Primary Polydipsia in Children: Two Case Reports

Primary polydipsia (PP) is marked by an increase in thirst, and most often presents in patients with psychiatric illnesses. Although uncommon in children, we experienced cases of PP in a 15-month-old boy and a 5-year-old girl. Both were admitted to the hospital with symptoms of polydipsia and polyuria that appeared 1–3 months before admission. Brain magnetic resonance imaging in both patients was normal. A water restriction test was performed after hospitalization and showed normal results. The symptoms improved after the parents were instructed to implement water-intake restriction for 2 weeks. Our report provides useful information for the treatment of PP in children.

A Case of a Girl with Arnold-Chiari Type 1 Malformation with Precocious Puberty / 가정의학회지

A small percentage of individuals have the neurological anomaly of central precocious puberty (CPP). Common neurologic causes of CPP include a tumor or congenital lesions. Although Arnold-Chiari malformation can be caused by congenital or acquired causes, it is unusual in patients with CPP. We present the case of a girl aged 4.5 years who complained of breast budding. Her neurological examination and growth pattern were normal. She had no endocrinological abnormality, except for true precocious puberty. We performed brain magnetic resonance imaging, which showed an Arnold-Chiari type 1 malformation. Currently, this case represents the youngest girl who exhibited both Arnold-Chiari type 1 malformation and precocious puberty. Furthermore, it is likely that there is a meaningful association between the brain lesion and precocious puberty in this case.

Clinical and Pathological Findings of Renal Biopsy in Children: Outcomes from a Single Center Over 27 Years

PURPOSE: To classify the results of renal biopsy in pediatric patients and to compare pathological findings with clinical features. METHODS: This study included data of 318 children who underwent renal biopsy at our hospital between December 1987 and November 2014. Biopsy specimens were examined histopathologically using light, immunofluorescence, and electron microscopy. RESULTS: Asymptomatic urinary abnormalities was the most common clinical diagnosis (35.9%), followed by nephrotic syndrome (29.3%), and acute glomerulonephritis (18.0%). Glomerular disease was identified in 98.1% of the renal biopsy specimens. The most common primary cause of glomerulonephritis was IgA nephropathy, with gross hematuria in 61.9% of the patients, hypertension in 14.2%, proteinuria >1.0 gm/24-hr in 33.3%, and impaired renal function in 3.6% patients. CONCLUSION: The most common clinical diagnosis was asymptomatic urinary abnormalities, with primary glomerular disease being the most common renal biopsy finding, and IgA nephropathy the most common histopathological lesion. This study provides a 27-year overview of pediatric renal disease at our center and underlines the importance of renal biopsy for accurate diagnosis and proper management.

Urinary Glucose Screening for Early Detection of Asymptomatic Type 2 Diabetes in Jeonbuk Province Korean Schoolchildren

This study aimed to investigate the prevalence of glucosuria and the characteristics of diabetes in schoolchildren as detected by a school urine glucose screening program implemented from 2010 to 2013 in the Jeonbuk province area of Korea. A total of 110 children without known diabetes were analyzed. They were checked with an oral glucose tolerance test (OGTT) with other laboratory tests and their clinical data were collected. A total of 707,238 schoolchildren from a school population of 1,064,999 were screened for glucosuria. In total, over a 4-year period, 545 schoolchildren (0.077%) were positive for glucosuria on the second urine test. The prevalence of glucosuria was more common among middle and high schoolchildren than among elementary schoolchildren. Among 110 students who completed the OGTT to confirm diabetes, 40 were diagnosed with diabetes mellitus (DM); 39 children, type 2 diabetes mellitus (T2DM) and 1 child, slowly progressive insulin dependent diabetes mellitus (SPIDDM). The mean annual incidence of diabetes was 5.6 per 100,000 schoolchildren and adolescents. The subjects with diabetes diagnosed through the urine screening test showed minimal or no symptoms of diabetes. The students with diabetes were more likely to be woman and obese, and they have a higher body mass index, higher cholesterol, triglyceride, insulin, C-peptide, and fasting glucosuria values than the students with normal glucose tolerance. We identified 40 new cases of diabetes in the Korean schoolchildren with asymptomatic glucosuria on urine glucose screening. This finding shows that school urine glucose screening is a feasible and simple method for early detection of asymptomatic T2DM.

