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

Abstract

Background Pituitary pars intermedia dysfunction (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 robust L2 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.

Science‐in‐brief: Report on the Global Equine Endocrinology Symposium

“…Basal ACTH has been the cornerstone of PPID diagnosis, 5,6 and further research refining the interpretation of basal ACTH concentrations was presented. A study based on a very large cohort of samples presented weekly diagnostic thresholds throughout the year test 7 . Importantly, this study showed a grey zone or a low (95% sensitivity) and high (95% specificity) diagnostic threshold for guiding clinical diagnosis depending on the pretest likelihood of PPID and whether or not the clinician is attempting to confirm or exclude PPID 7 .…”

“…A study based on a very large cohort of samples presented weekly diagnostic thresholds throughout the year test 7 . Importantly, this study showed a grey zone or a low (95% sensitivity) and high (95% specificity) diagnostic threshold for guiding clinical diagnosis depending on the pretest likelihood of PPID and whether or not the clinician is attempting to confirm or exclude PPID 7 . Work on development of a clinical sign score to help determine if endocrine testing is warranted was presented which was considered valuable in improving pretest probabilities.…”

Influence of endocrine disease on l‐lactate concentrations in blood of ponies

“…7 In our study, a single ACTH concentration was used to classify animals as having or not having increased autumnal ACTH concentrations using a previously established seasonal cutoff point from a study that used the same methodology. 30 While this approach is commonly used in daily equine practice, 31 use of a dynamic test to classify animals might have provided a more standardized approach. 39 It is also possible that the study was underpowered to detect subtle differences in l-lactate concentrations.…”

“…30 As second seasonal threshold of ≥76 pg/mL, again established using the same methodology, was also investigated. 31 Animals <1 year of age were excluded from the study.…”

“…A seasonally adjusted ACTH concentration ≥47 pg/mL was used as a cutoff point for increased autumnal ACTH concentrations as suggested in a study using the same methodology 30 . As second seasonal threshold of ≥76 pg/mL, again established using the same methodology, was also investigated 31 . Animals <1 year of age were excluded from the study.…”