Abstract <p>The aim of this study is to analyze the clinical characteristics of isolated growth hormone deficiency (IGHD) patients with <i>GH1</i>, <i>GHRHR</i>, and <i>GHSR</i> variants and their response to growth hormone (GH) treatment. Growth characteristics were retrospectively analyzed from GH treatment initiation in the Genhypopit cohort with likely pathogenic or pathogenic variants in <i>GH1</i>, <i>GHRHR</i>, or <i>GHSR</i>. Twenty-one patients (<i>GH1</i>: <i>n</i> = 13, <i>GHRHR</i>: <i>n</i> = 4, <i>GHSR</i>: <i>n</i> = 4) were followed up for 8.9&#xa0;years (0.4; 19.6). GHD was diagnosed earlier in patients with <i>GH1</i> or <i>GHRHR</i> variants than in those with <i>GHSR</i> variants (mean age at diagnosis: 3.1 and 2.0&#xa0;years vs. 6.9&#xa0;years, respectively). Patients with a family history of IGHD tend to have less severe short stature at diagnosis (− 2.2 vs. − 3.2 SDS, <i>p</i> = 0.053). Total height gain was significantly higher in patients with GH1 and <i>GHRHR</i> variants (+ 3.4 and + 3.8 SDS) than in those with <i>GHSR</i> variants (+ 1.8 SDS; <i>p</i> = 0.047). Total height gain was also associated with more severe initial growth delay (<i>p</i> &lt; 0.001), greater difference from target height (<i>p</i> = 0.003), and earlier treatment initiation (<i>p</i> = 0.006). Patients born small for gestational age (SGA) experienced a growth gain similar to patients born eutrophic without the need to increase GH doses. This height gain under GH treatment was higher than reported previously in patients with non-genetic IGHD.</p> <p><i>Conclusion</i>:&#xa0;Identifying a genetic cause of IGHD, particularly those involving variants in GH1 and GHRHR, is associated with significant height gain under GH treatment, regardless of their SGA status.</p> <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> <p><b>What is Known:</b></p> <p><i>• Recombinant growth hormone reliably improves growth in children with GHD.</i></p> </entry> </row> <row> <entry nameend="c2" namest="c1"> <p><b>What is New:</b></p> <p><i>• Children with genetic IGHD, have very favorable GH treatment responses, unaffected by SGA status.</i></p> <p><i>• There are genotype-specific differences in growth outcomes under treatment.</i></p> </entry> </row> </tbody> </tgroup> </Table>

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Growth hormone treatment outcomes in children with genetic isolated growth hormone deficiency

  • Karine Aouchiche,
  • Sarah Castets,
  • Isabelle Oliver Petit,
  • Anya Rothenbuler,
  • Patricia Bretones,
  • Natacha Bouhours-Nouet,
  • Thomas Edouard,
  • Francois Brezin,
  • Elsa Boncompain,
  • Catherine Fabre-Brue,
  • Maylis Lebeault,
  • Thierry Brue,
  • Cécile Thomas-Teinturier,
  • Alexandru Saveanu,
  • Rachel Reynaud

摘要

Abstract

The aim of this study is to analyze the clinical characteristics of isolated growth hormone deficiency (IGHD) patients with GH1, GHRHR, and GHSR variants and their response to growth hormone (GH) treatment. Growth characteristics were retrospectively analyzed from GH treatment initiation in the Genhypopit cohort with likely pathogenic or pathogenic variants in GH1, GHRHR, or GHSR. Twenty-one patients (GH1: n = 13, GHRHR: n = 4, GHSR: n = 4) were followed up for 8.9 years (0.4; 19.6). GHD was diagnosed earlier in patients with GH1 or GHRHR variants than in those with GHSR variants (mean age at diagnosis: 3.1 and 2.0 years vs. 6.9 years, respectively). Patients with a family history of IGHD tend to have less severe short stature at diagnosis (− 2.2 vs. − 3.2 SDS, p = 0.053). Total height gain was significantly higher in patients with GH1 and GHRHR variants (+ 3.4 and + 3.8 SDS) than in those with GHSR variants (+ 1.8 SDS; p = 0.047). Total height gain was also associated with more severe initial growth delay (p < 0.001), greater difference from target height (p = 0.003), and earlier treatment initiation (p = 0.006). Patients born small for gestational age (SGA) experienced a growth gain similar to patients born eutrophic without the need to increase GH doses. This height gain under GH treatment was higher than reported previously in patients with non-genetic IGHD.

Conclusion: Identifying a genetic cause of IGHD, particularly those involving variants in GH1 and GHRHR, is associated with significant height gain under GH treatment, regardless of their SGA status.

What is Known:

• Recombinant growth hormone reliably improves growth in children with GHD.

What is New:

• Children with genetic IGHD, have very favorable GH treatment responses, unaffected by SGA status.

• There are genotype-specific differences in growth outcomes under treatment.