PURPOSE: The aim of this study was to evaluate growth status using the insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations in children with subclinical hypothyroidism (SCH). METHODS: The study included 93 SCH patients (33 males and 60 females, age 8.1+/-1.9 years) and 94 healthy control subjects (31 males and 63 females, age 8.0+/-0.7 years). Patients' height and weight were measured, and their body mass index (BMI) and Z-scores were calculated. The relationship between growth parameters, including IGF-I and IGFBP-3 concentrations and thyroid functions (thyroid-stimulating hormone (TSH) and free thyroxine 4 (fT4) was explored. RESULTS: Although weight and BMI were greater in SCH patients, the Z-score of height, weight and BMI, and serum IGF-I and IGFBP-3 levels in SCH children were not significantly different compared to the control. In SCH patients, TSH showed a negative correlation with weight Z-scores (r=-0.23, P=0.028) and BMI Z-scores (r=-0.21, P=0.048). FT4 showed a positive correlation with IGFBP-3. CONCLUSION: The positive correlation of fT4 and IGFBP-3 and the negative relationship between TSH and weight and BMI Z-scores in SCH children suggest that subnormal thyroid functions could be related to growth impairment.
Body Mass Index ; Child ; Female ; Humans ; Hypothyroidism ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Male ; Thyroid Gland ; Thyroxine

PURPOSE: IGFBP-3 leads to the induction of insulin resistance in 3T3-L1 adipocytes. We carried out a series of experiments to elucidate the effects of IGFBP-3 on adipokines and gene expressions. METHODS: We treated fully-differentiated 3T3-L1 adipocytes with IGFBP-3 (0.5, 1, and 2 microg/mL) for one day and measured the mRNA levels of adiponectin, leptin, resistin, and TNF-alpha by RT-PCR, and adiponectin, leptin, resistin, and IL-6 protein levels in the culture supernatant were measured using multiplex adipokine assay ELISA Kits (Linco Research, St. Charles, Missouri). Gene expression in 3T3-L1 adipocyte cells using a microarray method was performed. RESULTS: IGFBP-3 inhibited the expression of adiponectin, leptin, resistin, and TNF-alpha mRNA. IGFBP-3 at 0.5 and 1 micro/mL decreased adiponectin release, but IL-6 release was increased at 2 micro/mL IGFBP-3. A dose-dependent inhibition of leptin was released by IGFBP-3 at 50%. Resistin release was decreased by 40%. The effect of IGFBP-3 on the gene expression in 3T3-L1 adipocyte cells using a microarray assay related to an increase of agouti-realted proteins (Agrp) and Janus kinase 2 (JAK2), and a decrease of the ras homolog gene family (Rhoq), acyl-CoA synthetase long-chain family member 6 (Acsl6), and the interleukin-1 receptor-associated kinase 1 (Irak1). CONCLUSION: IGFBP-3 regulates several adipokines gene expressions that are known to modulate insulin sensitivity, and this regulation may be attributable to the insulin resistance effect of IGFBP-3 on adipocytes.
Adipocytes ; Adipokines ; Adiponectin ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Insulin Resistance ; Insulin-Like Growth Factor Binding Protein 3 ; Interleukin-1 Receptor-Associated Kinases ; Interleukin-6 ; Janus Kinase 2 ; Leptin ; Ligases ; Proteins ; Resistin ; RNA, Messenger ; Tumor Necrosis Factor-alpha

