Respiratory failure in a diabetic ketoacidosis patient with severe hypophosphatemia

Phosphate is essential in regulating human metabolic processes, and severe hypophosphatemia can induce neurologic and hematological complications and result in respiratory failure and cardiac dysfunction. Therefore, correction of severe hypophosphatemia can be pivotal in the management of diabetic ketoacidosis (DKA). We report the case of a 14-year-old female who was diagnosed with type 1 diabetes and referred to our institute for treatment of DKA. Although the patient received fluid and continuous insulin administration according to the current DKA treatment protocol, generalized tonic seizures and cardiac arrest developed. After cardiopulmonary resuscitation, the patient recovered and was stable. Within 16 hours after DKA treatment, the patient developed respiratory failure with severe hypophosphatemia that required mechanical ventilation. Concurrent neurologic evaluation revealed no specific abnormalities. The patient recovered without any complications after correcting the hypophosphatemia. We suggest vigilant monitoring of the phosphate level in DKA patients and active replacement when required.

Visceral fat thickness and its associations with pubertal and metabolic parameters among girls with precocious puberty

PURPOSE: This study aimed to investigate associations of central obesity with sexual maturation and metabolic parameters in Korean girls with precocious puberty. METHODS: This retrospective study evaluated data from 72 girls under 8 years of age with a chief complaint of early breast development. The patients were categorized as central precocious puberty (CPP) subjects or non-CPP subjects based on their gonadotropin-releasing hormone stimulation test results. Visceral fat thickness (VFT) was measured using ultrasonography and defined as the distance from the linea alba to the aorta. Patient anthropometric, metabolic, and hormonal parameters were also evaluated. RESULTS: Increased VFT was correlated with an earlier onset of thelarche among all study subjects (r=-0.307, P=0.034). Overweight CPP subjects showed higher insulin resistance than normal weight CPP subjects. Insulin resistance was not significantly different between overweight and normal weight non-CPP subjects. VFT was not significantly different between CPP and non-CPP subjects (2.22±0.79 cm vs. 2.74±1.47 cm, P=0.169). However, overweight and obese CPP subjects (body mass index percentile>85%) had lower VFT than non-CPP obese subjects. CONCLUSIONS: Central obesity, defined using ultrasonography-measured VFT, might be associated with early pubertal development in Korean girls. However, VFT was not higher in CPP than non-CPP patients and was not significantly correlated with insulin resistance. Further longitudinal studies with a larger cohort are needed.

Diabetes mellitus due to agenesis of the dorsal pancreas in a patient with heterotaxy syndrome

Heterotaxy syndrome (HS) is a congenital disorder resulting from an abnormal arrangement of visceral organs across the normal left-right axis in the embryonic period. HS is usually associated with multiple anomalies, including defects of the major cardiovascular system and the extracardiovascular system such as intestinal malrotation, abnormal lung lobulation, bronchus anomalies, and pancreatic dysplasia. Although pancreatic dysplasia is occasionally accompanied with HS, the occurrence of diabetes mellitus (DM) due to pancreatic dysplasia in HS is rarely reported. We here report a case involving 13-year-old girl with DM caused by agenesis of the dorsal pancreas and HS diagnosed on the basis of the presence of a double-outlet right ventricle with bilateral pulmonary stenosis and intestinal malrotation with duodenal cyst. Timely diagnosis and treatment with insulin improved glycemic control.

Insulin resistance and bone age advancement in girls with central precocious puberty

PURPOSE: Precocious puberty has significantly increased recently. While obesity is associated with puberty timing, the relationship between obesity and central precocious puberty (CPP) remains controversial. The purpose of this study was to determine whether insulin resistance is associated with bone age (BA) advancement in girls with CPP. METHODS: We retrospectively analyzed the records of 804 girls referred for puberty evaluation. Anthropometric measurements, BA, sex hormone, sex hormone binding globulin (SHBG), and insulin levels, lipid profiles, and gonadotropin releasing hormone stimulation tests were assessed. Insulin resistance parameters were calculated using the homeostasis model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) models. RESULTS: BA, BA advancement, free estradiol index, insulin, and HOMA-IR increased significantly in girls with high body mass index (BMI) compared with that of girls with low BMI in cases of CPP. HOMA-IR was positively correlated with BA advancement and BMI but negatively correlated with SHBG. QUICKI was negatively correlated with BA advancement and BMI and positively correlated with SHBG. When HOMA-IR increased by 1, the odds for BA advancement increased 120% after adjusting for age and BMI (P=0.033). CONCLUSION: Insulin resistance could be associated with BA advancement in girls with CPP.

