Pediatric growth hormone therapy in Greece: analysis of the Hellenic cohort of the GeNeSIS study.

PURPOSE: To describe the data from the Greek cohort of the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). METHODS: GeNeSIS was a prospective, open-label, multinational, observational study collecting information on clinical outcomes and treatment safety of children with growth disorders treated with growth hormone (GH), according to national indications. After informed consent, 305 patients (143 females), including 255 patients with growth hormone deficiency (GHD) and 30 with Turner syndrome (TS), from eight investigational sites, were enrolled in Greece. Demographic data, treatment efficacy, and adverse events were reported at the discretion of attending physicians. RESULTS: Treatment with GH was undertaken for 247/255 patients with GHD and 29/30 with TS. The majority of patients treated with GHD (73.7%) and TS (84%) with recorded Tanner stage were prepubertal at enrolment. Among patients treated with GHD and TS, 70.45% and 55% were GH-naïve at study entry, respectively. Height standard deviation score (SDS), height velocity SDS, and height SDS-target height SDS numerically improved during the 4-year observation period. The effect of GH treatment was more prominent in the first year of treatment, especially in the GHD group. CONCLUSIONS: In the Greek cohort of GeNeSIS, GHD is the most frequent indication for GH treatment, followed by TS. While the latter is diagnosed somewhat earlier, GH treatment is not as efficacious as for patients with GHD. No major safety issues were reported during follow-up. The results, which are in accordance with the international literature, should be interpreted in the context of observational studies.

M-mode echocardiographic evaluation of systolic function, LV volume and mass in children on growth hormone therapy.

Since abnormal endogenous growth hormone (GH) secretion in adults is associated with cardiac dysfunction, it is important to ensure that GH therapy in children and adolescents does not cause similar effects. Forty-two growth hormone-deficient children (Group 1) (19 girls, 23 boys) were evaluated. Six girls and seven boys were prepubertal with a mean age of 6.65 yr (range 4.37-9.73 yr). Twenty-nine were pubertal (13 girls, 16 boys), mean age 13.57 yr (range 10.08-16.76 yr). The patients had been on long-term GH therapy for 34.97 +/- 18.78 months with an average weekly dose of 17.61 IU/m2/wk. The mean height SDS was -2.85 +/- 1.22 for boys and -2.5 +/- 0.64 for girls at the onset of therapy, and at the time of examination -1.8 +/- 1.32 for the boys and 1.87 +/- 0.94 for the girls. Thirty-four normal control subjects (Group 2) matched for age, sex and body size were also studied. Left ventricular volume (LV), mass and systolic function [shortening fraction (FS)] were evaluated by two-dimensional guided M-mode echocardiography. Blood pressure was also measured. No differences in blood pressure were observed between patients and controls. There was no correlation of GH dose and duration of therapy with LV measurements. No significant differences were found between Group 1 and Group 2. These observations suggest that long term administration of GH does not produce adverse cardiac effects in GH deficient children. Nevertheless, longer follow-up studies are still needed to confirm the safety of long-term rhGH treatment.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience.

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1-8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed.

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children.

UNLABELLED: The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7 girls, aged 3.7-13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5 0.7 IU/kg weekly SC). Serum levels of calcium, phosphate, alkaline phosphatase osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO4/GFR) were assessed. During therapy with hGH a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. CONCLUSION: GH treatment significantly influences mineral metabolism and the measurement of TPO4/ GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children.

Serum levels of IGFBP-3: usefulness in diagnosis of GH deficiency and relationship to measurements of GH secretion in children.

Aims of the study were to assess the relationship between serum levels of IGFBP-3 with IGF-I serum levels, peak GH levels in response to two stimulation tests (PKGH) and GH urinary excretion in children, and to examine the usefulness of IGFBP-3 for diagnosis of GH deficiency. Our study group consisted of 86 children with normal stature, 12 children with normal short stature and 12 children with GHD. In all children, serum levels of IGF-I and IGFBP-3 were measured and GH urinary excretion was assessed in overnight urine collections. Children with short stature had two stimulation tests and the peak GH level was used in the analysis. IGFBP-3 SDS was strongly correlated with IGF-I SDS (r = 0.63, p < 0.001), significantly correlated with peak GH (r = 0.42, p < 0.05) and weakly, but not significantly, correlated with urinary GH excretion. Among the 12 children with GHD, only two had normal IGFBP-3 values (sensitivity 83%). In contrast, all normal short children except one had IGFBP-3 levels within the normal range, defined by the 5th and 95th percentile (specificity 92%). Sensitivity and specificity of IGF-I were respectively 67% and 50%. In conclusion, IGFBP-3 levels are strongly correlated with IGF-I levels, weakly correlated with peak GH response to provocative tests and may serve as a valuable parameter, in combination with others, in the evaluation of the GH-IGF axis.