Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Standard Poodle Standard Poodle

Hypoadrenocorticism

Related terms: Addison’s disease, primary hypoadrenocorticism

Outline: In one survey, 8.6% of Standard poodles were found to have hypoadrenocorticism – low levels of adrenal hormones. This condition, the cause of which is unclear, has been found to be highly heritable (ie an affected parent is likely to pass it to its offspring) and it causes a variety of disease conditions associated with disturbances to metabolism. 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 standard poodles 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 exact 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

This varies 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 and Petersen 1995).

4. Number of animals affected

Famula et al (2003) surveyed 1722 Standard poodles and found that 8.6% had hypoadrenocorticism.

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 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 have been studied by Famula et al (2003). They found that the condition has a very high heritability of 0.75, which means that 75% of the factors that influence whether or not a dog develops hypoadrenocorticism are genetic. The genes responsible for hypoadrenocorticism in Standard poodles have not yet been determined and no genetic test is available.

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

No test is available to determine if an animal is likely to become affected. The genes involved have not yet been identified.

8. Methods and prospects for elimination of the problem

As far as we are aware, there are currently no organised schemes to limit the incidence of hypoadrenocorticism in Standard poodles. Whilst the genes involved have not been determined, because it is known to be a highly heritably disease, then breeding programmes that look to breed from lines of Standard poodles that have a history of showing a lower incidence of the disease than expected should be effective in reducing the number of affected dogs (Indrebo 2006). Better progress in reducing the incidence and suffering of dogs with hypoadrenocortism should be possible when more is known about the genetics underlying the disease.


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 of the secretions from the adrenal glands are fundamental to the effective functioning of the dog and thus 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 important in hypoadrenocorticism are outlined below.

Mineralocorticoids – The main mineralocorticoid 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 e.g. 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 and Petersen 1995).

Many other diseases can cause signs like this and sometimes neither the owner nor a veterinary surgeon may realise that hypoadrenocorticism is a possibility. 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 the appearance of the animal under X-ray and the results of these and other diagnostic tests are often vague and non-specific (see below). One particular feature of importance for diagnosis is high levels of potassium in the blood. 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, the dog must remain on lifelong hormone supplementation. Periodic blood testing is required to ensure that dosage is adequate (Kintzer and Petersen 1995, Scott-Moncrieff 2010).

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

A typical hypoadrenocorticism is also an important condition (Sadek and Schaer 1996, Thompson et al 2007). Dogs with atypical hypoadrenocorticism have adrenals that continue to secrete mineralocorticoids and are deficient only in glucocorticoids (Scott-Moncrieff 2010). It is often unclear why this happens but 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.

In general, about 70% of dogs with hypoadrenocorticism are female (Scott-Moncrieff 2010) but this sex predisposition does not seem to be the case in Standard poodles: in this breed, the sexes were found by Famula et al (2003) to be affected equally.

Other processes can also affect the hypothalamic-pituitary-adrenal axis and result in insufficient cortisol production by the adrenal glands Anything that affects this process can 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] by veterinary surgeons). 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 doseage usually reverses the hypoadrenocorticism.

However, the disease process of concern here, in Standard poodles, 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 Standard poodle.

Return to top

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).

Return to top

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 and Petersen 1995). Without diagnosis and treatment the disease may eventually lead to death.

Return to top

4. Number of animals affected

It has been known that Standard poodles are predisposed to hypoadrenocorticism since the condition was first recognised in dogs (Shaker et al 1988). Most dogs investigated for hypercalcaemia and hypoadrenocorticism were Standard poodles (Gow et al 2009). Famula et al (2003) surveyed 1722 Standard poodles and found that 8.6% had hypoadrenocorticism.

Return to top

5. Diagnosis

A veterinary surgeon may suspect hypoadrenocorticism when presented with a dog showing the clinical signs listed above or various changes found on routine haematology, biochemistry and ECG (electrocardiogram – observation of the electrical activity of the heart). However, many of these changes are not seen in atypical hypoadrenocorticism (Thompson et al 2007).

The definitive test for hypoadrenocorticism is an ACTH stimulation blood test. This involves giving the dog an injection of ACTH and measuring how the dog’s adrenal glands respond. In a normal dog the adrenals should produce an increased blood cortisol level in response to the 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).

Return to top

6. Genetics

The genetics of hypoadrenocorticism in the Standard poodle have been studied by Famula et al (2003). They found that the condition has a very high heritability of 0.75, which means that 75% of the factors that influence whether a dog develops or does not develop hypoadrenocorticism are genetic. They also suspected the involvement of a recessive gene but more recent research seems to suggest that this is not the case in the Standard poodle and that the condition is likely to be polygenetic – due to multiple genes (Green Tessier 2008).

Currently, the genes responsible for hypoadrenocorticism in Standard poodles have not been determined and so there is no genetic test available.

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 Standard poodle is likely to become affected. 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 elucidated and so it is not known whether unaffected carriers of the condition exist, although such carriers are likely if, as suspected by Famula et al (2003), a single recessive gene is responsible for the condition. If the assumption that it is a polygenetic condition (Green Tessier 2008) is correct then Standard poodles closely related to affected individuals would be at a higher risk of carrying disease-causing genes (Bell 2010).

Return to top

8. Methods and prospects for elimination of the problem

As far as we are aware, there are currently no organised schemes to limit the incidence of hypoadrenocorticism in Standard poodles. Whilst the genes involved have not been determined, because it is known to be a highly heritably disease, then breeding programmes that look to breed selectively from lines of Standard poodles that have a history of showing 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).

Such ‘breeding value’ takes into account genetic information and the presence/absence of disease both of the individual and its relatives. In the meantime, breeding from individuals that are normal and which have normal siblings and whose parents' siblings are normal have the greatest chance of carrying a low genetic load for the condition (Bell 2010).

In common with other complex, multi-gene issues, rapid progress in reducing the incidence and suffering of dogs with hypoadrenocortism may occur once more is known about the underlying genetics

Return to top

9. Acknowledgements

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

Return to top

10. References

Bartges JW and DL Nielson 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. World Small Animal Veterinary Association World Congress Proceedings

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

Famula TR, Belanger JM and Oberbauer AM 2003. Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle. Journal of Small Animal Practice 44: 8–12

Gow AG, Gow DJ, Bell R, Simpson JW, Chandler ML, Evans H, Berry JL, Herrtage ME and Mellanby RJ 2009 Calcium metabolism in eight dogs with hypoadrenocorticism. Journal of Small Animal Practice 50: 426–430

Green Tessier N 2008 http://www.poodleinfo.no/addison.html  accessed 21 12 10 

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 ME Petersen 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

Shaker E, Hurvitz AI and Peterson ME 1988 Hypoadrenocorticism in a family of standard poodles. Journal America Veterinary Medical Association 192: 1091-1092

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: 1190-1194

© UFAW 2011


Credit for main photo above:

By B. Schoener (Flying Spark at de.wikipedia) (Own work) [Public domain], via Wikimedia Commons