Increase of transient lower esophageal sphincter relaxation associated with cascade stomach.

We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0-60 min), late period (60-120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying.

The Impact of Age- and Sex-Specific Reference Ranges for Serum Thyrotropin and Free Thyroxine on the Diagnosis of Subclinical Thyroid Dysfunction: A Multicenter Study from Japan.

Background: Reference ranges for serum thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) established without considering age- and sex-based differences are currently used to evaluate thyroid function. Therefore, we investigated age- and sex-based differences in serum TSH and thyroid hormone levels in euthyroid individuals. Methods: We performed cross-sectional analyses of retrospective data collected from two Japanese institutions. We estimated sex-specific 95% reference ranges for TSH and fT4 according to age strata. Results: We included data from 14,860 participants undergoing screening with a Siemens thyroid testing kit and 8,132 participants undergoing screening with an Abbott kit during annual health check-ups at Takasaki Hidaka Hospital. In addition, 515 participants visiting a specialized thyroid-focused hospital were evaluated using Tosoh kits. The median TSH level of women in their 30s was 1.5 mIU/L (2.5th percentile, 0.5; 97.5th percentile, 4.6) using the Siemens kit, while that of women in their 60s was 1.9 (0.7-7.8) mIU/L. The corresponding levels were lower in men; the age-associated increase was small. The median serum fT4 level of men in their 30s was 1.3 (1.0-1.7) ng/dL and that of men in their 60s was 1.2 (1.0-1.6) ng/dL. These levels gradually but significantly decreased with age. fT4 levels in women were lower than those in men and remained consistent with age. Serum fT3 levels were significantly higher in men than in women and gradually but significantly decreased with age. The Abbott and Tosoh kits showed similar results. When using the Siemens kit, ∼60% (216/358) of women diagnosed with subclinical hypothyroidism using manufacturer-recommended reference ranges had normal results when age- and sex-specific reference ranges were applied, demonstrating the high percentage of overdiagnosis, especially in those aged ≥60 years. Conversely, some middle-aged individuals with normal thyroid function were reassessed and classified as having subclinical hyperthyroidism by age- and sex-specific reference ranges. Conclusions: Age- and sex-specific reference ranges should be used to avoid over- and underdiagnosis of subclinical thyroid dysfunction and appropriate therapies.

Seasonal Variation in Thyroid Function in Over 7,000 Healthy Subjects in an Iodine-sufficient Area and Literature Review.

Context: Seasonal variation in thyroid function, especially serum free triiodothyronine (FT3) and free thyroxine (FT4) levels, in healthy subjects remains unclear. Methods: We examined thyroid function, including serum FT3 and FT4 levels, in healthy Japanese subjects using data of more than 7,000 health check-up participants and applied the analysis of means with transformed ranks (ANOMTR) to compare each month. In addition, we reviewed reports published in the last 2 decades. Results: The median serum thyrotropin (TSH) level was the highest in January (1.61 mIU/L), and the lowest in May (1.16 mIU/L). ANOMTR revealed that serum TSH levels are high in winter and low in summer. Conversely, the median serum FT3 level was higher in July than in other months, and the ANOMTR plot demonstrated serum FT3 levels to be significantly higher in summer and lower in winter. In contrast, serum FT4 levels were more consistent throughout the year, but statistically, those in February and March, October, and November were higher than those in other months. ANOMTR revealed variations in serum FT4 levels to be small through the year but biphasic. Conclusions: Taken together with previous reports, our study demonstrated seasonal changes in the serum TSH levels to be high in winter in the northern hemisphere; however, the serum FT3 differed among countries, and those of Japanese, an iodine-sufficient country, were high in summer. In contrast, FT4 levels were more consistent. These changes should be taken into account to precisely evaluate thyroid function.

Association between high normal-range thyrotropin concentration and carotid intima-media thickness in euthyroid premenopausal, perimenopausal and postmenopausal women.

