Cushing's disease, results from excessive cortisol in the bloodstream and the symptoms all stem from long-term over-exposure to this hormone.

The adrenal glands, located above the kidneys, store and release cortisol in times of stress. If the body is exposed to this hormone for prolonged periods of time instead of during short stressful periods only, it can be debilitating.

Normally, the pituitary gland (located at the base of the brain) detects when cortisol levels in the blood are decreasing. In response, the pituitary secretes a stimulating substance, called ACTH, which causes the adrenal gland to release more cortisol. When the pituitary gland detects that cortisol levels are again appropriate, it stops its stimulatory message.

There are several mechanisms that can lead to Cushing’s syndrome:

Pituitary-Dependent Cushing's
Accounts for 85% of dogs with Cushing's disease. The pituitary gland grows a small tumor. The tumor is generally too small to cause any trouble due to its size and it is usually benign. This tumor causes an over production of ACTH, resulting in over-stimulated and enlarged adrenal glands that produce excess cortisol. Occasionally, these benign pituitary tumors are large enough to compress the brain causing neurological signs.

Adrenal-Dependent Cushing's
Occurs in 15% of dogs with Cushing's disease. An adrenal tumor is directly over-producing cortisone. The tumor is often large enough to see with radiographs or ultrasound and may be malignant. There is very little or no production of ACTH from the pituitary gland and as a result the opposite adrenal gland is usually atrophied/small.

Iatrogenic Cushings
Occurs with long term therapy with drugs containing corticosteroids.

Clinical Signs

  • Excessive drinking and urinating
  • Urinary incontinence
  • Increased or even Ravenous Appetite
  • Pot-bellied Appearance: This symptom, seen in over 90% of dogs with the disease.
  • Muscle Weakness: Muscle protein is broken down in Cushing’s syndrome. The result may be seen as exercise intolerance, lethargy, reluctance to jump up on furniture or climb stairs.
  • Skin Disease: The classical signs of endocrine (hormonal) skin diseases are:
    1. Hair loss on the main body sparing the head and legs
    2. Thin, wrinkled skin with poor wound healing
    3. Hair that does not grow back after clipping.
    4. Blackheads and darkening of the skin, especially on the abdomen.
    5. Persistent or recurring skin infections
    6. Another condition of the skin that may be observed is called calcinosis cutis, in which calcium deposits occur within the skin. These are raised, hard, almost rock-like areas that can occur almost anywhere on the body.
  • Other symptoms include: excessive panting and shortness of breath and high blood pressure. As the disease advances, untreated Cushing's disease puts a dog at risk for serious problems such as bladder stones, diabetes mellitus and pulmonary thromboembolism.


Diagnostics
General blood work will have certain indicators to suspect Cushings disease.
  • Some white blood cells will be increased while others are decreased.
  • Elevated liver enzymes especially serum alkaline phosphatase.
  • Elevated Cholesterol
Urinalysis often indicates infection and dilute urine.

Once Cushing’s is suspicious further diagnostics are then performed to confirm the disease. These test measure serum cortisol levels before and after an injection of ACTH and dexamethasone. CT and MRI can also be used to visualize tumors on the pituitary and adrenal gland. Ultrasound can be used to evaluate the size and symmetry of the adrenal glands or if an adrenal mass if present.
  • The Urine Cortisol/Creatinine Ratio
    This is a screening test for Cushing's disease. A positive test here does NOT confirm disease, but a negative test DOES rule it out.
  • The Low Dose Dexamethasone Suppression Test
    Dexamethasone is a cortisone-type hormone that is used therapeutically for numerous conditions. When given dexamethasone, the dog's pituitary gland will perceive that there is a steroid and shut off its stimulatory message to the adrenal glands. In the normal animal, this means that a drop in blood cortisol level will be seen 8 hours after a tiny dose of dexamethasone is given intravenously. If there is a pituitary tumor, the pituitary gland does not shut off its stimulatory message and it ignores the dexamethasone. No drop in cortisol level is seen at the end of eight hours.
  • The ACTH Stim Test
    In this test, a dose of ACTH is given to the patient. If a larger than expected rise in cortisol levels is measured in 2 hours, we may diagnose Cushing's syndrome.


Once a pet has been confirmed as having Cushing’s syndrome, the next step is to determine which form of Cushing’s syndrome the pet has since treatment is different for each form.

Treatment
Pituitary dependent cushings is treated with Trilostane. The medication acts on the adrenal glands to selectively suppress the production of cortisol. The drug protocol is complex and requires close veterinary monitoring. Radiation therapy is also available, but the cost is high. The average life span with medical treatment is about 2-3 years, although longer survival is possible. Benign and malignant tumors of the adrenal glands can be surgically removed in some cases. However, due to the complexity and surgical risk, most patients are treated with oral medication. Iatrogenic Cushing’s is often reversible if the causative drug can be tapered and, preferably, discontinued.