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Influence of the exon 3 deletion of GH receptor and IGF-I level at diagnosis on the efficacy and safety of treatment with somatotropin in adults with GH deficiency

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Abstract

Purpose

The treatment of adults with GH deficiency (GHD) with human recombinant growth hormone has interindividual variability and several factors influence it. The aims of this study were : 1—to analyze the GH receptor (GHR) genotype in terms of exon 3 deletion GHR (d3-GHR) in adults with GHD; 2—to assess the effects of d3-GHR on initial IGF-I levels; 3—to evaluate whether d3-GHR and/or initial IGF-I levels were associated with adverse effects and/or treatment discontinuation.

Methods

Forty-four adult patients with GHD were included. Demographic, clinical and biochemical characteristics were retrospectively evaluated at baseline and 6 months, 1 and 3 years after the initiation of treatment. d3-GHR was analyzed in 35 patients.

Results

37.1 % of patients were d3-GHR carriers (31.4 % heterozygous, 5.7 % homozygous). IGF-I at baseline was low in 64 % of patients and was not related to d3-GHR status. There was no association between the d3-GHR allele and baseline IGF-I (p = 0.14). Although adverse events were more frequent in the d3-GHR carriers (30.7 vs. 18.2 % in fl/fl) and in patients with normal IGF-I levels at diagnosis (43.7 vs. 17.8 % in patients with low IGF-I levels), this association was not statistically significant. d3-GHR status was not related to the incidence of adverse events (p = 0.4) or treatment discontinuation (p = 0.47). Baseline IGF-I levels were neither associated with adverse events (p = 0.08) nor treatment discontinuation (p = 0.75).

Conclusions

The d3-GHR allele was not related to baseline levels of IGF-I. Neither d3-GHR nor baseline IGF-I level was related to adverse events or treatment discontinuation.

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Acknowledgments

This work was supported by grant FISS 11/00161 (to I.B.) and IIR Program from Pfizer (to F.F.).

Conflict of interest

I.B. has received lecture fees from Novartis, Ipsen, and Pfizer, Advisor fees from Novartis, Pfizer and Novo-Nordisk and a research grant from Pfizer. All other authors have nothing to declare.

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Authors and Affiliations

  1. Endocrinology Division, Complejo Hospitalario Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, La Coruña, Spain

    P. Andujar-Plata, E. Fernandez-Rodriguez, F. F. Casanueva & I. Bernabeu

  2. Fundación Publica Galega de Medicina Xenómica (Unidad de Medicina Molecular), Complejo Hospitalario de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain

    C. Quinteiro

  3. CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain

    F. F. Casanueva

Authors
  1. P. Andujar-Plata
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  2. E. Fernandez-Rodriguez
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  3. C. Quinteiro
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  4. F. F. Casanueva
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  5. I. Bernabeu
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Correspondence to I. Bernabeu.

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Andujar-Plata, P., Fernandez-Rodriguez, E., Quinteiro, C. et al. Influence of the exon 3 deletion of GH receptor and IGF-I level at diagnosis on the efficacy and safety of treatment with somatotropin in adults with GH deficiency. Pituitary 18, 101–107 (2015). https://doi.org/10.1007/s11102-014-0562-0

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