The Use of miRNA Panel as a Growth Plate Marker of Short-Term Response to GH.

INTRODUCTION: Recombinant human growth hormone (GH) therapy shows variable growth responses in patients with growth hormone deficiency (GHD), highlighting the need for reliable biomarkers to predict individual sensitivity. OBJECTIVE: This study investigated circulating microRNAs (miRNAs) involved in growth plate regulation during GH therapy in prepubertal children with GHD, aiming to establish a miRNA panel correlating with GH responsiveness. PATIENTS AND METHODS: Sixteen patients were treated with daily recombinant GH (0.033 mg/kg) for 6 months. Two participants were excluded for protocol noncompliance, and one withdrew due to the spontaneous onset of puberty. Circulating levels of six miRNAs (miR-22-3p, miR-30c-5p, miR-140-5p, miR-340-5p, miR-494-3p, and miR-16-5p) were measured via digital PCR at baseline and at 1, 3, and 6 months of therapy. Clinical data (height, weight, growth velocity) and hormone levels were collected simultaneously. RESULTS: All miRNAs displayed a characteristic response pattern: significant increases at 1 and 6 months, with a transient decline at 3 months. Despite these changes, no significant correlations were identified between miRNA levels and growth velocity, height SDS, or IGF-1 levels. The study included treatment-naïve patients and those with prior GH therapy following a 30-day wash-out period. While the treatment-naïve group exhibited greater height-SDS gains (p = 0.008), no differences in miRNA expression were observed between groups, nor was there a correlation between miRNA levels and height-SDS increments. CONCLUSION: While this miRNA panel identified treatment-responsive miRNAs, it did not correlate with growth outcomes. Increasing the sample size and incorporating additional miRNAs could enhance its clinical utility for predicting GH treatment sensitivity in GHD patients. TRIAL REGISTRATION: NCT05946915.