Evaluation of the sensitivity and specificity of basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: A systematic review

Tatum, R.C.; McGowan, Catherine; Ireland, J.L.

doi:10.1016/j.tvjl.2021.105695

Cited by 14 publications

(10 citation statements)

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“…Three systematic reviews [2][3][4] were identified through searches in VetSRev, all of which met inclusion criteria, and no relevant evidence summaries were identified from Veterinary Evidence archive searches.…”

Section: Review Of Current Veterinary Evidence Summariesmentioning

confidence: 99%

“…1 Diagnosis and treatment of the condition can be challenging due to either conflicting literature or a lack of evidence. Most of the literature is expert opinion or case series, and there are only two systematic reviews of the accuracy of one available diagnostic test 2,3 and one systematic review of the efficacy of one treatment 4 to inform clinical decision-making. The development of clinical guidelines is standard practice in human healthcare, and these have been shown to influence clinical decision-making in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Review Of Current Veterinary Evidence Summariesmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Pituitary pars intermedia dysfunction is one of the most common endocrinopathies in horses; however, the pathophysiology of PPID is incompletely understood [ 33 , 34 , 35 , 36 , 37 , 38 ]. The disease is caused by loss of dopaminergic inhibition of the pituitary PI due to oxidative-stress and subsequent neurodegeneration of dopaminergic neurons within the hypothalamus [ 17 , 39 ].…”

Section: Pathophysiology Of Ppidmentioning

confidence: 99%

“…Meta-analyses and systematic reviews have been performed to establish the sensitivity and specificity of basal ACTH. Although not broken down by season, the median sensitivity and specificity of basal ACTH in one study were 75.5% and 95.2% respectively [ 36 ], while another study reported the mean sensitivity and specificity at 66% and 87% respectively [ 130 ]. Based on these results, basal ACTH is excellent for ruling out PPID, and less accurate for detecting the condition unless the horse has severe clinical signs.…”

Section: Diagnosismentioning

confidence: 99%

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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“… 5 Baseline ACTH concentration is considered as an excellent test to diagnose PPID with an overall test accuracy above 90%, a median sensitivity above 75% and a median specificity above 75%; however, in autumn, test characteristics decline reducing its diagnostic value. 6 , 7 Considering that baseline ACTH concentrations fluctuate with seasonal changes, stress, exercise and disease status, the thyrotropin‐releasing hormone (TRH) stimulation test was developed to standardize ACTH concentrations and improve diagnosis. 8 , 9 , 10 , 11 , 12 , 13 , 14 The results of TRH stimulation tests vary with environmental factors, the test still performs better than baseline ACTH with a greater accuracy, sensitivity, and specificity.…”

Section: Introductionmentioning

confidence: 99%

Repeatability of a thyrotropin‐releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses

Kam

McKenzie

Coyle

et al. 2021

Veterinary Internal Medicne

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Background Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy of horses diagnosed with a thyrotropin‐releasing hormone (TRH) stimulation test. Hypothesis/Objectives Describe the repeatability of TRH stimulation in horses with and without PPID in winter and autumn. Animals Twenty adult horses; 6 controls and 6 with PPID tested in autumn, 8 controls and 6 with PPID tested in winter with 3 controls and 3 with PPID tested in both seasons. Methods Thyrotropin‐releasing hormone stimulation was performed on 2 consecutive occasions, 1 week before and 1 week after the winter solstice and the autumn equinox. Blood was collected before and 30 minutes after IV injection of 1 mg of TRH. ACTH concentration was determined by a chemiluminescent assay. Repeatability and test‐retest reliability were assessed by repeated measures analysis of variance, intraclass correlation coefficient and within‐horse coefficients of variation (CV). Bland‐Altman plots were generated to visualize agreement between repetitions. Results In winter, no week effect was detected on the results of the TRH simulation and the test had an excellent test‐retest reliability. In autumn, after‐TRH ACTH concentrations were significantly lower on week 2 (P = .02) and the test only had a good test‐retest reliability. There were significantly larger within‐horse CV during autumn (P = .04) and after TRH stimulation (P = .04). There were 2 misclassifications in winter and 4 in autumn. Conclusions and Clinical Importance The TRH stimulation test was repeatable when performed 2 weeks apart in winter; however, in autumn, more variability in after‐TRH ACTH concentrations resulted in decreased repeatability.

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Evaluation of the sensitivity and specificity of basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: A systematic review

Cited by 14 publications

References 65 publications

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

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

Pituitary Pars Intermedia Dysfunction (PPID) in Horses

Repeatability of a thyrotropin‐releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses

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