Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Labrador Retriever Labrador Retriever

Hypoadrenocorticism

Related terms: Addison’s disease, primary hypoadrenocorticism

Outline: Hypoadrenocorticism is a condition associated with low levels of adrenal hormones. Its cause is unclear but it has been found to be highly heritable (ie an affected parent is likely to pass it to its offspring) and causes a variety of disease conditions associated with disturbances to metabolism that result from these low hormone levels. Affected dogs may show lethargy, depression, inappetance, vomiting, weakness, weight loss, dehydration, diarrhoea, hypothermia, shaking, increased drinking and urination, weak pulse, low heart rate, abdominal pain and intestinal bleeding, and are likely to experience malaise (a general feeling of ill-health), pain and other unpleasant feelings (eg nausea). The course of the disease tends to be prolonged, especially when diagnosis and treatment are delayed or not possible.


Summary of Information

(for more information click on the links below)

1. Brief description

In hypoadrenocorticism the adrenal glands under-produce hormones. The cause of this disease in Labrador retrievers is unknown but it may be the result of an autoimmune process (in which the immune system is triggered to cause damage to part of the body). There is clearly a genetic factor in the onset of the disease. Usually dogs with hypoadrenocorticism suffer from a lack of two types of hormones - corticosteroids and mineralocorticoids – and suffer from the disease consequences of the hormonal disturbances. The signs shown vary greatly and are often intermittent in the earlier stages of the disease. Symptoms include: lethargy/depression, not eating, vomiting, weakness and weight loss. Other signs, seen less often, include: dehydration, diarrhoea, hypothermia, shaking, increased drinking and urination, a weak pulse and low heart rate, abdominal pain and intestinal bleeding (Kintzer and Petersen 1995).

2. Intensity of welfare impact

Welfare problems caused by hypoadrenocorticism range from mild to severe. The hormonal disturbances cause the dog to feel ill and make it unable to function normally. There is sometimes significant pain (Saito et al 2002, Scott-Moncrieff 2010).

3. Duration of welfare impact

The welfare problems associated with hypoadrenocorticism vary considerably, partly depending on how promptly the condition is diagnosed and controlled: typically this will be weeks (Hardy 1995) but some dogs can suffer illness for up to a year (Kintzer & Petersen 1995).

4. Number of animals affected

It is known that Labrador retrievers are predisposed to developing hypoadrenocorticism but we are unaware of any data on the proportion of animals affected.

5. Diagnosis

A diagnosis of hypoadrenocorticism may be suspected by a veterinary surgeon when presented with a dog showing the typical clinical signs of the disease, and it can be confirmed by specific tests. The definitive test for hypoadrenocorticism is an ACTH stimulation blood test (which measures the capacity of the adrenal glands to produce hormones in response to stimulation).

6. Genetics

The genetics of hypoadrenocorticism in the Labrador retriever have not been studied, nor the genes responsible determined, but the breed is considered to be predisposed to the condition (Hardy 1995).There is no genetic test for the disease.

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

There are no tests to determine whether or not a Labrador retriever is likely to become affected with hypoadrenocorticism. The ACTH stimulation test is the definitive diagnostic test to confirm the disease but is of use only once the disease has developed.

The genes involved in hypoadrenocorticism have not yet been determined and it is not known whether unaffected carriers of the condition exist – animals that can pass the disease on to their offspring but that are unaffected themselves.

8. Methods and prospects for elimination of the problem

As far as we are aware, there is currently no organised scheme aimed at reducing the prevalence of hypoadrenocorticism in Labrador retrievers.

Whilst the genes involved have not been determined, breeding selectively from Labrador retrievers with relatives that have a history of no, or lower incidence of the disease than expected in the breed (breeding value) is likely to be effective in reducing the number of affected dogs (Indrebo 2006).

Progress in understanding the genetic basis of the disease would be likely to facilitate efforts to reduce its prevalence.

 

For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

Hypoadrenocorticism is the condition in which the adrenal glands under-produce hormones. Hormones are chemicals (produced by glands) that are involved in the regulation of physiological processes in the body. Some adrenal gland hormones are essential for regulating metabolic functions and are vital for life.

There are two adrenal glands and these are situated in the abdomen close to the kidneys. They produce a large number of different hormones.  The two of importance in hypoadrenocorticism are outlined below.

  • Mineralocorticoids – The main mineralocorticoid hormone is aldosterone. This is an integral part of the system that regulates and maintains blood pressure and the composition of body fluids. It helps regulate the balance of salts in the body eg sodium and potassium by affecting their excretion (Herrtage 1990). Aldosterone release is influenced directly by the level of potassium in the blood and by hormones produced in the kidneys.
  • Glucocorticoids (corticosteroids) – The main glucocorticoid is cortisol. Cortisol has a greater range of effects throughout the body than any other hormone (Herrtage 1990). It is involved in the regulation of the metabolic process by which cells process carbohydrates, fats and proteins and in the maintenance of proper structure and function of organs. Glucocorticoids are also important in the mechanisms for dealing with stresses such as infection or tissue damage.

