Abstract: Pituitary pars intermedia dysfunction (PPID) is a prevalent, age-related chronic disorder in equids. Diagnosis of PPID can be challenging because of its broad spectrum of clinical presentations and disparate published diagnostic criteria, and there are limited available treatment options. Objective: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature. Methods: Evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Methods: Research questions were proposed by a panel of veterinarians and developed into PICO or another structured format. VetSRev and Veterinary Evidence were searched for evidence summaries, and systematic searches of the NCBI PubMed and CAB Direct databases were conducted using keyword searches in July 2022 and updated in January 2023. The evidence was evaluated using the GRADE framework. Conclusions: The research questions were categorised into four areas: (A) Case selection for diagnostic testing, pre-test probability and diagnostic test accuracy, (B) interpretation of test results, (C) pharmacological treatments and other treatment/management options and (D) monitoring treated cases. Relevant veterinary publications were identified and assessed using the GRADE criteria. The results were developed into recommendations: (A) Case selection for diagnostic testing and diagnostic test accuracy: (i) The prevalence of PPID in equids aged ≥15 years is between 21% and 27%; (ii) hypertrichosis or delayed/incomplete hair coat shedding provides a high index of clinical suspicion for PPID; (iii) the combination of clinical signs and age informs the index of clinical suspicion prior to diagnostic testing; (iv) estimated pre-test probability of PPID should be considered in interpretation of diagnostic test results; (v) pre-test probability of PPID is low in equids aged <10 years; (vi) both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal adrenocorticotropic hormone (ACTH) or ACTH after thyrotropin-releasing hormone (TRH) stimulation. The overall diagnostic accuracy of basal ACTH concentrations for diagnosing PPID ranged between 88% and 92% in the autumn and 70% and 86% in the non-autumn, depending on the pre-test probability. Based on a single study, the overall diagnostic accuracy of ACTH concentrations in response to TRH after 30 minutes for diagnosing PPID ranged between 92% and 98% in the autumn and 90% and 94% in the non-autumn, depending on the pre-test probability. Thus, it should be remembered that the risk of a false positive result increases in situations where there is a low pre-test probability, which could mean that treatment is initiated for PPID without checking for a more likely alternative diagnosis. This could compromise horse welfare due to the commencement of lifelong therapy and/or failing to identify and treat an alternative potentially life-threatening condition. (B) Interpretation of diagnostic tests: (i) There is a significant effect of breed on plasma ACTH concentration, particularly in the autumn with markedly higher ACTH concentrations in some but not all 'thrifty' breeds; (ii) basal and/or post-TRH ACTH concentrations may also be affected by latitude/location, diet/feeding, coat colour, critical illness and trailer transport; (iii) mild pain is unlikely to have a large effect on basal ACTH, but caution may be required for more severe pain; (iv) determining diagnostic thresholds that allow for all possible contributory factors is not practical; therefore, the use of equivocal ranges is supported; (v) dynamic insulin testing and TRH stimulation testing may be combined, but TRH stimulation testing should not immediately follow an oral sugar test; (vi) equids with PPID and hyperinsulinaemia appear to be at higher risk of laminitis, but ACTH is not an independent predictor of laminitis risk. (C) Pharmacologic treatments and other treatment/management options: (i) Pergolide improves most clinical signs associated with PPID in the majority of affected animals; (ii) Pergolide treatment lowers basal ACTH concentrations and improves the ACTH response to TRH in many animals, but measures of insulin dysregulation (ID) are not altered in most cases; (iii) chasteberry has no effect on ACTH concentrations and there is no benefit to adding chasteberry to pergolide therapy; (iv) combination of cyproheptadine with pergolide is not superior to pergolide alone; (v) there is no evidence that pergolide has adverse cardiac effects in horses; (vi) Pergolide does not affect insulin sensitivity. (D) Monitoring pergolide-treated cases: (i) Hormone assays provide a crude indication of pituitary control in response to pergolide therapy, however it is unknown whether monitoring of ACTH concentrations and titrating of pergolide doses accordingly is associated with improved endocrinological or clinical outcome; (ii) it is unknown whether monitoring the ACTH response to TRH or clinical signs is associated with an improved outcome; (iii) there is very weak evidence to suggest that increasing pergolide dose in autumn months may be beneficial; (iv) there is little advantage in waiting for more than a month to perform follow-up endocrine testing following initiation of pergolide therapy; there may be merit in performing repeat tests sooner; (v) timing of sampling in relation to pergolide dosing does not confound measurement of ACTH concentration; (vi) there is no evidence that making changes after interpretation of ACTH concentrations measured at certain times of the year is associated with improved outcomes; (vii) evidence is very limited, however, compliance with PPID treatment appears to be poor and it is unclear whether this influences clinical outcome; (viii) evidence is very limited, but horses with clinical signs of PPID are likely to shed more nematode eggs than horses without clinical signs of PPID; it is unclear whether this results in an increased risk of parasitic disease or whether there is a need for more frequent assessment of faecal worm egg counts. Conclusions: Limited relevant publications in the veterinary scientific literature. Conclusions: These findings should be used to inform decision-making in equine primary care practice.
