Adrenalectomy is the preferred therapy for ADH. However, clients may decline this option because of cost, potential complications, and comorbidities. Mitotane is an adrenocorticolytic drug that was previously the primary treatment option for PDH and is still preferred by some clinicians. Please see Behrend for more information.³⁸ Trilostane is FDA approved for treatment of PDH and ADH. Although labeled to be administered once daily, there are several peer-reviewed references that have found that twice-daily use may be preferable. ^39–41 The FDA-approved dose is 2.2–6.7 mg/kg/day, but it has been commonly used at lower doses such as 2–3 mg/kg/day. Several members of the guidelines task force use a starting dosage of ~1 mg/kg twice per day, dependent on the FDA-approved commercially available capsule sizes.

Monitoring requires close attention to clinical signs and cortisol testing. There are many published monitoring and testing protocols; there is no universal consensus on one protocol.⁴² The ACTHST has historically been used for monitoring mitotane and trilostane therapy, but more recent research shows that ACTH-stimulated cortisol has poor correlation with clinical signs in dogs treated with trilostane. ^43,44 As the ACTHST is the only definitive diagnostic test for diagnosis of hypoadrenocorticism, the primary role for its use in monitoring treatment of naturally occurring CS is to rule out oversuppression of cortisol production. Because CS is a highly variable disease, clinician judgment and discretion are important in deciding on a specific monitoring protocol. There is consensus among the guidelines panel that the protocols and testing guidance described below have been effective. Initial response is assessed at 2 wk, then 1 mo later, and then every 3–6 mo. Clinical signs are the primary indicator of whether the patient is controlled or needs a dose adjustment.

Measurement of cortisol concentrations (before pill or following ACTHST) is recommended to help determine whether it is safe to continue with the current dose or to adjust the dose. Pre-pill cortisol testing involves obtaining a sample for cortisol measurement before the morning pill. The ACTHST should be done 3–5 hr after trilostane administration, with a lower dose of synthetic ACTH (1 mcg/kg IV) being acceptable for monitoring.⁴⁵ Timing of when the ACTHST is started following trilostane administration should be consistent between visits.

The primary purpose of the first recheck at 2 wk following initiation of trilostane treatment is to ensure cortisol is not becoming too low. Therefore, at the first 2 wk recheck following trilostane initiation, the guidelines authors do not usually recommend increasing the dose but may decrease the dose. After the first month of treatment, necessary dose increases are typically by 25–50% based on commercially available capsule sizes. Owners should not give trilostane if the dog is not feeling well. The guidelines task force does not routinely recommend, but recognizes, that patients are sometimes on unequal doses twice daily. Cortisol monitoring should always be performed following the higher dose. For example, if a patient is receiving 40 mg and 30mg, an ACTHST should be performed after the 40mg dose.

Clinical Tips

• A follow-up client questionnaire available here is a useful instrument for the client to complete at presentation of the patient. Answers to this questionnaire and follow-up questions about clinical signs are the primary determinants of whether the patient needs a dose adjustment.
• Cortisol measurements help determine whether the current dose is appropriate or if dose adjustment is needed for a patient.