Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID)

Kirkwood, Naomi; Hughes, Kristopher; Stewart, Allison J.

doi:10.3390/vetsci9100572

Cited by 5 publications

(10 citation statements)

References 68 publications

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“…Both tests should be interpreted in accordance with appropriate DCOV, RI or seasonal thresholds, depending on the clinical presentation and need to reduce false negative or false positive results. Diagnosis based on clinical signs alone is possible, though once clinical signs are obvious, the disease could be severe [ 113 ]. To increase quality of life and athletic performance, treatment with pergolide mesylate is recommended.…”

Section: Discussionmentioning

confidence: 99%

“…However, the disease can have severe, life threatening consequences and ability to diagnose subclinical or mild PPID and initiate treatment before end-stage disease may be beneficial [ 40 , 47 , 113 ]. A recent prospective case series measured basal and TRH-stimulated ACTH concentrations in seven horses with subclinical PPID, and found that TRH-stimulation testing in late summer or early autumn (February and March in Australia) identified most horses that transitioned to clinical PPID over a 3.5 year period [ 113 ]. This was a small case series, so further research is required to determine if early diagnosis is warranted.…”

Section: Diagnosismentioning

confidence: 99%

“…Pituitary size and histomorphology are also affected by season [ 115 ] and age [ 117 ] making the use of histopathology in diagnosis of PPID challenging [ 40 ]. Results of tests in horses that are affected by early or subclinical disease, are often equivocal [ 113 ]. Untreated PPID cases due to false-negative test results can lead to morbidity through muscle wastage, opportunistic infections, and difficulty thermoregulating.…”

Section: Diagnosismentioning

confidence: 99%

“…In early PPID or when clinical signs are mild, the TRH stimulation test is useful for increased accuracy of diagnosis [ 1 , 2 , 40 , 113 , 121 ]. Plasma ACTH is measured before and either 10 or 30 min after administration of 1 mg TRH IV (0.5 mg for ponies).…”

Section: Diagnosismentioning

confidence: 99%

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Pituitary Pars Intermedia Dysfunction (PPID) in Horses

Kirkwood

Hughes

Stewart

2022

Veterinary Sciences

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Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing hormone (TRH) used to assess ACTH response to TRH stimulation is not commercially available as a sterile registered product in many countries. The relationship between PPID and insulin dysregulation and its association with laminitis, as well as additional management practices and long-term responses to treatment with pergolide also require further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

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Pituitary Pars Intermedia Dysfunction (PPID) in Horses

Kirkwood

Hughes

Stewart

2022

Veterinary Sciences

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“…One systematic review 17 and 13 additional publications [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] were identified that provided data on the frequency of clinical signs within veterinary-diagnosed PPID cases, which were considered in combination with the outcomes from the panel Delphi consultation to categorise clinical signs by the index of clinical suspicion (Table 5). Generalised or regional hypertrichosis (± delayed/abnormal coat shedding) was the most commonly reported sign across all studies (Figures 1-5).…”

Section: Case Selection For Diagnostic Testing and Pretest Probabilitymentioning

confidence: 99%

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

Menzies‐Gow,

Banse,

Duff

et al. 2023

Equine Veterinary Journal

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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.

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