A Pediatric Case of Graves' Hyperthyroidism with Associated Glucose Intolerance Detected by a Urine Glucose Screening Program at School.

We report here a 13-year-old female with Graves' disease, whose diagnostic clue was glycosuria, which was detected by a urine glucose screening program at school. She had had mild general malaise, and a physical examination revealed a slightly enlarged thyroid gland. Hyperthyroidism (thyroid-stimulating hormone (TSH) < 0.01 µU/ml, free triiodothyronine (fT3) 23.57 pg/ml, free thyroxine (fT4) 3.38 ng/dl) and anti-thyroid autoantibodies (TRAb 43.6%) were detected in laboratory tests, and her plasma glucose at 120 minutes was 142 mg/dl in a 75 g oral glucose tolerance test. She was diagnosed as having borderline diabetes. These findings revealed a diagnosis of Graves' hyperthyroidism with associated impaired glucose tolerance. Although it is reported that many adults with hyperthyroidism develop disorders of glucose metabolism, pediatric patients rarely have complications of glucose intolerance or diabetes mellitus, and there are no previous reports of Graves' disease diagnosed by a urine glucose screening program at school. This case suggests a possibility of abnormalities in glucose metabolism even in pediatric cases of Graves' disease. To avoid overlooking the diagnosis of glucose intolerance associated with hyperthyroidism, a careful medical interview and examination should be performed even if the clinical features are mild.

[Evaluation of Clinical Features and Growth Hormone Deficiency in Short Children Born Small For Gestational Age].

Growth hormone (GH) therapy for short children born small for gestational age (SGA) has been approved in Japan. It is important to evaluate GH secretion ability before the initiation of GH therapy because there are some differences in dose and medical expenses between short children born SGA and GH deficiency (GHD). This study was designed to elucidate the incidence of GHD and to find a useful marker for detecting it in short SGA children. We retrospectively reviewed medical records to analyze the clinical features of short children born SGA and with GHD who had started GH therapy before the age of 6 in the University Hospital of Occupational and Environmental Health and Kyushu Rousai Hospital. Nine of 22 SGA subjects (41%) had GHD. There were no significant differences between two groups of short SGA children (GHD, non-GHD) in the median of height and serum insulin-like growth factors (IGF)-1 levels at birth or at the start of GH therapy. The probability of GHD was higher if the height standard deviation scores (SD) of the SGA children were lower than -3.2 (odds ratio, 11.6; 95% confidence interval, 1.52 - 89.1, P = 0.013). This study showed that there is an approximately 40% incidence of GHD in short SGA children needing GH treatment. We should do GH stimulation tests for short SGA children whose height SD is lower than -3 to determine the appropriate GH therapy.

CCL2 level is elevated with metabolic syndrome and CXCL10 level is correlated with visceral fat area in obese children.

Recent studies revealed that obesity is a low-grade, chronic inflammatory state that is accompanied by the enhanced production of multiple chemokines. In particular, metabolic syndrome (MS) and visceral adipose tissue (VAT) accumulation are significantly associated with certain chemokines in adults. However, little is known regarding this association in obese children. The aim of this study was to investigate the relationship between circulating chemokine levels and both MS and VAT accumulation in obese children. Forty-four obese schoolchildren (26 boys) with a percentage of overweight (POW) exceeding 20 were evaluated. The median age was 11.4 years (range: 6.8-16.5 years). Blood samples were drawn after overnight fasting, and serum chemokine levels (CCL2, CCL5 and CXCL10) were quantitated. Visceral fat area (VFA) determinations were conducted using computed tomography. The results showed that the median BMI Z-score, POW, waist circumference and VFA of the subjects were 2.24 SD, 49.8%, 88.3 cm and 80.8 cm2, respectively. Eighteen were diagnosed with MS. CCL2 was significantly increased in MS subjects compared with non-MS subjects (p<0.05). CXCL10 was positively correlated with VFA (r=0.425, p<0.01). There were no significant correlations between age and chemokine levels. We showed that CCL2 levels were elevated in MS and CXCL10 levels were associated with VFA in obese children. Our results suggest that CCL2 and CXCL10 play important roles in the progression of obesity-related metabolic complications in children.

