Growth hormone (GH) receptor isoform in acromegaly: lower concentrations of GH but not insulin-like growth factor-1 in patients with a genomic deletion of exon 3 in the GH receptor gene.

BACKGROUND A genomic deletion of exon 3 (d3-GHR) of the growth hormone (GH) receptor (GHR) has been linked to the effectiveness of GH therapy in children with GH deficiency. Carriers of the d3-GHR genotype had higher GH-induced growth rates than children homozygous for the full-length (fl)-GHR. The aim of this study was to test whether the relationship between GH and insulin-like growth factor-1 (IGF-1) concentrations is influenced by the GHR genotype in patients with acromegaly. METHODS Study participants were 44 adult patients with established diagnosis of acromegaly. The genotype of the GHR was determined in leukocyte DNA from peripheral blood. Clinical and biochemical findings at the time of diagnosis of acromegaly were obtained from the medical records of the patients. RESULTS fl-GHR homozygosity was found in 22 (50%) of patients, and 22 (50%) of patients had at least 1 d3 allele (d3-GHR). Demographic and clinical characteristics (age, height, weight, estimated duration of disease, and mean tumor size) of the 2 groups were comparable. Median (range) serum IGF-1 concentrations at the time of diagnosis were 670 (447-1443) microg/L in the fl-GHR group and 840 (342-1494) microg/L in the d3-GHR group (P = not significant). Basal GH concentrations were higher in the fl-GHR group [29.7 (3.8-159) microg/L] than in the d3-GHR group [8.4 (2.6-74 microg/L), P = 0.002], and so were mean (30.4 vs 6.1 microg/L, P = 0.005) and nadir (20.5 vs 5.1 microg/L, P = 0.003) GH concentrations during an oral glucose tolerance test. CONCLUSIONS The GHR fl/d3 genotype modulates the relationship between GH and IGF-1 concentrations in patients presenting with acromegaly.