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. 2021 Jan;35(1):560-570.
doi: 10.1111/jvim.16017. Epub 2020 Dec 24.

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

Remona Horn  1 , Allison J Stewart  1 , Karen V Jackson  1 , Elizabeth L Dryburgh  2 , Carlos E Medina-Torres  1 , François-René Bertin  1
Affiliations

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

Remona Horn et al. J Vet Intern Med. 2021 Jan.

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.

Keywords: diagnostic test; endocrinology; reference intervals; statistical methods; thyrotropin-releasing hormone.

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Conflict of interest statement

Elizabeth L. Dryburgh is employed by Boehringer‐Ingelheim Pty Ltd and François‐Rene Bertin and Allison J. Stewart have consulted for Boehringer‐Ingelheim Pty Ltd.

Figures

FIGURE 1
FIGURE 1
A, Monthly baseline ACTH concentrations (mean and SD of log‐transformed data) in mature horses grouped by age. Age groups are 10 to 14 years in black (n = 28), 15 to 19 years in blue (n = 28), and older than 20 years in red (n = 15). The data were log‐transformed for the analysis. * indicates P < .05 between groups. B, Monthly baseline ACTH concentrations (mean and SD of log‐transformed data) in mature horses grouped by sex. Females are in black (n = 36) and males in blue (n = 36). The data were log‐transformed for the analysis. * indicates P < .05 between groups. C, Monthly baseline ACTH concentrations (mean and SD of log‐transformed data) in mature horses grouped by body condition score (BCS). Groups are low BCS (1‐3) in black (n = 3), adequate BCS (4‐6) in blue (n = 27), or high BCS (7‐9) in red (n = 27). The data were log‐transformed for the analysis. * indicates P < .05 between groups
FIGURE 2
FIGURE 2
A, Monthly post–thyrotropin‐releasing hormone (TRH) stimulation ACTH concentrations (mean and SD of log‐transformed data) in mature horses grouped by age. Age groups are 10 to 14 years in black (n = 28), 15 to 19 years in blue (n = 27), and older than 20 years in red (n = 15). The data were log‐transformed for the analysis. * indicates P < .05 between groups. B, Monthly post‐TRH stimulation ACTH concentrations (mean and SD of log‐transformed data) in mature horses grouped by sex. Females are in black (n = 36) and males in blue (n = 36). The data were log‐transformed for the analysis. * indicates P < .05 between groups
FIGURE 3
FIGURE 3
Monthly diagnostic cutoff values (in black) and upper limits of reference intervals (in red) for baseline ACTH concentrations in mature horses
FIGURE 4
FIGURE 4
Monthly diagnostic cutoff values (in black) and upper limits of reference intervals (in red) for post–thyrotropin‐releasing hormone stimulation ACTH concentrations in mature horses
FIGURE 5
FIGURE 5
A, Monthly test accuracy for baseline (solid line) and post–thyrotropin‐releasing hormone (TRH) stimulation (dotted line) ACTH concentrations in mature horses. B, Monthly test sensitivity for baseline (solid line) and post‐TRH stimulation (dotted line) ACTH concentrations in mature horses using diagnostic cutoff values (in black) and upper limits of reference intervals (in red). C, Monthly test specificity for baseline (solid line) and post‐TRH stimulation (dotted line) ACTH concentrations in mature horses using diagnostic cutoff values (in black) and upper limits of reference intervals (in red)
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