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Growth hormone receptor exon 3 isoforms may have no importance in the clinical setting of multiethnic Brazilian acromegaly patients

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Abstract

Background

Acromegaly is associated with significant morbidity and increased mortality, but has a variable severity phenotype. The presence of the exon 3-deleted isoform of the growth hormone receptor (d3-GHR) may influence the disease phenotype and treatment outcomes, including the frequency of biochemical discordance after medical treatment.

Aims

The objective of this study was to analyze the influence of the d3-GHR isoform on clinical and biochemical characteristics and in the treatment outcomes of Brazilian multiethnic acromegaly patients.

Methods

We retrospectively analyzed our acromegaly outpatient clinic databank and collected demographic, clinical, biochemical and treatment outcome data from those patients who agreed to participate in the study. A blood sample was collected from all patients, the DNA was extracted and the GHR isoforms were evaluated by PCR, with the full length (fl)-GHR represented by a 935-bp fragment and the d3-GHR represented by a 532-bp fragment.

Results

A total of 121 patients were included. Fifty-six patients (46.3 %) were full-length homozygous (fl/fl), 48 (39.7 %) were heterozygous (fl/d3) and 17 (14.0 %) were d3-GHR homozygous (d3/d3). There was no difference between patients homozygous for the fl isoform and those harboring at least one d3-GHR allele in the demographic, clinical and biochemical data or in the treatment outcomes, including somatostatin receptor ligands (SRL) monotherapy, combination therapy with SRL and cabergoline and pegvisomant treatment. There was also no difference between the groups for the frequency of GH and IGF-I discordance after medical treatment.

Conclusion

GHR exon 3 genotyping appears to have no clinical significance, at least in Brazilian acromegaly patients.

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Disclosure

M.R.G has received unrestricted research grants and speaker fees from Novartis, Ipsen and Pfizer and has participated on advisory boards of Novartis and Ipsen. The other authors have nothing to disclose.

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Authors and Affiliations

  1. Neuroendocrinology Research Center/Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil

    Evelyn de Oliveira Machado, Leandro Kasuki & Mônica R. Gadelha

  2. Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Carlos Henrique Azeredo Lima, Liana Lumi Ogino, Leandro Kasuki & Mônica R. Gadelha

  3. Endocrine Section, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil

    Leandro Kasuki

Authors
  1. Evelyn de Oliveira Machado
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  2. Carlos Henrique Azeredo Lima
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  3. Liana Lumi Ogino
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  4. Leandro Kasuki
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  5. Mônica R. Gadelha
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Correspondence to Mônica R. Gadelha.

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de Oliveira Machado, E., Lima, C.H.A., Ogino, L.L. et al. Growth hormone receptor exon 3 isoforms may have no importance in the clinical setting of multiethnic Brazilian acromegaly patients. Pituitary 19, 375–380 (2016). https://doi.org/10.1007/s11102-016-0715-4

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  • DOI: https://doi.org/10.1007/s11102-016-0715-4

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