Successful sulfonylurea treatment in a patient with permanent neonatal diabetes mellitus with a novel KCNJ11 mutation / 소아과

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium (K(ATP)) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the K(ATP) channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

Gitelman syndrome combined with complete growth hormone deficiency

Gitelman syndrome is a rare autosomal recessive hereditary salt-losing tubulopathy, that manifests as hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is caused by mutations in the solute carrier family 12(sodium/chloride transporters), member 3 (SLC12A3) gene encoding the thiazide-sensitive sodium chloride cotransporter channel (NCCT) in the distal convoluted tubule of the kidney. It is associated with muscle weakness, cramps, tetany, vomiting, diarrhea, abdominal pain, and growth retardation. The incidence of growth retardation, the exact cause of which is unknown, is lower than that of Bartter syndrome. Herein, we discuss the case of an overweight 12.9-year-old girl of short stature presenting with hypokalemic metabolic alkalosis. The patient, on the basis of detection of a heterozygous mutation in the SLC12A3 gene and poor growth hormone (GH) responses in two provocative tests, was diagnosed with Gitelman syndrome combined with complete GH deficiency. GH treatment accompanied by magnesium oxide and potassium replacement was associated with a good clinical response.

Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice / 소아과

PURPOSE: Leptin has been considered a link between metabolic state and reproductive activity. Defective reproductive function can occur in leptin-deficient and leptin-excessive conditions. The aim of this study was to examine the effects of centrally injected leptin on the hypothalamic KiSS-1 system in relation to gonadotropin-releasing hormone (GnRH) action in the initial stage of puberty. METHODS: Leptin (1 microg) was injected directly into the ventricle of pubertal female mice. The resultant gene expressions of hypothalamic GnRH and KiSS-1 and pituitary LH, 2 and 4 hours after injection, were compared with those of saline-injected control mice. The changes in the gene expressions after blocking the GnRH action were also analyzed. RESULTS: The basal expression levels of KiSS-1, GnRH, and LH were significantly higher in the pubertal mice than in the prepubertal mice. The 1-microg leptin dose significantly decreased the mRNA expression levels of KiSS-1, GnRH, and LH in the pubertal mice. A GnRH antagonist significantly increased the KiSS-1 and GnRH mRNA expression levels, and the additional leptin injection decreased the gene expression levels compared with those in the control group. CONCLUSION: The excess leptin might have suppressed the central reproductive axis in the pubertal mice by inhibiting the KiSS-1 expression, and this mechanism is independent of the GnRH-LH-estradiol feedback loop.

A Case of Extreme Uterine Hypotrophy in Hypogonadotropic Hypogonadism with Partial GH Deficiency

Congenital hypogonadotropic hypogonadism is one of the causes of pubertal failure and primary amenorrhea, it is related to uterine hypotrophy. If the uterus is extremely hypotrophied, it is difficult to identify in imaging studies and can be misdiagnosed as a structural anomaly of internal genitalia. We report a case of extreme uterine hypotrophy in 18-year-old girl with primary amenorrhea that was finally diagnosed as hypogonadotrophic hypogonadism. The patient was initially suspected of Mullerian agenesis owing to the invisible uterus. After 4 months of treatment with estrogen, she showed significant growth of the uterus.

A Case of Extreme Uterine Hypotrophy in Hypogonadotropic Hypogonadism with Partial GH Deficiency

Congenital hypogonadotropic hypogonadism is one of the causes of pubertal failure and primary amenorrhea, it is related to uterine hypotrophy. If the uterus is extremely hypotrophied, it is difficult to identify in imaging studies and can be misdiagnosed as a structural anomaly of internal genitalia. We report a case of extreme uterine hypotrophy in 18-year-old girl with primary amenorrhea that was finally diagnosed as hypogonadotrophic hypogonadism. The patient was initially suspected of Mullerian agenesis owing to the invisible uterus. After 4 months of treatment with estrogen, she showed significant growth of the uterus.

