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 ± 2.9 years old; height -2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 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 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from -2.41 ± 0.71 to -1.81 ± 0.87; p < 0.001), and IGF-1 values (from -0.57 ± 1.23 to 0.63 ± 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

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 concer

Multicenter study on rhGH treatment in patients with SHOX-Deficiency.

Background: Mutations of the Short Stature Homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes(Xp22 and Yp11.3) are correlated with short stature. Patients with SHOX-Deficiency (SHOX-D) have different degrees of growthimpairment and generally remain short in adulthood. Turner Syndrome (TS) subjects present a SHOX haploinsufficiency that appears to be substantially responsible for their short stature. Considering the positive effects obtained with GH therapy in patients with TS, this treatment was also proposed in short stature due to isolated SHOX-D.Objective: The aim of our retrospective study was to analyze height gain and safety of rhGH therapy in patients with SHOX-D.Methods:We studied twelve patients (7 females, 5 males; age 8.7 ± 2.9 years; range 4.9-13.16 years)) with isolated SHOX-D geneticallyconfirmed, all with height SDS < 1.5, target height SDS -1.29 ± 0.65, and in 1 patient with SHOX-D combined with trichorhinophalangealsyndrome. All patients were treated for at least 1 year (2.49 ± 1.45; range 1-6.43) with rhGH (mean dosage of 0.026 ± 0.003mg/kg/day). Results:: GH treatment significantly improved Growth Velocity SDS (2.11 ± 1.42) and height SDS (from -2.03 ± 0.22 to -1.62 ± 0.45, p<0.03), without affecting BMI SDS (from 0.18 ± 1.06 to 0.45 ± 1.74). In the patient with SHOX-D and trichorhinophalangeal syndrome GH failed to improve height SDS. Madelung deformity, if present at the start of therapy, did not deteriorate during follow-up. The better catch-up growth was obtained in the 3 younger patients. There were no discontinuation due to adverse events and no serious adverse events were reported for subjects with SHOX-D.Conclusions: The growth velocity in subjects with SHOX-D was significantly accelerated during rhGH therapy and resulted in a significant gain of height. Our data confirm the few reported evidences showing that GH therapy has a positive statural effect in SHOX haploinsufficiency without cause serious adverse events. Further longitudinal studies are needed to confirm these preliminary results