Factors Associated with C-peptide Levels after Diagnosis in Children with Type 1 Diabetes Mellitus / 전남의대학술지

C-peptide is the best indicator of endogenous insulin secretion in patients with diabetes. This study investigated the relationship between C-peptide levels and clinical/laboratory parameters of children with type 1 diabetes mellitus (T1DM), as measured at 6-month intervals after diagnosis. We retrospectively reviewed the data of 34 children with newly diagnosed T1DM. The study subjects were subdivided into a rapid progression group with C-peptide levels 0.6 ng/mL at 36 months (n=7; Group B). Patients in Group A had a younger mean age at diagnosis (A: 9±4.3 years vs. B: 13.6±3.6 years; p=0.013) and lower body mass index (BMI) (A: 15.5±2.5 kg/m² vs. B: 18.7±3.3 kg/m²; p=0.035). There were fewer asymptomatic patients with glucosuria in Group A, with these patients showing more severe symptoms, such as diabetic ketoacidosis (p=0.035), than those in Group B. Group A also had lower initial C-peptide levels (A: 0.5±0.46 ng/mL vs. B: 1.87±1.08 ng/mL; p=0.001). There were no significant intergroup differences in sex, family history, baseline hemoglobin A1c (HbA1c), potential of hydrogen (pH), autoantibodies or serum insulin. Simple correlation analyses showed that C-peptide levels were correlated with age and BMI, but not with pH, insulin, or HbA1c. Younger patients, who had a lower BMI, significant symptoms with complications, and/or a low initial C-peptide level, tended to show a rapid rate of decrease in C-peptide levels. Early intensive insulin therapy to preserve beta-cell function should be considered in these groups.

Clinical and Laboratory Characteristics of Pediatric Diabetic Ketoacidosis: A Single-Center Study / 임상당뇨병

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute complication of pediatric type 1 diabetes mellitus (T1DM). We aimed to determine the risk factors and clinical characteristics of children and adolescents with DKA. METHODS: We retrospectively evaluated 59 episodes of DKA in 43 patients who were hospitalized for DKA between January 2006 and December 2015. DKA was classified as mild, moderate, or severe, according to patient history of DKA. The clinical and laboratory characteristics of these subgroups were compared. RESULTS: The average patient age was 11.98 ± 4.40 years (range, 1.3~17.9 years). Moderate episodes were the most common, with 21 episodes (35.6%), followed by 19 severe (32.2%) and 19 mild episodes (32.2%). Significant differences were observed between the subgroups regarding their characteristics of aggravated. Severe DKA episodes were more often observed during the winter season. Recurrent DKA cases were determined in 31 episodes (52.5%) who were significantly older, had higher body mass index, and lower serum C-peptide levels than the newly diagnosed DKA group. Female patients experienced severe and moderate cases more frequently (P = 0.041), which included two deaths. Only blood glucose levels were significantly higher in these fatal cases (P = 0.022). CONCLUSION: Even among the patients who had previously experienced DKA and older children with low serum C-peptide levels, there was no reduction in the severity of DKA. We recommend that patients with DKA be carefully treated and continuously informed regarding the importance of maintaining proper blood glucose levels, regardless of their previous history of DKA, age, or regularity of insulin therapy.

The Challenges of Diabetes Education for Young Diabetes Patients: A 1:1 Mentoring Program Teaching Method / 임상당뇨병

Diabetes is a chronic disease resulting from an absolute or relative shortage of insulin, and it is a disease that requires continuous management throughout the lifetime. Most past diabetes education programs used educational methods for training; however, only a small number of studies on individual education methods were conducted for diabetic patients. Along with individualized educational methods, various instructional methods for knowledge delivery and self-control have been attempted, and one of these is a one-on-one mentoring process. Through such a program, children can acquire knowledge and management of diabetes, and systematic management can be maintained through mentoring and use of diabetic resources. Also, shared cultural and life experiences between the mentor and the mentee can help the children overcome the identity crisis of adolescence to produce a suitable emotional experience. These positive effects can reduce the socio-economic costs associated with diabetes through improved management of problems that can arise in diabetics.