PURPOSE: The purpose of this test was to investigate the changes of serum IGF-1 and IGFBP-3 levels during a one-year gonadotropin releasing hormone agonist (GnRHa) treatment in central precocious puberty (CPP) girls. METHODS: From 2007 to 2009, 26 girls were enrolled in this study. They were diagnosed as having central precocious puberty and were treated with GnRHa (leuprolide actete) for one year. Their height, bone age, and serum IGF-1 and IGFBP-3 levels were evaluated every six months. RESULTS: At the time of diagnosis, their mean serum IGF-1 and IGFBP-3 levels were 302.90+/-102.54 ng/mL and 3,103.58+/-705.08 ng/mL, respectively. At six month after treatment, the serum IGF-1 and IGFBP-3 levels were slightly decreased. One year later, IGF-1 concentrations were higher than before treatment and IGFBP-3 levels were lower (P=NS). This result, however, was not statistically significant. CONCLUSION: Gonadal suppression with gonadotropin releasing hormones inversely influenced circulating IGF-1 and IGFBP-3 levels. However, the serum IGF-1 and IGFBP-3 levels were maintained at relatively steady levels, preserving a normal height velocity.
Gonadotropin-Releasing Hormone ; Gonadotropins ; Gonads ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Puberty, Precocious

PURPOSE: Diverse cytokines influence the pathogenesis of type 1 diabetes mellitus (T1DM) in different ways. We studied the profile of cytokines in sera from type 1 diabetic patients at diagnosis. METHODS: Serum levels of 11 cytokines (IL-1alpha, IL-1beta, IL-1Ra, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), INF-gamma, and TNF-alpha) from 38 newly-diagnosed T1DM patents and 39 healthy controls were measured, using multiplex immunoanalytic xMAP. RESULTS: Patients showed significantly higher levels of IL-1beta (P < 0.01), IL-10 (P < 0.01), and TNF-alpha (P = 0.019), than the healthy controls. In 12 of 35 patients, the insulin autoantibody (IAA) was positive (34%) and the level of IAA was correlated with IL-10 (r = 0.454, P = 0.006), and TNF-alpha (r = 0.368, P = 0.030). CONCLUSION: These results suggest that IL-1beta, TNF-alpha, and IL-10 play a role in the pathogenesis of T1DM, and the level of the IAA is correlated with IL-10 and TNF-alpha.
Autoantibodies ; Cytokines ; Diabetes Mellitus, Type 1 ; Humans ; Insulin ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-10 ; Interleukin-12 ; Interleukin-1beta ; Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha

As a result of recent advances in life science and technology, various therapeutic drugs have been developed and active research in the fields of medicine for the development of novel drugs are under progress. Among these researches, the Drug Delivery System (DDS) is an advanced technology that effectively delivers therapeutic drugs to desired targets and thereby reduces adverse effects and increases efficacy. The application of this technology in the industry is technology-intensive and high value-added and therefore suitable for Korea's condition which is poor of material resources while abundant of human resources. Therefore there are many efforts in developing DDS as a major fundamental industry in Korea. Therefore this technology has emerged as a new technology that has a substantial impact in the development and growth of biotechnology related industries in Korea. In this review, we introduce the basic concepts and principles of DDS, so that pediatric endocrinologists may obtain a more comprehensive understanding and may benefit in treating patients with this advanced technology.
Biological Science Disciplines ; Biotechnology ; Drug Delivery Systems ; Endocrinology ; Growth and Development ; Humans ; Korea

Adult growth hormone deficiency (GHD) is associated with increased morbidity and mortality and reduced quality of life. GH status should be reevaluated in the transitional age for continued treatment to complete somatic development. All children diagnosed with GHD should be retested by insulin provocative tests upon completion of skeletal growth. A low insulin-like growth factor (IGF)-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, however, a normal IGF-I does not rule out GHD. When the diagnosis of adult GHD is established, continuation of GH therapy is strongly recommended. Continued GH treatment from adolescence into early adulthood may contribute to the attainment of a normal bone and muscle mass and contribute to a decrease of the cardiovascular risk of GHD adults. There is ongoing debate about nearly every aspect of GH therapy.
Adolescent ; Adult ; Child ; Growth Hormone ; Humans ; Hypopituitarism ; Insulin ; Insulin-Like Growth Factor I ; Muscles ; Quality of Life