OBJECTIVE: There are currently no established cutoff levels for thyrotropin (TSH) within the reference intervals associated with carotid atherosclerosis to prevent the onset of cardiovascular diseases. The present study aimed to determine the TSH cutoff level associated with carotid maximum intima-media thickness (max IMT) in euthyroid premenopausal, perimenopausal and postmenopausal women. STUDY DESIGN: We conducted a cross-sectional study of 468 euthyroid women who had not been treated for or diagnosed with cardiovascular diseases and/or metabolic disorders among 1221 Japanese women who participated in a comprehensive medical examination at the Hidaka Hospital, Japan. Participants' weight, blood pressure, plasma glucose, serum lipoprotein, free thyroxine and TSH were measured and an interview about menstruation was conducted. Carotid ultrasonography was performed to determine max IMT. RESULTS: Max IMT significantly increased stepwise as menopausal status progressed (p < 0.001). Serum TSH levels were significantly higher in participants with carotid plaques, defined as max IMT ≥1.1 mm (p = 0.038), and were independently associated with the presence of carotid plaque using multivariate logistic regression analysis (ß =1.218, p = 0.036). In postmenopausal women, significantly higher carotid max IMT values were observed in women with serum TSH ≥2.5 µIU/mL compared with women with concentrations <2.5 µIU/mL (p = 0.018) without elevated total cholesterol and low-density lipoprotein cholesterol concentrations. These differences were not observed in premenopausal women. CONCLUSIONS: Laboratory finding of serum TSH concentration ≥2.5 µIU/mL may be useful to assess risk of atherosclerosis, especially in postmenopausal women.

A proposal of combined evaluation of waist circumference and BMI for the diagnosis of metabolic syndrome.

We performed a receiver operator characteristic (ROC) curve analysis of 3915 men and 2032 women. Subjects who were diagnosed with two or more factors among high blood pressure, hyperglycaemia or high triglyceride and/or low HDL were classified as the metabolic syndrome group. By performing a ROC curve analysis, we have determined the cut-off point of waist circumference (WC) and BMI to define metabolic syndrome and further calculated the sensitivity and specificity of these two factors for the diagnosis. Cut-off point for the diagnosis of metabolic syndrome was 85 cm (men) and 80 cm (women) in WC and 24 (men) and 23 (women) in BMI. By combining these two factors, the sensitivity for the diagnosis increased to more than 80%. We conclude that it is beneficial to combine both WC and BMI for diagnosis of metabolic syndrome.

Influence of Smoking on Thyroid Function in Japanese Subjects: Longitudinal Study for One Year of On-Off Smoking.

CONTEXT: We previously identified factors affecting thyroid status, including sex, age, and smoking. OBJECTIVE: In the current study, we increased the number of subjects examined and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab), in Japanese patients with euthyroxinemia and serum free T4 levels within the normal range. PARTICIPANTS: A total of 12,289 subjects who underwent health checkups were analyzed in a cross-sectional and longitudinal study. RESULTS: The mean age of subjects was 50 ± 10 years (age range: 21 to 88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese subjects with euthyroxinemia. Mean serum TSH levels were significantly lower in the smoking group than in the nonsmoking group except for women older than 50 years. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both sexes; however, smoking did not affect free T4 levels or positivity for TPO-Ab. Among men, the rate of smokers was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%; P < 0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels 1 year after the start of smoking in men (P < 0.05). CONCLUSION: Because smoking appeared to lower serum TSH levels in Japanese subjects with euthyroxinemia, their smoking status warrants careful consideration when evaluating subclinical thyroid function.

Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan.

CONTEXT: In patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan. OBJECTIVE: To investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups. PARTICIPANTS: Fifty Japanese patients with APAs and 27,572 health checkup patients as controls were examined. MAIN OUTCOME MEASURES: We investigated changes in estimated glomerular filtration rate (eGFR) after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD). RESULTS: The postoperative cutoff age of CKD is 50 years and age is a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients, CKD was 6% for those <50 years old and 40% for those ≥50 years old, indicating a higher prevalence of CKD with APAs than in control subjects. Median eGFR <50 mL/min/1.73 m2 did not significantly change after adrenalectomy but decreased from 67 to 42 mL/min/1.73 m2 in those with APAs ≥50 years old. Patients with APAs ≥50 years old who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower body mass index, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates. CONCLUSION: Age is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.

Non-alcoholic Fatty Liver Disease Is a Risk Factor for Type 2 Diabetes in Middle-aged Japanese Men and Women.

