A Change of Adrenal Androgen and Cortisol in Kawasaki Disease

PURPOSE: Endocrine and immune systems are connected and interdependent. Adrenal glands play an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. These steroids have an antagonistic effect on the T cell progression into Th1 and Th2 cells and on the induction of correlated interleukins. Therefore we evaluated the role of adrenal androgen and cortisol as immune modulators in Kawasaki disease(KD) with changes of T cell immunity. METHODS: From April to August in 2001, we examined serum DHEAS and 24 hour urine free cortisol(F) before administration of immunoglobulin and steroids by radioimmunoassay in 14 KD patients. It's clinical severity was determined by Harada score and coronary lesion. RESULTS:The age of the patient group ranged from 4 months to 4 years; its average age was 2.3 years. Three patients(21.4%) were below 1 year, 2(14.3%) between 1 and 2 years, 5(35.7%) between 2 and 3 years, 4(28.6%) between 3 and 4 years of age. Male to female ratio was 1:1.3. DHEAS was significantly decreased in patients(11.1+/-6.0 ng/dL) more than controls(81.6+/-13.3 ng/dL)(P<0.05). Twenty-four hour urine free cortisol was significantly increased in patients(36.9+/-21.9 ng/dL) more than controls(13.6+/-5.5 ng/dL)(P<0.05). Ratio of DHEAS/F was decreased remarkably in patients(0.33+/-0.20) more than controls(6.65+/-2.56)(P=0.016). There was no difference between ratio of DHEAS/F and Harada score, but its ratio was very low in patients with coronary aneurysm. CONCLUSION: These data demonstrate that there are changes of DHEAS and cortisol in acute stage of KD and the dis-equilibrium between two steroids may be relevant in the T cell immune response induction of Kawasaki disease. These changes support the use of DHEAS/F ratio as one of the predictive factors of coronary arteries complication.

Hormone Therapy of Male Hypogonadism / 대한소아내분비학회지

No abstract available.

A Case of Thyroxine Binding Globulin Deficiency with Hypothyroidism

A child diagnosed with congenital hypothyroidism after newborn screening and follow up thyroid function test at 1 month of life in another general hospital demonstrated euthyroid state with thyroxine(T4) supplementation until the age of 22 months of life, when he was transferred to our hospital, where he was diagnosed as thyroxine binding globulin(TBG) deficiency with low T4 and TBG. Withdrawal of T4 at age of 26 months was associated with hyperthyrotropinemic hypothyroidism. This patient is a case of TBG deficiency associated with hypothyroidism, and in rare instances, TBG deficiency may lead to hypothyroidism requiring hormone supplementation.

A Case of Congenital Partial Nephrogenic Diabetes Insipidus

The most common form of genetic nephrogenic diabetes insipidus(NDI), a rare inherited disorder, is congenital and is transmitted in an X-linked recessive mode. It is refractory to the antidiuretic effect of normal to moderately increased levels of plasma arginine vasopressin(AVP) but, in some cases, may respond to high levels of the hormone or its analogue, deamino-D-arginine vasopressin(DDAVP). X-linked congenital NDI has now been linked to over 128 different mutations in diverse coding regions of the AVP receptor 2(AVPR2) gene. The functional effects of these mutations vary from complete loss of responsiveness to a simple shift to the right in the dose response curve. We report a case of congenital partial NDI, with transversion of A to G at codon 280 of the AVPR2 gene, resulting in a subsequent change of amino acid from tyrosine to cysteine, and that has been effective with hydrochlorothiazide and high dose of DDAVP.

A Study on Correlation Among Cord Blood Arachidonic Acid Level, Birth Weight, and Placental Weight

PURPOSE: Arachidonic acid is known to have effects on cell growth as a controller of cell proliferation and a stimulator of platelet derived growth factor. We investigated the correlations among birth weight, placental weight and free arachidonic acid level in cord blood. METHODS: Twenty full-term well babies were included in this study. Those who had sepsis, IUGR, twin that may affect the level of arachidonic acid, birth weight, and/or placental weight were excluded. Free arachidonic acid level were measured by gas chromatographic-mass spectrometry. (GC-MS) Correlation Pearson Coefficients were used for statistical analyses. RESULTS: The correlation coefficients between birth weight and placental weight, birth weight and arachidonic acid level, and placental weight and arachidonic acid level were 0.727 (P0.05), 0.407 (P>0.05) respectively. CONCLUSION: There was statistically significant positive correlation between birth weight and placental weight. But since cord blood free arachidonic acid levels were not correlated with placental weight and birth weight, we conclude that cord blood free arachidonic acid level has no effects on fetal growth and placental growth.

