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Cushing's Disease (Hyperadrenocorticism)
Cushing's Disease (Cushing's Syndrome), named after a Boston surgeon who first described the disease in people, is caused by elevated concentrations of circulating cortisol. It usually occurs in middle aged to older dogs, however, exceptions may occur. Normally, the pituitary gland produces a hormone, adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal gland to produce cortisol, a glucocorticoid. But if things get out of whack in either the pituitary or adrenal gland, too much cortisol may be produced causing Cushing's Disease.
Causes:
  1. Spontaneous (80-85% of cases)-the adrenal cortex (outer part of adrenal gland) produces excess cortisol (corticosteroid) due to a small tumor on the pituitary gland which causes the excess production of ACTH. This is also called Pituitary Dependent Hyperadrenocorticism (PDH).
  2. Adrenal adenoma or carcinoma (15-20 % of cases)-tumor of the adrenal gland. Approximately one half are malignant.This type is more common in female dogs.
  3. Iatrogenic-excessive administration of glucocorticoids (steroids)
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Signs and symptoms: These will vary greatly depending on the amount of excess cortisol and the length of the illness.
  1. increased water consumption (polydipsia)
  2. increased urination (polyuria)
  3. enlarged liver
  4. hair loss--usually symmetrical and on the trunk
  5. thinning of the skin
  6. pot-bellied appearance
  7. lethargy
  8. muscle weakness and wasting
  9. anestrus
  10. obesity
  11. excessive panting
  12. testicular atrophy
  13. facial nerve palsy
  14. hyperpigmentation or depigmentation
  15. scaling
  16. wounds healing slowly
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Screening Tests

  1. ACTH Stimulation Test-screening test -patients with hyperadrenocorticism will show an elevated cortisol response to the administration of ACTH

  2. Low-Dose Dexamethasone Suppression Test (LDDST)

  3. Urinary Cortisol-Creatine Ratio-high ratio with Cushing's Disease

  • Lack of suppression--Cortisol production is not suppressed and levels remain above 1 ug/dl is consistent with Cushing's disease.
  • Suppression--Cortisol values that drop at 4 hrs and then increase to above 1 ug/dl at 8 hrs is consistent with PDH.
  • Escape from suppression--Levels of cortisol < 1 ug/dl at both the 4 and 8 hr testing suggests that Cushing's disease is not the problem.

  1. Note--False positive screening tests may occur in dogs with non-adrenal diseases e.g.,

    • diabetes mellitus
    • liver disease
    • renal disease

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Definitive testing to differentiate Pituitary Dependent from Adrenal Tumor Hyperadrenocorticism

  1. High-Dose Dexamethasone Suppression Test (HDDST)
    • Lack of suppression--Cortisol production is not suppressed and levels remain above 1.5 ug/dl is diagnostic for an adrenal tumor.
    • Suppression--If any cortisol value during the 8 hr testing falls below 1.5 ug/dl. This is consistent with PDH in 75% of dogs tested.
  2. Plasma ACTH Concentration
    • Normal to high--PDH
    • Low-adrenal tumor
  3. CRH Rsponse Test
    • Exaggerated plama cortisol response--PDH
    • No change in plasma cortisol level-adrenal tumor
Flow Chart of Cushing's Diagnosis from Auburn University College of Veterinary Medicine Endocrine Diagnostic Service

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Treatment:

  • Surgery--Not an option for pituitary tumors, but is a possibility for adrenocortico adenoma and small carcinoma if the dog is in otherwise good health and the tumor is benign. Malignant adrenal tumors that have already spread are poor surgical risks and medical management may be preferred. For pituitary tumors, radiation therapy has been used with success when the tumor is less than 15 mm in diameter. However, the radiation therapy will not be available at all clinics.

  • Medical management of Cushing's due to adrenal tumors uses a higher dose Lysodren than what is administered for PDH. The higher dosage usually causes more side effects.
For a more complete description of Cushing's disease treatments/options, please see the Cushing’s Syndrome Informational Website on the Mar Vista Animal Medical Center site.

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References:
  1. Tilley, LP, Smith, FWK, The 5 Minute Veterinary Consult, Canine and Feline. 1997, Williams & Wilkins.
  2. Mordecai Siegal (Ed.) The UC Davis Book of Dogs. 1995, HarperCollins Publishers.
  3. Bonagura, JD (ed.) Kirk's Current Veterinary Therapy XIII Small Animal Practice. 2000,W. B Saunders Company.
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Last updated: Tuesday, October 13, 2009
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