Objective Emerging studies have focused on the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM in a Japanese middle-aged health check population. Methods We conducted a 10-year observational study in a health checkup population of middle-aged Japanese men and women at Hidaka Hospital from 2004 to 2013. We excluded cases with an alcohol intake exceeding 20 g/day and those with impaired glucose tolerance. The remaining 1,544 men and 864 women were classified into fatty liver and non-fatty liver groups based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. A multiple regression analysis was performed for each variable to predict the risk of future diabetes. Results The median age of the participants was 46.0 years at the entry, and the follow-up period was 10 years. The incidence of diabetes in the fatty liver group was 12.5% (29/232) in men and 26.3% (10/38) in women, whereas the incidence of diabetes in the non-fatty liver group was 2.5% (34/1,312) in men and 1.8% (15/826) in women. The relative risk of diabetes associated with fatty liver was 4.8 [95% confidence interval (CI) 3.0-7.8, p<0.0001] in men and 14.5 (95% CI 7.0-30.1, p<0.0001) in women. Conclusion NAFLD was a significant predictor for future diabetes in a Japanese middle-aged health check population, especially in women.

Impact of the Visceral Fat Area Measured by Dual Impedance Method on the Diagnostic Components of Metabolic Diseases in a Middle-aged Japanese Population.

Objective The aim of this study was to examine the associations between the visceral fat area (VFA) and the subcutaneous fat area (SFA) as estimated by the dual impedance method with a body composition monitor (BCM) and the diagnostic components of metabolic syndrome in a middle-aged Japanese population. Methods The subjects included 303 men (average age 51.3±9.0 years old) and 345 women (average age 40.0±9.4 years old). The VFA and SFA were estimated by BCM, and the associations among the components of metabolic syndrome (waist circumference, blood pressure and related blood sample tests) were evaluated. Results VFA showed positive correlations with waist circumference, HbA1c, high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol, triglyceride and uric acid level in men, while showing positive correlations with waist circumference, HDL cholesterol, triglyceride and HbA1c in women. The estimated SFA showed positive correlations with systolic blood pressure, HDL/LDL cholesterol and triglyceride in men, and HDL cholesterol and triglyceride in women. A receiver operating characteristic (ROC) analysis showed the estimated VFA to be as effective as WC to identify subject with metabolic syndrome. Conclusion By estimating the VFA using BCM, it may be possible to identify patients at risk of developing metabolic syndrome and hyperuricemia.

Plasma adiponectin is a more specific marker of fatty liver than a marker of metabolic syndrome in Japanese men.

BACKGROUND: The association of plasma cardiovascular risk markers and metabolic syndrome (MetS) with non-alcoholic fatty liver disease (NAFLD) has not been well defined. METHODS: Japanese men (n = 809) had standard anthropometric measurements done, and had their liver fat quantitated by ultrasound. Three groups were identified: (1) normal controls without significant disease, (2) preliminary-metabolic syndrome (pre-MetS) cases and (3) MetS cases. Plasma adiponectin, high sensitivity-C reactive protein (hs-CRP), HOMA-IR, lipids, lipoproteins and liver enzymes were evaluated among the three groups. RESULTS: The prevalence of fatty liver was 13% in controls, 39% in pre-MetS and 62% in MetS. Plasma adiponectin and high density lipoprotein cholesterol (HDL-C) were significantly decreased, and HOMA-IR, hs-CRP, TG, remnant lipoproteins (RLPs) and small dense-LDL-C (sd LDL-C) were significantly increased in subjects with fatty liver compared to those without fatty liver. Multivariate analyses of serum parameters associated with fatty liver revealed that adiponectin and hs-CRP were more strongly associated with the presence of fatty liver than waist circumference. However, HOMA-IR, HDL-C, TG, RLP-C, RLP-TG and sd LDL-C were more strongly associated with waist circumference than with fatty liver. Factor analysis revealed that adiponectin and HDL-C were linked to liver enzymes, lipoproteins and HOMA-IR associated with fatty liver, but not with waist circumference. CONCLUSIONS: Adiponectin was found to be a more specific diagnostic marker for the presence of fatty liver regardless of MetS status, and was inversely correlated with liver enzyme concentrations. However, RLPs were found to be more specifically associated with the presence of MetS.

Subclinical hypothyroidism and indices for metabolic syndrome in Japanese women: one-year follow-up study.

