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Monitoring Trilostane Treatment

Florian Wuillemin, DEDV, Cummings School of Veterinary Medicine at Tufts University

Orla Mahony, MVB, DACVIM & DECVIM, Tufts University Cummings School of Veterinary Medicine

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In the Literature

Arenas Bermejo C, Pérez Alenza D, García San José P, et al. Laboratory assessment of trilostane treatment in dogs with pituitary‐dependent hyperadrenocorticism. J Vet Intern Med. 2020;34(4):1413-1422. 


Although mitotane was previously the most common treatment for dogs with pituitary-dependent hyperadrenocorticism (PDH), trilostane is now more commonly used. The adrenocorticotropic hormone (ACTH) stimulation test is a reliable method to monitor mitotane therapy, but it is less useful in determining which dogs receiving trilostane are overdosed, underdosed, or adequately dosed. In addition, results may vary depending on time of administration and when testing is performed. Alternative monitoring variables have been investigated, including endogenous ACTH (eACTH), cortisol:eACTH ratios, urine cortisol:creatinine ratios (UCCRs), and baseline cortisol before and/or after trilostane administration. However, none of these reliably discriminate between dogs that are adequately controlled and dogs that are over- or underdosed.

In this study, results of an ACTH stimulation test, urine specific gravity (USG), UCCR, and pre-and posttrilostane basal serum cortisol concentrations (SCCs) were assessed in 22 dogs with a confirmed diagnosis of PDH and receiving trilostane twice daily for at least 1 month. Dogs were screened in-hospital on 2 separate days. On the first study morning, pet owners were asked about their dog's response to trilostane treatment (ie, thirst, urination, appetite, behavior, and signs of illness); dogs were then classified as adequately dosed, underdosed, or overdosed. On the first day, urine previously collected at home by the owner was assessed for USG and UCCR. An ACTH stimulation test was also performed 3 hours after trilostane administration. On the second day, SCC was measured 30 minutes before trilostane administration, at the time of administration, and 1, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours after administration.

Results of ACTH stimulation tests, as well as assessment of USG, UCCR, and SCCs showed no significant difference between adequately dosed and underdosed dogs; there were no overdosed dogs. Trilostane suppressed SCC within 1 hour of administration and had a duration of action of <8 hours in most dogs.


Key pearls to put into practice:


Results of the ACTH stimulation test did not correlate with clinical signs in this study and did not help in identification of dogs requiring dose adjustment. An ACTH stimulation test can, however, be potentially useful in determining overdose with trilostane.


Dose adjustments should be based on the needs of the individual patient (eg, owner observation of thirst, urination, appetite, behavior, clinical signs of illness).


USG <1.020 may help identify a potential underdose, but the specificity of this variable is low, as some dogs may have concentrated urine while continuing to exhibit clinical signs of hyperadrenocorticism.

Suggested Reading

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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