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Patients with diffuse congenital hyperinsulinism (CHI) refractory to drug therapy require subtotal or near-total pancreatectomy. Although almost all patients develop diabetes postoperatively, the clinical course and timing of insulin therapy remain unclear. A 7-yr-old girl presented with recurrent hypoglycemia shortly after birth and a relatively elevated insulin level, which confirmed the diagnosis of CHI. Genetic analysis revealed compound heterozygous ATP-binding cassette, Subfamily C, Member 8 pathogenic variants and diffuse CHI was suspected. Because her condition was refractory to diazoxide and octreotide, she underwent a subtotal pancreatectomy at the age of 4 mo. The drug therapy was discontinued. Although an oral glucose tolerance test at the age of 2 yr showed hyperglycemia after loading, continuous glucose monitoring (CGM) revealed that her daily glucose trends were almost within the 70-180 mg/dL range, and mild hypoglycemia appeared during the daytime. After the age of 6 yr, CGM showed an elevation in glucose trends from midnight to early morning, suggesting that insulin secretion was attenuated and hepatic glucose production was insufficiently suppressed. Insulin therapy was initiated at the age of 7 yr. These results indicate that CGM can be useful for making treatment decisions.
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A multiphase CFD-DEM model was built to simulate the waste-to-energy gasifying and direct melting furnace in a pilot demonstration facility. The characterizations of feedstocks, waste pyrolysis kinetics, and charcoal combustion kinetics were first obtained in the laboratory and used as model inputs. The density and heat capacity of waste and charcoal particles were then modelled dynamically under different status, composition, and temperature. A simplified ash melting model was developed to track the final fate of waste particles. The simulation results were in good agreement with the site observations in both temperature and slag/fly-ash generations, verifying the CFD-DEM model settings and gas-particle dynamics. More importantly, the 3-D simulations quantified and visualized the individual functioning zones in the direct-melting gasifier as well as the dynamic changes throughout the whole lifetime of waste particles, which is otherwise technically unachievable for direct plant observations. Hence, the study demonstrates that the established CFD-DEM model together with the developed simulation procedures can be used as a tool for the optimisation of operating conditions and scaled-up design for future prototype waste-to-energy gasifying and direct melting furnace.
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Carbón Orgánico , Residuos Sólidos , Residuos Sólidos/análisis , Ceniza del Carbón , Temperatura , Calor , Incineración/métodosRESUMEN
As environmental factors are known to affect the timing of puberty, self-isolation during the coronavirus disease (COVID-19) pandemic may affect the incidence of central precocious puberty (CPP). This study aimed to evaluate the frequency of CPP during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan. We retrospectively analyzed the annual frequency of CPP occurrence before and after the first declaration of COVID-19 state of emergency in Japan at our hospital. We performed an interrupted time-series analysis to investigate the frequency of patients with CPP at our hospital from 2016 to 2021. There was a significant increase in the frequency of patients with CPP before and after the state of emergency declaration, both overall and among females. However, there was no significant increase in the number of males. There were no significant differences in the clinical, auxological, and endocrinological features between those diagnosed before and after the state of emergency. Overall, the frequency of CPP significantly increased during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan.
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Several excellent guidelines and expert opinions on congenital hypothyroidism (CH) are currently available. Nonetheless, these guidelines do not address several issues related to CH in detail. In this review, the authors chose the following seven clinical issues that they felt were especially deserving of closer scrutiny in the hope that drawing attention to them through discussion would help pediatric endocrinologists and promote further interest in the treatment of CH. 1. How high should the levothyroxine (L-T4) dose be for initial treatment of severe and permanent CH? 2. What is the optimal method for monitoring treatment of severe CH? 3. At what level does maternal iodine intake during pregnancy affect fetal and neonatal thyroid function? 4. Does serum thyroglobulin differ between patients with a dual oxidase 2 (DUOX2) variants and those with excess iodine? 5. Who qualifies for a genetic diagnosis? 6. What is the best index for distinguishing transient and permanent CH? 7. Is there any cancer risk associated with CH? The authors discussed these topics and jointly edited the manuscript to improve the understanding of CH and related issues.
