Context: Consensus is lacking as to whether the exon 3-deleted(d3)/full-length(fl)-GHR polymorphism is associated with responsiveness to GH therapy.

Objective: Evaluate, in short prepubertal AGA patients, two-year growth response to GH therapy (31.7 ± 3.5 µg/kg/day) according to exon 3-deleted/full-length-GHR genotypes.

Setting: Retrospective study.

Patients: One hundred and six short AGA children, 58 boys and 48 girls, 7.8 ± 2.3 yr, (d3/d3 n = 18, d3/fl n = 42, fl/fl n = 46). GH response to two provocative stimuli were under 10 ng/ml in 65 and one or both over 10 ng/ml in 41.

Main Outcome Measures: Patients were followed by a single clinical team, remained prepubertal during the study and exon 3-deleted/full-length-GHR genotypes were determined and analyzed in the same hospital.

Results: Growth velocity significantly (P < 0.0001) increased during the first and second years of therapy, as did height-SDS. These increases were similar in each exon 3-deleted/full-length-GHR genotype. Total two-year height gain (cm, SDS) did not differ statistically among genotypes: 15.5 ± 2.2 cm and 1.2 ± 0.5 SDS in d3/d3; 15.9 ± 2.0 cm and 1.3 ± 0.4 SDS in d3/fl; 15.4 ± 2.1 cm and 1.1 ± 0.3 SDS in fl/fl. No significant differences among the three genotypes were found in both sexes or in patients with different GH peak response to provocative stimuli for these parameters. An analysis of previously published studies was also performed.

Conclusions: These results confirm in AGA patients those previously found by us and others in SGA patients and suggest that nor sex, nor GH peaks after provocative stimuli might influence significantly the responsiveness to GH therapy according to the exon 3-deleted/full-length-GHR genotypes.