Evelyn de Oliveira Machado1, Carlos Henrique Azeredo Lima2, Liana Lumi Ogino2, Leandro Kasuki1,2,3, Mônica R Gadelha4,5. 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. 2. Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 3. Endocrine Section, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil. 4. 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. mgadelha@hucff.ufrj.br. 5. Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.
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.
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 acromegalypatients. METHODS: We retrospectively analyzed our acromegalyoutpatient 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 acromegalypatients.
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