Factors Associated with C-peptide Levels after Diagnosis in Children with Type 1 Diabetes Mellitus / 전남의대학술지

C-peptide is the best indicator of endogenous insulin secretion in patients with diabetes. This study investigated the relationship between C-peptide levels and clinical/laboratory parameters of children with type 1 diabetes mellitus (T1DM), as measured at 6-month intervals after diagnosis. We retrospectively reviewed the data of 34 children with newly diagnosed T1DM. The study subjects were subdivided into a rapid progression group with C-peptide levels <0.6 ng/mL at 36 months (n=27; Group A) and a slow progression group with C-peptide levels >0.6 ng/mL at 36 months (n=7; Group B). Patients in Group A had a younger mean age at diagnosis (A: 9±4.3 years vs. B: 13.6±3.6 years; p=0.013) and lower body mass index (BMI) (A: 15.5±2.5 kg/m² vs. B: 18.7±3.3 kg/m²; p=0.035). There were fewer asymptomatic patients with glucosuria in Group A, with these patients showing more severe symptoms, such as diabetic ketoacidosis (p=0.035), than those in Group B. Group A also had lower initial C-peptide levels (A: 0.5±0.46 ng/mL vs. B: 1.87±1.08 ng/mL; p=0.001). There were no significant intergroup differences in sex, family history, baseline hemoglobin A1c (HbA1c), potential of hydrogen (pH), autoantibodies or serum insulin. Simple correlation analyses showed that C-peptide levels were correlated with age and BMI, but not with pH, insulin, or HbA1c. Younger patients, who had a lower BMI, significant symptoms with complications, and/or a low initial C-peptide level, tended to show a rapid rate of decrease in C-peptide levels. Early intensive insulin therapy to preserve beta-cell function should be considered in these groups.

Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury

Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas.

Clinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single-Center Study from 2000 to 2013 / 전남의대학술지

We examined the clinical and laboratory characteristics of children newly diagnosed with diabetes mellitus (DM) in a single-center study. We retrospectively reviewed the data of 155 children with DM between January 2000 and December 2013. Of 155 diabetic children, 87 (56.1%) were diagnosed with type 1 DM (T1DM) and 68 (43.9%) with type 2 DM (T2DM). Mean ages at diagnosis were 8.95+/-3.89 years (T1DM) and 13.76+/-2.23 years (T2DM), respectively (p3.59 ng/mL for 36 months. However, serum C-peptide levels in T1DM were slightly increased up to 6 months after onset and gradually decreased to 0.32 ng/mL for 36 months. The prevalence of children with DM has increased over the last 14 years, and the proportion of T2DM patients has rapidly increased since 2009. Because childhood DM is associated with several metabolic and cardiovascular complications, children should be screened for early detection of DM, especially asymptomatic T2DM in children and adolescents.

Predictive factors for early response to methimazole in children and adolescents with Graves disease: a single-institute study between 1993 and 2013

PURPOSE: We aimed to investigate the predictive factors for early response to methimazole (MMI) in pediatric patients with Graves disease (GD). METHODS: Our study included 44 pediatric patients who were diagnosed with GD between January 1, 1993, and December 31, 2013, and were available for follow-up, achieving a normalization of thyroid functions (TFs) at the Chonbuk National University Hospital Pediatric Department. We retrospectively analyzed TFs such as tri-iodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and thyroid antibody levels at diagnosis. We also examined their family history of thyroid disease, symptoms at presentation, and normalization time for TF after treatment. We divided our clinical series of patients into the following 4 age groups: <7 years old, 7-12 years old, 13-15 years old, and 16-18 years old. RESULTS: At diagnosis, the time of normalization of T3 was significantly shorter in the higher antimicrosomal antibody (AMA) group compared with the lower AMA group (2.53 months vs. 6.18 months) (P<0.05). However, the time of normalization of T3/fT4/TSH had no significant correlations with other variables such as age, sex, a family history of thyroid diseases, thyroglobulin, thyroid-stimulating immunoglobulin, or antithyroglobulin antibody (ATA). CONCLUSION: Higher serological titers of AMA at diagnosis may have prognostic value in the response to initial MMI treatment in pediatric hyperthyroid GD patients.