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AIMS/INTRODUCTION: To investigate the genetic background of Japanese patients with suspected maturity-onset diabetes of the young (MODY). MATERIALS AND METHODS: On 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A > G analysis and methylation-specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency <0.001 and Combined Annotation Dependent Depletion score >20 (CS >20) were listed as rare variants of uncertain significance-CS >20. RESULTS: A total of 157 pathogenic/likely pathogenic variants and 44 rare variants of uncertain significance-CS >20 were identified. In the pathogenic/likely pathogenic variants, alterations in the GCK gene were the most common (82, 52.2%) followed by HNF1A (29, 18.5%), HNF4A (13, 8.3%) and HNF1B (13, 8.3%). One patient was a 29.5% mosaic with a truncating INSR variant. In the rare variants of uncertain significance-CS >20, 20 (45.5%) were in the genes coding for the adenosine triphosphate-sensitive potassium channel, KCNJ11 or ABCC8, and four were in the genes of the insulin-signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis. CONCLUSIONS: Causative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. ABCC8-MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY.
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Hiperinsulinismo Congénito , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Insulina/genética , Resistencia a la Insulina/genética , Pueblos del Este de Asia , Diabetes Mellitus Tipo 2/epidemiología , Mutación , Receptores de Sulfonilureas/genéticaRESUMEN
OBJECTIVE: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. DESIGN: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. METHODS: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. RESULTS: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p < .05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. CONCLUSIONS: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.
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Hipernatremia , Enfermedades Hipotalámicas , Órgano Subfornical , Animales , Niño , Femenino , Humanos , Hipotálamo , Inmunidad , Masculino , Ratones , Prolactina , Órgano Subfornical/fisiologíaRESUMEN
OBJECTIVES: Constitutional delay of growth (CDG) is usually associated with a delay in pubertal onset (CDGP) and a catch-up growth after puberty. Some individuals, however, have earlier-than-expected pubertal onset resulting in a shorter adult height. We investigated the current incidence of such individuals and that of 30 years ago. METHODS: The study subjects are 1,312 consecutive Japanese children referred to Osaka City General Hospital (OCGH) for short stature during 2010-2018, and a cohort of 11,256 individuals in the Ogi Growth Research (OGR, 1979-1992). Individuals with the height standard deviation score <-1.0, the bone age (BA)/chronological age (CA) ratio <0.8 at first visits, and without other identifiable causes of short stature were extracted from the record of OCGH. Similarly, individuals meeting the height and bone age criteria were extracted from the OGR record. The pubertal growth onset was auxologically determined as the upward shift from the prepubertal growth curve fitted to a quadratic function. Earlier-than-expected onset was defined as the onset earlier than the population average +1 year. RESULTS: From the OCGH cohort, 55 children (38 boys, 17 girls) met the criteria, and earlier-than-expected onset was observed in 34.2% of boys and 29.4% of girls. In the 73 short individuals with delayed bone age in the OGR cohort, earlier-than-expected onset was less common (13.0% for boys and 14.8% for girls). There was no significant association between the timing of pubertal growth onset and the BA/CA ratio, IGF-1, and midparental height. CONCLUSIONS: Earlier-than-expected pubertal growth onset is common in CDG and possibly increasing.