Clinical manifestations of Rathke’s cleft cysts and their natural progression during 2 years in children and adolescents

PURPOSE: Rathke’s cleft cyst (RCC) is an asymptomatic benign lesion. With increased interest in pediatric endocrinology, the prevalence of RCCs in children is also increasing. However, the clinical relevance and proper management of RCC is not well defined in children. Therefore, we investigated the clinical manifestations and radiologic features of RCC in children and adolescents, as well as the natural progression of RCC. METHODS: We retrospectively reviewed the medical records of 91 children and adolescents with RCC diagnosed with magnetic resonance imaging (MRI) in Severance Children’s Hospital from January 2006 to December 2015. The clinical, hormonal, and imaging findings were analyzed in patient groups classified according to age. The size of each cyst was assessed in sixty patients who underwent follow-up MRI during the 2 years. RESULTS: Female patients were predominant (64 vs. 27). The common clinical features at presentation were endocrine dysfunction (59.3%), headache (23.0%), and dizziness (4.4%). Symptoms related to endocrine disorders were more frequent in younger patients. In 7 patients managed surgically, the cysts were significantly larger and more frequently located in the suprasellar region. Of 60 nonsurgical patients with a follow-up MRI performed within 2 years after the diagnosis, the RCC size increased in about 26.7% (n=16). CONCLUSION: Although 94.4% of the patients with RCC had clinical symptoms, surgery was performed in only about 7.5% of patients. RCC is associated with pituitary insufficiency, thus, baseline and follow-up endocrine function tests are required. Additionally, regular MRI follow-up is required in long-term period to monitor change in size.

A boy with 46,X,+mar presenting gynecomastia and short stature

A 15-year-old boy was referred due to gynecomastia and short stature. He was overweight and showed the knuckle-dimple sign on the left hand, a short fourth toe on the left foot, and male external genitalia with a small phallus. His levels of estradiol and follicle-stimulating hormone were increased, and his testosterone concentration was normal. Other hormonal tests were within the normal range. Radiographs showed short fourth and fifth metacarpals and fourth metatarsal bones. The karyotype was reported as 46,X,+mar, and the marker chromosome was shown to originate from the Y chromosome, which was identified by fluorescence in situ hybridization. Polymerase chain reaction and direct sequencing were used to clarify the deleted loci of the Y chromosome by making use of Y-specific sequence-tagged sites (STSs). The sex-determining region Y and centromere were verified, and there were microdeletions on the long arm of the Y chromosome. The azoospermia factor (AZF) b region was partially deleted, and AZFa and AZFc were completely deleted. Two STS probes of sY143 and the Y chromosome RNA recognition motif in AZFb showed positive signals corresponding to Yq11.223. The karyotype of the patient was interpreted as 46,X,der(Y)del(Y)(q11.21q11.222)del(Y)(q11.23qter). Herein, we report a rare case of a boy presenting with gynecomastia and short stature with 46, X, +mar, which originated from the Y chromosome, which was identified to have Yq microdeletions.

A 1-month-old infant with chylomicronemia due to GPIHBP1 gene mutation treated by plasmapheresis

Chylomicronemia is a severe type of hypertriglyceridemia characterized by chylomicron accumulation that arises from a genetic defect in intravascular lipolysis. It requires urgent and proper management, because serious cases can be accompanied by pancreatic necrosis or persistent multiple organ failure. We present the case of a 1-month-old infant with chylomicronemia treated by plasmapheresis. His chylomicronemia was discovered incidentally when lactescent plasma was noticed during routine blood sampling during a hospital admission for fever and irritability. Laboratory investigation revealed marked triglyceridemia (>5,000 mg/dL) with high chylomicron levels. We therefore decided to perform a therapeutic plasmapheresis to prevent acute pancreatitis. Sequence analysis revealed a homozygous novel mutation in exon 4 of GPIHBP1: c.476delG (p.Gly159Alafs). Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) stabilizes the binding of chylomicrons near lipoprotein lipase and supports lipolysis. Mutations of GPIHBP1, the most recently discovered gene, can lead to severe hyperlipidemia and are known to make up only 2% of the monogenic mutations associated with chylomicronemia. The patient maintains mild hypertriglyceridemia without rebound after single plasmapheresis and maintenance fibrate medication so far. Here, we report an infant with chylomicronemia due to GPIHBP1 mutation, successfully treated by plasmapheresis.