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. Although the vast majority of KS cases are sporadic, some X-linked recessive (KAL1), autosomal dominant (FGFR1), and autosomal recessive (most commonly GNRHR) modes of inheritance have been described. Two boys were referred to our department because of cryptorchidism and the absence of puberty. Upon laboratory evaluation they were diagnosed with hypogonadotropic hypogonadism. Agenesis of the olfactory bulbs was detected in radiologic tests, and total deletion of the KAL1 gene was detected through multiplex ligation-dependent probe amplification (MLPA). Although cryptorchidism was diagnosed in the siblings, only the older brother suffered from sensorineural hearing loss and right renal agenesis, a feature that had been reported in X-linked KS. We describe herein the clinical heterogeneity of two affected brothers who carry a complete deletion in KAL1; this is the first case of familial Kallmann syndrome due to the complete deletion of the KAL1 gene reported in Korea.
Congenital Abnormalities ; Cryptorchidism ; Hearing Loss, Sensorineural ; Humans ; Hypogonadism ; Kallmann Syndrome ; Kidney ; Kidney Diseases ; Korea ; Male ; Multiplex Polymerase Chain Reaction ; Olfaction Disorders ; Olfactory Bulb ; Population Characteristics ; Puberty ; Siblings ; Wills

We report a case of Turner syndrome associated with idiopathic central diabetes insipidus in a 12-year-old girl, who presented with polyuria and polydipsia after a year. The patient was very short and and centrally obese, and was initially diagnosed with Turner syndrome, hyperlipidema, and diabetes mellitus. A water deprivation test revealed central diabetes insipidus, and sellar magnetic resonance imaging (MRI) showed a thickening of the pituitary stalk, with normal high signal intensity in the posterior pituitary gland. Replacement therapy with desmopressin was initiated, and follow-up sellar MRI findings after two years showed spontaneous regression of the thickened pituitary stalk. There are only few reports of concomitant Turner syndrome with central diabetes insipidus worldwide. Further observation is needed in order to disclose the cause of central diabetes insipidus in patients having Turner syndrome.
Child ; Deamino Arginine Vasopressin ; Diabetes Insipidus, Neurogenic ; Diabetes Mellitus ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Pituitary Gland ; Pituitary Gland, Posterior ; Polydipsia ; Polyuria ; Turner Syndrome ; Water Deprivation

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. Although the vast majority of KS cases are sporadic, some X-linked recessive (KAL1), autosomal dominant (FGFR1), and autosomal recessive (most commonly GNRHR) modes of inheritance have been described. Two boys were referred to our department because of cryptorchidism and the absence of puberty. Upon laboratory evaluation they were diagnosed with hypogonadotropic hypogonadism. Agenesis of the olfactory bulbs was detected in radiologic tests, and total deletion of the KAL1 gene was detected through multiplex ligation-dependent probe amplification (MLPA). Although cryptorchidism was diagnosed in the siblings, only the older brother suffered from sensorineural hearing loss and right renal agenesis, a feature that had been reported in X-linked KS. We describe herein the clinical heterogeneity of two affected brothers who carry a complete deletion in KAL1; this is the first case of familial Kallmann syndrome due to the complete deletion of the KAL1 gene reported in Korea.
Congenital Abnormalities ; Cryptorchidism ; Hearing Loss, Sensorineural ; Humans ; Hypogonadism ; Kallmann Syndrome ; Kidney ; Kidney Diseases ; Korea ; Male ; Multiplex Polymerase Chain Reaction ; Olfaction Disorders ; Olfactory Bulb ; Population Characteristics ; Puberty ; Siblings ; Wills

Hypercalcemia is not common, and occurs more frequently in children than in adults. Left untreated, hypercalcemia could result in a profound impact on growth and development. We report a case of recurrent idiopathic infantile hypercalcemia with poor weight gain, constipation, and a renal stone. We successfully treated the infantile hypercalcemia with a low-calcium diet and intravenous pamidronate.
Adult ; Child ; Constipation ; Diet ; Diphosphonates ; Growth and Development ; Humans ; Hypercalcemia ; Infant ; Kidney Calculi ; Weight Gain