Therapy goals with o,p'-DDD are to achieve resolution of the clinical signs. This typically correlates with an ACTH response
test that is suggestive of relative hypoadrenocorticism. Successful response to o,p'-DDD is indicated by pre- and post-ACTH
serum cortisol concentrations >1.5 mcg/dl and <5 mcg/dl.
The maintenance phase of therapy with o,p'-DDD should be initiated once a dog seems much improved or normal to an owner, or
if a post-ACTH serum cortisol concentration is <5 mcg/dl. It is important to emphasize that each dog must be treated individually.
Most dogs respond during the five- to nine-day induction period. It is unusual for a dog to require more than eight or nine
consecutive days of o,p'-DDD, just as it is unusual for a dog to respond in less than four days.
About 20 percent of dogs with PDH are not polydipsic. They, too, should be treated by their owners at home.
Absence of polydipsia simply eliminates one of the factors that can be monitored during the initial phases of therapy.
Lysodren does not affect the pituitary gland or tumor. Therefore, the excessive ACTH secretion associated with pituitary-dependent
hyperadrenocorticism continues or becomes exaggerated with therapy. Failure to continue o,p'-DDD therapy will result in regrowth
of the adrenal cortices and return of clinical signs. This recurrence typically occurs within one to 12 months of stopping
Maintenance therapy involves choosing an o,p'-DDD protocol and altering that regimen as required clinically for each dog.
Whenever possible, the weekly dose of medication should be divided into as many doses as possible. For example, if a 10-kg
dog is to receive 50 mg/kg per week, rather than give that dog one 500-mg tablet once weekly, we give one-fourth tablet four
In general, dogs that have post-ACTH serum cortisol concentrations <1mcg/dl have medication withheld for two weeks and then
are placed on 25 mg/kg per week. Four weeks after therapy is started, an ACTH stimulation test should be rechecked. If the
post-ACTH stimulation test result is 1.0-3.5 mcg/dl, 25 mg/kg per week should be initiated, with the recheck scheduled for
four weeks later. If the post-ACTH stimulation test result is 3.5-7.5 mcg/dl, 50 mg/kg per week should be initiated, with
a similar timing for the recheck. If the post-ACTH stimulation test result is greater than 7.5 mcg/dl, one should first be
certain that the medication is being given. If being given, remind owners that the drug should be administered immediately
after a meal since the medication is best and most consistently absorbed from a stomach that contains food.
If the owners are following these instructions, absorption can be enhanced by crushing the o,p'-DDD, and then suspending the
powder in corn oil. That suspended medication should then be mixed into the food. Never raise the dose and use corn oil for
the first time. Corn oil does enhance absorption of this drug.
The most important factor in dose determination is owner opinion, not some cortisol concentration after ACTH administration
or some other laboratory result. With this in mind, the post-ACTH serum cortisol concentration should be used as a guide in
determining whether a dose should be increased or decreased. If a dog is receiving one-fourth tablet of drug four times weekly,
and it has a post-ACTH serum cortisol concentration of 1.3 mcg/dl, we would recommend lowering the dose to three times weekly
and plan a re-check for three months later. If a similar dog is receiving one-fourth tablet four times weekly and has a post-ACTH
serum cortisol concentration of 8.9 mcg/dl, we would recommend increasing the dose to five times weekly and schedule a recheck
for three months later.
In this manner, the typical dog with pituitary-dependent hyperadrenocorticism is consistently being maintained without being
overdosed or underdosed for any length of time.
Medical therapy using trilostane
Trilostane is an enzyme blocker that prevents the synthesis of cortisol. In contrast to o,p'-DDD, a cytotoxic drug, trilostane
reportedly does not damage cells but is effective only until the drug is metabolized.