Absence of polydipsia simply eliminates one of the factors that can be monitored during the initial phases of therapy. Therapy
will be based on history, physical examination and the comparison of pre- and post-therapy ACTH-response test results. The
most important monitoring guide in these dogs is no different than for polydipsic dogs; it is their appetite. Reduction in
appetite in any dog receiving o,p'-DDD is an indication that the induction phase is completed or that over dosage is imminent.
Lysodren does not affect the pituitary gland. Therefore, the excessive ACTH secretion associated with hyperadrenocorticism
continues or becomes exaggerated with therapy. Failure to chronically continue o,p'-DDD therapy will result in re-growth of
the adrenal cortices and return of clinical signs. This recurrence typically occurs within one to 12 months of stopping therapy.
Maintenance therapy involves choosing an o,p'-DDD protocol and altering that regimen as required by the dog. Dogs that respond
to daily o,p'-DDD therapy within five to seven days are classified as sensitive and begin a maintenance schedule of 25 mg/kg
weekly of o,p'-DDD. Those that initially require seven to 10 days of therapy are classified as resistant and receive 50 mg/kg
weekly. An ACTH-response test is performed one month and three months after beginning the maintenance therapy and every three
to six months thereafter. If the plasma cortisol concentration after ACTH administration is normal or elevated, the o,p'-DDD
dosage or the frequency of administration is increased. If the post-ACTH plasma cortisol concentration is less than 1 microgram
per dl (sometimes less than 2 microgram per dl) the dose should be decreased. If a dog receiving o,p'-DDD ever becomes ill,
no o,p'-DDD should be given.
Medical therapy using trilostane
The first report on the use of trilostane for treating naturally occurring hyperadrenocorticism in dogs was an abstract on
four dogs with pituitary-dependent hyperadrenocorticism and one with adrenal-dependent hyperadrenocorticism. The dose used
in these five dogs ranged from 2.6 to 4.8 mg/kg daily. All the dogs demonstrated a good clinical response with resolution
of clinical signs and no adverse effects noted during three to seven months of therapy. Thereafter, several subsequent studies
critically evaluated the use of trilostane therapy for dogs with pituitary-dependent hyperadrenocorticism. There appears to
be a wide range of doses (total or per kg of body weight) are required to induce and maintain adequate adrenocortical suppression.
Dogs may be receiving 1.4 to 8.7 times the initial controlling dose. A frequent observation is that the dogs have an initial
sensitivity to trilostane that is short-lived and that the dose then has to be increased until the appropriate long-term dose
is achieved. The trend is for the dose to eventually plateau in each dog and not continually increase. Experience with this
drug is important. It may take an average of almost 40 to 90 days to achieve satisfactory control of pituitary-dependent hyperadrenocorticism.
The recommended starting dose is 10 mg/kg with upward or downward adjustments (20 to 30 mg/dog) based on periodic ACTH stimulation
test results performed three to eight hours after trilostane administration. Larger dogs require a lower dose per kilogram
than smaller dogs. Clinical response, ACTH stimulation and urine cortisol-to-creatinine results can and should be used in
monitoring therapy. The cost of therapy may be two to four times the cost of o,p'-DDD therapy. Trilostane may also be useful
for dogs with an adrenocortical tumor causing hyperadrenocorticism.
In the United Kingdom, trilostane is officially registered for use in dogs under the trade name Vetoryl. The product for use
in humans is listed as Modrenal. The current recommendations are to initially administer 30 mg daily to dogs weighing less
than 5 kg; 60 mg daily to dogs weighing 5 to 20 kg; and 120 mg daily to dogs weighing more than 20 kg. Re-evaluations are
suggested after one, three, six and 13 weeks, and then after six and 12 months. Each recheck should include a history, physical
examination and an ACTH-stimulation test. The ACTH-stimulation test should be completed two to six hours after administration
of the trilostane. The target range for serum or plasma cortisol concentration should be 1 to 2 micrograms per dl. Because
some dogs are stable for prolonged periods with cortisol concentrations less than 1 microgram per dl, it is assumed that such
concentrations represent the daily nadir and that average daily concentrations are higher or that precursors accumulate in
the serum and retain some biological activity, but these precursors are not assayed by the cortisol measurement.
What's your question?
Send your pediatric/geriatric related questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500 Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr. Hoskins in upcoming columns.
Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with
specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200, or e-mail: