Clinically and temporally specific diagnostic thresholds for plasma ACTH in the horse

Background Pituitarypars intermediadysfunction (PPID) is commonly investigated using plasma ACTH concentrations but problems exist with currently available diagnostic thresholds. Objectives To derive temporally specific diagnostic thresholds for equine plasma ACTH concentration to be used alongside clinical judgement in each individual week of the year and appropriate for the degree of clinical suspicion in any given case. Furthermore, to apply these thresholds to compare the prevalence of high and low ACTH in two subgroups of animals with high and low clinical suspicion of PPID. Study design A retrospective population study examining a large laboratory database of equine plasma ACTH concentrations using an indirect approach to calculate diagnostic thresholds. Methods Logs of plasma ACTH concentrations from 75 892 individual horses were examined using robustL(2)estimation of mixtures of two normal distributions in categories of each week and month of the year. Thresholds dividing the two populations of high-ACTH and low-ACTH horses were then established at different levels of sensitivity and specificity and compared with clinical subgroups of horses divided based on reported clinical signs, as having high (n = 4036) or low (n = 3022) clinical suspicion of PPID. Results For most of the year there were small interweek differences in diagnostic thresholds. However, from mid-June to early-December diagnostic thresholds showed greater interweek variability, reaching a maximum in late September and early October. Grouping of high- and low-ACTH compared favourably with grouping based on clinical signs. Main limitations Given the multiple sources of diagnostic samples, pre-analytical data could not be fully verified. Conclusions Diagnostic thresholds for equine plasma ACTH vary through the year. It is especially important to consider the temporally specific threshold between June and December. Different clinical thresholds can be used depending on the case circumstances and whether a false-positive or false-negative diagnosis is deemed least desirable.