Abstract
BACKGROUND: Pathological causes account for approximately 15%-20% of short-stature cases, whereas about 80% of short-statured children have no identifiable underlying etiology and are classified as idiopathic short stature (ISS). ISS represents a highly heterogeneous group, and ongoing debates persist due to the limited availability of observational data and advances in genetic research. Despite its high prevalence, long-term auxological data comparing familial, constitutional, and combined variants across pubertal stages remain limited. OBJECTIVES: Our study aimed to characterize the clinical and laboratory features at presentation and to evaluate the longitudinal growth patterns of children initially diagnosed with ISS. METHODS: A retrospective cohort of 171 children with ISS (46.2% female) was analyzed. Participants were classified as prepubertal (Group 1; n = 121) and pubertal (Group 2; n = 50), each further subdivided into familial (a), constitutional (b), and combined (c) subgroups. Anthropometric, familial, and biochemical parameters were assessed at presentation and final follow-up. Standard deviation scores (SDS) were calculated based on national growth references. Intergroup comparisons were performed using ANOVA or the Kruskal-Wallis test with post hoc corrections. Statistical significance was accepted at p < 0.05. RESULTS: Mean age at first evaluation was 7.94 ± 4.46 years; mean height SDS was -2.45 ± 0.34 with proportionate body proportions and normal birth parameters. Bone age averaged 6.57 ± 4.28 years (≈1.4-year delay). The prepubertal/pubertal distribution was 121 (70.8%) vs. 50 (29.2%); combined phenotypes comprised 53.5% of the cohort. Over 1.85 ± 1.40 years of follow-up, mean ΔHeight SDS was +0.35 ± 0.56; pubertal subgroups, particularly 2b and 2c, showed the most significant gains (ΔHeight SDS +0.58 and +0.53; both p < 0.001 vs. prepubertal). ΔHeight SDS correlated positively with baseline bone-age delay (p < 0.001) and inversely with age (p = 0.002). Growth velocity was normal in all. BMI SDS rose modestly overall (-0.63 ± 0.99 to -0.49 ± 0.92; p = 0.04) and remained below +2 SDS in all cases. CONCLUSIONS: ISS subtypes display distinct auxological courses. Bone-age delay is a key predictor of subsequent catch-up growth, most evident in pubertal CDGP and combined phenotypes. Given the high rate of spontaneous improvement, especially after pubertal onset, careful longitudinal monitoring should precede pharmacologic therapy.