Page 90 - Clinical Small Animal Internal Medicine

58 Section 2 Endocrine Disease

adequate suppression (pre and post less than 5 μg/dL)
Box 7.5 Treatment of canine hyperadrenocorticism
VetBooks.ir Adrenal‐directed therapy and prednisone therapy (if necessary) has been discon­
tinued. Failure to use maintenance therapy will result
Mitotane in regrowth of the adrenal cortex and recurrence of
clinical signs. Efficacy of maintenance therapy is moni­
Trilostane tored by an ACTH stimulation test in one month and
Ketoconazole every 3–4 months thereafter. The dose of mitotane
Aminogluthemide required for long‐term maintenance is quite variable
Metyrapone (26–330 mg/kg/week).
Etomidate Reasons for treatment failure include incorrect diag­
LCI699* nosis, the presence of an adrenal tumor (although some
Normocort*
adrenal tumors will respond well), loss of drug potency
due to poor storage or compounding of mitotane, or a
Pituitary‐directed therapy
need for a higher dose or duration of treatment in some
Somatostain receptor agonists (octreotide, pasireotide) dogs. Side‐effects of mitotane include gastric irritation,
D2 receptor agonists (cabergoline, bromocriptine) hypoadrenocorticism, and very occasionally neurologic
Tyrosine kinase inhibitors (gefitinib) signs. Mean survival time of 200 dogs treated with mito­
Cyclin‐dependent kinase inhibitors (roscovitine)* tane was 2.2 years (range 10 days to 8.2 years).
PPAR‐gamma agonists (rosiglitazone)*
Retinoic acid Trilostane
Temozolamide* Trilostane is a synthetic hormonally inactive steroid
mTor inhibitors (everolimus)* analog, which is a competitive inhibitor of the 3‐beta‐
hydroxysteroid dehydrogenase system. The drug blocks
Glucocorticoid receptor blockade synthesis of adrenal steroids, including cortisol and
Mifepristone* aldosterone. Trilostane is rapidly absorbed orally (peak
concentrations within 1.5 hours), although suppression
* = Currently no data in dogs with PDH. of plasma cortisol concentrations is short‐lived (<20
hours). The medication should be administered with
food (including the days when ACTH stimulation tests
atrophy, and congestion of the liver. Normal dogs and are scheduled to be performed) to aid in absorption.
cats are clinically quite resistant to the effects of the drug. Current recommendations for use of trilostane in dogs
Therapy with mitotane in both dogs and cats is begun are to start at a dose of 1–2 mg/kg q12–24h and then
at a dose of 50 mg/kg divided q12h. Glucocorticoids are increase or decrease the dose based on evaluation of
not usually administered concurrently, but a small sup­ ACTH stimulation tests performed 4–6 hours after drug
ply of prednisone should be made available to the owner administration. While there is no difference in whether
for emergencies. Mitotane at induction doses is typically the samples are drawn four or six hours post pill, it is
administered for 5–10 days, until water consumption important that the same sampling times are used in a
decreases to <100 mL/kg/day. It should be discontinued given patient. The hormonal endpoints are postcortisol
immediately if decreased appetite, depression, diarrhea, concentration of less than 6–9 μg/dL in conjunction with
or vomiting are observed. At this point, the pet should be remission of clinical signs. Twice‐a‐day therapy at a
reevaluated and an ACTH stimulation test performed. starting dose of 1–3 mg/kg may result in good control of
Prednisone treatment (0.2–0.5 mg/kg/day) should be ini­ clinical signs at a lower total daily dose with less risk of
tiated in patients showing clinical signs of hypocorti­ adverse effects than higher doses q24h. In addition, BID
solemia, until the results of the ACTH stimulation test dosing may be more effective in controlling hypercorti­
are known. In patients that are not polydipsic, patients in solemia more consistently throughout the day and may
which water consumption cannot be monitored, and be appropriate as a starting dose in dogs with diabetes
patients in which polydipsia is due to another underlying and other Cushing‐related complications.
disease (e.g., diabetes mellitus), mitotane should be We have recently evaluated the safety and efficacy of
administered for a maximum of 5–7 days prior to ACTH trilostane therapy in 15 cats with PDH at starting doses
stimulation testing. of 1–2 mg/kg q12–24h. Clinical signs (13 of 15 cats) and
The goal of treatment is to have both the pre‐ and ACTH stimulation testing results (13 of 15) improved
postcortisol measurement in the normal resting range with trilostane therapy. Diabetes mellitus was reported
(2–6 μg/dL). Maintenance therapy (50 mg/kg q7–10 in 9/15 cases. Insulin requirements decreased by 36%
days) is started once the ACTH stimulation test shows within two months in 6/9 diabetic cats. Median survival