TRH-Stimulationstests bei mindestens 15 Jahre alten Pferden und Ponys sowie nach Placebo-kontrollierter Therapie mit Pergolid
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Beschreibung
The TRH stimulation test is used to diagnose pituitary pars intermedia dysfunction (PPID) and is usually dosed with 1 mg TRH per horse (equivalent to 2 µg/kg at 500 kg bw). The main objective of this study was to compare ACTH release after 0.5 or 2 µg/kg TRH in horses and ponies aged at least 15 years (TRH dose comparison). In a further step, the effect of a four- to six-week treatment with pergolide on the results of the TRH stimulation test was to be investigated in a placebo-controlled manner (therapy study).
In the prospective, randomised cross-over dose comparison study, 18 horses and ponies (19.9 ± 4.1 years) participated. The inclusion criterion was a minimum age of 15 years. All received 0.5 and 2 µg/kg TRH (TRH Ferring, Kiel) intravenously in randomised order and with a wash-out phase of 10-14 days. ACTH measurements were taken immediately before (0) and 5, 10, 15, 30, 60, 90, 120 minutes after TRH injection. A linear mixed model with the fixed effects ‘sequence’ (0.5/2 or 2/0.5), ‘period’ (first or second TRH administration) and ‘TRH dose’ (0.5 or 2.0 µg/kg) and with the random effect ‘individual’ was selected for the statistics. The areas under the curves (AUCs) from 0 to 120 minutes after TRH injection were calculated as the main target parameters. In addition, the ACTH values at 0, 10 and 30 minutes after TRH as well as the maximum values and the time of their occurrence were tested for significant differences.
In the dose comparison between 0.5 and 2 µg/kg TRH, there were no significant differences in the ACTH AUCs, basal, ten-minute and maximum values. However, the ACTH thirty-minute values showed a highly significant reduction after 0.5 µg/kg TRH (p = 0.0005). No significant differences were found with regard to sequence and period.
Thus, 0.5 µg/kg TRH appears to be sufficient for PPID diagnostics when using the ACTH ten-minute values. However, there was a tendency in the medians towards lower values after the lower TRH dose. The TRH dose of 0.5 µg/kg should generally not be used for diagnosis using ACTH thirty-minute values, as this can lead to falsely low results.
Based on their results in the TRH dose comparison test with 2 µg/kg TRH, 13 subjects (19.8 ± 4.5 years) took part in the prospective, placebo-controlled therapy study. The inclusion criterion was an ACTH value of at least 100 pg/ml 10 minutes after 2 µg/kg TRH. The horses were therefore either in the interpretive zone or in the PPID likely category according to the recommendations of the Equine Endocrinology Group (2023) with regard to their PPID status. The test subjects initially received a placebo for four to six weeks and then the authorised active ingredient pergolide at the recommended dose of 2 µg/kg for the same period. Each time after the placebo or pergolide administration, new TRH stimulation tests were carried out with the TRH dosage of 2 µg/kg. A paired samples t-test was used for the statistical calculations. The ACTH AUCs and the ACTH values at 0, 10 and 30 minutes after TRH, the maximum values and the time of their occurrence after placebo and pergolide administration were compared. In addition, the results after the initial TRH test were compared with those after placebo and pergolide for significant differences.
Despite treatment with pergolide, the comparison of ACTH values (post placebo with post pergolide, initial with post pergolide and initial with post placebo) showed no significant differences for the most part. Only the ACTH ten-minute values were significantly (p = 0.04) lower after placebo (log10_ACTH10 min: 2.39 ± 0.31 pg/ml) than initially (log10_ACTH10 min: 2.47 ± 0.25 pg/ml).
Other studies have shown positive effects of pergolide, particularly on increased basal ACTH concentrations in horses suffering from PPID. Five of the 13 own test subjects also achieved a better PPID category when their ACTH ten-minute values were analysed. The lack of significantly lower ACTH levels stimulated by TRH after four to six weeks of pergolide administration means that a therapy control or pergolide dose adjustment based on the results of the TRH stimulation test does not appear to be useful.
Autor*in
Mareike Taube
Themen in »TRH-Stimulationstests bei mindestens 15 Jahre alten Pferden und Ponys sowie nach Placebo-kontrollierter Therapie mit Pergolid«
TRH Thyreotropin-Releasing-Hormon Endokrinologie Thyreotropin-Releasing-Hormon-Stimulationstest Hypothyreose Hyperthyreose Hypophyseninsuffizienz Schilddrüsenfunktionsstörungen Pferd Pony Pituitary Pars intermedia Dysfunction (PPID) Equus