Page 901 - Small Animal Internal Medicine, 6th Edition

CHAPTER 50 Disorders of the Adrenal Gland 873

therapy: an initial induction phase designed to gain control Maintenance Therapy
of the disorder, and a lifelong maintenance phase designed Mitotane must be administered periodically to prevent
VetBooks.ir to prevent recurrence of signs of the disease. recurrence of clinical signs. The maintenance phase of mito-
tane therapy should be initiated once the post-ACTH serum
Induction Therapy
appears healthy. The maintenance dose is defined as the
The mitotane dosage during induction therapy is approxi- cortisol concentration is less than 5 µg/dL and the dog
mately 50 mg/kg/day, divided into two doses. The daily weekly amount of mitotane administered, regardless of
dosage is reduced to 25 to 35 mg/kg in dogs without poly- whether the weekly dose is given once per week or is divided
dipsia or with concurrent diabetes mellitus. Gastrointestinal into multiple doses and given on several days. Adverse reac-
absorption of mitotane is enhanced in the presence of fat. tions caused by sensitivity to the drug are less likely to occur
Mitotane is more effective when each dose is ground up, when the weekly dose is divided and given on several days
mixed with a small amount of vegetable oil, and adminis- of the week. The typical initial weekly maintenance dosage
tered with food. Concurrent prednisone administration of mitotane is 50 mg/kg administered orally, divided into
(0.25 mg/kg q24h) during induction therapy is a matter of two or three doses, and administered on 2 or 3 days of each
personal preference. If prednisone is not used during induc- week. The maintenance dose of mitotane is decreased from
tion therapy, it should always be dispensed before induction 50 mg/kg/wk to 25 mg/kg/wk if the post-ACTH serum cor-
therapy is begun so that the client has prednisone on hand tisol concentration is less than 2 µg/dL (60 nmol/L) and the
should adverse reactions to mitotane develop. dog appears healthy. Mitotane treatment is discontinued and
The induction phase of mitotane treatment is typically prednisone treatment initiated if the post-ACTH serum cor-
done with the dog in the home environment. Client aware- tisol concentration is less than 2 µg/dL and the dog is exhib-
ness of the dog’s activity, mental awareness, appetite, water iting clinical signs of hypoadrenocorticism.
consumption, and overall well-being is imperative for The initial dose of mitotane during maintenance therapy
success. Clients are instructed to stop mitotane treatment is arbitrary, and subsequent adjustments are made on the
and contact the veterinarian if they observe lethargy, inap- basis of results of ACTH stimulation tests; the first test is
petence, vomiting, weakness, decreased water intake, or any performed 3 to 4 weeks after the start of maintenance therapy.
other change in the dog that does not seem right. The induc- The goal of maintenance therapy is to maintain the post-
tion phase of therapy is usually complete once any reduction ACTH serum cortisol concentration at between 2 and 5 µg/
in appetite is noted or once daily water consumption dL in an otherwise healthy dog. The dose and frequency of
decreases into the normal range (i.e., ≤80 mL/kg). Control administration of mitotane are adjusted, as needed, to main-
is confirmed with the ACTH stimulation test. The first tain a hypoadrenal response to ACTH administration. If the
ACTH stimulation test should be performed 5 to 7 days after post-ACTH serum cortisol is between 2 and 5 µg/dL, a
the start of induction therapy, even if clinical signs of hyper- change in treatment is not indicated and the ACTH stimula-
adrenocorticism persist. tion test should be repeated in 6 to 8 weeks. If the post-
The goal of therapy is to achieve a post-ACTH serum ACTH serum cortisol concentration is greater than 5 µg/dL,
cortisol concentration of 2 to 5 µg/dL (60-145 nmol/L). the amount of mitotane administered per week is increased.
Daily mitotane therapy and weekly ACTH stimulation tests If the post-ACTH serum cortisol concentration is less than
should be continued until a post-ACTH serum cortisol con- 2 µg/dL, the amount of mitotane administered per week is
centration falls within the desired range or until clinical decreased; mitotane therapy is temporarily discontinued if
signs of hypocortisolism (i.e., lethargy, inappetence, vomit- clinical signs of hypoadrenocorticism are present. An ACTH
ing) develop. In most dogs clinical signs resolve and a post- stimulation test is performed 3 to 4 weeks after a change is
ACTH serum cortisol concentration of less than 5 µg/dL is made to the dose or frequency of administration of mitotane.
achieved within 5 to 10 days of initiating treatment. A small Once the post-ACTH serum cortisol concentration is stable
number of dogs respond within 5 days, and an equally small and in the range of 2 to 5 µg/dL, the frequency of performing
number of dogs show minimal improvement after 20 or the ACTH stimulation test can be decreased.
more consecutive days of therapy. In most dogs an initially effective maintenance dose of
Reasons for a prolonged or poor response to mitotane mitotane becomes inadequate as the compensatory sustained
treatment include inadequate dose, inadequate absorption increase in plasma ACTH concentration counters the adre-
from the gastrointestinal tract, concurrent administration of nocorticolytic effects of mitotane. With time the dose and
drugs (e.g., phenobarbital) that could accelerate the metabo- frequency of administration of mitotane usually increases to
lism of mitotane and decrease its serum concentration, client compensate for this effect. Periodic ACTH stimulation
compliance issues, and existence of ADH rather than PDH. testing will identify when the post-ACTH serum cortisol
If tests to differentiate PDH from ADH were not performed, concentration increases above 5 µg/dL, allowing the clini-
dogs that are shown to be resistant to therapy, defined as cian to adjust the mitotane treatment protocol to maintain
showing little or no reduction in the post-ACTH plasma control of the disease. In some dogs, this can ultimately
cortisol concentration after 20 or more days of therapy, necessitate daily mitotane administration. Alternative
should undergo further evaluation (i.e., abdominal ultra- therapy (i.e., trilostane) should be considered for dogs that
sound) to rule out ADH. become insensitive to mitotane.