PPID in horses: pergolide vs placebo for ACTH, insulin and clinical signs — MAYBE (weak evidence)

In horses with pituitary pars intermedia dysfunction, does pergolide vs placebo improve ACTH/insulin measures and clinical signs (hypertrichosis, muscle loss)?

Shelf #237 · gate-verified and approved by the developer

MAYBE (weak evidence): There is no placebo-controlled trial of pergolide for ACTH, insulin or clinical signs in PPID — the 2020 systematic review found the literature to be mostly descriptive case series, cohort studies and non-randomised, uncontrolled field trials. Within those uncontrolled studies, overall clinical improvement was reported in more than 75% of cases, plasma ACTH fell in 44–74% of cases and normalised in only 28–74%. The one genuinely placebo-compared study carded here tested a different endpoint (faecal strongyle egg counts as an immune-function marker in pre-clinical PPID) and found pergolide made no difference versus placebo. Long-term open-label follow-up and before–after laboratory series are consistent with real clinical improvement on pergolide, but without a control group the size of any drug effect on ACTH or signs — and any effect on insulin, which the carded records do not report — cannot be separated from natural variation, season and concurrent management. Drafted Nov 10, 2026 (VetMed build, topic #237); all figures from abstracts fetched and verified at drafting.

Tatum 2020: pergolide evidence in PPID is mostly non-randomised and uncontrolled; ACTH normalised in only 28–74% of cases

Systematic review of pergolide efficacy studies (review's own wording)

Who: Horses: horses with pituitary pars intermedia dysfunction (PPID) in the 28 publications meeting the review's inclusion criteria, across varied study populations, diagnostic protocols, pergolide doses and follow-up periods.

Result: Most included studies were descriptive case series, cohort studies or non-randomised, uncontrolled field trials, and marked between-study variation precluded meta-analysis. In the vast majority of the included studies, pergolide was reported to provide overall clinical improvement in >75% of cases, but reported improvements in individual clinical signs varied widely. A reduction in plasma ACTH concentrations was reported in 44-74% of cases, while normalisation to within reported reference intervals occurred in 28-74% of cases.

Watch out: These are ranges across uncontrolled studies, not a treatment effect versus placebo: without a comparator, improvement percentages mix drug effect with season, clipping, diet and other management, and with regression to the mean after a high ACTH reading. The review is carded precisely because it establishes that the placebo-controlled trial this shelf's question asks about does not exist in the published record it searched (searches to July 2020).

Tatum RC, McGowan CM, Ireland JL. Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review. Vet J. 2020;266:105562. PMID: 33323174. Registry ID: none in the record. MeSH: Adrenocorticotropic Hormone · Animals · Horse Diseases · Horses · Pergolide · Pituitary Diseases · Pituitary Gland, Intermediate · Treatment Outcome

Christen 2018: pergolide vs placebo made no difference to faecal strongyle egg counts in pre-clinical PPID (the treatment made no difference)

Prospective study with pergolide vs placebo comparison (record's own wording; randomisation and blinding not stated)

Who: Horses: 48 horses in a prospective study — horses with suspected pre-clinical pituitary pars intermedia dysfunction (PPID) and healthy control horses; ACTH concentrations and faecal strongyle egg counts (eggs per gram, EPG) were tested.

Result: There were no significant differences in baseline EPG between horses with pre-clinical PPID and healthy controls. There was no significant difference in EPG between horses with PPID after treatment with pergolide and placebo-treated animals (the treatment made no difference). Using EPG as a marker of immune function, these results did not support a proposed decrease in immune function in horses with pre-clinical PPID.

Watch out: This is the only carded record with an actual placebo arm, and its endpoint is faecal egg count — an immune-function proxy in pre-clinical disease — not ACTH, insulin, hypertrichosis or muscle loss, so it neither proves nor refutes a pergolide effect on this shelf's named outcomes. The abstract does not state randomisation or blinding, and neither is claimed here. The record reports no group sizes or EPG values beyond the null comparisons above.

Christen G, Gerber V, van der Kolk JH, Frey CF, Fouché N. Fecal strongyle egg counts in horses with suspected pre-clinical pituitary pars intermedia dysfunction before and after treatment with pergolide. Vet J. 2018;235:60-62. PMID: 29704940. Registry ID: none in the record. MeSH: Adrenocorticotropic Hormone · Animals · Feces · Horse Diseases · Horses · Parasite Egg Count · Pergolide · Pituitary Diseases · Pituitary Gland, Intermediate · Prospective Studies · Strongyle Infections, Equine · Strongyloidea

Schott 2025: 14-year open pergolide follow-up in 30 PPID equids — sustained owner-reported improvement, endocrine normalisation in 75% at 5.5 years

Open field clinical efficacy study extension — long-term uncontrolled follow-up (record's own wording)

Who: Horses and ponies: 30 client-owned equids with PPID (28 horses and 2 ponies) enrolled after completing an open field clinical efficacy study of Prascend (pergolide tablets); 13 received 2 μg/kg PO q24h and 17 received 4 μg/kg PO q24h in the extended treatment study.