A Study on Correlation Among Cord Blood Arachidonic Acid Level, Birth Weight, and Placental Weight

PURPOSE: Arachidonic acid is known to have effects on cell growth as a controller of cell proliferation and a stimulator of platelet derived growth factor. We investigated the correlations among birth weight, placental weight and free arachidonic acid level in cord blood. METHODS: Twenty full-term well babies were included in this study. Those who had sepsis, IUGR, twin that may affect the level of arachidonic acid, birth weight, and/or placental weight were excluded. Free arachidonic acid level were measured by gas chromatographic-mass spectrometry. (GC-MS) Correlation Pearson Coefficients were used for statistical analyses. RESULTS: The correlation coefficients between birth weight and placental weight, birth weight and arachidonic acid level, and placental weight and arachidonic acid level were 0.727 (P0.05), 0.407 (P>0.05) respectively. CONCLUSION: There was statistically significant positive correlation between birth weight and placental weight. But since cord blood free arachidonic acid levels were not correlated with placental weight and birth weight, we conclude that cord blood free arachidonic acid level has no effects on fetal growth and placental growth.

Effect of Growth Hormone on Death of Sertoli Cell / 대한소아내분비학회지

PURPOSE: Growth hormone(GH) receptors have been detected in Sertoli cells and clinical observations suggested the involvement of GH action(either indirectly via IGF-I or directly) on testicular function. This study is aimed at assessing the effect of GH on cell death during Sertoli cell culture. METHODS: Sertoli cells(TM4, mouse, male, ATCC, USA) were cultured by using DMEM(Dulbecco' Modified Eagle' Medium, Biowhitteker, USA) and Fetal Bovine Serum(10%, GIBCO BRL, USA) with or without human recombinant growth hormone(Eutropin, LGCI, Korea) of different concentrations(10, 50, 100, 500 microgram/mL of media), in 34degress C, 5% CO2 incubator. After cultivation during 5 days, Sertoli cells were examined under light microscope(x400). RESULTS: Number of survival Sertoli cell was remarkably increased in the GH treated(50 microgram/mL in media) group(62.6+/-12.4) compare to control(22.4+/-4.8)(P<0.05). Degree of survival Sertoli cell was increased proportionaly until 50 microgram/mL in concentration of GH in media, but decreased in higher than it. CONCLUSION: GH has the protective effect on death of Sertoli cell and it depends on GH concentration.

Neuroprotective Effect of Growth Hormone in Neonatal Rat with Hypoxic Ischemic Brain Injury / 대한소아내분비학회지

PURPOSE: To investigate the neuroprotective effect of growth hormone(GH) on neuronal cell necrosis and apoptosis at 1 week and 3 weeks after hypoxic ischemic brain injury. METHODS: Sprague-Dawley rats, seven-day-old, were used. Rats were anesthetized with ether less than 5 minutes. The right carotid artery was cut between double ligation. And then, rats were allowed to recover for 30 minutes followed by exposure to 8% oxygen at 37 degrees C for 2 hours for hypoxic ischemic insult. The study group was divided into 2 groups, control group(N=3) and GH treated group(N=3). GH treated group received intraperitoneal injection of GH 1 IU 2 hours after hypoxic ischemic insult following daily adminstration as same dose for 5 days. Rats were decapitated at 1 week and 3 weeks after hypoxic ischemic brain injury. After then, right hippocampal CA1 and CA3 neurons of rat brains were examined. RESULTS: Necrosis was significantly less in GH treated group than control group, and was more prominent at 3 weeks in both groups. The apoptosis was not found in GH treated and control group. CONCLUSION: GH has a neuroprotective effect on neuronal cell deaths(especially necrosis) from 1 week to 3 week after hypoxic ischemic insult in neonatal rat.

