Growth hormone receptor exon 3 isoforms may have no importance in the clinical setting of multiethnic 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 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.
['de Oliveira Machado|Evelyn|E|', 'Lima|Carlos Henrique Azeredo|CH|', 'Ogino|Liana Lumi|LL|', 'Kasuki|Leandro|L|', 'Gadelha|Mônica R|MR|']
D000172:Acromegaly D000236:Adenoma D000328:Adult D001483:Base Sequence D001938:Brazil D005006:Ethnicity D005091:Exons D005260:Female D049912:Growth Hormone-Secreting Pituitary Adenoma D019382:Human Growth Hormone D006801:Humans D007334:Insulin-Like Growth Factor I D008297:Male D008875:Middle Aged D016133:Polymerase Chain Reaction D011986:Receptors, Somatotropin D017422:Sequence Analysis, DNA D017384:Sequence Deletion
Acromegaly d3-GHR Somatostatin receptor ligands Growth hormone receptor isoforms