welfare impact

Hypothyroidism is a life-long problem once it has begun for which there is no cure. The diagnosis is most often made in middle age. Treatment is usually successful but permanent disease and suffering may be seen in some cases, particularly those dogs that have developed more severe neurological problems (Panciera 1994).

4. Number of animals affected

Hypothyroidism is the commonest endocrine problems of dogs (Panciera 1994, Chastain & Panciera 1995) and Doberman pinschers have long been recognised as being predisposed to the condition (Nesbitt et al 1980, Scott & Paradis 1990, Hall et al 2003, Kennedy et al 2006a and 2006b, Graham et al 2007, Scott Moncrieff 2009, Davison 2010). The proportion of the breed that is affected is, however, unknown.

5. Diagnosis

Blood tests are needed to diagnose hypothyroidism. Often this is straightforward but it is not uncommon for multiple tests to be necessary. Measuring thyroxine (or T4 - the most important hormone produced by the thyroid) and thyroid stimulating hormone (TSH) levels at the same time is often useful and has become standard practice (Peterson et al 1997, Hall et al 2003, Scott Moncrieff 2009) but 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 Dobermans is 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 unaffected carriers of the gene(s) exist as there is no information about the heritability of hypothyroidism in Doberman pinschers. Measuring levels of certain antibodies has been suggested as a screening test for animals that might be at risk of hypothyroidism but which are currently normal, but this is unreliable (Graham et al 2007).

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 bred but the condition tends to be diagnosed sometime after an affected individual has reached an age from which it can be bred.


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1. Clinical and pathological effects

The thyroid glands are found 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 (found under the base of the brain), which is in turn under the control of part of the brain called the hypothalamus. To increase production of thyroid hormones from the thyroid glands the hypothalamus secretes thyroid releasing hormone (TRH). This in turn causes the pituitary gland to produce thyroid stimulating hormone (TSH) that directly causes thyroid gland cells to produce and secrete thyroid hormones. When circulating thyroid hormone is present in adequate levels the hypothalamus and pituitary detect this and switch off production of TRH, TSH and consequently the production of thyroxine. This control system is known as negative feedback (Davison 2010).

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”. Thyroid hormones are integral to many metabolic processes throughout the body and these processes go awry when levels are too low (Thoday 1990, Hall et al 2003).

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.  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 becomes 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. These antibodies are found in only 29% of affected Dobermans, a lower level than in some other predisposed breeds (Panciera 2009).

In idiopathic thyroid atrophy (‘Idiopathic’ means of unknown cause, ‘atrophy’ means withering away) the thyroid glands disappear 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). Judged by the number of individuals with detectable thyroid antibodies it seems that this form of the disease may be more common in Dobermans that lymphocytic thyroiditis (Graham 2008).

In healthy animals, thyroid hormone levels vary considerably between individuals and with breed, sex, age, and body weight. Some other diseases and any drugs can also affect levels and vets have to take these factors into account when making a diagnosis of the condition (see below) (Thoday 1990).

Generally in dogs, hypothyroidism is commonest in middle-aged animals, but in Dobermans the disease is often diagnosed at a younger age (Milne & Haynes 1981).

Low thyroid levels cause long-term problems (chronic) 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 can occur which, 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 e.g. in the brain, heart, kidneys. The immune system may be affected leading to greater risk of infections, particularly in the skin (Nesbitt et al 1980, Panciera 2000, Hall et al 2003). The condition may also affect reproduction (Panciera 2000, Johnson 2000).

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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 due to poor wound healing or increased susceptibility to infections as a result of compromised immune system).   Welfare may also be adversely affected by veterinary diagnostic investigations and the life-long monitoring of treatment that is necessary for adequate control.

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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. Treatment by administering thyroid hormone supplements by mouth once or twice daily 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).

