Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Golden Retriever 

Golden Retriever

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, affects up to 25% of Golden retrievers. 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

(for more information click on the links below)

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 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.

3. Duration of welfare impact

Once it has begun, hypothyroidism is a life-long problem and there is no cure. The diagnosis 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 commonest endocrine (hormonal) problem of dogs (Panciera 1994, Chastain & Panciera 1995) and Golden retrievers have long been recognised as being predisposed to the condition (Milne & Hayes 1981, Panciera 1994, Hall et al 2003, Kennedy et al 2006, Scott-Moncrieff 2009, Davison 2010). According to the 1998 Golden Retriever Club of America National Health Survey, the lifetime risk for a Golden retriever developing hypothyroidism was 1 in 4; the highest risk for any serious disease in this breed (http://www.grca.org/pdf/health/healthsurvey.pdf).

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. Measuring thyroxine (or T4 - the most important hormone produced by the thyroid gland) and thyroid stimulating hormone (TSH) levels simultaneously  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 Golden retrievers has been into the genes that control the immune system (Graham 2008) but understanding is still at an early stage and no genetic tests are currently available (Kennedy et al 2006, 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 - animals that do not have the disease themselves but are able to pass on the gene(s) that cause the disease to their offspring - and, as far as we know, there is no information about the heritability of hypothyroidism in Golden retrievers. 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 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 used for breeding. Unfortunately, the condition tends to be diagnosed only after the animal has reached breeding age.


For further details about this condition, please click on the following:
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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. When the level of circulating thyroid hormone is adequate, the hypothalamus and pituitary switch off TRH and TSH production. 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 essential for 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 a low level 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 which is then 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. Golden retrievers have relatively high levels of TgAA compared with other breeds (Scott- Moncrieff 2009): 69% have elevated levels (Panciera 2009).

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, andthese factors have to be taken into account when diagnosing the condition (see below) (Thoday 1990).

In dogs, hypothyroidism is commonest in middle-age, but in Golden retrievers the disease is often diagnosed in younger animals (Milne & Haynes 1981). The 1998 Golden Retriever Club of America National Health Survey found that the mean age for the diagnosis of hypothyroidism was 5 years old, and varied from as early as six months to 14 years (http://www.grca.org/pdf/health/healthsurvey.pdf).

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 e.g. 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).

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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. 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).

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4. Number of animals affected

Hypothyroidism is the commonest endocrine problem of dogs (Panciera 1994, Chastain & Panciera 1995) and Golden retrievers have long been recognised as being predisposed to the condition (Milne & Hayes 1981, Panciera 1994, Hall et al 2003, Kennedy et al 2006, Scott-Moncrieff 2009, Davison 2010). According to the 1998 Golden Retriever Club of America National Health Survey the lifetime risk for a Golden retriever developing hypothyroidism was 1 in 4; the highest risk for any serious disease in this breed (http://www.grca.org/pdf/health/healthsurvey.pdf).

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5. Diagnosis

The clinical presentation of the disease is very variable. None of the clinical signs that can occur are found in more than half of dogs affected with hypothyroidism. The commonest 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 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 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 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 pontential 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 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

Investigations have recently begun into genetic influences on hypothyroidism in Golden retrievers. Focus is on the genetics of immune system control (Graham 2008) but understanding is still at an early stage and no genetic tests to detect animals at risk or which may pass on the disease are currently available (Kennedy et al 2006, 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 (ie the possibility that animals may be able to pass on the disease to offspring without developing it themselves) nor about the heritability of hypothyroidism in Golden retrievers.

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 has proved to be too unreliable

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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 development of the condition (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). Hypothyroidism is one of several common significant welfare problems of Golden retrievers which appear to have a genetic basis and selection of animals for breeding should take account of all these conditions.

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 Golden retrievers) 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 Golden retrievers, 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.35th World Small Animal Veterinary Association World Congress Proceedings2-5th June 2010, Geneva, Switzerland

http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2010&Category=&PID=56159&O=Generic. Accessed 1.10.11.

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

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

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. pp 242

Johnson CA (2000) Effects of hypothyroidism on canine male infertility. Current Veterinary Therapy XIII Small Animal Practice. Editor W.B. 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 (2006) Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele. Tissue Antigens 68: 82–86

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 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

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 (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

http://www.grca.org/pdf/health/healthsurvey.pdf accessed 9.7.2011

© UFAW 2011


Credit for main photo above:

By Golden dust [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons