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The accuracy of ACTH as a biomarker for Pituitary Pars Intermedia Dysfunction in horses: A systematic review and meta-analysis

Meyer, J. C. and Hunyadi, L. M. and Ordóñez-Mena, J. M.

Equine Vet J (2021) :

DOI: 10.1111/evj.13500

Abstract

BACKGROUND: Accuracy of baseline ACTH for the diagnosis of PPID in horses varies between studies. OBJECTIVES: To estimate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses and appraise potential causes of heterogeneity. STUDY DESIGN: 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 pre-test 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. MAIN LIMITATIONS: 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 pre-test 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.

Citation

Meyer, J. C., Hunyadi, L. M., & Ordóñez-Mena, J. M. (2021). The accuracy of ACTH as a biomarker for Pituitary Pars Intermedia Dysfunction in horses: A systematic review and meta-analysis. Equine Vet J. https://doi.org/10.1111/evj.13500 meta-analysis, horse, diagnostic accuracy, Acth, Ppid, sensitivity, specificity

Keywords