The Serial Study Of The Diagnosis And Treatment Of Growth Hormone Deficiency In Children

Part 1The provocative effects of pyridostigmine (PD) on the secretion of growth hormone (GH) and the synergic effects of PD on GH secretion induced by growth hormone-releasing hormone (GHRH) in childrenObjective: To evaluate the provocative effects of pyridostigmine (PD) on the secretion of growth hormone (GH) and the synergic effects of PD on GH secretion induced by growth hormone-releasing hormone (GHRH) in normal children and children with growth hormone deficiency (GHD). Methods: GH provocative test was done by oral administration of PD in 15 healthy children and 35 patients with GHD. The GH test was also done by oral administration of PD plus injection of GHRH in 5 healthy children and 35 patients with GHD, and compared with results obtained by injection of GHRH only. The serum levels of GH were measured by radioimmunoassay. Results: The levels of serum GH in 13/15 healthy children (86.7%) raised markedly after the administration of PD and reached peak levels (33.86 ± 13.55μg/L) at 60 or 90 minutes. GH peak level and the positive reaction rate in PD test were similar to clonidine test (24.72±8.6μg/L, 86.7%) and L-dopa test (26.12±9.9μg/L, 93.3%). PD failed to increase the GH secretion (peak < 5 μg/L) in 24 patients (68.6%) among 35 children with GHD, but the GH reaction (GH peak > 5 μg/L) was found in the other 11 patients (31.4%) and GH peaks > 10μg/L in 2 patients. The GH peaks in the 11 patients were significantly higher than those reached in the L-dopa test and clonidine test (t = 4.4868, and 4.6268, P < 0.01). GH peak level (65.6±20.1μg/L) after administration of PD and GHRH were significant higher than the peak level (33.1 ±8.4μg/L) after injection of GHRH only in 5 healthy children, (t = 4.7766, P < 0.01). GH peak level was 13.3±9.8μg/L after injection of GHRH in 35 patients, including 19 cases (54.3%) who had GH positive reaction (GH peak level >10μg/L), 16 (45.7%) negative reaction (GH peak level<10μg/L). GH peak level was 25.7± 20.1 μg/L after administration of PD and GHRH in those patients, and significant higher than that of injection of GHRH only (t = 5.9208, P<0.01), and 22 cases (62.9%) had GH positve reaction. The increment of GH level after administration of PD and GHRH in patients who had positive reactive reaction in GHRH provocative test was more significant than the patients who had negative reaction. Conclusion: PD can effectively stimulate pituitary GH secretion in children. PD test is a simple and effective GH provocative test. PD has synergic effect on GH secretion induced by GHRH. GHRH plus PD provocative test is an effective method to assess the ability of pituitary GH secretion in patients with short stature.Part 2The clinical utilities of the measurements of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the diagnosis of growth hormone deficiency(GHD) in children[Objective] To observe the clinical utilities of the measurements of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the diagnosis of growth hormone deficiency (GHD) in children. [Methods] The serum IGF-1 and IGFBP-3- levels were measured by enzyme linked immunosorbent assy in 68 children with GHD, and compared with 30 cases of non GH deficient short stature and 60 normal children. [Results] The levels of serum IGF-1 and IGFBP-3 in GHD children were significantly lower than normal children (t = 5.99, P<0.01). The level of serum IGF-1 in the group of non GH deficient short stature (NGHDSS) was higher than in GHD group (t = 2.60, P<0.05), and lower than normal children (t =4.68, P<0.01). The level of serum IGFBP-3 in the group of NGHDSS was lower than normal children (t = 2.75, P<0.05), but no signicant difference to that of GHD group. [Conclusion] The measurements of serum IGF-1, IGFBP-3 levels have important value in the diagnosis of GHD in children. Part 3The therapeutic effect of Chinese domestic recombinant human growth hormone (r-hGH) and the influence of the replacement therapy on glucose metabolism, gastrin, motilin and vitamin D metabolism in children with growth hormone deficiency (GHD)[Objective] To evaluate the therapeutic effect and safty of Chinese domestic recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD). and observe the influence of the replacement therapy on glucose metabolism, gastrin, motilin and vitamin D metabolism in children with GHD.[Methods] The studies comprised of 68 children with GHD who were treated with Chinese domestic r-hGH replacement therapy for 12 months with a dosage 0. IU/(kg· d). The height, body weight, bone age, IGF-1 and IGFBP-3 levels (measured by enzyme linked immunosorbent assy) were examined before and after 3, 6, 12 months of the treatment. Oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were performed before and after 3 months of r-hGH replacement therapy in 15 children with GHD. Serum gastrin, motilin, 25(OH)D₃, 1,25-(OH)₂D₃ levels were measured in 20 GHD children before and after 3 months of rhGH therapy, and compared to 20 non-GH deficient short stature (NGHDSS) and 20 normal children.[Results] (1) The growth velocities after 3, 6 and 12 months therapy were significantly increased compared to the pretreatment (2) OGTTs were normal in 15 patients before treatment After 3 months of r-hGH therapy, fasting plasma glucose (PG) remained unchanged, but PG30min (P<0.01) ,PG1h (P<0.05) ,PG2h (P<0.05) and glucose areas under the curve (AUCglu) ( P<0.01 ) increased significantly. Although an upward displacement of the glucose curve after r-hGH treatment was observed, impaired glucose tolerance (IGT) and diabetes mellitus (DM) were not found in all patients. Fasting insulin (P<0.05) , INS30min (P<0.05) , INS1h (P<0.01) , INS2h (P<0.01) and insulin areas under the curve AUCins) (P<0.01) were all increased significantly. The Homa DR. also increased significantly (P<0.05). (3) The serum levels of gastrin were lower in GHD than those in NGHDSS and control group and were not increased significantly after treatment. (4) The serum levels of 25(OH)D3 were significantly lower in GHD than those in NGHDSS and control group. The serum levels of 25(OH)D₃ were significantly increased in children with GHD after 3 months of r-hGH therapy and were higher than those in control group. (5) The serum levels of 1,25-(OH)₂D₃ before treatment were similar among the children with GHD, NGHDSS and the controls, and were significantly increased in children with GHD after 3 months of r-hGH therapy and were higher than those in control group.[Conclusion] (1) The use of Chinese domestic recombinant human growth hormone (r-hGH) in children with GHD is effective and safe. (2) r-hGH replacement therapy in GHD children induced impairments in insulin sensitivity and glucose tolerance. It's necessary to monitor PG and INS during r-hGH replacement therapy. (3) The serum levels of gastrin were lower in chidren with GHD and NGHASS than those in normal controls, suggested GH may exert influence on the secretion of gastrin. (4) The serum levels of 25(OH)D3 and 1,25-(OH)₂D₃ were significantly increased in children with GHD after r-hGH therapy. r-hGH may improve the metabolism of vitamin D in GHD patients.