The secretion of these hormones (and others) by the adrenal glands is controlled by parts of the brain via a mechanism called the hypothalamic-pituitary-adrenal axis. The hypothalamus, which is part of the mid-brain, helps to control unconscious physiological processes such as metabolism. It does this by stimulating the pituitary gland, at the base of the brain, to produce hormones that, in turn, then affect the rest of the body. One of these hormones is adrenocorticotrophic hormone (ACTH) which stimulates the adrenal glands to produce cortisol (Herrrtage 1990).

Dogs with hypoadrenocorticism usually suffer from a lack of both corticosteroids and mineralocorticoids and the disease consequences and signs observed reflect this. The signs shown vary greatly, and are often intermittent in the earlier stages of the disease. Signs may also be worse when the dog has been stressed, for example during kennelling, after being traumatised or having another illness. A dog with a normal adrenal response would produce extra cortisol at these times as part of its physiological response to cope with the stressful event.

The signs that occur in more than 50% of affected dogs are mild and intermittent episodes of lethargy/depression, lack of appetite, vomiting, weakness and weight loss. Other signs, seen less often, include: dehydration, diarrhoea, hypothermia, shaking, increased drinking and urination, a weak pulse and low heart rate, abdominal pain and intestinal bleeding (Kintzer & Petersen 1995).

Many other diseases can cause signs like this and sometimes the real cause may not be determined.  If untreated, some dogs develop hypovolaemic shock (an adrenocortical crisis). They collapse with a weak pulse, low heart rate, abdominal pain, vomiting and diarrhoea and hypothermia. This is an emergency situation which is fatal without treatment, often due to heart failure or acute (sudden onset) kidney failure (Lifton et al 1996).

Hypoadrenocortism can cause many changes to blood composition and to the appearance of the animal on X-ray examination, and the results of these and other diagnostic tests are often vague and non-specific (see below). One particular feature of importance for the diagnosis of the disease is a high blood potassium concentration. This is a result of the lack of aldosterone secretion and is the immediate cause of some of the major signs seen, such as low heart rate and death.

Acute hypoadrenocortical crisis can be treated with hospitalisation, fluid administration and corticosteroids. In the longer term, affected dogs must remain on lifelong hormone supplementation. Periodic blood testing is required to ensure that dosage is adequate (Kintzer & Petersen 1995, Scott-Moncrieff 2010).

Some cases are detected by a veterinary surgeon investigating a different presenting problem. Of dogs with problems associated with high blood calcium concentration, 40% were diagnosed as suffering from hypoadrenocorticism (Elliott et al 1991). Affected dogs may also show hypoglycaemia (low blood sugar) (Scott-Moncrieff 2010) and megaoesophagus (a poorly functioning, dilated oesophagus so that swallowed food does not pass properly into the stomach) (Bartges & Nielson 1992, Scott-Moncrieff 2010). Another sign that has been attributed to hypoadrenocorticism is painful muscle cramps (Saito et al 2002).

Atypical hypoadrenocorticism is also an important condition (Sadek and Schaer 1996, Thompson et al 2007). In dogs with atypical hypoadrenocorticism, the adrenal glands continue to secrete mineralocorticoids and these animals are deficient only in glucocorticoids (Scott-Moncrieff 2010). It is unclear why this happens and some affected dogs go on to develop specific mineralocorticoid deficiency. This form is even more difficult to diagnose than typical hypoadrenocorticism as many of the more typical features of hypoadrenocorticism result from the mineralocorticoid deficiency.

More females are affected than males:  approximately 70% of dogs with hypoadrenocorticism are female (Scott-Moncrieff 2010).

Other processes can also affect the hypothalamic-pituitary-adrenal axis and result in insufficient cortisol production by the adrenal glands. For example, disease of the pituitary gland which compromises ACTH production can cause secondary hypoadrenocorticism, but this is rare. Also rarely, tumours in the adrenal glands or diseases which interfere with their blood supply can cause hypoadrenocorticism. The commonest cause of hypoadrenocorticism is actually over-treatment of hyperadrenocorticism (over-production of cortisol from the adrenal glands [Cushing’s disease]). Dogs being treated for hyperadrenocorticism have to be carefully monitored to detect iatrogenic hypoadrenocorticism (hypoadrenocorticism caused by medical intervention) and, in these cases, reducing treatment dosage usually reverses the hypoadrenocorticism.

However, the disease process of concern here, in Labrador retrievers, is of unknown cause. It may be the result of an autoimmune process (caused by the immune system attacking the adrenal glands). There is clearly a genetic factor in this process in certain breeds of dogs, including the Labrador retriever.

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2. Intensity of welfare impact

Welfare problems due to hypoadrenocorticism range from mild to severe. It is a condition that can usually be successfully treated (Hardy 1995) if modern veterinary facilities are available for diagnosis and treatment. However there is no cure and the condition requires ongoing care. The most severe welfare problems arise when the disease has not been diagnosed and treated. Hypoadrenocorticism causes the dog to feel ill and makes it unable to function normally. There is sometimes significant pain due to muscle cramps (Saito et al 2002, Scott-Moncrieff 2010).