Communication Skills Improvement of Medial Students According to Length and Methods of Preclinical Training / 한국의학교육

PURPOSE: The purpose of this study is to evaluate the changing pattern of communication skills of medical students according to length and methods of training. METHODS: We evaluated a 1-week communications training course in 2003, a 1-year course in 2004, and a 1-semester course in 2005 during development of our curriculum. We have conducted the 10-minute CPX on abdominal pain annually since 2002 to assess the clinical performance of medical students who have completed the 3rd year clerkship. We selected CPX videos that were appropriate for assessment. One hundred sixty-four videos were available (1-week didactics: 42 cases, 1-week training: 28 cases, 1-semester training: 50 cases, 1-year training: 44 cases). We developed a 10-item global rating checklist to assess communication skills. A 5-point Likert scale was used to evaluate each item (4-very likely, 0-least likely). Two expert standardized patient (SP) raters evaluated the communication skills of students independently. We analyzed the outcomes based on the training length and methods. The reliability (G coefficient) was 0.825 with 2 SPs and 1 station. RESULTS: The communication skills of students improved with practice and longer training, especially with regard to opening the interview, expressing empathy, understanding the patient's perspective, and preparing for the physical examination. Rapport-building, organization of the interview, understandable explanation, nonverbal communication, active listening and consideration during the physical examination was unchanged between durations of training. The scores for empathetic expression, active listening and understanding the patient's perspective were low across all groups. CONCLUSION: We should concentrate our efforts to improve students' skills in empathetic expression, active listening and understanding the patient's perspective.

Diagnosis and Treatment of Thyroid Nodule / 대한소아내분비학회지

No abstract available.

A Case of Thyroid Hormone Resistance (RTH) / 대한소아내분비학회지

Thyroid hormone resistance (RTH) is a rare autosomal dominant disease characterized by reduced tissue sensitivity to thyroid hormone. Approximately 90% of subjects with RTH have mutation in the thyroid hormone receptor beta (TRbeta) gene. Approximately 10% of subjects diagnosed as having RTH do not carry mutation in the TRbeta gene. We report a 12-year-old male. The patient was euthyroid in spite of high total and free T4 and T3 concentrations, while TSH is slightly increased. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequence analysis of TRbeta gene showed no mutation. We report a case of RTH without mutations in the TRbeta gene.

Mutational Analysis of PTPN11 Gene in Noonan Syndrome / 대한소아내분비학회지

PURPOSE: Noonan syndrome (NS), congenital malformation syndrome characterized by distinct facial anomalies, short stature and variable congenital heart defects, is thought to be caused by mutations of the gene for PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11). The aim of this study is to know the type and detection rate of mutations of PTPN11 in NS. METHODS: This study consisted of 17 NS patients (11 males and 6 females). All of the NS patients met the diagnostic criteria proposed by van der Burgt et al. The leukocyte genomic DNA of each patients was amplified by PCR for 7 exons, where the mutations had been reported so far, out of 15 exons of PTPN11 gene. And the PCR products were subjected to direct sequencing from both directions. RESULTS: All 17 NS patients were sporadic cases. Heterozygous PTPN11 mutations were identified in 3 of the 17 patients (17.6%, all males). All mutations were known missense mutations. They consist of two D61N in exon 3 and one S502T in exon 13. CONCLUSION: This study showed 17.6% (3/17) of detection rate of PTPN11 gene mutation in NS. This is smaller than that of previous reports. The further study with larger number of cases will be needed to analyse type of mutation and genotype-phenotype correlation.

Convulsion, Symptomatic Hyponatremia and Paralytic Ileus Following Tonsillectomy: A case report / 대한마취과학회지

Severe symptomatic hyponatremia shows high mortality in association with cerebral edema and central nervous system dysfunction. Postoperative hyponatremia is usually attributed to administration of hypotonic fluids while antidiuretic hormone is acting. However, we experienced a severe symptomatic hyponatremia in spite of infusion of lactated Ringer's solution perioperatively in a case of 4-year-old girl's tonsillectomy. Inappropriate secretion of ADH caused by pain, stress, anxiety, nausea, vomiting. Paralytic ileus developed several hours after surgery, severe hyponatremia (Na 119 mmol/L) with convulsion notified. After prompt infusion of sodium supplement and fluid restriction, the patient recovered uneventfully.

The Effects of Gonadotropin-Releasing Hormone Agonists on Final Height and its Related Factors in Patients with True Precocious Puberty / 소아과

PURPOSE: The aim of this study was to evaluate the effects of treatment with GnRH agonists on final height(FH) and the influencing factors on height gains. METHODS: Twenty-five girls and five boys with true precocious puberty, who were treated with GnRH agonists for more than one year and had attained final height, were evaluated retrospectively. We analysed auxological parameters at diagnosis, at the end of treatment, and at the attainment of final height, and calculated height gains. RESULTS: FH SDS was significantly higher than predicted adult height(PAH) SDS at diagnosis (-0.91+/-1.32, vs. -1.80+/-1.39, P<0.01). A group of initial PAH below the range of target height(TH) attained significantly more height gains and increments of height SDS than those in a group of initial PAH within the range of TH(8.37+/-2.56 cm vs. 1.38+/-6.42 cm, P<0.01; 1.30+/-0.74 vs. 0.35+/-1.28, P<0.05). Height gains were positively correlated with bone age advancement at diagnosis and height velocity during the first year of treatment(r=0.528, P<0.01 and r=0.454, P<0.05), while height gains were negatively correlated with initial PAH and bone age increments during treatment(r=-0.485, P< 0.05 and r=-0.613, P<0.01). CONCLUSION: This study suggests that GnRH agonist therapy for children with true precocious puberty improves the final height, and height gains are positively affected by bone age advancement at diagnosis and growth velocity during the first year of therapy, and negatively affected by PAH at diagnosis and degree of bone maturation during therapy.

