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Equine veterinary journal2021; 54(3); 457-466; doi: 10.1111/evj.13500

The accuracy of ACTH as a biomarker for pituitary pars intermedia dysfunction in horses: A systematic review and meta-analysis.

Abstract: Accuracy of baseline ACTH for the diagnosis of PPID in horses varies between studies. Objective: To estimate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses and appraise potential causes of heterogeneity. Methods: Systematic review and meta-analysis. Methods: A literature review identified studies reporting diagnostic accuracy data for extraction. Risk of bias was evaluated using QUADAS-2. Two random-effects models, the hierarchical summary receiver operating curve (HSROC) and the bivariate binomial normal model (BBN) were used to pool accuracy measurements. We performed meta-regression using study-level variables. The impact of diagnostic test accuracy on the frequency of false-positive and false-negative results at various pretest probabilities was calculated using the BBN model's accuracy results. Results: Patient selection and index test evaluation demonstrated significant risk of bias. Mean and 95% confidence intervals for sensitivity and specificity for all studies (n = 11) based upon the HSROC model were (0.72, 95% CI: 0.62 to 0.82) and (0.88, 95% CI: 0.79 to 0.93), respectively. When studies with a common positivity threshold of 35 pg/mL ACTH were evaluated (n = 6), sensitivity and specificity were (0.66, 95% CI:0.54 to 0.77) and (0.87, 95% CI: 0.74 to 0.94). In a hypothetical group of one thousand horses with PPID prevalence of 2%, 20%, and 90%, the frequency of resulting false-positive and false-negatives would be (127 and 7), (104 and 68) and (13 and 306), respectively. Factors leading to increased accuracy were case-control design, clinical reference standard and data-driven choice of ACTH threshold. Conclusions: A small number of primary studies (n = 11) were available, demonstrating significant biases. Conclusions: Less biased studies examining diagnostic accuracy of ACTH are needed. In horses with a high pretest probability of PPID, ACTH may be a functional "rule-in" test. Baseline ACTH is not recommended for screening purposes or use in horses without clinical signs of PPID.
© 2021 EVJ Ltd.
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Publication Date: 2021-09-24 PubMed ID: 34428330DOI: 10.1111/evj.13500Google Scholar: Lookup
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  • Journal Article
  • Meta-Analysis
  • Review
  • Systematic Review

Summary

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 research discusses the diagnostic accuracy of Adrenocorticotropic hormone (ACTH) as a biomarker for pituitary pars intermedia dysfunction (PPID), a hormonal disorder in horses. It finds that ACTH can be a useful diagnostic tool in horses showing clinical signs of PPID although not recommended for general screening or use in horses without signs of the disease.

Methodology

  • The researchers conducted a systematic review and meta-analysis, reviewing relevant literature to evaluate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses. This included screening and detection practices across different studies.
  • Risk of bias was assessed using a standardized tool named QUADAS-2, allowing for a structured review of the quality of the studies.
  • The researchers used two statistical models – the hierarchical summary receiver operating curve (HSROC) and the bivariate binomial normal model (BBN) – to combine measurements from multiple studies and estimate the overall performance of ACTH as a diagnostic biomarker.
  • They ran a meta-regression to identify variation between studies and find potential explanations for heterogeneity in the results. By considering study-level variables, the team attempted to clarify the conditions under which ACTH demonstrates optimal diagnostic accuracy.

Results

  • Findings from 11 studies showed a risk of bias, particularly in patient selection methods and the execution of the index test. Yet, the analysis produced favorable mean sensitivity and specificity scores, indicating good diagnostic performance of the ACTH biomarker.
  • When looking at six studies with a commonly used ACTH threshold, the sensitivity and specificity scores were slightly lower, but still demonstrated reasonable accuracy.
  • The research projected the frequency of false-positive and false-negative results for a theoretical group of one thousand horses. The error rates varied at different levels of PPID prevalence, increasing notably for higher prevalences.
  • In terms of improving accuracy, factors such as case-control design, a clinically-based reference standard, and a data-determined ACTH threshold were found to be favorable.

Conclusions

  • Overall, the study emphasized the need for more impartial studies to better ascertain the diagnostic accuracy of ACTH as a biomarker for PPID.
  • The findings suggest that ACTH can be a useful tool for diagnosing PPID in horses that show clinical signs of the disease. However, it is not recommended for preliminary screenings or use in horses that do not present these symptoms.

Cite This Article

APA
Meyer JC, Hunyadi LM, Ordóñez-Mena JM. (2021). The accuracy of ACTH as a biomarker for pituitary pars intermedia dysfunction in horses: A systematic review and meta-analysis. Equine Vet J, 54(3), 457-466. https://doi.org/10.1111/evj.13500

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 3
Pages: 457-466

Researcher Affiliations

Meyer, James C
  • Equine Sport Science, East Hampton, New York, USA.
Hunyadi, László M
  • School of Veterinary Medicine, Texas Tech University, Lubbock, Texas, USA.
Ordóñez-Mena, José M
  • Nuffield Department of Primary Care Health Sciences - University of Oxford, Oxford, UK.

MeSH Terms

  • Adrenocorticotropic Hormone
  • Animals
  • Biomarkers
  • Horse Diseases / diagnosis
  • Horses
  • Pituitary Diseases / diagnosis
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate
  • Prevalence

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Citations

This article has been cited 4 times.
  1. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  2. Lopes A, Huber L, Durham AE. The Seasonality of Serum Insulin Concentrations in Equids and the Association With Breed, Age, and Sex. J Vet Intern Med 2025 May-Jun;39(3):e70089.
    doi: 10.1111/jvim.70089pubmed: 40219807google scholar: lookup
  3. Fouché N, Doras C, Schüpbach-Regula G, Scherer A, Freudenschuss B, Gerber V. Association Between Adrenocorticotropic Hormone Concentration and Clinical Signs of Pituitary Pars Intermedia Dysfunction in Swiss and Austrian Equids. J Vet Intern Med 2025 Mar-Apr;39(2):e70008.
    doi: 10.1111/jvim.70008pubmed: 40095750google scholar: lookup
  4. Sundra T, Kelty E, Rossi G, Rendle D. Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction. Front Vet Sci 2024;11:1332337.
    doi: 10.3389/fvets.2024.1332337pubmed: 38511195google scholar: lookup
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