CONTEXT: Subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) increase with age; however, their relationship remains unclear. OBJECTIVE: Our objective was to investigate the relationship between SCH and indices of metabolic syndrome and follow up subjects for 1 year. DESIGN: Cross-sectional and longitudinal follow-up studies of cases were collected from Takasaki Hidaka Hospital between 2003 and 2007. PARTICIPANTS: Overall, 11 498 participants of health checkups were analyzed. The mean age was 48 ± 9 years. MAIN OUTCOME MEASURES: The relationship between SCH and indices of MetS were examined. RESULTS: Serum free T4 levels were lower in women than men in most of the age groups, and the prevalence of SCH, 6.3% in women vs 3.4% in men, increased with age, reaching 14.6% in 70-year-old women. Multivariate logistic-regression analyses revealed that waist circumference and the serum triglyceride and low-density lipoprotein-cholesterol levels were significantly higher in subjects with SCH than without among women. Reflecting these findings, the adjusted odds ratio of MetS in patients with SCH was higher than in the euthyroid subjects in women with an odds ratio of 2.7 (95% confidence interval 1.1-5.6; P = .017) but not in men. Furthermore, progression from euthyroid into SCH resulted in a significant increase in the serum triglyceride levels but not low-density lipoprotein-cholesterol in women. CONCLUSION: Japanese women exhibited a high prevalence of SCH associated with low free T4 levels. There was a strong association between SCH and several indices of metabolic syndrome in women. SCH may affect serum triglyceride levels and be a risk factor for metabolic syndrome.

Gastroptosis is associated with less dyspepsia, rather than a cause of dyspepsia, in Japanese persons.

OBJECTIVE: Gastroptosis is recognized by its characteristic appearance on barium studies. The present prospective study assessed the relationship between gastroptosis and dyspeptic symptoms. METHODS: Japanese subjects underwent health screening, and gastroptosis was diagnosed by barium studies. Consecutive subjects (500 women and 167 men) with gastroptosis were identified and the same number of age-matched subjects without gastroptosis were selected as controls. Dyspepsia was classified as reflux-like (heartburn and belching), dysmotility-like (bloating and fullness), or ulcer-like dyspepsia (epigastralgia) based on the Rome II criteria. RESULTS: Body mass index was significantly lower in women with gastroptosis than in controls [19.7 ± 1.83 (SD) vs. 23.4 ± 3.70, p<0.0001], and also in men (19.7 ± 2.00 vs. 23.9 ± 2.89, p<0.0001). The incidence of dyspepsia was significantly lower in women with gastroptosis than in controls (56/500 vs. 87/500, p<0.01) and also in men (10/167 vs. 25/167, p<0.05), especially in women with ulcer-like dyspepsia (15/500 vs. 32/500, p<0.05) and in men with reflux-like dyspepsia (2/167 vs. 12/167, p<0.05). By logistic regression analysis, gastroptosis was associated with a lower risk of dyspepsia (odds ratio: 0.62, 95% CI: 0.405-0.941, p=0.025) and ulcer-like dyspepsia (odds ratio: 0.36, 95% CI: 0.177-0.726, p=0.004) in women. CONCLUSION: Dyspeptic symptoms were significantly less common in subjects with gastroptosis. Accordingly, gastroptosis may protect against dyspeptic symptoms, rather than causing functional dyspepsia.

Sepsis and gas-forming splenic abscess by Clostridium septicum in a patient with type 2 diabetes.

Clostridium infections are rare but frequently associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 h. These infections are associated with various medical problems including diabetes mellitus. In this report, we describe a unique case of sepsis and a gas-forming splenic abscess caused by Clostridium septicum in a type 2 diabetes patient which was treatable solely with antibiotics.

An obese patient with slowly progressive type 1 diabetes diagnosed by ketoacidosis.

The patient was a 69-year-old woman with a family history of type 2 diabetes. Her body mass index was 31.5. She was diagnosed as type 2 diabetes 32 years previously, and treated with insulin for 8 years. She had no episode of weight loss. She was hospitalized with diabetic ketoacidosis for the first time. Her GAD antibodies were not detected. However, ICA antibodies and insulin antibodies were positively detected. She was diagnosed with type 1 diabetes. Interestingly, her diabetes state was controlled to the same level after recovery from ketoacidosis.