ESPE Abstracts

Background: To date, one randomized, controlled, clinical trial (RCCT) demonstrated that GH-treated patients with SHOX deficiency (SHOX-D) had GH-mediated height gain comparable to that of girls with Turner syndrome (TS). No new safety concerns were identified, but the study was limited by small sample size.

Objective and hypotheses: To examine long-term outcomes in patients treated in standard clinical practice, we assessed final height (FH) and safety outcomes in GH-treated patients diagnosed with SHOX-D using data collected in a multinational observational study (Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)).

Method: At time of analysis, 444 GH-treated patients with SHOX-D (59% girls), diagnosed by genetic analysis and/or investigator assessment, had baseline height available. FH (defined by one or more of the following: closed epiphyses, height velocity <2 cm/year, last bone age >14 years in girls/>16 years in boys) was available for 85 patients (72% girls).

Results: Mean±S.D. baseline age was 9.4±3.1 years, and height SDS was −2.4±0.8. Initial GH dose was 0.30±0.10 mg/kg per week, increasing at FH by <10%. FH at age of 15.5±1.5 years and after 4.2±2.3 years of GH treatment was −1.6±1.1 SDS; height gain from baseline was 0.9±1.0 SDS. Of 434 patients with SHOX-D and ≥1 follow-up visit (2.9±1.8 years follow-up), ≥1 adverse event was reported for 89 (21%) compared with 5214/18 929 (28%) for GeNeSIS overall and 710/1663 (43%) for TS. Adverse events reported for ≥1% of patients with SHOX-D were precocious puberty (3%), arthralgia (3%), hypothyroidism (1%), back pain (1%), and headache (1%). One death was reported, but no cases of malignancy or diabetes. IGF1 SDS was −1.8±2.7 at baseline, increased to 1.2±1.8 at 3 years of follow-up, and was >+2 S.D. for 26% of patients at ≥1 follow-up visit.

Conclusion: In conclusion, ‘real-world’ data from a large cohort of GH-treated patients with SHOX-D support the RCCT findings, with significant height gain to FH and no additional safety concerns.