Indices of Insulin Resistance in Children with Simple Obesity / 대한소아내분비학회지

PURPOSE:We performed this study to compare correlation between the indices of insulin resistance using fasting insulin and glucose level and body mass index (BMI), and to determine the clinical usefulness of glucose/insulin ratio (G/I ratio), which is easily available in clinical base. METHODS:Total 119 children with simple obesity, whose BMI is over 95th percentile, were evaluated. We calculated G/I ratio, logInsulin, HOMA-IR, logHOMA-IR, and QUICKI and evaluated their relationship to BMI. RESULTS:Children with high-degree obesity had higher insulin resistance than children with mild to moderate-degree obesity (logInsulin, 1.13+/-.23 vs 1.27+/-.29; logHOMA-IR, 0.46+/-.24 vs 0.61+/-.30; QUICKI, 0.33+/-.03, 0.31+/-.03)(P<0.01), and pubertal children had higher insulin resistance than prepubertal children (G/I ratio, 7.39+/-.07 vs 4.85+/-.29; logInsulin, 1.14+/-.27 vs 1.31+/-.22; logHOMA-IR, 0.47+/-.28 vs 0.65+/-.22; QUICKI, 0.33+/-.03 vs 0.31+/-.02) (P<0.001). BMI had correlation coefficient as -0.436 for QUICKI, -0.432 for G/I ratio, 0.430 for logInsulin, and 0.425 for logHOMA-IR (P=0.000). G/I ratio was well correlated with QUICKI (r=0.901, P=0.000), logHOMA-IR (r=-0.865, P=0.000), and logInsulin (r=0.899, P=0.000). The changes of BMI were correlated with changes of G/I ratio (r=-0.547, P<0.01), QUICKI (r=-0.464, P=0.01), and logHOMA-IR (r=0.429, P<0.05). CONCLUSION: This study revealed that the degree of BMI had statistically significant correlation with insulin resistance, which can be reflected by G/I ratio, logHOMA-IR and QUICKI. G/I ratio was well correlated with logHOMA-IR and QUICKI, which suggests that G/I ratio could be used as an bedside index of insulin resistance. The changes of G/I ratio were more correlated with changes of BMI than those of logHOMA-IR and QUICKI.

Factors Affecting the Increments of Body Mass Index in Adult Survivors of Childhood Brain Tumors / 소아과

PURPOSE: The purpose of this study was to evaluate the factors affecting the increments of body mass index(BMI) in adult survivors from childhood brain tumors. METHODS: We retrospectively reviewed medical records of 63 patients who were diagnosed with brain tumors and treated at Seoul National University Children's Hospital between 1982 and 2000. We evaluated the factors affecting adult BMI(aBMI) at attainment of final adult height(FAH). Observed factors were as follows : characteristics of tumors, modes of treatment for tumors, existence of growth hormone deficiency(GHD) and growth hormone(GH) replacements, cumulative BMI changes according to GH replacements. RESULTS: aBMI in patients with GHD was greater than that in patients without GHD(23.5+/-3.9 kg/ m2 vs 20.4+/-2.8 kg/m2, P=0.012). Among patients with GHD, GH replacement didn't make any difference in aBMI between treated and untreated patients. Cumulative BMI changes from diagnosis of tumor to attainment of FAH( BMI) were positively correlated with cumulative BMI changes before and during GH replacement(r=0.740, P<0.001 and r=0.574, P<0.001, respectively). When analyzed by multiple stepwise linear regression, the strongest related factor for increment of BMI was the increment of cumulative BMI changes before GH replacements. BMI increments velocity(cumulative BMI change/year) before and during GH replacements were 2.3+/-2.5 kg/m2/year and 0.9+/-1.6 kg/m2/ year, respectively(P=0.005). Patients with extensive surgery were greater aBMI(P=0.036). CONCLUSION: This study suggests that GHD and damage of hypothalamus by tumor and/or modes of treatment contribute to the increment of BMI in adult survivors of childhood brain tumors. Early GH replacements may possibly prevent severe hypothalamic obesity, which should be further clarified.