What You Should Know About Cushing’s Disease

What is Cushing’s Disease?

Cushing’s disease is an endocrine disorder caused by an increase of cortisol secretion from the adrenal glands. In a healthy pet, stress will trigger the brain to release a series of hormones that instruct the adrenal glands to release cortisol. Once blood cortisol concentrations reach a certain level, cortisol applies negative feedback to the brain to stop the release of these hormones restoring balance. This is known as the hypothalamic pituitary adrenal axis or HPA axis. 

More specifically the hypothalamus, a small region in the brain releases the hormone corticotropin-releasing factor (CRF), which signals the pituitary gland, a pea sized gland at the base of the brain to release adrenocorticotropic hormone (ACTH). The adrenocorticotropic hormone binds to the adrenal cortex stimulating the release of cortisol. Once a certain blood cortisol concentration is reached, cortisol applies negative feedback to the  hypothalamus and pituitary gland stopping the release of the hormones, CRF and ACTH therefore restoring homeostasis. 

Cortisol serves an important purpose as it regulates a lot of body processes. It regulates metabolism and the immune response, as well as providing glucose, an immediate energy source to fuel the body’s “fight or flight” response or “survival mode” when in danger. 

Three Possible Causes

  1. Pituitary dependent Cushing’s (PDH) is caused by a tumor (typically a microadenoma) in the pituitary gland. Around 85% of dogs with Cushing’s disease are diagnosed with the pituitary dependent form.
  2. Adrenal dependent Cushing’s (ADH)  is caused by an adrenal gland tumor. 
  3. Iatrogenic Cushing’s is caused by long term, frequent administration of steroids.

Clinical Symptoms Include…

  • Polyuria/Polydipsia (increased urination + thirst)
  • Increased hunger
  • Symmetrical alopecia (hair loss) – especially around the sides of chest or abdomen
  • Panting 
  • Pendulous abdomen
  • Calcinosis cutis – buildup of salt deposits in the skin causing red raised lesions 
  • Lethargy
  • Anorexia
  • Circling
  • Ataxia (impaired coordination/balance)
  • Seizures 
  • Skin fragility syndrome (cats only) – skin becomes thin, weak and can easily slough off with little force

How is Cushing’s Disease Diagnosed?

There are several screening tests available used to diagnose Cushing’s disease. There is no perfect test and false positives and false negatives are not uncommon depending on the type of test. Therefore, a couple different tests may be required in order to obtain a positive diagnosis of Cushing’s disease and differentiate the type. 

 Urine Cortisol/Creatinine Ratio

A test performed on a urine sample that can rule out Cushing’s if test results are within normal limits, but can not definitely diagnose if positive as the urine cortisol/creatinine ratio can be elevated in dogs that don’t have adrenal disease. 

 ACTH Stimulation Test 

A baseline blood sample is taken followed by an IV injection of Cortrosyn, a synthetic derivative of adrenocorticotropic hormone. Another sample is obtained 1 hour after administration. Typically, a patient with Cushing’s disease will have an exaggerated response. This test does not differentiate between pituitary dependent and adrenal dependent Cushing’s disease. It is most useful for diagnosing iatrogenic Cushing’s in dogs as they typically have little to no response.

 Low Dose Dexamethasone Suppression Test (LDDST)

This is the preferred diagnostic test for Cushing’s disease. A baseline blood sample is obtained followed by an IV dose of dexamethasone. At 4 and 8 hours post administration, another blood sample is obtained to evaluate the change in blood cortisol concentration in response to the dexamethasone injection. 

Typically dogs with PDH either show suppression or no suppression at 4 hours depending on their sensitivity to the dexamethasone dose and no suppression at 8 hours. This is because dogs with PDH clear dexamethasone from circulation in less than 8 hours compared to 12 hours in a healthy patient. PDH can be diagnosed if suppression followed by an escape occurs. 

Dogs with ADH act independently of ACTH and do not show suppression. 

Compared to the ACTH stimulation test, LDDST has less false negatives, but more false positives.

 High Dose Dexamethasone Suppression Test (HDDST)

This test is very similar to the LDDST, however a much larger dose of dexamethasone is administered. This test is primarily used to differentiate the PDH from ADH type. This dose of dexamethasone is strong enough to cause suppression at 4 and 8 hours in most dogs with PDH but rarely causes suppression in dogs with ADH.  

Ultrasound of Adrenal Glands

An ultrasound of the adrenal glands is indicated for suspected adrenal tumors. In ADH, one adrenal gland is typically enlarged, while the other is much smaller or undetectable. In pituitary  dependent Cushing’s disease, both adrenal glands may look normal or enlarged.

Treatment Options

The pituitary dependent form is treated with oral medications, including the preferred medication mitotane (Lysodren) or trilostane (Vetoryl). The preferred, most effective method of treating the adrenal dependent form is surgical removal of the defective adrenal gland. For iatrogenic cases, tapering doses of steroids is typically effective.


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