Sporadic pseudohypoparathyroidism type-1b with asymptomatic hypocalcemia.

Pseudohypoparathyroidism type 1b (PHP-1b) is usually diagnosed on various symptoms of hypocalcemia. Previous studies reported a few cases of autosomal dominant pattern PHP-1b identified on familial analysis with asymptomatic hypocalcemia. Herein we report the case of a 6-year-old male patient with sporadic PHP-1b incidentally detected on preoperative examination. He had neither characteristic findings of Albright hereditary osteodystrophy nor evidence of tetany. Sporadic PHP-1b was diagnosed on the basis of clinical observation and laboratory examination. In addition, genetic testing using methylation-specific multiplex ligation-dependent probe amplification indicated broad methylation abnormalities and confirmed the sporadic form of PHP-1b. Sporadic PHP-1b might often be overlooked when diagnosis is done simply on definitive clinical features. To avoid this, DNA sequencing and methylation analysis should be performed even in the absence of definitive clinical features.

Reducing exposure levels of immersion washing workers to ortho-phthalaldehyde by improving exhaust systems.

OBJECTIVES: The American Conference of Governmental Industrial Hygienists recommends a threshold limit value-ceiling (TLV-C) of 0.1 ppb for occupational exposure to ortho-phthalaldehyde (OPA) used in washing endoscope probes. To adhere to this extremely low exposure limit, this case study aimed to reduce OPA exposure concentrations of workers during immersion washing of an endoscope probe body. This was achieved by attaching a new duct and hood to the existing ceiling exhaust system. METHODS: The type of hood was determined by calculating and comparing the capture velocity obtained by assuming either an exterior or an enclosing hood. Additionally, the effect on improving the working environment was tested before and after the installation of the hood by measuring the OPA vapor concentration. RESULTS: The calculated capture velocities of the exterior and enclosing hoods were 0.05 m/s and 0.19 m/s, respectively. Considering the operability, the exterior hood was more appropriate; however, the calculated capture velocity indicated potential inadequacy in meeting the TLV-C requirement, leading to the adoption of the enclosing hood. The OPA vapor concentration in ceiling value measurements taken after the enclosing hood was fitted was reduced to 0.2 ppb, that is, 1/10 of the original concentration. CONCLUSIONS: Although the environmental concentration after the improvement still exceeded the TLV-C of 0.1 ppb, this study's findings indicate that even substances with extremely low occupational exposure limits can be managed with appropriate local exhaust ventilation.

The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

OBJECTIVES: The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. METHODS: A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. RESULTS: Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). CONCLUSIONS: The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

OBJECTIVES: There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. METHODS: A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. RESULTS: The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P = .013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P = .043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P = .227). CONCLUSIONS: The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.

The effect of environmental factors in childcare facilities and individual lifestyle on obesity among Japanese preschool children; a multivariate multilevel analysis.

Lifestyle in preschool children is associated with the onset of childhood obesity. However, the effect of environmental factors in childcare facilities on lifestyle and obesity in preschool children is unknown. The aim of this study was to determine the effect of environmental factors in childcare facilities on the association between obesity and individual lifestyle in preschool children.Subjects included 2902 infants, aged 4 to 6 years old in Kitakyushu City, Japan. A stratified multilevel analysis was conducted with 2 strata: factors related to individual lifestyle and maternal factors as the individual level and factors related to the childcare facility as the environmental level. Two-level multilevel regression analysis was conducted with the presence or absence of obesity.The proportion of infants with obesity was 4.2%. The childhood obesity was significantly associated with the mastication, nutritional methods during infancy, absence of breakfast, presence of skipping meals due to overeating of snacks, usual play activity, screen time on weekdays, maternal body mass index, and maternal weight increase during pregnancy at the individual level. On the other hand, childhood obesity had a significantly negative association with the receiving snacks in facilities by using multilevel analysis.The present study revealed that establishing and maintaining environmental factors in childcare facilities may play important roles in the prevention of obesity from early childhood.

Status and trends in the use of insulin analogs, insulin delivery systems and their association with glycemic control: comparison of the two consecutive recent cohorts of Japanese children and adolescents with type 1 diabetes mellitus.

