Endocrine journal最新文献

Iodine is an essential trace element crucial for thyroid hormone synthesis. While iodine deficiency has been recognized as a global health concern due to its association with hypothyroidism, certain regions may face challenges related to excessive iodine intake. The impact of excessive iodine intake during the perinatal period on higher brain functions remains unclear. To address this gap, we conducted a study using an animal model to elucidate the effects of perinatal iodine excess on higher brain functions. Dams received specific drinking water (control, ×20 iodine (KIO₃ 37.4 mg/L), ×200 iodine (KIO₃ 374 mg/L)) from prior to mating until weaning. Pups received the corresponding drinking water until the end of the experiment. Behavior test battery was utilized to investigate the behavioral outcomes associated with perinatal iodine excess. Excessive iodine intake increased learning acquisition in females whereas it decreased exploration of social novelty in males. Conversely, mRNA levels of several genes related to learning and memory in the hippocampus were rarely affected. Overall, the present study highlights the consequences of excessive iodine intake during developmental periods. However, these effects were mild and varied by sex, warranting the further investigation.

Total ankle arthroplasty (TAA) is an effective treatment for end-stage ankle arthritis. However, the procedure is not without risks due to various factors, one of which is diabetes mellitus (DM). Currently, it remains uncertain whether diabetes is a risk factor for increased adverse outcomes and complications following total ankle arthroplasty. Therefore, this study aims to investigate the impact of diabetes on patients undergoing TAA. A systematic search was conducted for relevant studies published before December 2023 in PubMed, Embase, Cochrane Library, and Web of Science. The study assessed demographic data, postoperative complications, and functional outcomes of diabetic and non-diabetic patients following primary TAA. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality, and meta-analysis was performed using Stata 15.1, with forest plots generated for each variable. This meta-analysis included 14 studies involving 20,557 patients (3,847 with diabetes and 16,710 without). Compared to non-diabetic patients, those with diabetes had higher revision rates, postoperative infection rates, and 30-day readmission rates, longer hospital stays, and significantly different improvements in the SF-36 Physical Component Summary (PCS) score. Diabetic patients undergoing TAA are more likely to require revision surgery, face a higher risk of surgical site infections or periprosthetic joint infections, and experience increased hospital stay and 30-day readmission rates. These findings are crucial for guiding perioperative management of diabetic patients undergoing TAA and for explaining the associated surgical risks to patients.

We report the findings of a 10-year study that followed the relationship between serum 25-hydroxyvitamin D (25OH vitamin D) levels and the onset of prediabetes, analyzed based on sex. One hundred eighty-seven participants were followed who had a baseline hemoglobin A1c (HbA1c) value below 6.0% and fasting plasma glucose level below 100 mg/dL. The cut-off values for vitamin D concentration were 27.7 ng/mL for men and 17.1 ng/mL for women, based on the receiver operating characteristic curve. The prediabetes incidence was significantly higher in women with a vitamin D concentration ≤17.1 ng/mL [HR = 7.08 (2.08-24.2), p = 0.002] than in men with a concentration ≤27.7 ng/mL [HR = 2.30 (0.63-8.35), p = 0.21], based on the cumulative incidence function curve. Multivariate analysis revealed that an abdominal circumference ≥90 cm and 25OH vitamin D concentration ≤17.1 ng/mL were independent, significant and intervenable risk factors for prediabetes in women. Low levels of vitamin D in women can be a predictive factor in the development of diabetes after 10 years.

Recombinant human growth hormone (GH; somatropin) treatment has beneficial effects on body composition in patients with Prader-Willi syndrome (PWS). However, this treatment option is limited to children in most countries and to children with short stature in countries such as the USA and Japan. The aim of this multicohort study was to evaluate the effect of somatropin on body composition and to assess its safety in Japanese pediatric and adult participants with PWS. GH-naïve pediatric participants (n = 6) received somatropin 0.245 mg/kg/week, GH-treated pediatric participants (n = 7) received somatropin 0.084 mg/kg/week, and adult participants (n = 20) received somatropin 0.042 mg/kg/week for 1 month, followed by 0.084 mg/kg/week. The study met its primary endpoint in the adult cohort because the least squares mean (95% CI) of the change from baseline to Month 12 in lean body mass (LBM) (%) was greater than the prespecified efficacy criterion of 0. LBM (%) was higher at 12 months in GH-naïve pediatric participants, while GH-treated pediatric participants showed little deterioration in LBM despite reduced GH dosage. Treatment-emergent adverse events (TEAEs) were experienced by five (83.3%), five (71.4%), and 19 (95.0%) participants in the GH-naïve pediatric cohort, GH-treated pediatric cohort, and adult cohort, respectively. Most TEAEs were mild or moderate in severity. Three participants reported four serious TEAEs, and none were treatment related. Somatropin improved body composition in adult participants, enabled maintenance of body composition in pediatric participants, and demonstrated a favorable safety and tolerability profile in all PWS cohorts. (ClinicalTrials.gov ID: NCT04697381).

