Hypoadrenocorticism

Hypoadrenocorticism or Addison's disease is caused by decreased secretion of mineralocorticoids (mainly aldosterone) and glucocorticoids.

In dogs and cats, the primary form of the disease is caused by immune-mediated destruction of the adrenal cortex. Other, less frequent causes have been described, such as infection (blastomycosis, tuberculosis), bleeding into the adrenal glands, tumour metastasis, trauma and amyloidosis. In cats, hypoadrenocorticism caused by lymphomatous infiltration of the adrenal glands has been described.

Secondary hypoadrenocorticism occurs when secretion of ACTH by the pituitary gland is inhibited, leading to atrophy of the adrenal cortex. Secretion inhibition can be caused by long-term treatment with corticosteroids, and more rarely by tumours, trauma or congenital defects of the gland. Secondary hypoadrenocorticism is rare in dogs and cats.

Glucocorticoid deficient hypoadrenocorticism is known as atypical Addison's disease. Secondary hypoadrenocorticism is always atypical, and primary hypoadrenocorticism may be atypical in the early phase of the disease, prior to the destruction of the zona glomerulosa of the adrenal gland.

The primary form usually occurs in young dogs (between 2 and 6 years of age), usually female (up to 70% of cases). It does not appear to target any particular breed, although a genetic component is suspected in some breeds (Leonberger, Standard Poodles and Labrador Retriever). In cats, the age range is wider, and there is no predisposition in terms of breed or sex.

Symptoms

The animal will often have a history of vomiting and diarrhoea that respond to nonspecific treatment, but reappear within a few days or weeks. As the disease progresses, the animal might exhibit signs of collapse, hypothermia, polyuria and polydipsia. Symptoms may appear and disappear in cycles.

Most common symptoms: lethargy / anorexia / weakness / intermittent vomiting / weight loss / dehydration / diarrhoea / hypothermia / tremors.

Less common symptoms: polyuria-polydipsia / weak pulse / bradycardia / melena / painful abdomen / megaoesophagus-regurgitation.

In these cases, the differential diagnosis should include inflammatory bowel disease (IBD), intestinal parasitism (trichuriasis), and kidney failure (especially in cats).

During an acute Addisonian crisis, animals present a weak pulse, bradycardia, prolonged capillary refill time, severely depressed level of consciousness, and severe muscle weakness. The differential diagnosis should include acute cardiogenic shock, hypovolaemic shock and septic shock.

Both dogs and cats show similar symptoms. Vomiting, polyuria and polydipsia are observed in 30% of cases, but diarrhoea has not been described.

Interpretation of laboratory tests

General tests:

Complete blood count: mild normocytic, normochromic, non-regenerative anaemia in chronic cases, which may be masked if the animal is dehydrated. There is typically no stress leukogram, and the eosinophil and lymphocyte count is usually normal or elevated.

Biochemistry: Hypoadrenocorticism is usually diagnosed on the basis of electrolyte alterations: hyponatraemia, hyperkalaemia and hypochloraemia, with a sodium-potassium ratio of less than 20:1. These changes are highly suggestive of hypoadrenocorticism, but are not exclusive to the disease. Electrolyte tests may be normal in animals with atypical (glucocorticoid deficient) forms of the disease.
Phosphorus and calcium are usually elevated (in 80% and 30% of animals, respectively) and glucose is decreased. Urea is usually elevated, and is often accompanied by a slight increase in creatinine (prerenal uraemia). Transaminases and bilirubin may be elevated in one-third of affected dogs (not in cats). Some animals may present hypoalbuminemia.

Urine test: Urine-specific gravity in affected animals is often low (< 1030) due to renal medullary washout due to sodium depletion.

Specific tests

ACTH stimulation test
Used to confirm suspected cases of hypoadrenocorticism. Affected animals show low or undetectable baseline cortisol that remains at these levels after ACTH administration. (< 5 μg/dL in the post-ACTH sample).
In secondary hypoadrenocorticism, the response to exogenous ACTH is decreased, but less than in the primary form.
If the animal has received corticosteroids, the results may not be reliable (except dexamethasone, which does not interfere with the results).

Baseline ACTH
Used to differentiate between primary and secondary hypoadrenocorticism. In primary hypoadrenocorticism, plasma ACTH concentrations are very high (> 100 pg/mL). In secondary hypoadrenocorticism (caused by lack of pituitary ACTH), endogenous ACTH levels are decreased (< 20 pg/mL).
This hormone is far more labile than cortisol, so it is essential to handle the sample correctly.
If the animal has received corticosteroids, the results may not be reliable (iatrogenic suppression of ACTH).

Canine plasma aldosterone
Used to assess aldosterone secretion in secondary hypoadrenocorticism and to diagnose some rare cases in which the animal presents hyperkalaemia with hyponatraemia and altered sodium/potassium ratio but a normal response to the ACTH stimulation test.

Modified Thorn’s test (indirect determination of cortisol)
A rapid test to confirm or rule out hypoadrenocorticism. The test is performed at the same time as the ACTH stimulation test. A normal leukocyte response in a dog suspected of having the disease indicates that it has adequate adrenal reserve and there is no need to perform a cortisol test. If the response is consistent with hypoadrenocorticism, the samples must be used for a cortisol test to confirm the diagnosis.

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