Internal Medicine Clinical Update: Hyperadrenocorticism -Treatment Protocol

Portrait of Michael GoldsteinSpontaneous hyperadrenocorticism (HAC) has pituitary-dependent (PDH) and adrenal-dependent (ADH) forms. This is the second part of the clinical update on HAC which will cover the most current trends in the treatment of this endocrinopathy.

The aim of treatment is to eliminate clinical signs caused by chronic glucocorticoid excess. The risks of not treating HAC include the development of pancreatitis, diabetes mellitus and urolithiasis. There are surgical or medical treatment options for either PDH or ADH.

HAC diagnosed in 80-85% of dogs is secondary to PDH. A transsphenoidal hypophysectomy can be performed with moderate success but the procedure is associated with serious complications and is currently not performed in Ontario. The two effective medical treatments are Trilostane (Vetyrol) and Mitotane (Lysodren). Mitotane was once considered the mainstay of medical management of PDH, but due to expense, a higher rate of side effects, and the increased availability of Trilostane, its use has decreased dramatically.

Trilostane is currently regarded as the treatment of choice for dogs with PDH. The drug is a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase/isomerase enzyme system which is essential for the synthesis of many steroids, including cortisol. Trilostane is effective in greater then 75% of dogs with PDH, with polyuria and polydipsia usually resolving within 4 weeks and the dermatologic signs resolving within 4 months. There is no consensus on the ideal Trilostane dose and treatment protocol. The dosing range is 2 to 5 mg/kg every 24 hours. My recommendation is to start at 2 mg/kg every 24 hours, which should be given with a full meal to improve absorption.

The efficacy and required dosages are assessed using ACTH stimulation tests. Trilostane has a relatively short-lasting effects and results of the ACTH stimulation test can vary considerably with the time of testing. As such my recommendation is to perform the ACTH stimulation test 2 to 4 hours after dosing. Post-ACTH cortisol concentrations should be between 40 nmol/L and 120 nmol/L, in conjunction with resolution of clinical signs.

I recommend performing an ACTH stimulation test 7 to 10 days after initiating therapy to screen for low cortisol levels, in order to prevent a Trilostane overdose. Dose adjustments should not be made for normal or high cortisol levels at this early stage, as a change may increase the risk of Trilostane overdose.  Monitoring for efficacy should be done monthly for the first 3 consecutive months, followed by monitoring every 3 months for the first year, after which every 4 to 6 months may be appropriate. See the algorithm below for Trilostane therapy and dose adjustments.

Twice-daily, low dose treatment has been documented to be effective at controlling clinical signs with no increased risk of adverse effects. However, the once-daily dosing is more convenient for pet owners, with increased owner compliance and reduction in the need for compounded formulations of the drug. The twice-daily dosing may be preferred in patients having a post ACTH cortisol concentration between 40 nmol/L and 120 nmol/L but withpersistent clinical signs associated with HAC.

Adrenalectomy is the treatment of choice for ADH. When the tumor is removed there is a decreased risk of metastasis and the treatment may be curative. However, the procedure has been associated with a 5-29% perioperative mortality rate. The median survival time for dogs with a successful adrenalectomy was 23-32 months. Medical management of dogs that cannot undergo surgery can be achieved with either Trilostane or Mitotane. A recent study demonstrated the choice between the two drugs did not influence overall survival time (15.6 months). However 60% of dogs treated with Mitotane had clinical adverse effects compared to 23% treated with Trilostane. Since dogs with ADH treated with Trilostane had similar survival time and fewer adverse effects, Trilostane is my choice for medically managing dogs with ADH. The same dosing is used as for PDH and the doses required to achieve clinical stabilization do not appear to increase with time in dogs that respond to the initial dose.

If you have any questions regarding hyperadrenocorticism or any other cases do not hesitate to contact Dr. Michael Goldstein at 416-784-4444. Please ask about joining our circle of care!

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