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Pubertad Tardía/epidemiología , Adolescente , Determinación de la Edad por el Esqueleto , Factores de Edad , Estatura , Niño , Femenino , Humanos , Masculino , Pubertad Tardía/fisiopatologíaRESUMEN
AIMS/INTRODUCTION: We aimed to investigate the nationwide incidence, treatment details and outcomes of patients with endogenous hyperinsulinemic hypoglycemia (EHH), including those with transient/persistent congenital hyperinsulinism (CHI), insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata's disease) in Japan. MATERIALS AND METHODS: A nationwide, questionnaire-based survey was carried out to determine the number of patients with EHH who were treated for hypoglycemia or hypoglycemia-related complications in 2017-2018. The questionnaires were sent to all hospitals in Japan with >300 beds, and with pediatric and/or adult clinics likely managing EHH patients. The secondary questionnaires were sent to obtain the patients' date of birth, sex, age at onset, treatment details and post-treatment outcomes. RESULTS: A total of 447 patients with CHI (197 transient CHI, 225 persistent CHI and 25, unknown histology), 205 with insulinoma (118 benign, 18 malignant and 69 unknown subtype), 111 with non-insulinoma pancreatogenous hypoglycemia syndrome (33 post-gastric surgery HH, 57 postprandial HH, 10 nesidioblastosis and 11 unknown subtype) and 22 with insulin autoimmune syndrome were identified. Novel findings included: (i) marked improvement in the prognosis of persistent CHI over the past 10 years; (ii) male dominance in the incidence of transient CHI; (iii) non-insulinoma pancreatogenous hypoglycemia syndrome emerging as the second most common form of EHH in adults; (iv) frequent association of diabetes mellitus with insulin autoimmune syndrome; and (v) frequent post-treatment residual hypoglycemia and impaired quality of life. CONCLUSIONS: The first nationwide, all age group survey of EHH showed the current status of each type of EHH disorder and the unmet needs of the patients.
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Hiperinsulinismo/epidemiología , Hipoglucemia/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Hiperinsulinismo Congénito/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Insulinoma/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Nesidioblastosis/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Significant differences in levothyroxine (LT4) dosages for congenital hypothyroidism (CH), which can be permanent (P-CH) or transient (T-CH), and their respective cutoff values have been reported. In Japanese children, however, these values are unknown, and were thus determined in this retrospective single-center study, which included 34 patients- 19 with P-CH and 15 with T-CH. The LT4 dosages of the two groups at ages 1 and 3 yr were compared, and receiver operating characteristic (ROC) analysis was performed to identify the cutoff dosages. The results showed that the LT4 dosages of the P-CH and T-CH groups differed significantly at both ages. When LT4 dosage cutoff at 1 yr of age was set at 2.4 µg/kg/d, the sensitivity and specificity were 93% and 74%, respectively, and when it was set at 1.3 µg/kg/d at 3 yr of age, they were 80% and 84%, respectively, suggesting that when LT4 dosages are ≤2.4 µg/kg/d at 1 yr and ≤1.3 µg/kg/d at 3 yr of age, T-CH should be suspected.
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Mitochondrial acyl-CoA dehydrogenase 9 (ACAD9) deficiency is one of the common causes of respiratory chain complex I deficiency, which is characterized by cardiomyopathy, lactic acidemia, and muscle weakness. Infantile cardiomyopathy is the most common phenotype and is usually lethal by the age of 5 years. Riboflavin treatment is known to be effective in ~65% of the patients; however, the remaining are unresponsive to riboflavin and are in need of additional treatment measures. In this report, we describe a patient with ACAD9 deficiency who developed progressive cardiomyopathy at 8 months of age. As the patient's left ventricular ejection fraction (LVEF) kept decreasing to 45.4% at 1 year 8 months, sodium pyruvate treatment was introduced together with a beta-blocker and coenzyme Q10. This resulted in a steady improvement, with full and sustained normalization of cardiac function without riboflavin. The therapy, therefore, might be a useful addition for the treatment of ACAD9 deficiency.
