Impaired GH Secretion in Patients with SHOX Deficiency and Efficacy of Recombinant Human GH Therapy.

Background/Aims: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. Patients and Design: We studied 16 patients (10 females; 9.7 \ub1 2.9 years old; height -2.46 \ub1 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 \ub1 0.053 mg/kg/week). Results: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from -1.03 \ub1 1.44 to 2.77 \ub1 1.95; p = 0.001), height SDS (from -2.41 \ub1 0.71 to -1.81 \ub1 0.87; p < 0.001), and IGF-1 values (from -0.57 \ub1 1.23 to 0.63 \ub1 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = -0.618, p = 0.032), bone age (r = -0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. Conclusion: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern