Economic evaluation of a weekly administration of a sustained-release injection of recombinant human growth hormone for the treatment of children with growth hormone deficiency

PURPOSE: From a societal perspective, we evaluated the cost-effectiveness of a novel sustained-release injection of recombinant human growth hormone (GH) administered on a weekly basis compared with that of the present daily GH injection for the treatment of children with GH deficiency. METHODS: Health-related utility for GH therapy was measured based on the visual analogue scale. During July 2008, caregivers of 149 children receiving GH therapy form 2 study sites participated in a web-based questionnaire survey. The survey required the caregivers to rate their current subjective utility with daily GH injections or expected utility of weekly GH injections. Because there was no difference in the costs of the daily and weekly therapies, for the purposes of this study, only drug acquisition costs were considered. RESULTS: Switching from daily to weekly injection of GH increased the utility from 0.584 to 0.784 and incurred an extra cost of 4,060,811 Korean won (KW) per year. The incremental cost-utility ratio (ICUR) for a base case was 20,305,055 KW per quality-adjusted life year (QALY) gained. Scenario analyses showed that the ICUR ranged from 15,751,198 to 25,489,929 KW per QALY. CONCLUSION: The ICUR for a base case and worst case scenario analyses ranged from 0.85 to 1.37-times per capita gross domestic product of Korea, which is considered to be within the generally accepted willingness-to-pay threshold. Thus, it is concluded that switching from daily to weekly injection of GH would be cost-effective.ope

A Case of the Hypercalcemia Induced by the Coenzyme Q10 and Alphacalcidol Treatment in a Patient with Kearns-Sayre Syndrome and Hypoparathyroidism

Kearns-Sayre Syndrome (KSS) is rare mitochondrial disorder characterized by chronic progressive external ophthalmoplegia, atypical retinal pigmentation and complete heart block. It is occasionally combined endocrinologic symptoms such as hypoparathyroidism, short stature, diabetes mellitus and hypothyroidism. We reported the effect of Coenzyme Q10 on total serum calcium concentration in 17 years old girl with KSS and hypoparathyroidism. The patients was treated with alfacalcidol (1α-OHD3), Coenzyme Q10 and oral calcium agent. Total serum calcium concentration had even remained within normal range and hypercalcemia was developed suddenly after treatment of combination of Coenzyme Q10 and alfacalcidol (1α-OHD3). After stop of all medication, her total calcium concentration was decreased to 7.6 mg/dL and remained in normal range with oral calcium (2 g/day) and Coenzyme Q10 (150 mcg/day) daily. The action of Coenzyme Q10 is not clearly defined but, we could explain Coenzyme Q10 activates the capacity of the patient to produce the active form of Vitamin D, 1alpha-OHD3.ope

The Effect of Metformin in Obese Pediatric Patients with Type 2 Diabetes

Purpose Metformin is well-established oral hypoglycemic agent for adults and children with type 2 diabetes mellitus. In adults, metformin is effective as initial monotherapy with lack of weight gain. But, its beneficial role on obesity in children is less clearly defined. We assessed the effects of metformin in obese children with type 2 diabetes. Methods We evaluated body weight, height, body mass index, fasting blood sugar, HbA1c, lipid profiles in obese 36 children with type 2 diabetes treated with oral hypoglycemic agents at baseline, after 1 year and 2 years of treatment. We divided the subjects into three groups: metformin monotherapy, combination metformin with sulfonylurea, sulfonylurea monotherapy. The changes from baseline in three groups were measured. Results The decrease in body mass index, blood sugar & HbA1c was observed after treatment with metformin monotherapy group. Metformin monotherapy group after 1 & 2 years of treatment had a greater effect for body mass index (-1.9±1.7 kg/m2, -1.5±1.6 kg/m2,P<0.05). Conclusion The Metformin monotherapy for obese children with type 2 diabetes improves glycemic control with benefits of significant improvement in body mass index.ope