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Acidosis/tratamiento farmacológico , Acil-CoA Deshidrogenasa/deficiencia , Acil-CoA Deshidrogenasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Carvedilol/administración & dosificación , Enfermedades Mitocondriales/tratamiento farmacológico , Debilidad Muscular/tratamiento farmacológico , Piruvatos/administración & dosificación , Ubiquinona/análogos & derivados , Acidosis/complicaciones , Acidosis/patología , Antagonistas Adrenérgicos beta/administración & dosificación , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/patología , Cardiomiopatías/complicaciones , Cardiomiopatías/patología , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/patología , Quimioterapia Combinada , Femenino , Humanos , Recién Nacido , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/patología , Debilidad Muscular/complicaciones , Debilidad Muscular/patología , Pronóstico , Ubiquinona/administración & dosificación , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: Congenital hypothyroidism (CH) can be divided into 2 types, transient CH (T-CH) and permanent CH (P-CH), depending on the requirement of levothyroxine (LT4) for life-long treatment. Several studies have recently reported that the LT4 dosage is useful for predicting the LT4 requirement, but none of the studies followed their patients to puberty. OBJECTIVE: To determine the cutoff value for the LT4 dosage as a predictor of the LT4 requirement after puberty in patients with CH. METHODS: The LT4 dosage and clinical data on 99 patients with CH who were followed at the participating hospitals from the neonatal period to 15 years of age or older were retrospectively analyzed. Based on their LT4 requirement at their last hospital visit, the participants were divided into the P-CH group (n = 75), who were treated with LT4, and the T-CH group (n = 24), who were not. RESULTS: At age 1 year, a higher LT4 dosage was required for the P-CH group (median 3.75 vs. 2.88 µg/kg/day; p < 0.001). When the LT4 dosage cutoff value at age 1 year was set at 4.79 and 1.74 µg/kg/day, the specificity of P-CH and T-CH (for denying T-CH and P-CH, respectively) was 100 and 97%, respectively. CONCLUSIONS: An LT4 dosage above 4.7 µg/kg/day and below 1.8 µg/kg/day at age 1 year may help predict P-CH and T-CH, respectively.
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Hipotiroidismo Congénito/tratamiento farmacológico , Tiroxina/administración & dosificación , Adolescente , Niño , Preescolar , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Estudios RetrospectivosRESUMEN
AIMS/INTRODUCTION: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; also known as MODY2) is a benign hyperglycemic condition, which generally does not require medical interventions. The only known exception is increased birthweight and related perinatal complications in unaffected offspring of affected women. As previous data were obtained mostly from white Europeans, the present study analyzed the pregnancy outcomes of Japanese women with GCK-MODY to better formulate the management plan for this population. MATERIALS AND METHODS: The study participants were 34 GCK-MODY families whose members were diagnosed at Osaka City General Hospital during 2010-2017. A total of 53 pregnancies (40 from 23 affected women, 13 from 11 unaffected women) were retrospectively analyzed by chart review. RESULTS: Birthweights of unaffected offspring born to affected women were significantly greater as compared with those of affected offspring (P = 0.003). The risk of >4,000 g birthweight (16%), however, was lower as compared with that previously reported for white Europeans, and none of the offspring had complications related to large birthweight. Insulin treatment of the affected women resulted in a significant reduction in the birthweights of unaffected offspring. Perinatal complications including small-for-gestational age birthweight were found only in affected offspring born to insulin-treated women. CONCLUSIONS: In Japanese GCK-MODY families, unaffected offspring born to affected women were heavier than affected offspring. However, insulin treatment of affected women might not be advisable because of the lower risk of macrosomic birth injury, and an increased risk of perinatal complications in affected offspring.
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Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Glucoquinasa/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Recién Nacido , Japón/epidemiología , Masculino , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
Hypopituitarism could have been overlooked so far in the patients with 9q subtelomere deletion syndrome (9qSTDS); thus, further investigations or reevaluation of clinical information, especially hormonal evaluations, are warranted to determine whether hypopituitarism is a rare or relatively common presentation in patients with 9qSTDS.
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Achondroplasia (ACH) is the most common form of skeletal dysplasia causing rhizomelic, short-limb short stature. Short- and long-term clinical trials have been conducted with rhGH, with similar results across these studies. At supraphysiological dose of GH, height gain of 1-1.5 SDS on the population curve was observed during the first 1-3 years, which was then followed by a smaller increase in growth rate persisting for 5-6 years. These studies led to the approval of rhGH for ACH in Japan where rhGH has been used for 20 years at 0.05 mg/kg/day. Although the available data are still limited, compared to untreated controls, total gain in adult height has been greater in males than in females, reported at 3.5-8.0 cm and 2.8-4.2 cm, respectively. Serious adverse events have been rare although some were potentially life-threatening and need careful monitoring. These results should serve as a comparator for novel emerging treatments for ACH.
