The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.
46, XX Testicular Disorders of Sex Development ; Diagnosis ; Disorders of Sex Development ; Female ; Fluorescence ; Genes, sry ; Genetic Counseling ; Genitalia, Male ; Gonads ; Humans ; In Situ Hybridization ; Korea ; Male ; Phenotype ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Sexual Development* ; Testis

Acute suppurative thyroiditis is a rare disease because the thyroid gland is remarkably resistant to infection. We present a 2-year-old girl with refractory acute suppurative thyroiditis due to a pyriform sinus fistula (PSF). She complained of fever and painful anterior neck swelling. Her condition did not completely improved by multiple parenteral antibiotics along with incision and drainage. Barium esophagogram to detect PSF demonstrated no specific finding. Computed tomography scan showed air bubble superior to the left thyroid gland which indicated a possible fistula connected to the pyriform sinus. An intraoperative laryngoscopy revealed a 2-mm-sized fistula opening. The fistula was successfully treated by chemocauterization with trichloroacetic acid.
Anti-Bacterial Agents ; Barium ; Cautery ; Child, Preschool ; Drainage ; Female ; Fever ; Fistula* ; Humans ; Laryngoscopy ; Neck ; Pyriform Sinus* ; Rare Diseases ; Thyroid Gland ; Thyroiditis ; Thyroiditis, Suppurative* ; Trichloroacetic Acid

There is a wide variety of genital abnormalities observed in patients with Denys-Drash syndrome (DDS). WT1 is thought to influence the genes related to genital development and mutations in this gene have been associated with DDS. DDS should be considered in the differential diagnosis of newborns with genital anomalies. In contrast to other conditions with 46,XY disorders of sex development, individuals with DDS often have duplicated genital organs (a double vagina, cervix or uterus). A double uterus has not yet been reported with 1390G>A (Arg464 Asn) mutation. However, duplicated genitals have been reported with other genetic mutations in patients with DDS. The duplicated genitals in DDS may be associated with low anti-Mullerian hormone (AMH) secretion. Measurement of the AMH levels may add to our understanding of variations in genital development and their abnormalities in disorders such as DDS. In conclusion, this is first case of low level of AMH and double uterus in 1390G>A (Arg464 Asn) mutations of DDS male.
46, XY Disorders of Sex Development ; Anti-Mullerian Hormone* ; Cervix Uteri ; Denys-Drash Syndrome* ; Diagnosis, Differential ; Female ; Genitalia ; Humans ; Infant, Newborn* ; Male ; Uterus ; Vagina*

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.
Brain ; Gigantism* ; Glucose Tolerance Test ; Growth Hormone* ; Growth Hormone-Secreting Pituitary Adenoma ; Growth Plate ; Humans ; Magnetic Resonance Imaging ; Male ; Neoplasm, Residual ; Pituitary Neoplasms* ; Reoperation ; Somatostatin

PURPOSE: Vitamin D deficiency has been linked to chronic diseases, such as diabetes mellitus, obesity and autoimmune disease. However, data on the vitamin D status and its association with precocious puberty in girls are limited. We aimed to investigate the association between serum 25-hydroxyvitamin D (25OHD) and precocious puberty in girls. METHODS: A total of 60 girls with central precocious puberty (CPP) and 30 control girls were enrolled. Anthropometric measurement and serum level of 25OHD were estimated for all subjects. RESULTS: There was a significant difference in the mean serum 25OHD concentration between the precocious puberty group and the control group (17.1+/-4.5 ng/mL vs. 21.2+/-5.0 ng/mL, P<0.05). Forty-two of the 60 girls with CPP (70%) had vitamin D deficiency (defined as serum 25OHD<20 ng/mL) and 18 (30%) had vitamin D insufficiency. Of the 30 girls in the control group, vitamin D deficiency was seen in 13 subjects (43.3%), 15 subjects (50%) had vitamin D insufficiency, and 2 subjects (6.7%) had sufficient serum vitamin D (defined as serum 25OHD>30 ng/mL). Vitamin D deficient girls had a significantly higher odds ratio (OR, 3.05; 95% CI, 1.22-7.57, P=0.021). CONCLUSION: These results showed that vitamin D levels may be associated with precocious puberty. Further studies are required to establish the potential effect of vitamin D status on puberty.
Adolescent ; Autoimmune Diseases ; Chronic Disease ; Diabetes Mellitus ; Female ; Humans ; Obesity ; Odds Ratio ; Puberty ; Puberty, Precocious* ; Vitamin D Deficiency ; Vitamin D*

Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2-p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature.
Acidosis ; Dehydration ; Epithelial Sodium Channels ; Failure to Thrive ; Humans ; Hyperkalemia ; Hyponatremia ; Infant, Newborn* ; Kidney ; Korea ; Male* ; Pseudohypoaldosteronism* ; Receptors, Mineralocorticoid*

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.
Chromosome Disorders ; Disorders of Sex Development ; Female ; Genes, sry* ; Genitalia ; Gonadal Dysgenesis, Mixed* ; Gonads ; Humans ; Karyotype ; Male ; Mass Screening ; Monosomy ; Mosaicism ; Sex Differentiation ; Turner Syndrome*

