Long-Term Growth Hormone Therapy Improves Adult Height in Children with Indian Hedgehog-Related Short Stature.

INTRODUCTION

Evidence for growth hormone therapy in Indian hedgehog (IHH)-related short stature is limited. The aim of present study was to assess growth outcomes in children with heterozygous pathogenic IHH variants treated with recombinant human growth hormone (rhGH).

METHODS

This is a retrospective cohort of 19 children with short stature carrying heterozygous deleterious IHH variants treated with daily rhGH (33-50 µg/kg/day); 10 attained adult height. Outcomes were height SD score (SDS), height velocity, and adult height SDS.

RESULTS

At treatment start, median height SDS was -2.6 (IQR: -3.0; -2.2) and height velocity 5.1 cm/year (IQR: 4.3; 6.2). After 1 year, height velocity increased to 9.2 cm/year (IQR: 7.9; 10.3) and height SDS to -1.9 (IQR: -2.3; -1.6), with Δheight SDS 0.7 (IQR: 0.5; 1.0). Over a median of 4.0 years of therapy (IQR: 3.4; 5.7), total Δheight SDS was 1.2 (IQR: 0.8; 1.5), and 16/19 (84%) had height SDS ≥ -2.0 at last follow-up. At last follow-up, patients with predicted loss-of-function variants (n = 6) showed higher height SDS than those with missense variants (n = 13) (-0.8 [IQR: -0.9; -0.7] vs. -1.7 [IQR: -1.9; -1.6]) and greater Δheight SDS (1.4 [IQR: 1.2; 1.9] vs. 0.8 [IQR: 0.7; 1.3]). Among those reaching adult height, adult height SDS was -1.7 (IQR: -1.9; -1.6) after a median of 5.8 years of therapy (IQR: 4.0; 7.3), with Δheight SDS 0.8 (IQR: 0.7; 1.4).

CONCLUSIONS

rhGH therapy was associated with clinically meaningful height gains, including adult height improvement, in children with IHH-related short stature; variant class may modify response.