Predictive factors for early response to methimazole in children and adolescents with Graves disease: a single-institute study between 1993 and 2013

PURPOSE: We aimed to investigate the predictive factors for early response to methimazole (MMI) in pediatric patients with Graves disease (GD). METHODS: Our study included 44 pediatric patients who were diagnosed with GD between January 1, 1993, and December 31, 2013, and were available for follow-up, achieving a normalization of thyroid functions (TFs) at the Chonbuk National University Hospital Pediatric Department. We retrospectively analyzed TFs such as tri-iodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and thyroid antibody levels at diagnosis. We also examined their family history of thyroid disease, symptoms at presentation, and normalization time for TF after treatment. We divided our clinical series of patients into the following 4 age groups: <7 years old, 7-12 years old, 13-15 years old, and 16-18 years old. RESULTS: At diagnosis, the time of normalization of T3 was significantly shorter in the higher antimicrosomal antibody (AMA) group compared with the lower AMA group (2.53 months vs. 6.18 months) (P<0.05). However, the time of normalization of T3/fT4/TSH had no significant correlations with other variables such as age, sex, a family history of thyroid diseases, thyroglobulin, thyroid-stimulating immunoglobulin, or antithyroglobulin antibody (ATA). CONCLUSION: Higher serological titers of AMA at diagnosis may have prognostic value in the response to initial MMI treatment in pediatric hyperthyroid GD patients.

Targeted exome sequencing resolves allelic and the genetic heterogeneity in the genetic diagnosis of nephronophthisis-related ciliopathy

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.

Clinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single-Center Study from 2000 to 2013 / 전남의대학술지

We examined the clinical and laboratory characteristics of children newly diagnosed with diabetes mellitus (DM) in a single-center study. We retrospectively reviewed the data of 155 children with DM between January 2000 and December 2013. Of 155 diabetic children, 87 (56.1%) were diagnosed with type 1 DM (T1DM) and 68 (43.9%) with type 2 DM (T2DM). Mean ages at diagnosis were 8.95+/-3.89 years (T1DM) and 13.76+/-2.23 years (T2DM), respectively (p<0.001). There were significant differences in HbA1c, C-peptide, and glutamic acid decarboxylase antibody levels between the T1DM and T2DM groups. Annual numbers of children with DM have increased, and since 2011 the number of children with T2DM has surpassed the number with T1DM. The most common clinical symptom in T1DM was polyuria, and 26.4% of children with T1DM presented initially with diabetic ketoacidosis. In contrast, 60.3% of T2DM children showed glucosuria in a school urine screening, and only 19.1% presented with polydipsia. The rate of positivity for at least more than one islet autoantibody was 77.1% in T1DM and 26.3% in T2DM. Serum C-peptide levels in T2DM were increased up to 12 months after onset and remained >3.59 ng/mL for 36 months. However, serum C-peptide levels in T1DM were slightly increased up to 6 months after onset and gradually decreased to 0.32 ng/mL for 36 months. The prevalence of children with DM has increased over the last 14 years, and the proportion of T2DM patients has rapidly increased since 2009. Because childhood DM is associated with several metabolic and cardiovascular complications, children should be screened for early detection of DM, especially asymptomatic T2DM in children and adolescents.

Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus

Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery / 가정의학회지

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

Serum vitamin D status in children and adolescence with diabetes according to season and age

