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Growth hormone insensitivity syndromes (GHIS) involve impaired growth due to low IGF-I. Combination therapy with growth hormone (GH) and insulin-like growth factor-I (IGF-I) shows improved growth outcomes in children with GHIS.

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Area of Science:

  • Pediatric Endocrinology
  • Growth Hormone Therapy
  • Metabolic Disorders

Background:

  • Normal linear growth depends on growth hormone (GH) and insulin-like growth factor-I (IGF-I).
  • GH Insensitivity Syndromes (GHIS) are characterized by diminished GH action, leading to reduced IGF-I availability and growth failure.
  • Previous treatments with pituitary-derived GH had limited efficacy in GHIS patients.

Purpose of the Study:

  • To evaluate the efficacy of recombinant human insulin-like growth factor-I (rhIGF-I) monotherapy versus combination therapy in GHIS.
  • To explore potential explanations for suboptimal growth responses in GHIS patients treated with rhIGF-I.
  • To identify future therapeutic strategies for improving growth outcomes in GHIS.

Main Methods:

  • Review of treatment outcomes for GHIS patients with rhIGF-I monotherapy and rhGH/rhIGF-I combination therapy.
  • Analysis of the impact of rhIGF-I on endogenous GH levels via negative feedback.
  • Comparison of growth responses in prepubertal children with short stature and low IGF-I.

Main Results:

  • rhIGF-I treatment accelerates growth in GHIS children but often yields less substantial catch-up growth compared to rhGH in GH Deficiency.
  • rhIGF-I monotherapy can reduce endogenous GH levels, potentially limiting catch-up growth.
  • Combination therapy with rhGH and rhIGF-I demonstrated superior growth responses compared to rhIGF-I monotherapy in specific pediatric populations.

Conclusions:

  • Combination therapy of rhGH and rhIGF-I holds promise for improving growth outcomes in most GHIS patients, except those lacking functional GH signaling.
  • Future treatments may involve post-GH receptor signaling agonists or long-acting rhGH combined with rhIGF-I.
  • Additional etiological factors should be investigated if growth deficits persist despite current treatments.