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3. Duration of welfare impact

This will vary considerably according to how long it takes for the condition to be diagnosed and controlled; typically this will be weeks (Hardy 1995) but some dogs can suffer illness for up to a year (Kintzer & Petersen 1995). Without diagnosis and treatment the disease may eventually lead to death.

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4. Number of animals affected

It is known that Labrador retrievers are predisposed to hypoadrenocorticism but we are unaware of any data on the proportion of the breed that are affected.

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5. Diagnosis

A veterinary surgeon may suspect hypoadrenocorticism when presented with a dog showing the clinical signs listed above (see ‘Clinical and pathological effects’) or when discovering various changes found during routine haematology, biochemistry and ECG test (electrocardiogram – observation of the electrical activity of the heart). However, many of these changes are not seen in atypical hypoadrenocorticism (Thompson et al 2007). Examination of the adrenal gland using ultrasonography can be useful (Wenger et al 2010).

The definitive test for hypoadrenocorticism is an ACTH stimulation blood test. This involves injection of ACTH and measuring how the adrenal glands respond. In a normal dog, the adrenals increase blood cortisol level in response to ACTH but in a dog with hypoadrenocorticism the cortisol level stays low. In unusual cases, other hormone tests can be useful (Hall et al 2003).

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6. Genetics

The genetics of hypoadrenocorticism in the Labrador retriever have not been studied, nor the genes responsible determined, but the breed is considered to be predisposed to the condition (Hardy 1995).There is no genetic test for the disease.

Return to top

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

There are no tests to discover if a Labrador retriever is likely to become affected. The ACTH stimulation test is the definitive diagnostic test but is of use only once the disease has developed.

The genes involved in hypoadrenocorticism have not yet been determined and it is not known whether there are unaffected carriers (ie animals which can pass on the disease to their offspring without developing the disease themselves).

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8. Methods and prospects for elimination of the problem

As far as we are aware, there is currently no scheme aimed at reducing the prevalence of hypoadrenocorticism in Labrador retrievers. Whilst the genes involved have not been determined, breeding selectively from Labrador retrievers with relatives that have a history of no or a lower incidence of the disease than expected in the breed (breeding value) is likely to be effective in reducing the number of affected dogs (Indrebo 2006, Bell 2010).

The ‘breeding value’ of individuals takes account of information about genetic relatedness and the presence or absence of genetic diseases in the individual and its relatives.

Progress in understanding the genetic basis of the disease would be likely to facilitate efforts to reduce its prevalence.

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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

Bartges JW and Nielson DL (1992) Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog. Journal of the American Veterinary Medical Association 201: 889-91

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/proceedings/Proceedings.plx?CID=WSAVA2010&Category=&PID=56159&O=Generic. Accessed 1.10.11.

Elliott J, Dobson JM, Dunn JK, Herrtage ME and Jackson KF (1991) Hypercalcaemia in the dog: a preliminary study of 40 cases. Journal of Small Animal Practice 32: 564–571

Hall E, Murphy K and Darke P (2003) Hypoadrenocorticism (Addison’s disease). In: Notes on Canine Internal Medicine. Blackwell Publishing. pp238

Hardy RM (1995) Hypoadrenal gland disease. In: Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat, 4th edition. pp 1579

Herrtage ME (1990) The adrenal glands. In: Manual of Small Animal Endocrinology. Editor M. Hutchinson. British Small Animal Veterinary Association, Cheltenham. pp75

Indrebo A (2006) Healthy Dog Breeding -The Value of Breeding Programmes. World Small Animal Veterinary Association Proceedings

Kintzer PP and Petersen ME (1995) Hypoadrenocorticism in dogs. In: Current Veterinary Therapy XII edited by R.W. Kirk. W.B. Saunders Company, Philadelphia. pp 425

Lifton SJ, King LG and Zerbe CA (1996) Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995). Journal of the American Veterinary Medical Association 209: 2076-2081

Sadek D and Schaer M (1996) Atypical Addison's disease in the dog: a retrospective survey of 14 cases. Journal of the American Animal Hospital Association 32: 159-163

Saito M, Olby NJ, Obledo L and Gookin JL (2002) Muscle Cramps in Two Standard poodles  With Hypoadrenocorticism. Journal of the American Animal Hospital Association 38: 437-443

Scott-Moncrieff JC (2010) Hypoadrenocorticism in Dogs and Cats: Update on Diagnosis and American College of Veterinary Internal Medicine Forum

Thompson AL, Scott-Moncrieff JC and Anderson JD (2007) Comparison of classic hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases (1985-2005). Journal of the American Veterinary Medical Association 230: 1190-4

Wenger M, Mueller C, Kook PH and Reusch CE (2010) Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases. Veterinary Record 167: 207-210

© UFAW 2011


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