Congenital hypopituitarism in children. Molecular-genetic characteristics

In connection with the ambiguity in the interpretation of the results of stimulation tests in congenital hypopituitarism, children need to search for molecular genetic markers of the disease. Molecular genetic analysis in patients with congenital hypopituitarism (genes GH1, GHRH, GHRHR,BTK, GHSR, PROP1, POU1F1, HESX1, LHX3, LHX4, SOX3, SOX2, OTX2, GLI2, ARNT2, ARPC5L, DLK1, DRD2, PAX6, RNPC3, SHH, SPCS2, SPCS3), was carried out by new-generation sequencing (NGS) with “Amplisek” technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. A difference in the incidence of mutations in patients with multiple deficiency of adenohypophysis hormones (27.7%) and in patients with isolated growth hormone insufficiency (9.6%) was revealed. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of Saint Petersburg were studied. Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.

Results of growth hormone substitution therapy in children with brain tumours

Aim of the study. To estimate the effectiveness and safety of substitution therapy with growth hormone (GH) in children with various brain tumours. Materials and methods. The study involved 68 patients admitted to N.N. Burdenko Institute of Neurosurgery between 2001 and 2011 including 35 ones with craniopharyngioma, 18 with medulloblastoma, and 15 with germ cell tumours (GCT) in the chiasmosellar region. All patients suffered growth hormone insufficiency and received GH replacement therapy. Their antropometric characteristics (height and growth rate) and IGF-1 levels were measured before, 6 and 12 months after the onset of the treatment. The doses of GH varied from 0.03 to 0.034 mg/kg/day. Results. The substitution therapy with GH resulted in an increase of the growth rate in patients with craniopharyngioma from 2.3±1.6 to 9.4±1.9 cm/year (p<0.001), in those with GCT from 1.2±0.9 to 7.4±2.6 cm/year (p=0.01), and in patients with medulloblastoma from 2.3±1.5 to 6.2±2.6 cm/year (p<0.01). The growth rate in patients treated by spinal irradiation was lower than that in those given no such treatment (6.0±2.3 cm/year and 9.2±2.1 cm/year respectively; p<0.001). The tumour recurred in eight of 35 (23%) patients with craniopharyngioma during GH therapy. The frequency of relapses was not significantly different from that in patients who did not receive growth hormone. Patients with medulloblastoma and GCT did not develop relapses. No adverse reactions to GH therapy were documented in this study.