Idiopathic Short Stature Phenotypes among Korean Children: Cluster Analysis

Abstract

Idiopathic short stature (ISS) is a heterogeneous group and their responsiveness to growth hormone treatment varies among individuals. The aim of this study was to identify homogeneous phenotypes to better assess response before the initiation of treatment. We focused on person-centered approaches using a latent profile analysis. Clinical data of 218 children (127 boys and 91 girls) aged 4-15 years were obtained from the "LG Growth Study" which is a non-interventional Korean multicenter registry for growth hormone treatment. Growth hormone dose, first-year difference in height standard deviation score (Delta height SDS), mid-parental height SDS, and initial bone age were inputted into the model. The distribution of scatter plot was clearly distinguished at the chronological age of 8.83 years, Delta height SDS of 0.82 and mean GH dose of 0.36 mg/kg/week. The latent profile analysis revealed three distinct phenotypes names as follows: younger good responder (n = 56), older good responder (n = 111), and older poor responder (n = 51) groups. Despite more than twice the mean growth hormone dose, the older poor responder group showed the least improvement in the mean Delta height SDS. The pretreatment height velocity and peak growth hormone level were lower for the older poor responder group compared with those of the older good responder group. The statistically optimal cutoff point for predicting poor response was 3.41 cm/year for pretreatment height velocity and 9.18 ng/mL for peak growth hormone level. This study offers a new multidimensional approach to enable personalized growth hormone treatment optimization according to ISS phenotypes.