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study provides a detailed guide for diagnosing and managing Pituitary Pars Intermedia Dysfunction (PPID), a common age-related equine disease. Applying the GRADE framework, the researchers systematically reviewed available literature, categorized their results into areas like case selection, diagnostic testing, interpretation of test results, treatment options, and monitoring. This comprehensive approach is expected to help inform decision-making in equine primary care.
Research Parameters and Methods
The researchers employed an evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
A panel of veterinarians posed research questions, which were later turned into a structured format such as PICO (problem, intervention, comparison, outcome).
Databases like VetSRev, Veterinary Evidence, NCBI PubMed, and CAB Direct were searched for relevant literature using targeted keywords. The literature search was first conducted in July 2022 and later updated in January 2023.
The evidence collected was evaluated utilizing the GRADE framework.
Evidence Evaluation and Recommendations
Using the collected literature, the research questions were grouped into four areas: case selection for diagnostic testing, interpretation of test results, pharmacological treatments, and monitoring treated cases. The findings were developed into recommendations under each area.
The prevalence of PPID in equids aged over 15 was found to be between 21% and 27%. Particular clinical signs and age combined increased the suspicion of PPID.
The researchers advised that the pre-test probability of PPID should be considered in interpreting diagnostic test results, noting that the pre-test probability is low in equids under 10 years.
The study recommended monitoring of ACTH concentrations and adjusting pergolide doses accordingly, though it’s unclear if this is associated with improved outcomes.
Interpretation of Diagnostic Tests
Factors such as breed, latitude/location, diet/feeding, coat color, illness severity, and trailer transport significantly affect plasma ACTH concentration.
The study reported that mild pain is unlikely to have a substantial impact on basal ACTH, but greater caution may be required for more severe pain.
Researchers found equids with PPID and hyperinsulinaemia to be at a higher risk of laminitis, although ACTH is not an independent predictor of laminitis risk.
Pharmacological Treatments and Management Options
Pergolide was found to improve most clinical signs associated with PPID in the majority of affected animals.
Researchers reported that chasteberry has no effect on ACTH concentrations, and adding it to pergolide therapy does not provide any benefits.
The study also found no evidence that pergolide has adverse cardiac effects or affects insulin sensitivity in horses.
Monitoring Treated Cases
The researchers gave weak evidence to suggest that increasing pergolide dose in autumn months was beneficial.
They also found no evidence suggesting that changes in ACTH concentrations measured at specific times of the year led to improved outcomes.
The study identified poor compliance with PPID treatment, but the impact on clinical outcomes is unclear.
Lastly, the research found that horses with clinical signs of PPID are likely to shed more nematode eggs than horses without clinical signs of PPID.
Conclusions
The research concluded upon the need for more relevant scientific literature in veterinary science for better understanding and management of PPID.
The findings of this study can serve as a valuable resource to inform decision-making in equine primary care practices.
Cite This Article
APA
Menzies-Gow NJ, Banse HE, Duff A, Hart N, Ireland JL, Knowles EJ, McFarlane D, Rendle D.
(2023).
BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.
Equine Vet J, 56(2), 220-242.
https://doi.org/10.1111/evj.14009
Patel GW, Roderman N, Gehring H, Saad J, Bartek W. Assessing the effect of the surviving sepsis campaign treatment guidelines on clinical outcomes in a community hospital.. Ann Pharmacother 2010;44:1733-1738.