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Acondroplasia , Hormona del Crecimiento/uso terapéutico , Acondroplasia/tratamiento farmacológico , Estatura , Femenino , Humanos , Japón , MasculinoRESUMEN
BACKGROUND: Causative mutations cannot be identified in the majority of Asian patients with suspected maturity-onset diabetes of the young (MODY). OBJECTIVES: To elucidate the genetic basis of Japanese patients with MODY-like diabetes and gain insight into the etiology of patients without mutations in the major MODY genes. SUBJECTS: A total of 263 Japanese patients with early-onset, non-obese, MODY-like diabetes mellitus referred to Osaka City General Hospital for diagnosis. METHODS: Mutational analysis of the four major MODY genes (GCK, HNF1A, HNF4A, HNF1B) by Sanger sequencing. Mutation-positive and mutation-negative patients were further analyzed for clinical features. RESULTS: Mutations were identified in 103 (39.2%) patients; 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B. Contrary to conventional diagnostic criteria, 18.4% of mutation-positive patients did not have affected parents and 8.2% were in the overweight range (body mass index [BMI] >85th percentile). HOMA-IR at diagnosis was elevated (>2) in 15 of 66 (22.7%) mutation-positive patients. Compared with mutation-positive patients, mutation-negative patients were significantly older (P = 0.003), and had higher BMI percentile at diagnosis (P = 0.0006). Interestingly, maternal inheritance of diabetes was significantly more common in mutation-negative patients (P = 0.0332) and these patients had significantly higher BMI percentile as compared with mutation-negative patients with paternal inheritance (P = 0.0106). CONCLUSIONS: Contrary to the conventional diagnostic criteria, de novo diabetes, overweight, and insulin-resistance are common in Japanese patients with mutation-positive MODY. A significant fraction of mutation-negative patients had features of early-onset type 2 diabetes common in Japanese, and non-Mendelian inheritance needs to be considered for these patients.
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Diabetes Mellitus Tipo 2/genética , Factores Nucleares del Hepatocito/genética , Herencia Materna , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , Niño , Preescolar , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Quinasas del Centro Germinal , Humanos , Japón/epidemiología , Masculino , Adulto JovenRESUMEN
Chromosome 6q24-related diabetes mellitus is the most common cause of transient neonatal diabetes (TNDM), accounting for approximately two-thirds of all TNDM cases. Patients with 6q24-TNDM develop insulin-requiring diabetes soon after birth, followed by the gradual improvement and eventual remission of the disorder by 18 mo of age. The most important clinical feature of affected patients is a small-for-gestational age (SGA) birth weight, which reflects the lack of insulin in utero. It is believed that 6q24-TNDM is caused by the overexpression of the paternal allele of the imprinted locus in chromosome 6q24, which contains only two expressed genes, PLAGL1 and HYMAI. Identified mechanisms include: (1) duplication of the paternal allele, (2) paternal uniparental disomy, and (3) hypomethylation of the maternal allele. Many patients with TNDM relapse after puberty. Relapsed 6q24-related diabetes is no longer transient and typically occurs in non-obese patients who are autoantibody negative. Thus, these patients possess features indistinguishable from those of maturity-onset diabetes of the young (MODY). Conversely, it has been shown that not all patients with 6q24-related diabetes have a history of TNDM. 6q24-related diabetes should therefore be considered as one of the differential diagnoses for patients with MODY-like diabetes, especially when they are SGA at birth.
