Hyperadrenocorticism

Hyperadrenocorticism or Cushing's syndrome is a condition associated with an excess of circulating cortisol. Three endogenous etiologies and one iatrogenic cause are distinguished:

• PITUITARY ORIGIN (80% of cases). There is a lesion in the pituitary gland (adenoma or pituitary hyperplasia); these are tumors that secrete an excess of ACTH, stimulating cortisol secretion by the adrenal cortices and causing bilateral adrenal hyperplasia. The feedback mechanism of ACTH secretion by cortisol is lost.
• ADRENAL ORIGIN (10-20% of cases). These are generally unilateral (affecting a single adrenal gland), causing an excess of cortisol (independent of ACTH). High cortisol levels result in a feedback inhibition with very low ACTH levels, leading to atrophy of the contralateral (unaffected) gland.
• ADRENAL AND PITUITARY ORIGIN (5% of cases). There is a pituitary lesion and a cortisol-secreting adrenal tumor, which is rare (lesions are observed in both locations).
• IATROGENIC. Excessive and prolonged administration of corticosteroids.

Clinical Signs

1. Very frequent
2. Different from bilateral alopecia in hypothyroidism, where the skin is thicker

Interpretation of Laboratory Results

General Tests

• Complete Blood Count: Leukocytosis (30%) with relative lymphopenia, neutrophilia, monocytosis, and eosinophilia (85%).
• Blood Biochemistry:
  • ALP increases 4 to 20 times above normal.
  • Increased ALT, GGT, triglycerides, cholesterol.
  • Increased glucose.
  • Decreased urea and creatinine due to hyposthenuria.
• Urinalysis: Specific gravity in dogs is < 1.006. Ketonuria and glucosuria may also appear.

Specific Tests

Results must always correlate with a clinical history, a thorough examination, and compatible imaging diagnostics.

Tests may yield erroneous results if the animal is under stress, has other conditions such as diabetes mellitus, or is receiving medications like anticonvulsants or corticosteroids (for the latter, treatment must be suspended for at least 30 days before performing any adrenal function test).

Baseline cortisol levels have little relevance on their own as concentrations vary throughout the day.

• Low-dose dexamethasone suppression test with three cortisol measurements (sensitivity: 85-97% / specificity: 44-73%). This is the most sensitive test for diagnosis.
  Cortisol levels are measured at baseline, 4 hours after intravenous administration of dexamethasone (0.01 mg/kg), and at 8 hours. In healthy dogs, cortisol levels will decrease (< 1.5 µg/dL); in dogs with HAC, cortisol levels remain elevated.
  This test also differentiates between pituitary and adrenal HAC. In pituitary HAC, most dogs exhibit an "escape pattern," with low cortisol at 4 hours followed by high cortisol at 8 hours, as well as levels at 4 and 8 hours lower than 50% of the baseline value but above 1.5 µg/dL at 8 hours.
• Cortisol/creatinine ratio:
  Cortisol is excreted in urine, and its elimination increases in HAC cases, but it is not very specific.
• ACTH stimulation test with two cortisol measurements (sensitivity: 50-80% / specificity: 60-80%).
  Baseline cortisol and post-ACTH cortisol levels are determined 60-90 minutes after ACTH administration. A dose of 0.125 mg/animal is used for animals under 5 kg, and 0.25 mg/animal for those over 5 kg, intramuscularly. If synthetic ACTH is used, the dose is 0.02 ml/kg.
  Elevated post-ACTH cortisol levels confirm the diagnosis of Cushing's syndrome. However, levels must be 3 times higher than baseline cortisol to be compatible with Cushing's.
  This test is preferably used for Cushing's monitoring. For treatment follow-up, baseline cortisol is measured, trilostane is administered, 4 hours are waited, ACTH is administered, and 60-90 minutes are waited for the second blood draw to measure post-ACTH cortisol.
  Complete monitoring (physical exam, electrolytes, analysis, and ACTH test) should be performed at one week, one month, three months, and every six months.

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