BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction

Abstract

BackgroundPituitary 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.ObjectivesTo develop evidence‐based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature.Study designEvidence‐based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework.MethodsResearch 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.Results and recommendationsThe 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.Main limitationsLimited relevant publications in the veterinary scientific literature.ConclusionsThese findings should be used to inform decision‐making in equine primary care practice.

Clinical insights: Advances in equine endocrinology

“…1,2 This relatively high prevalence, especially in aged animals, reinforces the importance of the selection of PPID as the topic for development of British Equine Veterinary Association (BEVA) primary care clinical guidelines, which are included in this special collection. 3 The goal of these guidelines is to provide evidence-based recommendations for the diagnosis and management of PPID directed at equine practitioners in an ambulatory setting. The panel utilised a previously established framework to identify clinical questions relevant to PPID, and to make recommendations related to those questions based on appraisal of the currently available literature.…”

“…The panel utilised a previously established framework to identify clinical questions relevant to PPID, and to make recommendations related to those questions based on appraisal of the currently available literature. [3][4][5] Hypertrichosis and altered/delayed hair coat shedding have long been described as an extremely common, almost pathognomonic, clinical sign of PPID in equids. 6,7 That assessment is supported by the evidence review conducted by Menzies-Gow and colleagues, which found evidence for a high clinical suspicion of PPID in animals with haircoat changes and stressed the importance of considering both animal age and clinical signs in case selection for PPID testing.…”

“…6,7 That assessment is supported by the evidence review conducted by Menzies-Gow and colleagues, which found evidence for a high clinical suspicion of PPID in animals with haircoat changes and stressed the importance of considering both animal age and clinical signs in case selection for PPID testing. 3 Clinical signs such as hyperhidrosis, regional adiposity, epaxial muscle atrophy, laminitis, weight loss, recurrent infections or delayed healing, behaviour changes, or polyuria and polydipsia may prompt moderate suspicion of PPID, unless seen in animals <10 years of age in which the prevalence of PPID is extremely low. Colbath et al 8 explored an infrequently described clinical finding in aged horses with advanced PPID, namely pathological fractures.…”

“…13 In this collection, Menzies-Gow and colleagues found support for the currently recommended diagnostic approaches of assessment of basal plasma ACTH concentrations or ACTH responses to exogenous thyrotropin-releasing hormone (TRH) administration. 3 Their evidence review demonstrated that these tests have good to excellent diagnostic accuracy depending on the pre-test probability of disease, which increases with increasing age and clinical signs described above. However, there is also substantial evidence that many factors-particularly breed and season, but also geographic location, coat colour, diet, illness, and recent transport-impact test results and thus must be considered for accurate interpretation.…”

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“…EVJ is proud to have published BEVA Primary Care Clinical Guidelines on analgesia, 6 wound management 7 and pituitary pars intermedia dysfunction 8 . We are equally delighted to have published a small but growing group of systematic reviews, particularly in recent years, where high‐quality evidence is now available for equine anaesthesia, 9–11 PPID 12 and laminitis, 13,14 spinal disorders, 15 respiratory disorders, 16,17 lameness in working equids, 18 clinical predictive models, 19 vaccine efficacy, 20,21 sarcoid treatment, 12 use of furosemide, 22 reproduction, 23,24 physiotherapy, 25 diagnostic imaging 26 and on the prevalence of a range of infectious diseases 27–32 .…”