Result: Five equids died and 24 were euthanized (five for chronic laminitis) during the study period (median survival time, 3.6 years; range 0.6-10.5 years). Seven of 13 equids on the lower dose had a dosage increase to 4 μg/kg PO q24h between 1.7 to 4.7 years of treatment. After 5.5 years, owners of 13 surviving equids reported sustained clinical improvement and endocrine test results normalized in 75%. After 9.5 years of treatment, only two of six surviving equids had normal endocrine test results. The authors conclude long-term pergolide produces clinical improvement in nearly all affected animals and normalization of endocrine test results in some cases.

Watch out: Open-label and uncontrolled: owner-reported improvement in survivors of a progressive disease is subject to expectancy and survivorship effects (only 13 of 30 equids remained at 5.5 years, and 6 at 9.5 years), and there is no untreated group to show what would have happened without pergolide. The underlying sponsor field efficacy study was itself open, per this record — it is not a placebo-controlled trial.

Schott HC, Strachota JR, Marteniuk JV, Refsal KR. Long-Term Response of Equids With Pituitary Pars Intermedia Dysfunction to Treatment With Pergolide. J Vet Intern Med. 2025;39(3):e70109. PMID: 40317948. Registry ID: none in the record. MeSH: Animals · Pergolide · Horses · Horse Diseases · Pituitary Gland, Intermediate · Pituitary Diseases · Male · Female · Treatment Outcome · Dopamine Agonists

Durham 2022: after starting pergolide, TRH-stimulated ACTH fell in 88% of 64 suspected PPID cases but normalised in only 24% of positive tests

Before–after laboratory case series (uncontrolled)

Who: Horses: laboratory submissions from 64 suspected equine PPID cases, each with an initial pre-treatment thyrotropin releasing hormone (TRH) stimulation test and a follow-up test within 100 days of starting medical therapy with pergolide.

Result: Significant improvements were seen in both the baseline and TRH-stimulated ACTH concentrations within 100 days, with no further improvements in the subset examined thereafter. Although 88% (n = 56/64) of all cases showed a decreased response to TRH post-treatment, only 24% (n = 9/38) of horses with positive pre-treatment TRH stimulation tests normalised following treatment, a further 34% (n = 13/38) improved into an equivocal category, and most commonly (42%; n = 16/38) horses with positive pre-treatment tests remained positive following treatment, although 75% (n = 12/16) of these showed a numerically lower post-treatment response.

Watch out: Before–after change in submitted laboratory cases, with no untreated comparison group: ACTH is seasonal and variable, and horses are typically started on treatment after a high result, so some fall is expected without any drug effect. Results from tests conducted between 1 July and 30 November were excluded by the author, which limits but does not remove seasonal confounding.

Durham AE. The effect of pergolide mesylate on adrenocorticotrophic hormone responses to exogenous thyrotropin releasing hormone in horses. Vet J. 2022;285:105831. PMID: 35477010. Registry ID: none in the record. MeSH: Adrenocorticotropic Hormone · Animals · Horse Diseases · Horses · Pergolide · Pituitary Diseases · Thyrotropin-Releasing Hormone

Synthesis: pergolide is widely reported to help PPID signs, but no placebo-controlled trial backs the ACTH or clinical-sign claim

Synthesis

Who: Synthesis of the cards above: Tatum 2020 (systematic review, 28 publications in PPID horses), Christen 2018 (48 horses, pergolide vs placebo, faecal egg-count endpoint), Schott 2025 (30 client-owned PPID equids, open long-term follow-up) and Durham 2022 (64 suspected PPID cases, before–after TRH testing).

Result: The honest answer to 'pergolide vs placebo' is that the comparison has not been run for ACTH, insulin or clinical signs: the supporting evidence is uncontrolled, and within it ACTH normalises in a minority-to-modest share of horses (28–74% across studies; 24% of positive TRH tests in the before–after series) even as owners report clinical improvement in most. The single placebo-compared study found no pergolide effect on its (different) endpoint. Pergolide may well work — the uncontrolled signal is consistent — but on the VetMed scale that is MAYBE (weak evidence), not a proven benefit.

Watch out: No carded record reports insulin outcomes, so this shelf makes no claim about insulin. Clinicians should also not read 'ACTH fell in 88%' (Durham 2022) as a drug effect size: it is a before–after proportion with no control arm.

Synthesis of Tatum RC et al. PMID: 33323174; Christen G et al. PMID: 29704940; Schott HC et al. PMID: 40317948; Durham AE. PMID: 35477010. Registry IDs as on the individual cards.

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