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Hyperadrenocorticism (Cushing's Syndrome) in Dogs

By: Dr. Douglas Brum

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The diagnosis of Cushing's syndrome involves two steps.

  • To determine whether or not Cushing's syndrome is present
  • To determine whether the Cushing's syndrome is pituitary-dependent or adrenal-dependent

    A good medical history and complete physical examination are crucial to establishing a diagnosis. No single laboratory test conclusively establishes a diagnosis of Cushing's syndrome. The diagnosis must be made on the basis of the medical history, physical findings and results of carefully selected laboratory tests and diagnostic imaging procedures. Often, Cushing's syndrome is suspected on the basis of clinical findings, but the diagnosis remains elusive even after completion of appropriate diagnostic tests.

    Diagnostic Tests

  • A complete blood count (CBC) evaluates the red and white blood cells. Some dogs with Cushing's syndrome have what is called a "stress leukogram" due to the effects of high blood cortisone concentration. The term stress leukogram refers to a specific white blood cell distribution in the blood. This distribution includes a high total white blood cell count with increased numbers of neutrophils and monocytes and decreased numbers of lymphocytes and eosinophils. Each of these cells is a different type of white blood cell.

  • The biochemical profile is a useful diagnostic test, because the majority of dogs with Cushing's syndrome have an abnormally high concentration of alkaline phosphatase. The enzyme alkaline phosphatase is produced in the liver in response to stimulation by cortisone or as a consequence of primary liver disease. An abnormally high concentration of alkaline phosphatase is one of the most consistent abnormalities found in dogs with Cushing's syndrome. Other biochemical abnormalities may include mild increases in other liver enzymes (e.g. alanine aminotransferase), mildly increased blood glucose concentration, and high blood cholesterol concentration.

  • The urinalysis also may provide clues to the presence of Cushing's syndrome. Due to the presence of increased water consumption and increased urination, dilute urine often is observed in dogs with Cushing's syndrome. Urine concentration is assessed by a test that measures urine specific gravity that compares the concentration of urine to pure water. Dilute urine is found in approximately 85 percent of dogs with hyperadrenocorticism. Unfortunately, many other diseases also result in dilute urine. Occasionally, protein is present in the urine. Urinary tract infections are common in dogs with Cushing's syndrome, and urine culture should be performed as part of the clinical assessment.

  • Radiographs (X-rays) of the chest are taken to evaluate the dog for evidence of pulmonary infection (pneumonia) or metastatic disease (nodules in the lungs caused by distant spread of an adrenal tumor).

  • Abdominal radiographs (X-rays) are taken to evaluate the adrenal glands for evidence of enlargement or calcification, which may indicate the presence of an adrenal tumor. Malignant adrenal tumors are more likely to be calcified than are benign tumors. Bladder stones also may be observed in dogs with Cushing's syndrome. Hepatomegaly (increased liver size) also is a common finding on abdominal radiographs in dogs with Cushing's syndrome.

  • The urine cortisol-to-creatinine ratio can be used as a screening tool in the evaluation of dogs suspected to have Cushing's syndrome. A negative result strongly suggests that a dog does not have Cushing's syndrome, but a positive test result does not necessarily mean that a dog does have Cushing's disease. False-positive results occur because the stress of non-adrenal illnesses can lead to an abnormal cortisol-to-creatinine ratio. Regardless, the urine cortisol-to-creatinine ratio is a useful and easy screening test because it only requires a single morning urine sample.

  • Abdominal ultrasound examination is much more sensitive than abdominal radiographs in evaluating the animal for adrenal gland enlargement due to hyperplasia or a tumor. Presence of a single enlarged adrenal gland is suggestive of an adrenal tumor. Enlargement of both adrenal glands is suggestive of adrenal gland enlargement (hyperplasia) due to a pituitary tumor. If indicated, a liver biopsy can be obtained by ultrasound guidance and the tissue evaluated by a pathologist for microscopic changes associated with high blood cortisone concentration. The kidneys and bladder also can be evaluated during abdominal ultrasound examination to evaluate for the presence of stones or infection.

    A conclusive diagnosis of hyperadrenocorticism is based on measurement of blood cortisol concentration before and after stimulation with adrenocorticotropic hormone (ACTH stimulation test) or before and after suppression by intravenous administration of a potent cortisone-like drug called dexamethasone (dexamethasone suppression test). An exaggerated response to stimulation with ACTH and lack of suppression after dexamethasone administration are expected when blood cortisol concentrations are measured in dogs with Cushing's syndrome. Measuring a single blood cortisol concentration at rest is of little or no value because blood cortisol concentrations in normal dogs and those with Cushing's syndrome can vary greatly.

  • The ACTH stimulation test works on the principle that the adrenal glands of the dog with Cushing's syndrome are hypersensitive to ACTH. Blood cortisol concentration is measured before injection of the pituitary adrenocorticotropic hormone (ACTH). Depending on the type of ACTH used, a second blood cortisol concentration is determined 1 or 2 hours later. Blood cortisol concentration is expected in increase after ACTH stimulation both in normal dogs and in those with Cushing's syndrome, but the response should be exaggerated in dogs with Cushing's syndrome. The ACTH stimulation test is useful, but it is not definitive. Only approximately 80 percent of dogs with Cushing's syndrome are identified by this test and some dogs with Cushing's syndrome have normal test results (false-negative results). Furthermore, dogs that do not have Cushing's syndrome but have some other stressful non-adrenal illness may have abnormal test results (false-positive results).

    The ACTH stimulation test is also the best method of diagnosing Iatrogenic Cushing's disease. Dogs with the iatrogenic disease will actually have a decreased response to ACTH due to suppression of the production of endogenous (produced within the body) cortisol. This suppression of adrenal cortisol production is caused by the chronic administration of medications containing glucocorticoids.

  • Low dose dexamethasone suppression test. Dexamethasone is a potent steroid hormone similar to cortisone. Even a low dose of dexamethasone should markedly decrease cortisol secretion by the normal adrenal gland as a result of the normal "feed-back" loop to the pituitary gland. Blood cortisol concentration is measured before dexamethasone injection, 4 hours after injection, and 8 hours after injection. In normal dogs, blood cortisol concentrations should be suppressed at both 4 and 8 hours after injection of dexamethasone. Lack of suppression suggests the presence of hyperadrenocorticism. The low dose dexamethasone test identifies most (95 percent) dogs with Cushing's syndrome, but some (5 percent) affected dogs demonstrate suppression (false-negative results) and some dogs with non-adrenal illness will not demonstrate suppression (false-positive results).

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