Three Cases of Congenital Adrenal Hyperplasia Owing to Multiple Mutations of CYP21 Gene / 대한소아내분비학회지

Congenital adrenal hyperplasia(CAH) results from an inherited defect in enzymatic steps required to synthesize cortisol from cholesterol. 21-hydroxylase deficiency accounts for 95% cases of CAH. We have analyzed CYP21 genes of CAH by PCR direct sequencing. Our results shows three cases of CAH owing to multiple mutations of CYP21 gene; first case, IVS2AS, A/G, -13, Ile172Asn; second case, IVS2AS, A/G, -13, Ile236Asn, Val237Glu, Met239Lys; third case, Ile172Asn, C to G at 1590nt, Val281Leu, Arg484Pro, G to A at 2697nt. Mutations such as Ile236Asn, Val237Glu, Met239Lys, and Arg484Pro are first noted in Korea.

A Case of Type I Glycogen Storage Disease with Decreased Growth Hormone Secretion / 대한소아내분비학회지

Glycogen storage diseases(GSD) are inherited disorders affecting glycogen metabolism and type I GSD is due to the absence or deficiency of glucose-6-phosphatase(G6Pase) enzyme in the liver, kidney, and intestinal mucosa. The defect leads to inadequate hepatic conversion of G6P to glucose and thus make affected individuals susceptible to fasting hypoglycemia, and the accumulation of glycogen occurs in the liver and other organs. Type Ia is the most common form of GSD and clinically growth retardation may manifest of GSD itself rather than growth hormone deficiency(GHD), but we experienced a case of type I GSD with GHD in a 14-year-o1d male. The height was 125 cm, compatible with 50 th percentile of height of 8 years of age. He has doll-like face with fat cheek, relatively thin extremities, and metabolic acidosis, hyperuricemia, hypoglycemia, hyperlipidemia. GH stimulation test with clonidine and L-dopa revealed that the patient had decreased GH secretion. After laboratory work up including liver biopsy, he was diagnosed as type I GSD. Hypoglycemia was managed with frequent feeding with high starch diet(uncooked cornstarch). Metabolic acidosis and hyperuricemia were treated with sodium bicarbonate, allopurinol and probenecid. The patient is being followed at out-patient clinic with clinical improvement after of diet therapy and GH administration.

Recent Advances in Growth Hormone Receptor

No abstract available.

Two Cases of Ectopic Pancreas Located the in the Pyloric Region

Ectopic pancreas is defined as being the presence of pancreatic tissue outside its usual or habitual location and without anatomic relation either of continuity or of vascularization with the pancreatic proper. The most common developing sites are the stomach(especially greater curvature of antrum), duodenum and proximal jejunum. Most lesions do not cause any clinical symptoms, but sometimes nonspecific significant symptoms appear. We report 2 cases of ectopic pancreas located in the pyloric region in a 13 year-old girl and a 12 year-old boy who had symptoms of epigastric pain, nausea, vomiting and dyspepsia. Gastrofiberscopy revealed 2 cm sized submucosal mass with double circular folds and 0.8 cm sized submucosal polypoid mass with central umbilication in the posterior wall of the pyloric region respectively. Wedge resections were performed, although the 12 year-old boy required a second operation due to pyloric obstruction. Histologic findings showed pancreatic acini and Langerhan's islet within gastric submucosa and muscle layer, and pancreatic acini and duct within gastric submucosa layer respectively. Symptoms disappeared after complete removal of the ectopic pancreas by operation.

The Neuroprotective Effect of Growth Hormone on Neuronal Injury of Brain in Pilocarpine induced Status Epilepticus / 대한내분비학회지

