Growth hormone therapy and near-final height in SHOX deficiency and turner syndrome: a real-world single-center retrospective cohort study.

UNLABELLED: Short stature homeobox-containing (SHOX)-gene haploinsufficiency causes short stature both in isolated SHOX deficiency and in Turner syndrome (TS), yet head-to-head data on growth-hormone (GH) outcomes remain scarce. We therefore compared growth response and near-final height (NFH) after GH therapy between girls with SHOX deficiency and those with TS. Single-centre retrospective cohort study. In this single-centre retrospective cohort, we reviewed 44 pre-pubertal girls who received daily GH (mean 0.045 mg/kg/day) between 2015 and 2024 and subsequently reached NFH (bone age ≥ 14 y; height velocity < 2 cm/year). Ten had molecularly confirmed SHOX deficiency and 34 had karyotype-proven TS. Baseline auxology, annual height velocity, pubertal timing, treatment duration, NFH standard-deviation score (SDS) and total height SDS gain were analysed. Mean chronological and bone ages at GH initiation were similar (10.7 ± 1.9 vs 10.4 ± 2.7 years). Baseline height SDS was lower in TS (-3.51 ± 1.0) than in SHOX (-2.66 ± 0.8). First-year growth velocity was higher in SHOX (8.55 ± 1.4 cm/year) than TS (6.72 ± 1.9 cm/year; p = 0.01). Puberty began earlier in SHOX (11.6 ± 1.3 years) than TS (13.7 ± 1.5 years; p < 0.01), and GH exposure was shorter (2.00 ± 0.4 vs 4.38 ± 2.3; p < 0.01). Observed NFH-SDS was similar between groups (SHOX - 2.46 ± 1.2 vs TS - 2.47 ± 1.0). Unadjusted height-SDS gain was greater in TS (1.04 ± 0.1 vs 0.20 ± 0.2; p = 0.04). In exploratory ANCOVA models adjusting for baseline age, baseline height SDS, and GH treatment duration, adjusted height-SDS gain did not differ significantly between groups.

CONCLUSIONS

TS was associated with a greater unadjusted height-SDS gain, whereas SHOX deficiency was characterized by earlier puberty and shorter GH exposure. Although observed NFH-SDS was similar, these findings highlight how differences in pubertal timing and treatment duration may influence growth outcomes in routine clinical practice and should be interpreted as reflecting real-world growth trajectories rather than intrinsic biological responsiveness to GH therapy.

WHAT IS KNOWN: • Growth hormone therapy is an established treatment for short stature in both SHOX deficiency and Turner syndrome. • Treatment response is influenced by several factors, including age at treatment initiation and pubertal development.

WHAT IS NEW: • This study provides a real-world comparison of growth hormone treatment outcomes in girls with SHOX deficiency and Turner syndrome. • Spontaneous pubertal progression in SHOX deficiency versus medically induced puberty in Turner syndrome may substantially influence the duration of the therapeutic growth window and the observed growth response.