Cat & Dog - Adrenal Gland Dysfunction (Cushing's Syndrome & Addison's Disease)

These notes should be read in conjunction with the handouts for dogs on Cushing's syndrome and Addison's disease.

The adrenal glands are closely associated with the kidneys.  Each has a central portion (the medulla) which is approximately one fifth of the total size of the gland and produces adrenalin, the so-called 'emergency hormone'.  Surrounding the medulla is the cortex and this produces several hormones.  The most important are the corticosteroids, further classified into glucocorticoids and mineralocorticoids.  The most important glucocorticoid is hydrocortisone (cortisol or cortisone) while the main mineralocorticoid is aldosterone.

Cortisol regulates the body's metabolism and controls inflammation.  Carefully controlled production is essential and is achieved through adrenocorticotrophic hormone (ACTH), which is produced by the pituitary gland in the brain.

Aldosterone regulates the amount of water in the body.  It is an important hormone but is not controlled by ACTH.

Cushing's syndrome

Cushing's syndrome is the result of hyperadrenocorticism (production of too much cortisol).  This is one of the most common endocrine (hormone) disorders of dogs but it is rare in cats.  The most common form of Cushing's syndrome in dogs is due to over stimulation of the adrenal gland due to the production of too much ACTH by the pituitary gland.

What are the other causes of Cushing's syndrome?

Sometimes excess cortisol is produced by the adrenals even though ACTH levels are normal.  Often 'Iatrogenic Cushings' occurs from the long term use of preparations containing cortisone, for example, in dogs with allergic skin who often require cortisone treatment to relieve the inflammation.

If treatment is to be effective it is important to identify the type of Cushing's syndrome present if at all possible.

Addison's disease

This is the opposite of Cushing's syndrome.  It is caused by too little production of corticosteroids (both glucocorticoids [cortisol] and mineralocorticoids [aldosterone] by the adrenal glands).  It is usually due to immune mediated destruction of the adrenal glands although occasionally lack of ACTH produced in the pituitary gland can contribute.   Very simply it can be thought of as the opposite of Cushing's.

Addison's disease (hypoadrenocorticism) is a rare condition in dogs and extremely rare in cats.

How are these conditions diagnosed?

Characteristic physical signs give the first clue.  However these are not specific and can be associated with other diseases.  As a consequence blood tests have to be carried out.  A complete blood count (CBC) and biochemistry tests will give an indication of other problems.  Urine analysis is also necessary to check for diabetes and other problems.

Once these results have been assessed other specific tests are then carried out.

What are the usual diagnostic tests?

• ACTH stimulation tests - Cushing's syndrome.  ACTH produced in the brain controls the amount of cortisol produced by the adrenal glands.  As the blood level of cortisol rises there is a 'feed-back' on the pituitary gland, reducing the level of ACTH.  In the normal animal the cortisol level then starts to fall.  The ACTH stimulation test mimics the effect of natural ACTH and demonstrates the ability of the animal's adrenal glands to produce cortisol in response to the injection.  Two blood samples are required, about a couple of hours apart.  A patient with Cushing's syndrome may show a high cortisol level initially with a further increase after the synthetic ACTH injection.  This is usually seen with 'pituitary' Cushing's syndrome (the most common). It can also occur with the less common form 'adrenal' Cushing's syndrome.  Dogs with possible Iatrogenic Cushings (due to administration of corticosteroids for other reasons, such as skin problems) usually show either a very mild or no response to the ACTH stimulation test.  
• ACTH stimulation tests - Addison's disease.  An ACTH stimulation test is also used for the diagnosis of Addison's disease.  Patients with Addison's disease have a low cortisol level in the first blood sample and the sample taken after the injection of ACTH shows little or no increase in circulating cortisol.Once diagnosed the pet's history has to be carefully evaluated.  Sometimes if there has been treatment with corticosteroid drugs which have suddenly been stopped, temporary Addison's disease can result.  Many cases are due to immune mediated destruction of the adrenal cortex while other causes are due to reduction in the ACTH by the pituitary gland in the brain.  Causes can be differentiated by blood tests involving cortisol and ACTH levels.  
• Dexamethasone suppression test.  A low dose dexamethasone suppression test is a similar type of test.  A low dose of synthetic corticosteroid preparation (dexamethasone) is injected.  Three separate blood samples are required.  This test is used to differentiate pituitary origin from adrenal origin Cushing's syndrome.    

Further tests such as the high dose dexamethasone suppression test and measurement of circulating ACTH may have to be made in order to arrive at a definitive diagnosis.