Hyperadrenocorticism

Hyperadrenocorticism or Cushing's syndrome is caused by excessive levels of cortisol in the blood. The aetiology can be either iatrogenic or endogenic:

• PITUITARY-DEPENDENT (80% of cases). Excessive ACTH production stimulates the adrenal glands, causing increased cortisol secretion.
• ADRENAL-DEPENDENT (20% of cases).
  The adrenal glands increase the secretion of cortisol without prior stimulation.
• IATROGENIC (rare in cats). Induced by prolonged administration of glucocorticoids.

Symptoms

Interpretation of laboratory tests

General Tests

• Complete blood count: Stress leukogram (rare in cats) - Leucocytosis (30%) with relative lymphopaenia, neutrophilia, monocytosis and eosinophilia (85%). Monocytosis is rare in cats.
• Blood biochemistry: ALP values are between 4 and 20 times higher than normal (more moderate increase in cats). GPT, GGT, TRI, Cholesterol, GLU are elevated. Elevated glucose levels in cats are important. BUN and CRE decrease.
• Urine test: Urine-specific gravity in dogs is < 1006, but is normal in cats. Ketonuria and glucosuria are also detected (very important in cats).

Specific tests

All tests are performed after the animal has fasted for at least 12 hours.

The results should always be consistent with the findings of the clinical history and complete examination.

Tests may give spurious results if the animal is under stress, suffers from other diseases such as diabetes mellitus or is receiving anticonvulsants or corticosteroids.

Most urine tests determine blood cortisol levels. Baseline cortisol values have little relevance per se, since levels vary throughout the day.

• Low-dose dexamethasone suppression test:
  The test has a sensitivity of 90% for pituitary-dependent hyperadrenocorticism and practically 100% for adrenal-dependent hyperadrenocorticism. This, together with the availability of dexamethasone, makes it the first choice.
  Take a preliminary blood sample and determine baseline cortisol levels.
  • Dogs: 1.08 - 7.80 µg/dL.
  • Cats: 0.80 - 5.50 µg/dL.
  Inject 0.01 mg/kg iv dexamethasone.
  Collect a second blood sample 8 hours later.
  Normal: Cortisol secretion reduced to < 1.5 µg/dL.
  Hyperadrenocorticism: Cortisol secretion is not inhibited and therefore levels do not fall to < 1.5 µg/dL.
  If another sample is drawn after 3 hours, cortisol will be 50% lower than the baseline value. In animals with Cushing's disease it does not decrease at all, or a slight decrease indicates a pituitary aetiology. The test is less reliable in cats, since cortisol is hardly suppressed in healthy animals (less sensitive to dexamethasone-induced suppression). Cats with severe non-adrenal pathologies may not show any suppression.
• • ACTH stimulation test:
  This is performed for several reasons: the results of the previous test are inconclusive; treatment needs to be followed up; or to diagnose iatrogenic Cushing's. It has a sensitivity of 85% for pituitary-dependent hyperadrenocorticism and 50% for the adrenal-dependent form. In cats, it gives more reliable results than the dexamethasone test.
  Inject 0.125 mg iv ACTH in cats and dogs weighing less than 5 kg and 0.25 mg iv in dogs weighing more than 5 kg. In dogs, draw a blood sample after 1 hour. In cats, draw a blood sample after 30 - 60 minutes.
  • Dogs:
    Normal - cortisol levels 2 to 3 times higher than baseline, but < 21.72 µg/dL.
    Hyperadrenocorticism - extremely high increase over baseline values > 21.72 µg/dL.
  • Cats:
    Normal - cortisol levels 2 to 3 times higher than baseline, but < 15.2 µg/dL.
    Hyperadrenocorticism - extremely high increase over baseline values > 15.2 µg/dL.
    Iatrogenic Cushing's - very low baseline values (< 1µg/dL) that do not increase post-ACTH.
• High-dose dexamethasone suppression test:
  nce hyperadrenocorticism has been diagnosed, this test determines whether it is pituitary- or adrenal-dependent. The test has a sensitivity of 85% for pituitary-dependent hyperadrenocorticism and between 95% and 98% for adrenal-dependent hyperadrenocorticism.
  The protocol is the same as the low dose test, but 0.1 mg/kg iv dexamethasone is injected.
  • Pituitary-dependent: < 1.5 µg/dL at 8 hours.
  • Adrenal-dependent: > 1.5 µg/dL at 8 hours.
  If an additional sample is drawn at 3 hours, a decrease of 50% below the baseline value will be observed in animals presenting pituitary-dependent hyperadrenocorticism, but not in the adrenal-dependent form.
• Plasma ACTH levels:
  Used to determine the aetiology of Cushing's or as a diagnostic aid in inconclusive cases.
  Contact the laboratory.
• Urinary cortisol:creatinine ratio
  Useful for ruling out hyperadrenocorticism, and also for strengthening a previous diagnosis, depending on the results. Urine should be collected in the home to avoid false positives caused by stress.
  Contact the laboratory.

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