Cushing's Disease and Lysodren (Mitotane)

Cushing's Disease is a uncommon condition in older dogs, often mistaken for the aging process itself.  Yet Cushing's disease is treatable, and that treatment can result in a longer, more comfortable life for the dog and its owner.


Cushing's Disease is a fairly rare endocrine diseases of dogs

An endocrine disease is a disease affecting one of the many glands that make hormones.  Hormones are chemicals that the body makes to regulate itself.  A more common example of an endocrine disease would be diabetes.  When the pancreas goes bad, not enough insulin is produced, and we have an abnormal hormonal condition known as diabetes.

In the case of Cushing's Syndrome, the hormone in question is cortisol.  Cortisol is a hormone made by the adrenal glands.  In patients with Cushings Syndrome, too much cortisol is produced.  This abnormal condition is also called hyperadrenocorticism, which we call Cushing's Syndrome for short.


Cushing's Disease has many symptoms

Cortisol has many target tissues, and it affects each target tissue in a different way.  Thus, we see many different symptoms in Cushing's Syndrome.

  • increased/excessive water consumption (polydipsia)
  • increased/excessive urination (polyuria)
  • urinary accidents in previously housetrained dogs
  • increased/excessive appetite (polyphagia)
  • sagging, bloated, pot-bellied appearance
  • weight gain or its appearance, due to fat redistribution
  • loss of muscle mass, giving the appearance of weight loss
  • bony, skull-like appearance of head
  • exercise intolerance, lethargy, general or hind-leg weakness
  • excess panting, seeking cool surfaces to rest on
  • symmetrically thinning hair or baldness (alopecia) on torso
  • other coat changes like dullness, dryness
  • slow regrowth of hair after clipping
  • thin, wrinkled, fragile, and/or darkly pigmented skin
  • easily damaged/bruised skin that heals slowly
  • hard, calcified lumps in the skin (calcinosis cutis)
  • susceptibility to infections (especially skin and urinary)
  • diabetes, pancreatitis, seizures

There are also some other signs of Cushing's Syndrome that are only evident on blood tests.  We see elevations in liver enzymes (ALP, ALT, and AST), decreased thyroid levels, a stress leukogram, and high blood pressure.  There are so many different symptoms of Cushing's Disease that it is actually very uncommon for any one patient with Cushing's Disease to show all the symptoms at the same time.


It can be quite difficult to diagnose Cushing's Syndrome

There are four different tests that can be used to test for Cushings' Disease:  the ACTH stimulation test, the Low-Dose Dexamethazone Suppression test, the High-Does Dexamethazone Suppression test, and the Urine Creatinine:Cortisol Ratio test.  Which one to use is a very complex decision, and involves both the art and the science of veterinary medicine.  It may take two different tests to become relatively sure our patient has Cushing's Disease.  Like many things in life, there are no sure things, and we may never be 100% sure that a patient has or doesn't have Cushing's Disease.  We use our best judgement combined with common sense and a healthy dose of caution and treat the way we feel is best for the patient.


Cushing's Syndrome can be treated with a drug called Mitotane

Although Trilostane is the current preferred medication for Cushing's Syndrome, for some patients Mitotane might work best.

Mitotane is not a nice drug.  It is fairly expensive, and has the added benefit of being somewhat toxic.  Mitotane selectively targets the adrenal glands, which is just the ticket if they are making too much cortisol.  The goal is to remove just enough adrenal tissue to restore the cortisol levels to normal.  The trick is getting the just enough part right.  Every individual is different, and each requires a different dose.

Mitotane is started at a high dose given twice a day until enough adrenal tissue is gone to allow the cortisol levels to return to normal.  This is called the induction dose, and for most dogs it can take anywhere from5 to 9 days.  However, some will be finished with indiction in 3 days, and some will take longer than 10.  It is best to start Lysodren therapy on a Sunday to minimize the chances of having problems on a weekend.

It takes careful observation to tell when a patient has reached the end of the induction phase.  Dogs that get treated for Cushing's Disease are drinking a lot of water, and they have a voracious appetite.  When the water consumption OR the appetite decrease, we have reached the end of the induction phase.  We are not talking about major changes, either.  A slight decrease in appetite, say where the dog still eats well but does not wolf the food down like he did before is enough.  If you have any questions at all about whether your dog has reached the end of the induction phase, please call immediately and discuss your observations with the veterinarian. If your dog has not responded to Mitotane therapy by eight or ten days, we will need to examine him and perform the ACTH stimulation test to see what is going on.


There are serious consequences for over-shooting the induction phase end-point

If we over-shoot the end-point, we will see signs of toxicity.  Sings of toxicity include lethargy, staggering or incoordination, weakness, loss of appetite, vomiting, and/or diarrhea.  If you see any of these symptoms, call the veterinarian immediately.  We often send home a small supply of a drug called prednisone.  This is a rescue drug that can be given if we have signs of toxicity.  Give the prednisone only if the veterinarian directs you to give it.


When we think we have reached the end of the induction phase, we do an ACTH stimulation test

If the test shows good control, we will enter the maintenence phase.  In the maintenance phase, Mitotane is given at a much lower dose two days a week. It is still a good idea to give it just after a meal.  We will need to do an ACTH Stimulation test 1 month after starting maintenence to make sure we are doing well.  The ACTH Stimulation test needs to be repeated in 3 months, then every 4 to 6 months after that.  Cushing's Syndrom patients will also need other labwork done at least annually.


If signs of toxicity develop

If signs of toxicity develop, such as lethargy, staggering or incoordination, weakness, loss of appetite, vomiting, and/or diarrhea, give a rescue dose of prednisone and contact the veterinarian immediately.  Similarly, be sure and notify the veterinarian if signs of increased water consumption or increased appetite develop.


The prognosis for dogs with Cushing's Disease is good with treatment

We expect symptoms of Cushing's to fully resolve over the course of 4-6 months. Excess drinking and urinating abate quickly. It may take several months for hair and coat improvement to be observed. Dogs generally are more comfortable after the disease is under control and may live happily for years. However, Cushing's disease is managed, not cured, and maintaining a dog with Cushing's disease requires vigilance and commitment on the part of the owner, as well as on-going testing.

Left untreated, Cushing's disease will progress. As excess cortisol is immunosuppressive, Cushingoid dogs are prone to various infections. They are also predisposed to developing hypothyroidism, pancreatitis, diabetes, seizures, hypertension, congestive heart failure, blood clots, and liver and kidney failure. It should not go without noting that many of these dogs are at risk of early euthanasia due to incontinence resulting from increased water consumption.  Although the treatment for Cushing's Disease is not without it's own problems, the treatment is much better than the disease, and treatment will prolong the patient's life and improve the quality of life as well.


Cushing's Syndrome is not an inexpensive condition

The last time I checked, which was October of 2015, Mitotane cost a little over $10.00 per pill.  If everything goes perfectly, starting a 20-pound dog on Mitotane and continuing for one year will cost about $700 between testing and medications.  For an 80-pound dog, it will cost over $3,000 a year.