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 (Δheight 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, Δheight 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 Δheight 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.

<p>Association Between Serum Calcium and Phosphorus Levels and Insulin-Like Growth Factor-1 in Chinese Children and Adolescents with Short Stature</p>

“…There are more male patients than females in our study population. This is similar to some previous reports, [33][34][35] considering that men may be more willing to seek medical treatment due to social, family values and other factors.…”

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database

“…Clinical and laboratory records of 3199 prepubertal children with IGHD (n = 2195), ISS (n = 523), and SGA (n = 481), who had received rhGH therapy (Eutropin 1 inj., and Eutropin 1 Pen inj., LG Chem Ltd., Korea) for � 2 years between February 2001 and February 2020, were initially enrolled. The inclusion criteria were as follows: 1) Height below the third percentile according to the 2017 Korean National Growth Charts [16] at the time of hospital visit for IGHD and ISS cases, and at birth and at the time of hospital visit for SGA cases; 2) Two separate GH stimulation test results using insulin, clonidine, L-arginine, L-dopa, or glucagon; 3) children with a peak GH level less than 5 ng/mL (complete IGHD, CGHD) and between 5 to 10 ng/mL (partial IGHD, PGHD) [17][18][19][20][21] were classified as growth hormone deficient and those with that more than 10 ng/mL as ISS and SGA. The exclusion criteria were as follows: 1) Inappropriate auxological data at diagnosis; 2) no rhGH therapy within 1 month after diagnosis; 3) no clinical data, for serum IGF-I and IGFBP-3 levels before and 1 year after rhGH therapy; 4) age at the beginning of the therapy � 10 years; 5) rhGH therapy length under 2 years; 6) weekly rhGH (Eutropin 1 Plus inj., LG Chem Ltd., Korea); 7) patients with a pubertal sign before or during the 2-year rhGH therapy; 8) children with pituitary or hypothalamic lesions, chromosomal and genetic anomalies, and chronic diseases, as well as endocrinological, skeletal or nutritional abnormalities.…”

Neonatal Risk Factors for Growth Retardation in Infants With Congenital Heart Disease

“… 16 Short stature is defined as a height < 2-standard deviations for age and gender, with no structural or functional cause. 17 We examined the potential risk factors for GR among neonatal CHD patients.…”