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Mutations in DUOXA2, encoding dual oxidase maturation factor 2, is a rare genetic cause of congenital hypothyroidism. Only four biallelic DUOXA2 mutation carriers have been described to date. This study was conducted to report the clinical and genetic findings of a DUOXA2 mutation-carrying family, and to review the previously reported cases. The proband was a 4-year-old girl, who was diagnosed as having congenital hypothyroidism in the frame of newborn screening. She had a high serum TSH level (138 mU/L) and a low free T4 level (0.4 ng/dL). Ultrasonography revealed goiter. She was immediately treated with levothyroxine. At age 3 years, reevaluation of her thyroid function showed a slightly elevated serum TSH level (11.0 mU/L) with normal free T4 level. Screening of the eleven congenital hypothyroidism-related genes demonstrated a previously reported nonsense DUOXA2 mutation (p.Tyr138*) in the homozygous state. Unexpectedly, we also found that the elder brother of the proband, who had no significant past medical history, had the identical homozygous mutation. Using expression experiments with HEK293 cells, we confirmed that p.Tyr138* was a loss-of-function mutation. In the literature, clinical courses of three patients were described, showing characteristic age-dependent improvement of the thyroid function. In conclusion, The proband showed comparable clinical phenotype to previously reported cases, while her brother was unaffected. The phenotypic spectrum of DUOXA2 mutations could be broader than currently accepted.
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Hipotiroidismo Congénito/genética , Proteínas de la Membrana/genética , Glándula Tiroides/diagnóstico por imagen , Tirotropina/sangre , Tiroxina/uso terapéutico , Preescolar , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Femenino , Células HEK293 , Homocigoto , Humanos , Recién Nacido , Masculino , Mutación , Tamizaje Neonatal , Hermanos , Tiroxina/sangre , Resultado del Tratamiento , UltrasonografíaRESUMEN
There have been reports of the use of levothyroxine or levothyroxine plus liothyronine for consumptive hypothyroidism caused by hepatic hemangiomas. Administration of levothyroxine without liothyronine can be inadequate to maintain normal levels of both free T3 and free T4 in some patients. However, there is no report of treatment with liothyronine plus propranolol. We herein present a case in which we used liothyronine therapy for multifocal hepatic hemangiomas in a Japanese patient with low free T3 and normal free T4 levels. A 2-month-old Japanese male was referred to our hospital because of jaundice. Abdominal computed tomography showed multifocal hemangiomas in both lobes of the liver. TSH level was elevated, free T3 level was low, free T4 level was normal, and hypothyroidism due to hepatic hemangiomas was diagnosed. In addition to propranolol, liothyronine was started. We used liothyronine without levothyroxine for hypothyroidism because only free T3 level had decreased, whereas free T4 level remained in the normal range. The TSH and free T3 levels normalized in this patient in less than 1 month. The liothyronine dose was gradually reduced with regression of the hemangiomas, and liothyronine administration was discontinued at the age of 5 months. At the age of 11 months, growth and neurological development of the patient met age-specific norms, and he was euthyroid at that time. This is the first report demonstrating the use of liothyronine with propranolol for treatment of this type of consumptive hypothyroidism.
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Hemangioma/fisiopatología , Terapia de Reemplazo de Hormonas , Hipotiroidismo/tratamiento farmacológico , Neoplasias Hepáticas/fisiopatología , Glándula Tiroides/efectos de los fármacos , Triyodotironina/uso terapéutico , Hemangioma/diagnóstico por imagen , Hemangioma/tratamiento farmacológico , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/etiología , Hipotiroidismo/fisiopatología , Lactante , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Hígado/fisiopatología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Propranolol/uso terapéutico , Índice de Severidad de la Enfermedad , Glándula Tiroides/fisiopatología , Tiroxina/sangre , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Triyodotironina/sangre , Ultrasonografía Doppler , Vasodilatadores/uso terapéuticoRESUMEN
The precision of current source estimation of electroencephalography by referring the shape of the brain acquired as MRI was considered. The location of the candidate current dipoles was limited to on the surface of the cortex, and the orientation was constrained to the vertical to the surface. Electric stimulation of median nerve was executed to confirm whether it works appropriately by checking the estimated active area on the cortex.