Background Treatment for type 1 diabetes mellitus (T1DM) has greatly changed by the general use of insulin analogs and continuous subcutaneous insulin infusion (CSII). To investigate whether these advances have been translated into continued improvement in glycemic control in Japanese children and adolescents, we analyzed the registration data of the two consecutive recent cohorts of Japanese childhood-onset T1DM patients. Methods The registration data including hemoglobin A1c (HbA1c), hypoglycemia and insulin regimen were compared between the two cohorts (862 patients in the 2008 cohort and 1090 in the 2013 cohort). Results The proportion of subjects with multiple daily insulin injection therapy (MDI) and CSII significantly increased (p<0.0001) from 67.4% and 9.7% to 71.8% and 23.4%, respectively. In the 2013 cohort, almost all patients were treated with basal-bolus treatment using insulin analogs. The use of CSII increased in all age groups, especially in the age group 0-5 years. The rates of overall, moderate and severe hypoglycemia significantly declined from 10.24, 10.18 and 0.056 events/100 persons/period in the 2008 cohort to 0.66, 0.62 and 0.033 in the 2013 cohort (p<0.0001, <0.0001, 0.04), respectively. Contrarily, there were no significant changes in HbA1c values between the two cohorts. Conclusions The popularization of the basal-bolus treatment using insulin analogs hascontributed to a significant decrease in hypoglycemia. In contrast, the intensive insulin treatment may not be enough for the satisfactory improvement of glycemic control in Japanese children and adolescents with T1DM. Considerable points remain, such as diabetic education and support to motivate patients.

Plasma but not serum brain-derived neurotrophic factor concentration is decreased by oral glucose tolerance test-induced hyperglycemia in children.

BACKGROUND: Little is known regarding the relationships among circulating brain-derived neurotrophic factor (BDNF) levels and glucose or insulin in children and adolescents. The objective of this study was to investigate whether circulating BDNF levels would change during the oral glucose tolerance test (OGTT). METHODS: We performed the OGTT and measured the serial changes in BDNF levels in both plasma and serum. RESULTS: There were 22 subjects in the normal type (N) group and 20 in the borderline/diabetic type (B/D) group, defined by the results of the OGTT. Serum levels of BDNF were almost five times higher and plasma levels gradually decreased during the OGTT, whereas serum levels showed no significant change. The reduction of plasma BDNF level changes from baseline to 120 min were significantly different between the N and B/D groups (36.3% vs. 20.8%, p=0.023). CONCLUSIONS: Our results showed that plasma levels of BDNF are more sensitive to acute changes in glucose or insulin levels than serum.

Tamoxifen treatment for pubertal gynecomastia in two siblings with partial androgen insensitivity syndrome.

BACKGROUND: Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). CASE REPORTS: Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. RESULTS: Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. CONCLUSION: The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.

An Infantile Case of Transient, Severe Hypercholesterolemia with Normalization after Complete Weaning from Breast-feeding.

A 20-d-old boy was referred to our department because of hyperthyrotropinemia at neonatal mass screening and diagnosed with neonatal transient hyperthyrotropinemia. A follow-up examination when the patient was 5 mo old revealed severe hypercholesterolemia. Familial hypercholesterolemia was first suspected because of the patient's significantly high levels of total and low-density lipoprotein cholesterol. The parent's serum lipid profiles were examined and found to be normal. He was completely breast-fed until 6 mo of age. Breast milk was still the main source of food for a period following weaning. At 14 mo old, the patient was weaned completely from breast milk, and his serum cholesterol levels decreased dramatically. According to the normal lipid profiles of the patient's parents and the spontaneous normalization of serum cholesterol levels after complete weaning from breast milk, breast-feeding was suggested to be responsible for his transient severe hypercholesterolemia. It is well documented that breast-fed infants have higher serum cholesterol levels than formula-fed infants. However, there is no reported case with severe hypercholesterolemia equivalent to or higher than the levels observed in the case of familial hypercholesterolemia. Although the exact mechanism is unknown, it is necessary to consider that a small number of cases develop severe hypercholesterolemia related to breast-feeding.