BACKGROUND: Several growth factors, including growth hormone (GH) and Insulin like growth factor-I, have been reported to have a neuroprotective effect in experimental models of hypoxic ischemia. This study is aimed at assessing the clinical significance of growth hormone for neuroprotection in status epilepticus induced neuronal cell deaths. METHODS: Pilocarpine induced status epilepticus (SE) was studied in rats (male, Sprague-Dawley). Rats were divided into pre- or post-treatment groups that had either a low (5 U/kg/day) or high (10 U/kg/day) dose of recombinant human GH (Eutropin, LGCI, Korea), and then subdivided into 24 hour, 72 hour and 1 week groups. This was done in the pretreatment groups for 5 days before SE and in the post-treatment groups for 5 days after 2 hrs of SE injection, after SE, the GH was daily injected via intraperitoneal route. Status epilepticus was induced by pilocarpine (360 mg/kg) with scoplamine (1 mg/kg) 30 minutes before pilocarpine injection using a stereotaxic instrument and EEG monitoring. Rats were killed at 24 and 72 hours after the SE in the pretreatment groups and at 1 week after the SE in the post-treatment groups for pathology studies. Neuronal injuries in the rat brain were studied by Hematoxylin & Eosin stain and the TUNEL method. RESULTS: Neuronal necrosis was found in the hippocampal CA1 and CA3 regions in all experimenatal groups after SE, and was more severe in the CA3 region. Apoptosis was found only in the pre-GH treated group and there were TUNEL-positive and morphologically necrotic cells in the hippocampal CA1 and CA3 regions at 72 hours after SE. Neuronal necrosis and apoptosis were significantly decreased in the high dose GH treated groups (p0.05). CONCLUSION: Growth hormone has a neuroprotective effect in neuronal cell death (necrosis and apoptosis) that is caused by pilocarpine induced status epilepticus in a dose dependent manner and prevents the activation of apoptosis by SE in neurons which eventually become necrotic.

Two Cases of Growth Hormone Therapy in Idiopathic Dilated Cardiomyopathy

Growth hormone receptor gene is expressed in the myocardium and growth hormone(GH) administration has been shown to increase cardiac insulin-like growth factor-I(IGF-1) contents. The cardiac myocyte express IGF-I receptors and IGF-I promotes cardiac hypertrophy. Furthermore GH therapy has been reported to have beneficial effects in the treatment of dilated cardiomyopathy in adults. We have studied the effect of short term growth hormone treatment in two cases of a 5 year-old girl and a 15 year-old boy presenting idiopathic dilated cardiomyopathy. Transthoracic echocardiography revealed that the left ventricular chamber was markedly dilated and the global left ventricular systolic function was severely reduced in both. Medical treatments such as inotropic agents, diuretics and angiotensin converting enzyme(ACE) inhibitor were tried but we could not attain remarkable improvement. Finally, we started growth hormone treatment (0.35 U/kg/week, Eutropin, LGCI, Korea) and after treatment for 3 months, we attained a remarkable hemodynamic improvement in the 5 year-old girl with remarkable IGF-I increase after GH treatment, but not in the 15 year-old boy without IGF-I increase. The treatment was safe without side effects. However, no beneficial effects on cardiac function or structure were detected at 6 months of post-treatment.

The Roles of Sex Hormone in Pubertal Growth / 대한소아내분비학회지

No abstract available.

Expression of Growth Hormone Receptor Gene During 3T3-L1 Differentiation / 대한소아내분비학회지

PURPOSE: Growth hormone(GH) produces a variety of effects in adipose tissue via GHRs on the cell membrane. In mouse, alternative splicing of the nascent transcript from the GHR gene produces two major transcripts:GHR mRNA and GHR binding protein(GHBP) mRNA. These two transcripts share the common extracellular ligand-binding domain, but differ in the C-terminal sequence. Since GHR plays an important role in mediating the actions of GH in adipose metabolism, I initiated these studies to examine GHR gene expression during mouse 3T3-Ll preadipocyte-adipocyte differentiation. METHODS: GHR and GHBP transcripts were detected by RNase protection assay (RPA) using the antisense riboprobes complementary either to the specific sequence of the GHR or to the sequence shared by both GHR and GHBP mRNAs. RNA prepared from 3T3-L1 cells at day 0(preadipocytes) and day 7(adipocytes) after treatment with actinomycin D was analyzed by RPA. RESULTS: After stimulation of differentiation, mRNA abundance increased 25-fold and reached a maximal level by day 7 of adipogenesis. The GHR mRNA:GHBP mRNA ratio was 1.3+/-.15 and remained unchanged during differentiation. The decay rate for both mRNAs, estimated by treating the cells with actinomycin D, was approximately 24 hours and showed no significant difference between preadipocytes and adipocytes. CONCLUSION: GHR gene expression is upregulated during preadipocyte-adipocyte differentiation.