Cerebral salt-wasting syndrome (CSWS) is a rare disease characterized by a extracellular volume depletion and hyponatremia induced by marked natriuresis. It is mainly reported in patients who experience a central nervous system insult, such as cerebral hemorrhage or encephalitis. The syndrome of inappropriate antidiuretic hormone secretion is a main cause of severe hyponatremia after hematopoietic stem cell transplantation, whereas CSWS is rarely reported. We report 3 patients with childhood acute leukemia who developed CSWS with central nervous system complication after hematopoietic stem cell transplantation. The diagnosis of CSW was made on the basis of severe hyponatremia accompanied by increased urine output with clinical signs of dehydration. All patients showed elevated natriuretic peptide and normal antidiuretic hormone. Aggressive water and sodium replacement treatment was instituted in all 3 patients and 2 of them were effectively recovered, the other one was required to add fludrocortisone administration.
Central Nervous System ; Cerebral Hemorrhage ; Dehydration ; Diagnosis ; Encephalitis ; Fludrocortisone ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Hyponatremia ; Leukemia ; Natriuresis ; Polyuria ; Rare Diseases ; Sodium ; Water

PURPOSE: This study investigated blood glucose levels in preterm babies according to gestational age (GA). METHODS: Subjects were 141 preterm infants with a GA<34 weeks. Data on blood glucose levels, GA, body weight, glucose infusion rate, and other contributing factors in the first 7 days after birth were analyzed. Hypoglycemia was defined as a blood glucose level of <40 mg/dL up to 24 hours after birth and as <50 mg/dL thereafter. Hyperglycemia was defined as a blood glucose level >180 mg/dL. RESULTS: During the 7 days after birth, hypo- and hyperglycemia occurred in 29 (29 of 141, 20.6%) and 42 (42 of 141, 29.8%) neonates, respectively. During the first 2 hours, 18 neonates (12.8%) exhibited hypoglycemia, and only 2 (2 of 141, 1.4%) developed hyperglycemia. From 6 to 24 hours, hypo- and hyperglycemia were observed in 0 and 9 (9 of 141, 6.4%) neonates, respectively. Infants small for their GA (SGA) were at risk for hypoglycemia both within 24 hours (odds ratio [OR], 2.718; P=0.045) and during days 2 to 7 (OR, 4.454; P=0.006), and hyperglycemia during days 2 to 7 (OR, 3.200; P=0.005). Low 1-minite Apgar score was risk factor for both hypo- and hyperglycemia during days 2 to 7 (OR, 0.756; P=0.035 for hypoglycemia and OR, 0.789; P=0.016 for hyperglycemia). Both hypo- and hyperglycemia within 24 hours were less common in those who started feeding (OR, 0.294; P=0.013 for hypoglycemia and OR, 0.162; P=0.011 for hyperglycemia). CONCLUSION: Careful blood glucose level monitoring is required in preterm infants, especially SGA infants or those with low Apgar score. Early feeding could be beneficial for maintaining euglycemia.
Apgar Score ; Birth Weight ; Blood Glucose* ; Body Weight ; Gestational Age* ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Infant ; Infant, Newborn ; Infant, Premature* ; Parturition* ; Risk Factors

PURPOSE: This study investigated the incidence trends and associated factors of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents under 15 years of age in Busan and Gyeongnam, Korea from 2001 to 2010. METHODS: Medical records of newly diagnosed diabetes patients (n=328; 160 males, 168 females) were collected in questionnaire form from 5 tertiary and 42 general hospitals in Busan and Gyeongnam. RESULTS: The average crude incidence rate of T1DM and T2DM was 2.01/100,000 (95% confidence interval [CI], 1.76-2.28) and 0.75/100,000 (95% CI, 0.60-0.92), respectively. The incidence rate ratio (IRR) of T1DM was 1.31 (95% CI, 1.01-1.69), and that of T2DM was 1.97 (95% CI, 1.25-3.11) in the latter half-decade (2006 to 2010) compared to the early half-decade (2001 to 2005). There were gradually increasing incidence trends in both T1DM and T2DM over the 10-year period (P for trend: T1DM, 0.0009; T2DM, <0.0001). Age-specific IRR was highest in the 10- to 14-year-old group, regardless of diabetes type. In particular, a rapid increase in incidence of T2DM occurred in the 10- to 14-year-old group. IRR for females was 1.07 (95% CI, 0.83-1.38) for T1DM and 1.56 (95% CI, 1.01-2.41) for T2DM. IRR for Busan (urban) was 1.41 (95% CI, 1.09-1.83) for T1DM and 1.49 (95% CI, 0.96-2.30) for T2DM. CONCLUSION: T1DM and T2DM incidence both increased over time in youth under age 15 living in Busan and Gyeongnam; in particular, the incidence of T2DM in adolescents increased more rapidly.
Adolescent* ; Busan* ; Child* ; Cohort Studies* ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Female ; Hospitals, General ; Humans ; Incidence* ; Korea ; Male ; Medical Records ; Retrospective Studies*