Woolf S, Schunemann HJ, Eccles MP, Grimshaw JM, Shekelle P. Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations.. Implement Sci 2012;7:61.
Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G. GRADE guidelines: 2. Framing the question and deciding on important outcomes.. J Clin Epidemiol 2011;64:395-400.
Schunemann H, Brozek J, Guyatt G, Oxman A. Handbook for grading the quality of evidence and strength of recommendations using the GRADE approach (updated October 2013).. 2013.
Grindlay DJ, Brennan ML, Dean RS. Searching the veterinary literature: a comparison of the coverage of veterinary journals by nine bibliographic databases.. J Vet Med Educ 2012;39:404-412.
Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.. J Clin Epidemiol 2011;64:383-394.
What is GRADE. BMJ best practice. BMJ; 2023. www.bestpractice.bmj.com/toolkit/learn-ebm/what-is-grade/
Erdody M, Galinelli N, Bamford NJ, Mackensie S, Warnken T, Harris PA. Plasma immunoreactive β-endorphin concentrations and spontaneous blink rate as an index of stresss, measured in a population of aged horses and ponies with and without PPID.. 5th Global Equine Endocrine Symposium Bern, Switzerland: National Horse Center; 2023.
Hsu J, Brozek JL, Terracciano L, Kreis J, Compalati E, Stein AT. Application of GRADE: making evidence-based recommendations about diagnostic tests in clinical practice guidelines.. Implement Sci 2011;6:62.
Bradaric Z, May A, Gehlen H. Use of the chasteberry preparation Corticosal® for the treatment of pituitary pars intermedia dysfunction in horses.. Pferdeheilkunde 2013;29:721-728.
Schramm E, Schwarz A, Alber H, Alber G. Effects of the multi-compound complex in Corticosal® in 177 horses with PPID in a retrospective veterinary questionnaire analysis in Germany.. Pferdeheilkunde 2018;34:538-549.
Christiansen A. Prevalence of equine Cushing's syndrome among older horses in southern Vestsjaelland. Denmark. Dansk Veterinaertidsskrift 2009;92:24-29.
Nanao Y, Ueno T. Two cases of equine Cushing's disease in thoroughbred mares.. J Jpn Vet Med Assoc 2012;65:771-775.
Grubbs ST, Neal DL, Keefe DJ. Development and evaluation of a clinical sign scoring system for pituitary pars intermedia dysfunction in horses.. 4th Global Equine Endocrine Symposium Gut Ising, Germany: Boehringer Ingelheim; 2020.
Erdody M, Mackenzie S, Galinelli N, Bamford NJ, Warnken T, Sillence MN. Muscle atrophy scores in a population of aged horses and ponies with and without PPID.. 5th Global Equine Endocrine Symposium Bern, Switzerland: National Horse Center; 2023. p. 27.
Christen G, Precht C, van der Kolk J, Fouche N, Gerber V. Age over 25 years, but not plasma adrenocorticotropic hormone concentration above the seasonally adjusted reference range is predictive for radio-graphically assessed changes of chronic laminitis in elderly horses.. Schweiz Arch Tierheilkd 2020;162:781-785.
McFarlane D, Paradis MR, Zimmel D, Sykes B, Brorsen BW, Sanchez A. The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and alpha-melanocyte-stimulating hormone plasma concentrations in horses.. J Vet Intern Med 2011;25:872-881.
Haffner JC, Hoffman RM, Grubbs ST, Shepard KN, Neal DL, Pearce GL. The thyrotropin releasing hormone procedure produces repeatable ACTH concentrations in PPID-negative and PPID-positive horses.. 66th Annual Convention of the American Association of Equine Practitioners Las Vegas, NV: American Association of Equine Practitioners; 2020. p. 303-307.
Fazio E, Medica P, Aronica V, Grasso L, Ferlazzo A. Circulating β-endorphin, adrenocorticotrophic hormone and cortisol levels of stallions before and after short road transport: stress effect of different distances.. Acta Vet Scand 2008;50:6.
