Cushing's syndrome

Overview 

  • Named after a neurosurgeon who first described the syndrome in people in 1912 

  • Also known as Cushing’s disease or Hyperadrenocorticism (HAC)  

  • Caused by excess cortisol production due to a tumor in either the pituitary gland or adrenal gland  

  • Treated through medication, surgery or radiation 

How do cortisol levels affect how the body operates? 

Cortisol is produced by the adrenal glands, and it is essential for regulating processes such as metabolism, stress response and immune function. 

A dog’s body has two adrenal glands, each located near a kidney, and each adrenal gland has two main parts: 

  • Cortex: produces cortisol and other hormones 

  • Medulla: produces adrenaline  

What are the signs of Cushing’s syndrome? 

Behavior changes  

  • Increased drinking (polydipsia) and increased urination (polyuria), which occur in 80-90% of cases 

  • Increased appetite (polyphagia) 

  • Increased panting   

  • Lethargy  

Changes in appearance  

  • Pot belly (enlarged abdomen) 

  • Hair loss (symmetrical alopecia) 

  • Thinning of the skin  

  • Calcification of the skin (calcinosis cutis)   

Associated medical conditions  

Types of Cushing’s syndrome 

There are two common forms of this disease: 

Pituitary-dependent (80-85% of all cases) 

  • A small, benign tumor (adenoma) of the pituitary gland in the brain starts producing an excess of the hormone ACTH, which then stimulates the adrenal glands and makes them produce an excess of cortisol.  

Adrenal-dependent 

  • A tumor of one or both adrenal glands, resulting in excess cortisol production  

    • Benign (adenomas): 50% 

    • Malignant (carcinomas): 50%  

    • Possibility of spreading to other organs (14-50% of cases) 

A third form results from administering cortisol as a medication, and this type is known as Iatrogenic Cushing’s syndrome.  

What dogs have the greatest risk? 

Breed predisposition 

  • Pituitary-dependent (predominantly smaller breeds): Bichon Frise, Border Terrier, Jack Russell Terrier, Lhasa Apso, Miniature Schnauzer, Staffordshire Terrier (American/Bull), Yorkshire Terrier, Miniature Poodles, Dachshunds and others 

  • Adrenal-dependent (predominantly larger breeds): Staffordshire Terrier (American/Bull) and German Shepherd  

  • Breeds least likely to be affected: Golden Retriever, Labrador Retriever, Border Collie and Cocker Spaniel 

Age 

Middle-aged to older dogs 

Sex

No confirmed difference between males and females 

Diagnosis  

Your dog should have a combination of behavioral and physical signs listed above, and the final diagnosis will depend on both the presentation of clinical signs and the results of extensive testing. 

Your vet will want to do the following tests to assess your dog’s overall health: 

  • Complete blood count (CBC) to look at blood cells 

  • Chemistry panel to assess organ health 

  • Urinalysis to assess kidney function and screen for urinary tract infection 

More advanced testing may include the following: 

  • Chest X-rays if your dog is experiencing breathing issues and to screen for cancer 

  • Abdominal ultrasound to assess adrenal gland size and shape, examine the rest of the abdominal organs (e.g. liver, gall bladder) and check for other tumors 

  • Blood pressure measurement 

  • Urine culture and sensitivity (to confirm a urinary tract infection) 

Specific adrenal gland function testing (multiple tests may be necessary): 

  • Low Dose Dexamethasone Suppression Test (LDDST)  

    • Preferred screening test for Cushing’s syndrome (in most cases)  

  • High Dose Dexamethasone Suppression Test (HDDST)  

    • Used to help distinguish between the two most common forms  

  • Other screening tests:  

    • ACTH Stimulation Test 

    • Urine Cortisol: Creatinine Ratio (UCCR)  

    • Measurement of blood ACTH level 

How is it treated? 

Underlying conditions must be addressed in addition to the effects caused by the disease itself. 

Pituitary-dependent treatments 

  • Trilostane (trade name: Vetoryl)  

    • FDA-approved oral medication  

    • Decreases production of cortisol 

    • Possible side effects include decreased appetite, vomiting, diarrhea, lethargy, adrenal gland destruction and death 

    • Requires diligent monitoring  

  • Mitotane  

    • “Off-label” oral medication  

    • Destroys adrenal cells that produce cortisol; potentially reversible 

    • Possible side effects include decreased appetite, vomiting, diarrhea, weakness, irreversible destruction and death 

    • Requires diligent monitoring  

  • Selegilene (trade name: Anipryl)  

    • Questionable efficacy  

    • No longer recommended  

  • Radiation therapy of the pituitary tumor   

    • Has been used successfully with larger tumors (macroadenomas) 

    • Expensive 

    • Limited availability  

  • Surgical removal of the pituitary tumor  

    • Has been performed successfully 

    • Expensive 

    • Limited availability 

    • Possible complications 

Adrenal-dependent treatments 

  • Surgical removal of the adrenal tumor (adrenalectomy)  

    • Preferred treatment whenever possible 

    • Complicated procedure, requires close monitoring after the operation  

    • Potentially serious complications (e.g. hemorrhage, death) 

    • Smaller tumors have better outcomes  

  • Medical therapy  

    • Prior to surgery to improve the patient’s condition 

    • Used when surgery is not an option  

    • Can improve clinical signs but the tumor remains unchanged 

    • Trilostane 

    • Mitotane 

How should you evaluate different courses of treatment? 

Treatment is typically pursued when the clinical signs start affecting a dog’s quality of life, and also when it’s necessary to reduce the complications associated with Cushing’s syndrome. 

It’s important to talk with your veterinarian about how to weigh the risks of surgery or the possible side effects of available medications. Financial constraints may also impact the course of treatment. 

What is the prognosis for Cushing’s syndrome? 

General prognosis 

With an accurate diagnosis, appropriate treatment and monitoring, Cushing’s syndrome can be very well managed. Many of your dog’s abnormal signs will show improvement within a few weeks, but improvements in their skin and haircoat may take several months. 

Pituitary-dependent prognosis 

Medical therapy with trilostane or mitotane has an average survival time of 2 to 2.5 years. 

Surgical removal or radiation of the pituitary tumor has an average survival time of 2 to 5 years. 

Adrenal-dependent prognosis 

Surgery has a 10-25% risk of mortality, and with the surgical removal of the adrenal tumor, patients’ average survival time is 1.5 to 4 years. 

Medical therapy with trilostane or mitotane has an average survival time of 1 year.