Spontaneous growth hormone secretory characteristics in children with partial growth hormone insensitivity

OBJECTIVE To investigate the characteristics of spontaneous GH secretion in four male children with short stature due to partial GH insensitivity. Their molecular defect consists of inclusion of a mutant intronic pseudoexon in the region of the GH receptor involved in homodimerization. SUBJECTS The subjects were two pairs of brothers who were first cousins, aged 10.4-14.2 years, heights -3.3 to -5.6 SDS, from a consanguineous Pakistani family. Basal serum IGF-I levels were extremely low (20-29 mg/l; NR > 50), with absent or minimal response to human recombinant GH (hGH) stimulation. Serum IGFBP-3 SDS levels were also low (-2.9 to -8.9). GH binding protein (GHBP) levels were normal (28.1-51.7%). METHODS Spontaneous GH secretion was studied by intermittent (20 min) venous sampling from 2000 to 0800 h. The secretion profiles were analysed using the Pulsar programme and compared to data from a reference population of 76 prepubertal Swedish children [median age 10.7 years, median height -1.1 SDS (-2.0 to 1.4)] according to Swedish growth standards. RESULTS Median (range) Pulsar-derived values in the four patients and controls were, respectively: GH(max) (mU/l) 276.6 (178.7-325.8) and 27.2 (13.1-94.9), mean GH (mU/l) 64.5 (41.9-77.8) and 5.8 (3.2-20.6), baseline (mU/l) 12.3 (11.7-20.1) and 1.1 (0.2-6.1), AUC(b) (mU/l x 24 h) 1210 (684-1555) and 112.5 (60.6-316.4), i.e. all parameters of GH secretion in the four patients were markedly elevated compared with the control population. CONCLUSIONS Spontaneous GH secretion is elevated in partial GH insensitivity. This investigation could be of diagnostic value in children with short stature.