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Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 395–407 (2006)Cite this article

Abstract

Advances in the diagnosis and treatment of growth hormone insensitivity disorders have occurred in the past 15 years. We discuss the current status of endocrine and molecular evaluation, focusing on the pediatric age range. All the identified mutations of the growth hormone receptor are included. Treatment with recombinant human insulin-like growth factor (rhIGF) 1 in classical cases is summarized and new targets for treatment are discussed, together with therapy using the complex formed between rhIGF1 and rhIGF-binding protein 3.

Key Points

  • Growth hormone insensitivity disorders represent a broad category of clinical, endocrine and genetic abnormalities

  • A definitive list of the known mutations in the growth hormone receptor that occur in patients with growth hormone insensitivity is included in this article

  • Recombinant human insulin-like growth factor 1, or the complex of recombinant human insulin-like growth factor 1 plus insulin-like growth-factor-binding protein 3, is effective as growth-promoting therapy for children with growth hormone insensitivity disorders, and offers hope of long-term benefits

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Figure 1: Variation in clinical phenotype from Laron syndrome (triangles) to idiopathic short stature (circles) across the spectrum of 58 patients with growth hormone insensitivity from the European series5
Figure 2: Growth hormone receptor structure and its mutations in patients with idiopathic short stature

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Authors and Affiliations

  1. Professor and Head of the Paediatric Endocrinology Unit,

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

  2. Research Fellow and Specialist in Adult Endocrinology,

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

  3. Postdoctoral Research Worker,

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

  4. Academic Head of the Department of Endocrinology and Head of the Molecular Endocrinology Unit, Professor of Medicine,

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

  5. Reader in Paediatric Endocrinology, all in the William Harvey Research Institute, St Bartholomew's Hospital and the London School of Medicine & Dentistry, London, UK

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

  6. Vice President Medical Affairs, Insmed Inc., Glen Allen, VA, USA

    Martin O Savage, Kenneth M Attie, Alessia David, Louise A Metherell, Adrian JL Clark & Cecilia Camacho-Hübner

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Corresponding author

Correspondence to Martin O Savage.

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Competing interests

Martin O Savage is an Investigator in a Phase III study on effects of rhIGF–rhIGFBP3 (recombinant human insulin-like growth factor 1–rhIGF binding protein 3) treatment in growth-hormone-insensitivity syndrome organized by Insmed Inc., Glen Allen, VA, USA.

Keneth M Attie is Vice President Medical Affairs at Insmed Inc., Glen Allen, VA, USA. This company is organizing a Phase III study of rhIGF1–rhIGFBP3 (recombinant human insulin-like growth factor 1–rhIGF binding protein 3) treatment of growth-hormone-insensitivity syndrome.

Cecilia Camacho-Hübner is a Principal Investigator in a Phase III study on effects of rhIGF1–rhIGFBP3 (recombinant human insulin-like growth factor 1–rhIGF binding protein 3) treatment in growth-hormone-insensitivity syndrome organized by Insmed Inc., Glen Allen, VA, USA.

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Savage, M., Attie, K., David, A. et al. Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders. Nat Rev Endocrinol 2, 395–407 (2006). https://doi.org/10.1038/ncpendmet0195

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