Alternatives to ACTH Stimulation for Monitoring Trilostane Therapy
World Small Animal Veterinary Association Congress Proceedings, 2018
Carmel T. Mooney, MVB, MPhil, PhD, DECVIM-CA, MRCVS
Small Animal Clinical Studies, School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland

Since trilostane was first used to manage hyperadrenocorticism in dogs, the ACTH stimulation test has been recommended to monitor treatment efficacy. Although therapeutic cut-offs have changed over time, most endocrinologists are comfortable with interpretation of results and advising on any necessary dose changes. Its limitations are recognised. Timing of the ACTH stimulation test is crucial and it should be carried out 2–4 hours after treatment.1 It is known that results of stimulation tests started at 2 or 4 hours after trilostane can yield significantly different results2 and thus should be standardised for each individual dog. Additionally, although considered excellent at identifying excessively controlled dogs, escape from inhibition can occur some hours later and, therefore, altering drug dosage may not be necessary.3

Several studies have investigated alternative means of monitoring trilostane therapy using the ACTH response test for comparison. Varying but usually limited success has been reported for baseline cortisol, endogenous ACTH, cortisol/ACTH ratio, acute phase proteins, and the urine corticoid:creatinine ratio.4-7 None have gained widespread acceptance. However, these reports have been criticised for using the ACTH stimulation test for comparison as it has been suggested that it was never appropriately validated for the purpose of monitoring trilostane efficacy. Additionally, it has also been suggested that the results of the ACTH stimulation test correlate poorly with clinical control as assessed by owner questionnaire.8 The recent problems with regard to availability of ACTH and its expense have highlighted the need for alternative monitoring strategies. One recent study evaluated the results of the ACTH stimulation test, baseline cortisol (3 hours post-pill) and pre-trilostane cortisol (24 hours after trilostane administration for once daily dosing or 12 hours for twice daily dosing) concentration compared with clinical control as assessed by owner perception.9 Results indicated that baseline cortisol and pre-trilostane cortisol were better than the post-ACTH stimulation cortisol at differentiating between dogs with excellent clinical control and those that were inadequately controlled. The pre-trilostane cortisol was slightly better that the baseline cortisol and had the added benefit of being more useful at signaling potential oversuppression. It is this measurement that is now recommended for monitoring trilostane therapy. Broadly speaking a pre-trilostane cortisol >40 and <138 nmol/L, >138 nmol/l or <40 nmol/L indicates adequate, inadequate, or excessive control, respectively. However, interpretation should only be carried out in light of clinical findings. Dogs with persistent clinical signs despite adequate cortisol concentration may still require an increased dose or frequency of administration. Dogs with good clinical control and cortisol concentrations suggestive of inadequate control may benefit from split dosing and dogs with excessive cortisol control may benefit from a lower dose. Dogs presenting ill when on trilostane therapy warrant an ACTH stimulation test to fully evaluate adrenal reserve.


1.  Griebsch C, Lehnert C, Williams GJ, et al. Effect of trilostane on hormone and serum electrolyte concentrations in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med. 2014;28:160–165.

2.  Bonadio CM, Feldman EC, Cohen TA, et al. Comparison of adrenocorticotropic hormone stimulation test results started 2 versus 4 hours after trilostane administration in dogs with naturally occurring hyperadrenocorticism. J Vet Intern Med. 2014;28:1239–1243.

3.  Midence JN, Drobatz KJ, Hess RS. Cortisol concentrations in well-regulated dogs with hyperadrenocorticism treated with trilostane. J Vet Intern Med. 2015;29:1529–1533.

4.  Arteaga A, Dhand NK, McCann T, et al. Monitoring the response of canine hyperadrenocorticism to trilostane treatment by assessment of acute phase protein concentrations. J Small Anim Pract. 2010;51:204–209.

5.  Cook AK, Bond KG. Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism. J Am Vet Med Assoc. 2010;237:801–805.

6.  Galac S, Biujtels JJCWM, Kooistra HS. Urinary corticoid:creatinine ratios in dogs with pituitary-dependent hypercortisolism during trilostane treatment. J Vet Intern Med. 2009;23:1214–1219.

7.  Burkhardt WA, Boretti FS, Reusch CE, et al. Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism. J Vet Intern Med. 2013;27:919–923.

8.  Boretti FS, Holzthum J, Reusch CE. Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment. SAT Schweizer Archiv fur Tierheilkunde. 2016;158:631–638.

9.  Macfarlane L, Parkin T, Ramsey I. Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs. Vet Rec. 2016;doi:10.1136/vr.103744.


Speaker Information
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Carmel T. Mooney, MVB, MPhil, PhD, DECVIM-CA, MRCVS
Department of Small Animal Clinical Studies
School of Veterinary Medicine
University College Dublin
Belfield, Dublin 4, Ireland

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