A Case of Poland Syndrome with Diabetic Ketoacidosis / 대한소아내분비학회지

Poland syndrome is characterized by an absent of the pectoralis major muscle, with ipsilateral defect of the upper extremity, usually syndactyly. The incidence of this syndrome has been estimated at 1 per 32,000 persons and more than 400 patients have been described worldwide after Alfred Poland's report. but there was no report of Poland syndrome associated with Diabetic Mellitus in childhood. Recently, we experienced a 14 year-old female patient who showed typical Poland syndrome, a left pectoralis muscle hypoplasia and left synbrachydactyly, associated with Diabetes mellitus complicated by ketoacidosis.

A Case of Multiple Ectopic Thyroid Glands with Goiter and Compensated Hypothyroidism Diagnosed by Computerized Tomography / 대한소아내분비학회지

Ectopic thyroid is an uncommon embryological aberration characterized by the presence of thyroid tissue at a site other than in its usual pretracheal region. Usually it occurs along the path of descent of the developing thyroid primodium from the foramen cecum, commonest being lingual followed by sublingual and in the anterior midline of neck at, or below, the level of the hyoid bone. It is unusal for lingual thyroid to present simultaneously with another ectopic thyroid, so we report a case of 12-year-old girl who had multiple ectopic thyroid glands with goiter and compensated hypothyroidism diagnosed by computerized tomography in lingual and infrahyoid area.

Role of Sp Family Transcription Factors in Growth Hormone Receptor Gene Expression / 대한소아내분비학회지

PURPOSE: The growth hormone receptor(GHR) is essential for the actions of growth hormone on postnatal growth and metabolism. GHR transcripts are characterized by the presence of disparate 5'untranslated exons. In contrast to L1 transcript, factors regulating the expression of the GC rich L2 transcript have remained unidentified. The purpose of this study is in order to characterize the mechanisms regulating expression of the L2 transcript in the murine GHR gene METHODS: Transient transfection experiments including deletional analysis and co-transfection assay were performed to find a region containing promoter activity in the L2 5'flanking sequence using BNCL2(mouse liver) cells, CV-1(African green monkey kidney) cells, HRP.1 trophoblasts and Drosophila Schneider(SL2) cells. Sequencing analysis was performed to find the region contained consensus binding sites for transcription factors. Standard gel shift(Electrophoretic mobility shift assay, EMSA) and supershift analysis using liver nuclear extracts was performed to establish proteins(transcription factors) bound this regulatory element. RESULTS: The 5'flanking region of the L2 untranslated region(UTR) exhibited promoter activity in BNCL2(mouse liver), CV-1(monkey kidney) cells and HRP.1 trophoblasts. Deletional analyses indicated the presence of a Sp binding site important for transcription of the L2 UTR and localized the major regulatory region within 75 bp of the 5'transcription start site. Sequencing analyses revealed the region contained consensus binding sites for the Sp family of transcription factors. EMSA and supershift EMSA revealed that in mouse liver nuclear extracts that Spl and Sp3 bound to this cis-element. Functional studies in Drosophila SL2 cells and BNCL2(mouse liver) cells established the ability of Sp3 and Sp1 to stimulate transcriptional activity via this cis-element. Functional studies in Drosophila SL2 cells demonstrated a functional interaction between Sp3 and Sp1 at this DNA-binding site. CONCLUSION: Sp family transcription factors play a role in regulation of L2 transcript gene expression in the 5'flanking region of the murine GHR gene.

A Case of Primary Mucinous Adenocarcinoma of the Colon in Children / 대한소아혈액종양학회지

Carcinomas are malignant neoplasms composed of epithelial cells and epithelial cancers are rare in the young. When it comes to colorectal carcinoma, the incidence of the large bowel has been noted with increasing frequency in the younger population, but this disease has remained very rare in children. Only 1% of all malignant growths of the large intestine arise in persons under 20 years of age. Inspite of these facts, the colon is the most common site of gastrointestinal carcinoma in children. While the prognosis is relatively acceptable in adults, it is very gloomy in children. Of all the histologic categories of colorectal cancer, the mucinous variety, which accounts for approximately 15% of adult colorectal carcinoma, is the predominant histologic variety in patients younger than 20 years of age at the time of diagnosis. Now, only two cases of carcinoma of the colon in children under 15 years of age have been reported in Korea. We report a case of mucinous adenocarcinoma of the colon in a 14-year-old boy with a brief review of the cases on record.