Male patients presenting with rapidly progressive puberty associated with malignant tumors

In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

Ultrasound measurement of pediatric visceral fat thickness: correlations with metabolic and liver profiles

PURPOSE: Abdominal obesity is a fundamental factor underlying the development of metabolic syndrome. Because of radiation exposure and cost, computed tomography or dual-energy X-ray absorptiometry to evaluate abdominal adiposity are not appropriate in children. Authors evaluated whether ultrasound results could be an indicator of insulin resistance and nonalcoholic fatty liver disease (NAFLD). METHODS: We enrolled 73 subjects (aged 6-16 years) who were evaluated abdominal adiposity by ultrasound. Subcutaneous fat thickness was defined as the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT) was defined as the thickness from the linea alba to the aorta. Anthropometric and biochemical metabolic parameters were also collected and compared. The subjects who met 2 criteria, radiologic confirmed fatty liver and alanine aminotransferase >40, were diagnosed with NAFLD. RESULTS: There was a strong positive correlation between VFT and obesity. VFT was highly correlated with the homeostasis model assessment for insulin resistance score (r=0.403, P<0.001). The area under the curve for VFT as a predictor of NAFLD was 0.875 (95% confidence interval [CI], 0.787-0.964). VFT of 34.3 mm was found to be the discriminating cutoff for NAFLD (sensitivity, 84.6%; specificity, 71.2%, respectively). CONCLUSION: Ultrasound could be useful in measuring VFT and assessing abdominal adiposity in children. Moreover, increased VFT might be an appropriate prognostic factor for insulin resistance and NAFLD.

Ultrasound measurement of pediatric visceral fat thickness: correlations with metabolic and liver profiles

PURPOSE: Abdominal obesity is a fundamental factor underlying the development of metabolic syndrome. Because of radiation exposure and cost, computed tomography or dual-energy X-ray absorptiometry to evaluate abdominal adiposity are not appropriate in children. Authors evaluated whether ultrasound results could be an indicator of insulin resistance and nonalcoholic fatty liver disease (NAFLD). METHODS: We enrolled 73 subjects (aged 6-16 years) who were evaluated abdominal adiposity by ultrasound. Subcutaneous fat thickness was defined as the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT) was defined as the thickness from the linea alba to the aorta. Anthropometric and biochemical metabolic parameters were also collected and compared. The subjects who met 2 criteria, radiologic confirmed fatty liver and alanine aminotransferase >40, were diagnosed with NAFLD. RESULTS: There was a strong positive correlation between VFT and obesity. VFT was highly correlated with the homeostasis model assessment for insulin resistance score (r=0.403, P<0.001). The area under the curve for VFT as a predictor of NAFLD was 0.875 (95% confidence interval [CI], 0.787-0.964). VFT of 34.3 mm was found to be the discriminating cutoff for NAFLD (sensitivity, 84.6%; specificity, 71.2%, respectively). CONCLUSION: Ultrasound could be useful in measuring VFT and assessing abdominal adiposity in children. Moreover, increased VFT might be an appropriate prognostic factor for insulin resistance and NAFLD.

Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy

Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg). The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications.

Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia

PURPOSE: In male patients with congenital adrenal hyperplasia (CAH), the presence of testicular adrenal rest tumors (TARTs) have been reported, however their prevalence and clinical manifestations are not well known. Untreated TARTs may lead to testicular structural damage and infertility. This study was conducted to investigate the prevalence of TARTs in male patients with CAH, and characterize the manifestations to identify contributing factors to TART. METHODS: Among 102 CAH patients aged 0-30 years, 24 male patients have been regularly followed up in our outpatient clinic at Severance Children's Hospital from January 2000 to December 2014. In order to reveiw the characteristics of TART patients, we calculated the mean levels of hormones during the 5 years before the time of investigation. Five patients underwent follow-up scrotal ultrasonography (US) after adjusting the dosage of glucocorticoids. RESULTS: TARTs were detected in 8 of the 13 patients (61.5%). The median age of TARTs diagnosis was 20.2 years with the youngest case being 15.5 years old. The mean serum level of adrenocorticotropic hormone (ACTH) was higher in the TARTs patient group compared to the non-TARTs group (P<0.05). The tumor size decreased in 3 cases, slightly increased in 1 case, and had no change in another case. CONCLUSION: The serum ACTH level might be associated with the growth promoting factor for TARTs, but the exact mechanism has not been clearly identified. Screening for TARTs using US is important in male patients with CAH for early-detection and prevention of ongoing complications, such as infertility.

XYY syndrome: a 13-year-old boy with tall stature

When evaluating the underlying causes of tall stature, it is important to differentiate pathologic tall stature from familial tall stature. Various pathologic conditions leading to adult tall stature include excess growth hormone secretion, Marfan syndrome, androgen or estrogen deficiency, testicular feminization, and sex chromosome anomaly, such as Klinefelter syndrome and XYY syndrome. Men with 47,XYY syndrome can exhibit multiple phenotypes. A 13-year-old boy visited the hospital for evaluation of tall stature. The boy had no other physical abnormalities except tall stature. All biochemical and imaging studies were within the normal ranges. He was diagnosed with XYY syndrome in this chromosome study. When evaluating men with tall stature, XYY syndrome should be ruled out.

