ESPE Abstracts (2015) 84 P-2-408

ESPE2015 Poster Category 2 GH & IGF (40 abstracts)

Does Skeletal Disproportion in Children with Idiopathic Short Stature Influence Response to GH Therapy?

Wayne S Cutfield a , Anders Lindberg b , Paul Hofman a , Jose Derraik a , Mitchell E Geffner c & Cecilia Camacho-Hubner a,

aPediatric Endocrinology, Liggins Institute, University of Auckland, Auckland, New Zealand; bPfizer Health AB, Sollentuna, Sweden; cCenter for Endocrinology, Diabetes, and Metabolism, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA; dEndocrine Care, Pfizer Inc., New York, NY, USA

Background: Children with ISS have an array of causes that lead to short stature and/or poor growth velocity. Genetic causes of short stature, notably SHOX mutations, can be associated with subtle skeletal disproportion with shorter limbs, manifesting as increased sitting-to-standing height ratios or SDS.

Objective and hypothesis: Children with ISS and skeletal disproportions have a diminished growth response to GH treatment compared to children with proportionate short stature after 1 year (short-term) and at near-adult height (NAH; long-term).

Method: ISS patients registered in Pfizer international growth database with a stimulated peak GH >10 μg/l and treated with GH were included. Short- and long-term growth responses were analyzed. Sitting height % SDS was grouped as: normal (SDS −1.0–<1.1), mild (SDS 1.1–<2.1), and moderate (SDS >2.1) disproportionate short stature. Wilcoxon rank sum test was used for univariate statistical comparisons. ANOVA was used for group comparisons. P-value <0.05 was considered significant.

Results: Prior to GH treatment, the ISS group displayed Gaussian distribution for skeletal proportion. For short-term analyses, the number of patients in each group was: normal (n=193), mild (n=191), and moderate (n=140). The corresponding number of patients in each group attaining NAH was: normal (57), mild (52), and moderate (28). Short-term growth responses, expressed as Studentized Residuals using the KIGS ISS 1st-year prediction model (Ranke MB et al. Horm Res 2007; 68:53–62), showed a trend toward poorer growth response with greater severity of disproportion (mean values; normal=−0.04, mild=−0.16, and moderate=−0.25, P=0.07). Long-term growth showed a larger difference, expressed as delta height SDS from GH start to NAH (median values; normal/mild=1.75 vs moderate=1.39, P<0.05)

Conclusion: Children with ISS and skeletal disproportion (shorter limbs) have reduced long-term height responsiveness to GH compared to those without disproportion suggesting subtle GH resistance in the former.

Conflict of interest: C Camacho-Hubner and A Lindberg are employees of Pfizer Inc. W Cutfield is a member of the KIGS Steering Committee.

Funding: Pfizer International Growth Database (KIGS) currently is a static database sponsor by Pfizer Inc. No authors were paid to conduct the research study submitted in this abstract.

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