How should I dose and monitor pergolide in horses with pituitary pars intermedia dysfunction?

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Pergolide mesylate is initiated at 2 μg/kg PO q24h and monitored with basal plasma adrenocorticotropic hormone (ACTH) measurement at 4–6 week intervals until clinical signs and/or endocrine results stabilize or improve. 1 The starting dose is 2 μg/kg PO q24h, which is the licensed dose in both the UK (Prascend, Boehringer Ingelheim) and the US.111 A dose of 4 μg/kg PO q24h has also been used in long-term treatment, with 7 of 13 horses on the lower dose requiring escalation to 4 μg/kg PO q24h between 1.7 and 4.7 years into treatment.7 Importantly, not all horses require progressive dose increases — some respond favorably to the initial dose long-term.7 Plasma ACTH begins to fall within 12 hours of the first dose, with further reductions occurring over the first 10 days of treatment.2 Alterations in the thyrotropin-releasing hormone (TRH) stimulation response are detectable by day 8, with no further change identified at day 18.2 Despite this rapid onset, the Prascend datasheet recommends repeating endocrinologic testing every 4–6 weeks until stabilization.1 After 5.5 years of treatment, owners of 13 surviving horses reported sustained clinical improvement, and endocrine test results normalized in 75% of those animals. After 9.5 years, only 2 of 6 surviving horses maintained normal endocrine test results, reflecting the progressive nature of the disease.7 Median survival time from enrollment was 3.6 years (range 0.6–10.5 years), with 5 horses euthanized specifically for chronic laminitis.7 Monitoring in practice is frequently inadequate. Only 76% of pergolide-treated, PPID-positive horses had any recorded monitoring, and fewer than half of those monitored (48.1%) had follow-up basal ACTH testing within the recommended 1–3 months of diagnosis.1 Repeating basal ACTH at 1 month after treatment initiation has been proposed as a means of identifying false-positive results at initial testing.1 Twice-daily dosing may reduce ACTH fluctuation. Pergolide has a terminal eliminati