PURPOSE: It is known that children with diabetes have more severe vitamin D deficiency than healthy children. This study aimed to investigate serum vitamin D status and analyze the relationships between serum vitamin D levels and clinical parameters in children with diabetes. METHODS: We checked serum vitamin D levels of children with diabetes aged below 18 years who were treated at our Department of Pediatrics between December 2011 and February 2012 (winter) as well as between June 2012 and August 2012 (summer). We retrospectively analyzed relationships between their serum vitamin D levels and clinical parameters. RESULTS: The serum 25-hydroxyvitamin D level in children with diabetes during winter was markedly lower than during summer (10.8+/-5.1 ng/mL vs. 17.6+/-5.6 ng/mL); vitamin D deficiency was more prevalent during winter (95% vs. 62%). However, there was no difference between children with diabetes and healthy children. In children with type I diabetes mellitus, among all the clinical parameters, age had the greatest negative correlation with serum vitamin D level. CONCLUSION: In children with diabetes, serum vitamin D levels showed marked seasonal variation. However, no clear relationship was identified between vitamin D deficiency and diabetes. This was because the control group had an equally high vitamin D deficiency rate. Additional studies including other clinical parameters after vitamin D supplementation in children with diabetes should be considered.

Congenital Thoracic Ectopic Kidney associated with Diaphragmatic Hernia in a 15-month-old Boy

Congenital thoracic ectopic kidney is a very rare developmental disorder and the rarest type of ectopic kidney. This condition is usually asymptomatic and detected incidentally on routine chest radiography. Most cases of thoracic ectopic kidney develop in adulthood and during the neonatal period, and congenital thoracic ectopic kidney rarely develops in children. Most patients are asymptomatic, and the treatment depends on the diagnosis. Herein, we report a rare case of ectopic thoracic kidney associated with a diaphragmatic hernia in a 15-month-old male infant, who presented with periodic severe irritability. The thoracic ectopic kidney was detected as a mass in the right base of the chest on routine chest radiography.

Thyroid autoimmunity in children and adolescents with newly diagnosed type 1 diabetes mellitus

PURPOSE: This study aim to investigate the occurrence of autoimmune thyroid disease in children and adolescents at onset of type 1 diabetes mellitus (T1DM) and to assess whether the presence of diabetes-specific autoantibodies can predict the autoimmune thyroid disorder. METHODS: Seventy-three children with T1DM were recruited. Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulin autoantibodies (IAA), and thyroid antibodies were determined in all patients at the time of diagnosis. RESULTS: The majority of patients (87.7%) had at least one pancreatic antibody (74.0% for GADA, 20.5% for ICA, and 24.7% for IAA). Thyroid autoantibodies were found in 19 of 73 patients (26.0%) at diagnosis. Thyroid autoimmunity (TA) incidence was not statistically significant by GADA or ICA positivity, but significantly higher by IAA positivity (P=0.03), and IAA positivity showed odds ratio, 4.931; 95% confidence interval, 1.323-18.381 for TA. CONCLUSION: The IAA positivity in children and adolescents with TIDM was strongly related to positivity of thyroid autoantibodies and thus it could serve as an index for early prediction of the development of the thyroid autoimmune disorder among children and adolescents with TIDM.

Fasting serum C-peptide is useful for initial classification of diabetes mellitus in children and adolescents

PURPOSE: With rising obesity rates in children, it is increasingly difficult to differentiate between type 1 and type 2 diabetes mellitus (T1DM, T2DM) on clinical grounds alone. Using C-peptide as a method of classifying diabetes mellitus (DM) has been suggested. This study aimed to find a correlation between fasting C-peptide level and DM types in children and adolescents. METHODS: A total of 223 diabetic children, newly diagnosed at 5 hospitals between January 2001 and December 2012, were enrolled in this study. Initial DM classification was based on clinical and laboratory data including fasting C-peptide at diagnosis; final classification was based on additional data (pancreatic autoantibodies, human leukocyte antigen type, and clinical course). RESULTS: Of 223 diabetic children, 140 were diagnosed with T1DM (62.8%) and the remaining 83 with T2DM (37.2%). The mean serum C-peptide level was significantly lower in children with T1DM (0.80 ng/mL) than in children with T2DM (3.91 ng/mL). Among 223 children, 54 had a serum C-peptide level 3.0 ng/mL; 48 of them (97.9%) were diagnosed with T2DM. CONCLUSION: In this study, we found that if the C-peptide level was 3.0 ng/mL, a T1DM diagnosis is unlikely. This finding suggests that serum fasting C-peptide level is useful for classifying DM type at the time of diagnosis in youth.