Abstract
BackgroundResults of ACTH stimulation test (ACTHst), pre‐ and post‐trilostane serum cortisol concentrations (SCCs), urine concentration (urine‐specific gravity [USG]), and urine cortisol : creatinine ratios (UCCRs) are common variables used to monitor trilostane treatment of dogs with pituitary‐dependent hyperadrenocorticism (PDH). However, none has consistently discriminated dogs receiving an adequate dose (A) from those overdosed (O) or underdosed (U).ObjectivesTo assess and compare recommended monitoring variables, including serial SCCs in a cohort of dogs with PDH treated with trilostane.AnimalsPrivately owned dogs with PDH (n = 22) and 3 healthy dogs (controls).MethodsProspective, multicenter, 2‐day study. On day “a” (randomized): ACTHst was completed. Day “b” (>2 to <7 days later): SCCs were assessed −0.5 hours, immediately before, and 1, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours after trilostane administration. On the first study day, urine collected at home was assessed for USG, UCCR and owner opinions regarding PDH were categorized as: A (clinical signs resolved), U (remains symptomatic), or ill (possible O).ResultsAt 27 pairs of evaluations, 7 dogs were categorized as A, 19 U, and 1 possible O (excluded from the study). There was overlap in SCC results from the A and U dogs at every time point. Results of USG, UCCR, and ACTHst did not discriminate A from U dogs. Trilostane suppresses SCC within 1 hour of administration and its duration of action in most PDH dogs is <8 hours.Conclusions and Clinical ImportanceNo single variable or group of variables reliably discriminated A dogs from U dogs during trilostane treatment for PDH.
Highlights
Perhaps because results of the ACTH stimulation test (ACTHst) were considered so reliable in monitoring mitotane treatment, the test began being used for the same purpose in trilostane-treated dogs in initial reports 8-11 and in the manufacturer's insert.[12]
No study has validated the 4 to 6 hour recommendation, it has been reported that results of ACTHst initiated 3 hours after trilostane administration were significantly different from tests started 9 hours after, and those started 2 hours after were significantly different from those started 4 hours after.[14,15]
Our working hypothesis was that urinespecific gravity (USG) results would discriminate dogs receiving an adequate dose (>1.020) from underdosed dogs (
Summary
Between 1970 and 2000, the most common medical treatment for dogs with pituitary-dependent hyperadrenocorticism (PDH) wasJ Vet Intern Med. 2020;1–10.wileyonlinelibrary.com/journal/jvimARENAS BERMEJO ET AL.mitotane (o,p'-DDD), a cytotoxic drug that targets adrenocortical cells.[1,2,3,4] Since 2000, the most common medical treatment for dogs with PDH has been trilostane, a competitive inhibitor of the 3β-hydroxysteroid dehydrogenase-isomerase enzyme system.[5,6,7,8,9,10,11,12]Several different mitotane protocols were suggested for dogs with PDH.[3,4] Regardless of protocol, authors consistently considered ACTH stimulation test (ACTHst) results to be a reliable objective indicator of mitotane overdose, underdose, or adequate dosage, regardless of when the test was begun relative to time of previous mitotane administration.[1,2,3,4] Perhaps because results of the ACTHst were considered so reliable in monitoring mitotane treatment, the test began being used for the same purpose in trilostane-treated dogs in initial reports 8-11 and in the manufacturer's insert.[12]. Adding to the confusion, suggested ACTHst starting times in published studies have varied from as early as 2 hours to as late as 12 or 24 hours after trilostane administration.[13,14,15,16,17,18] Regardless of timing issues, and perhaps more important, concerns persist that ACTHst results do not reliably indicate which dogs are overdosed, underdosed, or dosed adequately.[13,14,16,19,20]. Results of ACTH stimulation test (ACTHst), pre- and post-trilostane serum cortisol concentrations (SCCs), urine concentration (urine-specific gravity [USG]), and urine cortisol : creatinine ratios (UCCRs) are common variables used to monitor trilostane treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH).
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