The Effect of Blood Zinc Level on the Growth of Children

Purpose: Zinc is an essential nutrient, which is required to maintain the normal structure and/or function of multiple enzymes. Therefore, zinc nutriture has been known to influence the physical growth of young children. This study was desinged to evaluate the relationship between blood zinc levels and growth parameters in children. Methods: Two hundred eighty three children (150 boys and 133 girls) who visited the Youngdong Severance Hospital as short stature were enrolled in this study. Height standard deviation score (Ht. SDS), weight standard deviation score (Wt. SDS), and pubertal stage were obtained for each children. Blood samples were collected for zinc, alkaline phosphatase (ALP), insulin-like growth factor binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1), and free thyroxine (fT4). The relationship between blood zinc levels and growth status, and growth factors were analyzed. Results: The Ht. SDS and Wt. SDS were -0.16±0.99, 0.16±0.88 respectively for the low blood zinc level group; the Ht. SDS and Wt. SDS were -0.16±0.97, 0.08±0.93 respectively for the normal blood zinc level group. Between two groups, Ht. SDS, Wt. SDS, bone age, pubertal stage, ALP, and IGF-1 showed no significant differences, while IGFBP-3 and fT4 showed significant differences (P<0.05). The mean zinc concentrations showed no significant difference between the normal stature group and short stature group (101.60±41.11 μg/dL, 93.72±35.38 μg/dL respectively). The Ht. SDS, Wt. SDS, pubertal stage, ALP, and IGF-1 showed no significant correlation with the zinc levels, while the IGFBP-3 and fT4 showed significant correlation (P<0.05). Conclusion: We could not find any significant relationship between blood zinc level and growth status. However, interpretation of our results should be cautious in aspect that the result might come from the subjects with mild zinc deficiency. Further study is required to investigate the severe zinc deficiency patients and zinc replacement study.ope

Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls

Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.ope

Recurrence of Brain Tumors in Patients Treated with Growth Hormone

Purpose Growth hormone (GH) has been used successfully in the treatment of short stature secondary to GH deficiency in survivors of childhood brain tumors. There has been concerned that GH might increase the risk of tumor recurrence in spite of improvement of growth. Methods Data for tumor recurrence from 1997 to 2006 were analysed retrospectively in 56 patients with craniopharyngioma, 78 patients with medulloblastomas, 14 patients with germinomas and 139 patients with astrocytomas or gliomas after GH treatment. Serum insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were measured. Results 57 GH deficient and growth retarded patients (17.4%) were treated with recombinant human GH and followed up 60 months after starting GH treatment. 6 patients (10.5%) (5 craniopharyngioma, 1 germinoma) were recurred among patients with GH therapy, but 17 patients (5.2%) were recurred among patients with non GH therapy. Tumor recurrence in GH treated group was not higher than in non GH treated group. There was no significant change in serum IGF-1, IGFBP-3 level and IGF-1/IGFBP-3 ratio. Conclusion Tumor recurrence rates in surviving patients with brain tumors receiving GH treatment do not appear to be increased compared with non GH treatment. However, longer follow-up regarding recurrences and secondary neoplasms remains to be essential.ope

Prevalence of the Nonalcoholic Fatty Liver Disease in Obese Children

Purpose : Obesity is, along with metabolic syndrome, closely related with nonalcoholic fatty liver disease. This study tried to evaluate the prevalence of nonalcoholic liver disease in obese children and verify the factors associated with the disease. Methods : Two hundred and seventy nine children who showed a body mass index of 95 percentile over the baseline in health examinations of surrounding schools were evaluated. Questionnaires, body measurements, blood examinations, and ultrasonographic measurements of abdominal fat were examined. Results : Out of 279 children enrolled for the study, 27 children were found to possess nonalcoholic liver disease(9.7%). Among those found to be positive for nonalcoholic liver disease, it’s prevalence increased to 15.2%(22 out of 144 children) among children with severe obesity. Factors known to be involved with metabolic syndrome, namely waist/hip circumference ratio and thickness of abdominal fat, were found to be closely related to nonalcoholic fatty liver as well. Conclusion : The prevalence of nonalcoholic fatty liver in obese children was 9.7%, with higher incidence observable in severer obesity. Factors responsible for metabolic syndrome were closely associated with nonalcoholic fatty liver disease, and the level of insulin resistance, which is an useful index in both diseases, can be utilized in evaluation of the effect of treatment and control of risk factors.ope

Effects of growth hormone treatment onglucose metabolism in idiopathic short stature

