Association of Post-ACTH Cortisol Levels & Final Trilostane Dosage

In the Literature

Gouvêa FN, Vargas AM, Guimarães EC, et al. Association between post-ACTH cortisol and trilostane dosage in dogs with pituitary-dependent hypercortisolism. Domest Anim Endocrinol. 2024;89:106871. doi:10.1016/j.domaniend.2024.106871

The Research …

Trilostane, a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase, has been the most common therapy for pituitary-dependent hyperadrenocorticism in dogs for >20 years. In addition to decreasing cortisol, trilostane decreases aldosterone, although secondary hyperkalemia is rare.¹ Trilostane therapy increases endogenous ACTH and causes adrenal gland hyperplasia.² Clinical studies support divided administration regimens as a safer alternative to the once-daily dose (2.2-6.7 mg/kg PO) that was initially approved.^3-5

The authors of this retrospective study hypothesized that dogs with higher post-ACTH cortisol concentrations (cpACTH) during an ACTH stimulation test performed at the time of diagnosis would require higher trilostane maintenance doses. Cases (n = 43) that met the criteria of the ACVIM consensus statement on canine hyperadrenocorticism were identified,⁶ and dogs with cpATCH above the median (27 mg/dL) were compared with those below the median (Figure).

FIGURE

Basal cortisol concentrations and cpACTH before (orange) and after (blue) trilostane therapy

^a Pre-Rx cutoff, median concentration of pretherapy cpACTH; post-Rx cutoff, highest observed posttherapy cpACTH

^b Multiply by 27.6 to convert cortisol concentrations in mg/dL to the SI unit, nmol/L.

Initial doses of commercially available trilostane (n = 30) or compounded trilostane (n = 13) were 0.5 to 1 mg/kg PO every 12 hours. ACTH stimulation testing was performed every 4 to 6 weeks. Hyperadrenocorticism was considered controlled when cpACTH was ≤7 mg/dL, clinical signs resolved, and laboratory abnormalities normalized. An average of 3 recheck ACTH stimulation tests was required, and no adverse effects were observed.

Dose escalation was required in 88.4% of cases, and median final doses (commercially available trilostane, 2.5 mg/kg; compounded trilostane, 1.6 mg/kg) significantly exceeded median initial doses (commercially available trilostane, 0.6 mg/kg; compounded trilostane, 0.73 mg/kg). The median final dose was significantly higher for commercially available trilostane compared with compounded trilostane. Dogs above the median cpACTH were ≈2 times as likely to eventually require a higher dose than dogs below the median; however, the authors maintained that the same initial dose regimen is recommended, despite the increased likelihood of additional time needed to achieve optimal control.

Compounding was performed by a single pharmacy in this study. Prior studies with samples from multiple compounding pharmacies have found that ≈40% of compounded trilostane did not meet regulatory standards for potency and the actual content varied from 39% to 153% of the labeled content.⁷ This may explain the product differences noted in the current study.

… The Takeaways

Key pearls to put into practice:

• Trilostane therapy that starts with 0.5 to 1 mg/kg PO every 12 hours and gradually increases in dose is recommended for treatment of pituitary-dependent hyperadrenocorticism in dogs to minimize signs of hypoadrenocorticism.

• Periodic (ie, every 4-6 weeks) ACTH stimulation testing is recommended to monitor trilostane therapy. cpACTH >7 mg/dL, particularly when noted concurrently with unresolved clinical signs, indicates a dose increase is warranted. Dose escalation is common, possibly due in part to adrenal hyperplasia during therapy.

• Pet owners should be informed that cpACTH ≥27 mg/dL at the time of diagnosis indicates the trilostane dose will likely need to be gradually increased to achieve disease control. As basal (ie, pre-ACTH) cortisol had no predictive value in this study, basal cortisol measurement may be eliminated as a cost-savings measure, especially in patients without signs of hypoadrenocorticism.

• Most studies have evaluated dosage and efficacy of commercially available trilostane. Greater variability should be expected from compounded trilostane.