Haffner JC, Grubbs SG. The effect of trailering on thyrotropin releasing hormone stimulation of adrenocorticotropic hormone concentration in horses.. 5th Global Equine Endocrine Symposium Bern, Switzerland: National Horse Center; 2023. p. 17-18.
Haffner JC, Hoffman RM, Grubbs SG. A combined TRH-insulin procedure identifies pituitary pars intermedia dysfunction and insulin dysregulation in horses.. 5th Global Equine Endocrinology Symposium Bern, Switzerland: National Horse Center; 2023.
Fredrick J, McFarlane D, Yang F. ACTH releasing following TRH stimulation in thrifty horses compared to metabolically normal horses.. ACVIM Forum Nashville, TN; 2014.
Durham AE. Is equine pituitary pars intermedia activity subdued in the spring?. Dorothy Havemeyer Foundation Equine Endocrinology Summit Miami, FL; 2017.
Haffner JC, Hoffman RM, Grubbs ST. The effect of trailering and dentistry on resting adrenocorticotrophic hormone concentrations in horses.. 4th Global Equine Endocrine Symposium Gut Ising, Germany: Boehringer Ingelheim; 2020.
Potier J, Durham AE. The effect of latitude and breed on circannual ACTH concentrations in the UK.. 4th Global Equine Endocrine Symposium Gut Ising, Germany: Boehringer Ingelheim; 2020.
Durham AE, Shreeve H. Horse-factors influencing the seasonal increase in plasma ACTH secretion.. Dorothy Havemeyer Equine Endocrine Summit Coral Gables, FL; 2017.
Beech J. Comparison of Vitex agnus castus extract and pergolide in treatment of equine Cushing's syndrome.. Proc Am Assoc Equine Pract 2002;48:175-177.
Arana-Valencia N, Thompson DL, Oberhaus EL. Dopaminergic and Antidopaminergic effects on heart rate in healthy horses when challenged with brief 2-minute exercise bouts.. J Equine Vet 2018;71:120-128.
Gehlen H, May A, Bradaric Z. Comparison of insulin and glucose metabolism in horses with pituitary pars intermedia dysfunction treated versus not treated with Pergolide.. J Equine Vet 2014;34:508-513.
Rendle DI, Frost R, Byrne A. Efficacy of a novel palatable pergolide paste formulation for the treatment of pituitary pars intermedia dysfunction (PPID) in ponies.. Equine Vet J 2018;50:16.
Rendle DI, Taylor E, Duz M, Parkin TD, Copas VEN, Durham AE. Effects of pergolide mesylate on plasma adrenocorticotropic hormone concentration in horses with pituitary pars intermedia dysfunction.. Equine Vet J 2013;45:19.
Froin HR, Assmann G, Hoppen HO. Effective long-term treatment of equine pituitary pars intermedia adenomas with dopamine agonist.. Exp Clin Endocrinol Diabetes 1998;106:23.
Williams PD. Equine Cushing's syndrome-retrospective study of twenty four cases and response to medication.. Proceedings of British Equine Veterinary Association Congress 1995.
Anon. Prascend Freedom of Information Summary.. 2011.
Schott HC, Coursen CL, Eberhart SW, Nachreiner RJ, Refsal KR, Ewart SL. The Michigan Cushing's project.. American Association of Equine Practitioners 2001.
Peters D, Erfle J, Slobojan GT. Low-dose pergolide mesylate treatment for equine hypophyseal adenomas (Cushing's syndrome).. Proceedings of the American Association of Equine Practitioners, Lexington, KY 1995.
Walsh DM, McGowan CM, McGowan T, Lamb SV, Schanbacher BJ, Place NJ. Correlation of plasma insulin concentration with laminitis score in a field study of equine Cushing's disease and equine metabolic syndrome.. J Equine Vet 2009;29:87-94.
Hague N, Durham AE, Menzies-Gow NJ. The effect of pergolide dosing compliance on the laboratory control of pituitary pars intermedia dysfunction.. 4th Global Equine Endocrine Symposium Gut Ising, Germany: Boehringer Ingelheim; 2020.
Potier J, Durham A. Association between ACTH, insulin, glucose, and triglycerides with laminitis in PPID.. 4th Global Equine Endocrine Symposium Gut Ising, Germany: Boehringer Ingelheim; 2020.