o,p’ -DDD Treatment of Pituitary Cushing’s Syndrome

Hyperadrenocorticism (Cushing’s Syndrome) refers to a clinical
condition that results from having excess cortisone in the
system. A minority of dogs with this disease have a tumor in one
of the two glands that produce cortisone (the adrenal glands).
Your dog, like more than 80 per cent of dogs with the naturally
acquired form of this disease, has a small tumor at the base of
the brain in an area called the pituitary gland. The pituitary
gland controls adrenal function. A tumor in the pituitary can
cause excess demand for cortisone production, which, in turn,
causes excess cortisone throughout the body and results in
symptoms recognized by owners (“pituitary-dependant” Cushing’s
syndrome). The most common symptoms of Cushing’s syndrome in
dogs include excess urination and water consumption, a voracious
appetite, hair loss, muscle weakness, a “potbellied” appearance,
panting, thin skin, and lethargy.

Virtually all dogs with Cushing’s syndrome have at least one or
two of these signs, but it would be uncommon for a dog to have
all of these symptoms. By evaluation a variety of test results,
your veterinarian has diagnosed your dog as having a pituitary-
dependant Cushing’s. Now treatment with o,p’ -DDD has been
recommended.

During World War II, scientists did research on the insecticide
DDT in an attempt to create an extremely toxic form. One of the
forms of DDT created was o,p’ -DDD (Lysodren; mitotane), a
chemical that can destroy the cortisone-producing cells of
adrenal glands in dogs. The drug has been used successfully in
thousands of dogs with Cushing’s, but you must remember that it
is a “poison” and that it must be used appropriately. The
protocol we use in treating dogs with this drug is
straightforward.

A day or two before starting treatment, begin feeding your dog
one third of its normal food allotment twice daily (each 24
hours it should receive a total of two thirds of the normal
amount). This should make your dog even more hungry, but this is
just for a brief time (we do not recommend use of this drug in
dogs with a poor appetite). After 1 to 2 days of reduced
feeding, begin giving the o,p’ -DDD at a dose of 25 mg/kg of
body weight twice daily (a dog weighing 22 pounds would receive
one half tablet twice daily; the tablets contain 500mg). The
drug should be given immediately after the dog eats. So, feed
the dog, note how long it takes to finish the meal, and then
give the medication (the drug is absorbed best from a stomach
containing food).

The key to treating these dogs is watching them eat and knowing
when to stop giving the o,p’-DDD. As long as their appetite is
ravenous, give the medication. As soon as you see any reduction
in appetite, STOP giving the drug. Reduction in appetite may be
noted as the dog taking longer to finish the meal; eating half
of the food, wandering away for a drink, and then finishing; or
simply looking up at the owner once or twice before finishing.
In other words, we do not want the dog to stop eating entirely,
we wish to see a “reduction” in appetite as a signal to stop the
medication. Other signals include reduced water intake,
vomiting, diarrhea, and listlessness, but appetite reduction
usually precedes these more worrisome symptoms. Most dogs
respond to this drug in 5 to 9 days, a few respond in as little
as 1 to 3 days, and some may take longer than 14 days.

No dog should receive o,p’ -DDD for more than 8 days without
being tested for the effect of the drug. The test is done by you
veterinarian and takes 1 to 2 hours. We typically start the
treatment on a Sunday and plan the recheck test 8 days later
(Monday), and more than 85 per cent of owners have stopped
medication on the Thursday, Friday, Saturday, or Sunday before
the test is preformed on Monday. When the o,p’ -DDD has been
demonstrated to have had an effect, the dog can be returned to a
normal amount of food. The dog will continue to receive o,p’
-DDD for the rest of its life.

The initial maintenance dose is usually approximately 50 mg/kg
per week (a 22 pound dog would receive one-half tablet twice
weekly). That dose is likely to be increased or decreased on the
basis of testing performed 1 month after maintenance treatment
has been started and testing preformed every 2 to 4 months
thereafter. The average dog (11.5 years old when the syndrome is
diagnosed) treated in this manner lives about 30 months (some
live a few weeks and some 6 to 10 years). The dogs with the
longest survival have the owners who are committed to helping
their pet, diligent veterinarians, and luck. Close observation
and frequent veterinary rechecks can only help in the long-term
management of these dogs.

The above is general veterinary information. Do not begin
any course of treatment without consulting your regular
veterinarian. All animals should be examined at least once every
12 months.