27 Hyperadrenocorticism
Hyperadrenocorticism is a syndrome characterized by clinical and biochemical changes related to a state of glucocorticoid excess. It can be caused by an adrenocortical neoplasm (adrenal dependent hyperadrenocorticism [ADH]), by excessive production of adrenocorticotropic hormone (ACTH) by a pituitary tumor or pituitary hyperplasia (pituitary-dependent hyperadrenocorticism [PDH]), or as a result of glucocorticoid administration (iatrogenic). Adrenal tumors are found in 15% to 20% of cases and the remaining 80% to 85% of dogs with spontaneous hyperadrenocorticism have PDH.
A history of polyuria and polydipsia is reported in more than 75% of dogs with hyperadrenocorticism. Polyphagia is also frequently noted. Changes in the integument are common, and include bilaterally symmetrical alopecia, thin hair coat, slow hair regrowth after clipping, hyperpigmentation, thin skin, comedones, calcinosis cutis, and seborrhea. Dogs with hyperadrenocorticism are prone to recurrent pyoderma and Malassezia infection. An enlarged, pendulous abdomen also is common, occurring because of muscle weakness and hepatomegaly. Mild to moderate obesity with distribution of fat to the trunk also alters the dog’s appearance. Weakness and lethargy are often noted. Excessive panting also occurs in some dogs.
Behavioral changes, dullness, pacing, ataxia, tetraparesis, circling, blindness, and seizures are the predominant clinical findings in addition to the typical signs of hyperadrenocorticism that are usually present.
Nonspecific findings on a complete blood count may include mild erythrocytosis and stress leukogram. An elevated serum alkaline phosphatase (ALP) activity is found in most dogs with hyperadrenocorticism. This is primarily the steroid isoenzyme and the degree of elevation may be marked. Serum alanine aminotransferase (ALT) activity may also be elevated, but this is a less consistent finding and the elevation is not as great as for ALP. Hypercholesterolemia and mild hyperglycemia are common. Urine specific gravity usually indicates isosthenuria or hyposthenuria. Proteinuria may be present secondary to glomerular leakage or infection.
Urinary tract infection is found in about 50% of dogs with hyperadrenocorticism, and most dogs do not have clinical signs associated with the infection. In addition, pyuria and bacteriuria are absent in about one third of infections associated with hyperadrenocorticism. These findings indicate that it is appropriate to culture the urine of all dogs with hyperadrenocorticism regardless of the results of urinalysis.
Most dogs with hyperadrenocorticism have multiple clinical signs of their disease and the decision to test these dogs is straightforward. Dogs with few clinical signs, (e.g., just polyuria/polydipsia [PU/PD] or serum enzyme abnormalities) may also be tested, although if the results indicate hyperadrenocorticism, the dog may not necessarily require treatment. Because false positive results on adrenal function tests occur with some frequency, it is important to consider the entire clinical picture when interpreting the test results.
Conditions other than primary adrenal disease can greatly affect the accuracy of adrenal function tests. More than half of dogs with a significant systemic illness will have a false-positive result on the low-dose dexamethasone suppression test (LDDST). The ACTH response test for hyperadrenocorticism is affected less frequently, but false-positive results are still common. Because it is rarely if ever necessary to make a diagnosis of hyperadrenocorticism on an emergency basis, adrenal function testing should be postponed until the illness can be resolved or stabilized for 2 to 4 weeks.
There is no single best test for all situations. Overall, the low-dose dexamethasone suppression test (LDDST) is more sensitive than the ACTH response test and has the advantage of differentiating PDH from ADH in 25% to 50% of cases. On the other hand, the LDDST is more susceptible to the effects of conditions other than primary adrenal disease, so false-positive results are much more likely on the LDDST.
Urinary cortisol excretion is dependent on the average plasma cortisol concentration over the period of time that the urine was produced. Almost all dogs with hyperadrenocorticism have an elevated urine cortisol:creatinine ratio. However, this ratio is also elevated in many if not most dogs with conditions other than primary adrenal disease, so this test has low specificity despite its high sensitivity. Because the stress of a visit to the veterinary practice can elevate the dog’s urine cortisol:creatinine ratio, urine samples for this test should be collected by the owner at home. Although it is not recommended for routine use, the urine cortisol:creatinine ratio can be a useful screening test in that a negative result makes hyperadrenocorticism unlikely.
The advantages of the ACTH response test are that it is less often affected by nonadrenal illness, it can be performed more rapidly, it is diagnostic of iatrogenic hyperadrenocorticism, and it can be used to monitor the response to treatment with mitotane. Therefore the ACTH response test is preferred if an animal is suspected of having nonadrenal illness or has a history of recent corticosteroid administration. The ACTH response test is performed by obtaining blood samples to test for cortisol levels before and 1 hour after intravenous (IV) or intramuscular (IM) administration of 5 μg/kg (maximum dose of 250 μg) synthetic ACTH. The ACTH can be frozen and stored for 6 months, allowing for a number of tests to be performed using the same vial.
The advantages of the LDDST is that it is more sensitive than the ACTH response test particularly in dogs with adrenal tumors, it can differentiate between PDH and ADH in up to 50% of dogs with hyperadrenocorticism, and it does not require ACTH. The LDDST is preferred by many as the primary screening test for diagnosis of hyperadrenocorticism.