Growth hormone treatment and risk of malignancy / 소아과

Growth hormone (GH) treatment has been increasingly widely used for children with GH deficiencies as the survival rate of pediatric patients with malignancies has increased. Both GH and insulin-like growth factor-I have mitogenic and antiapoptotic activity, prompting concern that GH treatment may be associated with tumor development. In this review, the authors examined the relationship between GH treatment and cancer risk in terms of de novo malignancy, recurrence, and secondary neoplasm. Although the results from numerous studies were not entirely consistent, this review of various clinical and epidemiological studies demonstrated that there is no clear evidence of a causal relationship between GH treatment and tumor development. Nonetheless, a small number of studies reported that childhood cancer survivors who receive GH treatment have a small increased risk of developing de novo cancer and secondary malignant neoplasm. Therefore, regular follow-ups and careful examination for development of cancer should be required in children who receive GH treatment. Continued surveillance for an extended period is essential for monitoring long-term safety.

Relationship between serum 25-hydroxyvitamin D concentration and risks of metabolic syndrome in children and adolescents from Korean National Health and Nutrition Examination survey 2008-2010

PURPOSE: Previous studies have revealed many inconsistent results regarding the relationship between vitamin D and metabolic syndrome. The purpose of our study was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and factors that characterize metabolic syndrome in Korean children and adolescents. METHODS: We analyzed data from 2,880 children and adolescents aged 10-18 years collected from the 2008-2010 Korean National Health and Nutrition Examination Survey. We investigated the data according to quartiles of 25(OH)D concentrations. RESULTS: Systolic blood pressure and diastolic blood pressure with adjustment for sex and age differed significantly between the serum 25(OH)D groups and exhibited negative trend as 25(OH)D concentrations increased. The number of subjects with metabolic syndrome was greater in the low 25(OH)D groups (I, II, and III quartile) than in the high 25(OH)D group (IV quartile) (P=0.029). BMI and waist circumference were lower in the high 25(OH)D group. Serum 25(OH)D concentration correlated negatively with homeostasis model assessment estimate of insulin resistance (rho=-0.073, P<0.001) and correlated positively with quantitative insulin sensitivity check index (rho=0.095, P<0.001). CONCLUSION: Low serum 25(OH)D level is associated with an increase of insulin resistance and metabolic syndrome in children and adolescents.

Etiologies and characteristics of children with chief complaint of short stature

PURPOSE: Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature. METHODS: We retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed. RESULTS: Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%). CONCLUSION: A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.

Regression and progression of microalbuminuria in adolescents with childhood onset diabetes mellitus

PURPOSE: Although microalbuminuria is considered as an early marker of nephropathy in diabetic adults, available information in diabetic adolescents is limited. The aim of this study was to investigate prevalence and frequency of regression of microalbuminuria in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients with childhood onset. METHODS: One hundred and nine adolescents (median, 18.9 years; interquartile range (IQR), 16.5-21.0 years) with T1DM and 18 T2DM adolescents (median, 17.9 years; IQR, 16.8-18.4 years) with repeated measurements of microalbuminuria (first morning urine microalbumin/creatinine ratios) were included. The median duration of diabetes was 10.1 (7.8-14.0) years and 5.0 (3.5-5.6) years, respectively, and follow-up period ranged 0.5-7.0 years. Growth parameters, estimated glomerular filtration rate, glycosylated hemoglobin (HbA1c) and lipid profiles were obtained after reviewing medical record in each subject. RESULTS: The prevalence of microalbuminuria at baseline and evaluation were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. Regression of microalbuminuria was observed in 13 T1DM patients (56.5%) and 3 T2DM patients (37.5%), and progression rate was 10.5% and 20% in T1DM and T2DM respectively. In regression T1DM group, HbA1c at baseline and follow-up was lower, and C-peptide at baseline was higher compared to persistent or progression groups. In T2DM, higher triglyceride was observed in persistent group. CONCLUSION: Considerable regression of microalbuminuria more than progression in diabetes adolescents indicates elevated urinary microalbumin excretion in a single test does not imply irreversible diabetic nephropathy. Careful monitoring and adequate intervention should be emphasized in adolescents with microalbuminuria to prevent rapid progression toward diabetic nephropathy.

Turner syndrome with spinal hemorrhage due to vascular malformation

Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS.

Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

PURPOSE: It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin(R)) effect on growth promotion and safety after short-term GH treatment. MATERIALS AND METHODS: This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. RESULTS: After 26 weeks of GH treatment, the height velocity significantly increased by 6.36+/-3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57+/-0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. CONCLUSION: This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.