The ACTH ratio validates the thyrotropin-releasing hormone stimulation test to diagnose pituitary pars intermedia dysfunction but does not enhance performance.

Overview

• This study evaluated whether using the ratio of post- to pre-thyrotropin-releasing hormone (TRH) stimulated plasma ACTH concentrations improves the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses.
• While the ratio reflects pituitary response to TRH and supports the TRH stimulation test’s validity, it does not perform better than simply using post-TRH ACTH levels alone for diagnosing PPID.

Background and Objective

• PPID is a common endocrine disorder in horses caused by dysfunction of the pituitary pars intermedia.
• Diagnosing PPID can involve measuring plasma ACTH levels before and after stimulation with TRH, a hormone that triggers ACTH release.
• This study aimed to assess whether calculating a ratio of post-TRH to pre-TRH plasma ACTH concentrations enhances diagnostic accuracy compared to using post-TRH ACTH concentrations alone.

Study Design and Methods

• A prospective, case-controlled study was conducted over one year (January to December 2018).
• Twenty-one horses diagnosed with PPID and 63 healthy control horses were included.
• Each horse received an intravenous injection of TRH.
• Plasma ACTH concentrations were measured before TRH administration (pre-TRH) and 30 minutes after TRH administration (post-TRH).
• The post-/pre-TRH ACTH ratio was calculated by dividing the post-TRH ACTH concentration by the pre-TRH concentration.
• Statistical analysis included a linear mixed-effect model to assess the effects of PPID status and month on the ACTH ratio.
• The diagnostic value of the ACTH ratio was evaluated using receiver operating characteristic (ROC) curves to calculate accuracy, sensitivity, specificity, and diagnostic cutoffs based on the Youden index.

Key Findings

• Both the presence of PPID and the month of testing significantly influenced the post-/pre-TRH ACTH ratio, consistent with the known seasonal variation in ACTH levels.
• Horses with PPID generally had higher post-/pre-TRH ACTH ratios compared to controls in 7 out of 12 months assessed.
• Diagnostic performance of the ACTH ratio varied by month, showing accuracy that ranged from fair to good.
• Despite fair to good accuracy, the ratio consistently exhibited low positive likelihood ratios, meaning it was limited in ruling in disease presence.
• Using the ratio did not improve diagnostic sensitivity or specificity compared to using just the post-TRH ACTH concentration alone.

Interpretation and Conclusions

• The post-/pre-TRH plasma ACTH ratio reflects the pituitary pars intermedia’s response to TRH stimulation, validating the use of the TRH stimulation test for diagnosing PPID.
• However, calculating the ratio does not enhance the test’s diagnostic performance beyond that achieved by measuring post-TRH ACTH concentration only.
• Therefore, clinicians are recommended to use the TRH stimulation test but can rely on the post-TRH ACTH concentration alone without calculating the ratio.
• This simplifies the diagnostic process while maintaining reliable diagnosis of PPID.

Clinical Implications

• The TRH stimulation test remains a valuable diagnostic tool for equine PPID.
• Measuring post-TRH ACTH concentration is sufficient for diagnosing PPID without calculating ratios.
• Seasonal variations impact ACTH levels and should be considered when interpreting test results.
• This research helps optimize diagnostic workflows by focusing on the most effective and practical metrics.