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: GHmax (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), AUCb (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.