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4. Number of animals affected

Hypothyroidism is the commonest endocrine problem of dogs (Panciera 1994, Chastain & Panciera 1995) and Doberman pinschers have long been recognised as being predisposed to the condition (Nesbitt et al 1980, Scott & Paradis 1990, Hall et al 2003, Kennedy et al 2006a and 2006b, Graham et al 2007, Scott Moncrieff 2009, Davison 2010) but details of the proportion of the breed that is affected are lacking.

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5. Diagnosis

The clinical presentation is so variable, none of the individual clinical signs are found in more than half of dogs affected with hypothyroidism; the commonest sign being obesity which is found in 41% of dogs (Panciera1994). 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 a 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 but, as outlined above, this varies with many factors and the effects of other significant non-thyroidal illnesses are often important. Measuring T4 and TSH levels at the same time is often useful and has become standard practice (Peterson et al 1997). In a dog with typical clinical signs and where the results of blood tests are typical of hypothyroidism, this combination of tests may be enough to make the diagnosis (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 but 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 the dog being treated incorrectly, possibly for years (Peterson et al 1997, Scott Moncrieff 2009).

Testing for the presence of lymphocytic thyroiditis may be performed 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 they 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

Genetic influences on hypothyroidism in Dobermans have recently begun to be investigated. Focus is 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 the breed disposition suggests it, there is no specific information on carrier status and there no information about the heritability of hypothyroidism in Doberman pinschers.

Measuring levels of anti-thyroid antibodies has been suggested as a screening test for animals that might be at risk of hypothyroidism which are currently normal but this is too unreliable. Only 26% of affected Dobermans show abnormally elevated levels of these antibodies (Graham et al 2009).

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8. Methods and prospects for elimination of the problem

It is likely that the condition is multifactorial and there is evidence for both genetic and environment influences (Graham 2008). Good general advice for prospective breeders concerning conditions where the mode of inheritance is unknown is to avoid breeding from animals with larger numbers of affected relatives – including siblings and siblings of parents and, instead to use healthy animals with no affected relatives (Bell 2010). With the current state of knowledge on the causal factors of hypothyroidism it is difficult to provide more specific advice; particularly because the condition is only one of several significant welfare problems common in Doberman pinschers which appear to have a genetic basis and selection of animals for breeding (if within the breed) should take account of all these conditions.

Affected dogs should not be bred, but 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 predisposition are elucidated and a predictive test validated.

Bell (2010) has suggested that dogs at risk of hypothyroidism (which would include all Dobermans) 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 in any breed but especially in Dobermans,  as there is not a good 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. World Small Animal Veterinary Association World Congress Proceedings

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

Chastain CB, Panciera D and Waters C (1999) Thyroid Stimulating Hormone Stimulation Test in Cardiomyopathic Doberman Pinschers: A Retrospective Study. Small Animal Clinical Endocrinology 9 5

Davison LJ (2010) Thyroid Testing: When, How and What It Tells Us. Proceedings of British Small Animal Veterinary Congress.

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: 256-259

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

Graham PA (2008) Etiopathogenesis of Canine Hypothyroidism. Proceeding of the American College of Veterinary Internal Medicine

Hall E, Murphy K and Darke P (2003) Hypothyroidism. In: Notes on Canine Internal Medicine. Blackwell, Oxford. pp242

Johnson CA (2000) Efects 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

Milne KL and Hayes HM Jr (1981) Epidemiologic features of canine hypothyroidism. The Cornell Veterinarian 71: 3-14

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 Assocition 204: 761-767

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

Panciera DL (2009) Clinical Manifestations of Canine Hypothyroidism: When Should I Test? Atlantic Coast Veterinary Conference Proceedings

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 DW and Paradis M (1990) A survey of canine and feline skin disorders seen in a university practice: Small Animal Clinic, University of Montréal, Saint-Hyacinthe, Québec (1987-1988). Canadian Veterinary Journal 31: 830–835

Scott-Moncrieff JC (2009) Canine Hypothyroidism. Western Veterinary Conference 2009

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

© UFAW 2011