Purpose: To study the effects of growth hormone(GH) treatment on glucose metabolism and insulin resistance in children with idiopathic short stature(ISS). Methods: Glucose and insulin concentrations were measured during oral glucose tolerance test (OGTT) before and after GH treatment(0.6-0.7 IU/kg/week) in 20 patients with ISS. Insulin resistance was assessed by homeostasis model assessment(HOMA). Results: During OGTT, the mean blood glucose level did not show any significant changes after GH treatment. However, mean blood insulin levels of fasting and 30 minutes of OGTT showed significant increases after GH treatment, accompanying significant increases of insulin resistance. There was no difference in change of glucose, insulin levels and insulin resistance before and after GH treatment between two groups of body mass indices(BMI) of 2525. There also was no significant difference between two groups of with and without family histories of diabetes mellitus (DM). There was no case of newly developed impaired glucose tolerance, fasting glucose tolerance, nor newly developed DM. Conclusion: GH treatment with doses of 0.6-0.7 IU/kg/week for mean 9.6 months in patients with ISS did not show any significant changes in blood glucose levels during OGTT. However, GH treatments induced considerably higher fasting insulin levels compared to pretreatment, resulting in statistically higher insulin resistance. Higher BMI and family history of DM did not induce any significant changes in glucose, insulin level and insulin resistance after GH treatment than the other groups.ope

Growth Hormone Receptor Mutation and Partial Growth Hormone Insensitivity in Children with Idiopathic Short Stature

Purpose : Children with idiopathic short stature(ISS) are classified on the ba_is of exclusion criteria. Short stature with normal or increased circulating growth hormone(GH and low IGF-I levels indicates that partial growth hormone insensitivity(GHI) may play a role in ISS. The present study was performed to investigate whether partial GHI is observed in children with idiopathic short stature and whether partial GHI is related to growth hormon( receptor, GHR) defect. Methods : Twenty-five children with ISS were studied and 30 no -mal children were enrolled as control. Anthropometric measurement and IGF-I generation test were performed. The GHR gene was amplified *by PCR, from leukocyte-derived DNA and sequenced directly. Results : IGF-I level was increased after GH treatment, but there was no significant correlation between delta IGF-I and delta HTSDS, as well as between delta IGFBP-3 and delta HTSDS indicating partial GHI in children with ISS. When GHR genes were analyzed. polymorphism was observed. That is, adenine which is third base for 168 th amino acid was guanine. Furthermore this finding was observed in 100% of 55 children examined, which was a rather higher incidence compared to previous reports from other country. The first base of 526 th amino acid was either adenine or cytosine or heterozygous of adenine and cytosine, suggesting an occurrence of I526L variant. Deletions of one or two bases in flanking region of exon 3 and 8 were confirmed in Koreans, the same as it occurs in Japanese. There are differences in the sequences of human GHR gene among different ethnic populations. Wide variations of phenotype in ISS cannot clearly be explained by GHR gene alone. Variations or polymorphism of GHR genes remains to be functionally analysed. Conclusion : ISS might be due to the partial GHI which is resuls from mutation of GHR genes.ope

Obesity and Cardiovascular Risk Factors in Korean Children and Adolescents Aged 10–18 Years from the Korean National Health and Nutrition Examination Survey, 1998 and 2001

Childhood obesity is directly related to cardiovascular disease (CVD) risk factors, but there is limited information on their relation in Korean children and adolescents. The authors investigated the association between obesity and CVD risk factors among 2,272 Korean boys and girls aged 10–18 years, who participated in the Korean National Health and Nutrition Examination Survey in 1998 and 2001. Obesity was defined by body mass index cutoff points provided by the US Centers for Disease Control and Prevention. The prevalence of obesity increased significantly from 5.4% in 1998 to 11.3% in 2001 (p < 0.0001). Korean obese children and adolescents in 1998 and 2001 had 4.6- and 4.9-fold risks for systolic hypertension, 4.2- and 2.8-fold risks for high levels of total cholesterol, 9.4- and 2.7-fold risks for high levels of low density lipoprotein cholesterol, 4.1- and 3.7-fold risks for low levels of high density lipoprotein cholesterol, and 5.3- and 2.8-fold risks for high levels of triglycerides, compared with their normal-weight counterparts (p < 0.05 in all). Approximately 60% of Korean obese children and adolescents had at least one CVD risk factor. These findings suggest that Korean obese children and adolescents have an increased risk of CVD.ope