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      Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses

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          Abstract

          Background

          Diagnosis of pituitary pars intermedia dysfunction (PPID) is problematic because of large variations in ACTH concentrations.

          Hypothesis/Objectives

          Compare the test characteristics of baseline and post–thyrotropin‐releasing hormone (TRH) stimulation plasma ACTH concentrations in horses using diagnostic cutoff values (DCOVs) and reference intervals (RIs) and determine the clinical consequences of using each method.

          Animals

          One hundred six mature horses: 72 control cases and 34 PPID cases.

          Methods

          Prospective case‐controlled study. Horses underwent monthly TRH stimulation tests. Diagnostic cutoff values were determined monthly by receiver operating characteristic curves using the Youden index. Reference intervals were determined monthly by a robust method. For each case age, sex and body condition score (BCS) were recorded.

          Results

          Baseline ACTH concentrations varied by month ( P < .001) with significant “month × age” ( P = .003), “month × sex” ( P = .003), and “month × BCS” ( P = .007) effects. Baseline ACTH concentrations were accurate to diagnose PPID (0.91 ± 0.06) with DCOVs increasing the test sensitivity (0.61 ± 0.21 to 0.87 ± 0.05, P = .002) and RI increasing test specificity (0.85 ± 0.12 to 0.98 ± 0.01, P = .01). Thyrotropin‐releasing hormone stimulation improved test accuracy (0.91 ± 0.06 to 0.97 ± 0.03, P = .004).

          Conclusions and Clinical Importance

          ACTH concentrations follow a circannual rhythm and vary with physiological factors. As using DCOVs increases the ability to detect mild cases and using RI decreases the risk of unnecessary treatments, ACTH concentrations should be interpreted within a specific clinical context. The TRH stimulation test improves the diagnosis of PPID.

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          Most cited references 57

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          Measuring the accuracy of diagnostic systems.

           J Swets (1988)
          Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
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            Relationship between condition score, physical measurements and body fat percentage in mares.

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              ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other related topics.

              Reference intervals (RI) are an integral component of laboratory diagnostic testing and clinical decision-making and represent estimated distributions of reference values (RV) from healthy populations of comparable individuals. Because decisions to pursue diagnoses or initiate treatment are often based on values falling outside RI, the collection and analysis of RV should be approached with diligence. This report is a condensation of the ASVCP 2011 consensus guidelines for determination of de novo RI in veterinary species, which mirror the 2008 Clinical Laboratory and Standards Institute (CLSI) recommendations, but with language and examples specific to veterinary species. Newer topics include robust methods for calculating RI from small sample sizes and procedures for outlier detection adapted to data quality. Because collecting sufficient reference samples is challenging, this document also provides recommendations for determining multicenter RI and for transference and validation of RI from other sources (eg, manufacturers). Advice for use and interpretation of subject-based RI is included, as these RI are an alternative to population-based RI when sample size or inter-individual variation is high. Finally, generation of decision limits, which distinguish between populations according to a predefined query (eg, diseased or non-diseased), is described. Adoption of these guidelines by the entire veterinary community will improve communication and dissemination of expected clinical laboratory values in a variety of animal species and will provide a template for publications on RI. This and other reports from the Quality Assurance and Laboratory Standards (QALS) committee are intended to promote quality laboratory practices in laboratories serving both clinical and research veterinarians. © 2012 American Society for Veterinary Clinical Pathology.
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                Author and article information

                Contributors
                f.bertin@uq.edu.au
                Journal
                J Vet Intern Med
                J Vet Intern Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                0891-6640
                1939-1676
                24 December 2020
                Jan-Feb 2021
                : 35
                : 1 ( doiID: 10.1111/jvim.v35.1 )
                : 560-570
                Affiliations
                [ 1 ] School of Veterinary Science The University of Queensland Gatton Queensland Australia
                [ 2 ] Boehringer Ingelheim Pty Ltd North Ryde New South Wales Australia
                Author notes
                [* ] Correspondence

                François‐René Bertin, School of Veterinary Science, Veterinary Science Building (8114), The University of Queensland, Gatton, QLD 4343, Australia.

                Email: f.bertin@ 123456uq.edu.au

                Article
                JVIM16017
                10.1111/jvim.16017
                7848300
                33368633
                © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 5, Tables: 2, Pages: 11, Words: 8436
                Product
                Funding
                Funded by: Boehringer Ingelheim Pty Ltd
                Funded by: The University of Queensland
                Categories
                Standard Article
                EQUINE
                Standard Articles
                Endocrinology
                Custom metadata
                2.0
                January/February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:01.02.2021

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