This study aimed to confirm the applicability of the product of depth and width of the right thyroid lobe measured by ultrasonography, as an index of estimated thyroid volume in patients with Hashimoto thyroiditis. This study included 118 patients with Hashimoto thyroiditis and 163 patients with Graves' disease. The product of depth and width of the right thyroid lobe ranged from 1.7 to 10.2 (median, 4.4) cm² for Hashimoto thyroiditis and 2.6 to 10.8 (median, 5.8) cm² for Graves' disease. The estimated volume obtained by ellipsoidal approximation correlated well with the product of depth and width of the right thyroid lobe in Hashimoto thyroiditis (ρ = 0.820, p < 0.0001) and Graves' disease (ρ = 0.928, p < 0.0001), respectively. However, the correlations were not identical. The comparison of 72 patients with Hashimoto thyroiditis and 72 patients with Graves' disease who were matched for the product of depth and width revealed no significant difference in the estimated thyroid volume. These results show that the product of depth and width of the right thyroid lobe can be applied to indicate thyroid volume instead of the estimated volume obtained from ellipsoidal approximation in both Hashimoto thyroiditis and Graves' disease within the range of volumes investigated in this study.

This phase 1 dose-escalation study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of K1-70^TM, a TSH-receptor-specific monoclonal autoantibody that inhibits ligand binding and receptor activation, in Japanese Graves' disease (GD) patients. Twelve patients were enrolled, divided into four dosage cohorts (5 mg, 25 mg, 75 mg, and 150 mg), and monitored for 100 days post-administration. The primary objective was to assess safety and tolerability, and the secondary objectives were evaluation of PK and thyroid function. Exploratory analyses focused on the dynamics of the anti-TSH receptor antibodies and Thyroid eye disease (TED). K1-70^TM demonstrated a favorable safety profile, with no reports of serious adverse events. Mild to moderate treatment-emergent adverse events, such as headache and fatigue, were observed in 83.3% of the participants, but none were deemed severe. PK analysis revealed a dose-dependent increase in half-life, suggesting prolonged systemic exposure at higher doses. Thyroid function remained stable at lower doses, but there were dose-dependent reductions at higher doses that were managed with adjunctive L-thyroxine therapy. Marked reductions in TSAb levels were observed across all cohorts, indicating effective suppression of TSH receptor activity. An improvement in proptosis was noted in 50% of the eyes, suggesting a potential therapeutic benefit against inactive-phase TED. These findings support K1-70^TM as a promising targeted therapy for GD and TED, and they warrant further studies involving larger patient populations and active disease phases to confirm its efficacy and safety (jRCT Registration Number: JRCT2080224902).

Esaxerenone, a nonsteroidal mineralocorticoid receptor blocker, may be an effective treatment for diabetes-associated mineralocorticoid receptor-related hypertension, but there have been few studies of its use in clinical practice. We aimed to determine the effects of esaxerenone on blood pressure (BP) and metabolic parameters of hypertensive subjects with diabetes in a clinical practice setting. We performed a retrospective multicenter observational study of hypertensive subjects with type 2 diabetes/prediabetes. We first compared the values of parameters at baseline and after 6 months of esaxerenone administration, then compared the changes in the parameters in propensity score-matched subjects who initiated esaxerenone or amlodipine administration. Correlation analysis was performed to identify factors associated with these changes. The single-arm analysis showed that esaxerenone caused significant reductions in systolic and diastolic BP from 155.2 ± 17.7 and 83.3 ± 12.3 mmHg at baseline to 132.9 ± 15.5 and 72.3 ± 12.9 mmHg, respectively, after 6 months of treatment (p < 0.01). In addition, body mass index (BMI), glycated hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, estimated glomerular filtration rate, and urine albumin/creatinine ratio (UACR) significantly decreased (p < 0.05). The esaxerenone group showed significantly larger reductions in systolic BP, AST, ALT, and UACR than the amlodipine group (p < 0.05). Furthermore, there was a negative correlation between the change in ALT and baseline BMI (p < 0.05). Esaxerenone has an antihypertensive effect, reduces the albuminuria, and reduces the activities of liver enzymes in hypertensive subjects with type 2 diabetes/prediabetes. The present findings suggest that esaxerenone has pleiotropic effects in such subjects.

Levothyroxine (LT4) is the established treatment for hypothyroidism but some controversies, such as whether combining it with liothyronine (LT3) for hypothyroid patients and whether prescribing it to euthyroid patients, exist on its use. This survey was conducted to investigate current trends about thyroid hormone use in hypothyroid and euthyroid patients in Japan. Members of the Japan Thyroid Association (JTA) were invited to participate in an online questionnaire based on the THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) survey. Anonymous responses from 207 of 874 (23.7%) JTA-certified thyroid specialists were analyzed. LT4 was the first line treatment for hypothyroidism by all respondents. 18.8% and 28.0% would also use LT3 and LT3 + LT4 combination, respectively. LT3 + LT4 combination was preferred for patients on LT4 with residual symptoms or low serum T3 levels. Psychological factors and comorbidities were considered as the main contributors to residual symptoms. Respondents would prescribe thyroid hormones in euthyroid subjects for female infertility with positive anti-thyroid antibodies (46.9%), for Hashimoto's disease with a huge goiter (29.0%), and for pregnant or infertile women with TSH between 2.5-4 mU/L irrespective of anti-thyroid antibody status (43.0 and 76.8%, and 46.9 and 77.3%, respectively). In conclusion, Japanese thyroid specialists chose LT4 as first line treatment for hypothyroidism in accordance with current guidelines. The use of LT3 + LT4 combination is less frequent in Japan than in other countries, whereas the use of thyroid hormones for non-hypothyroid indications is similarly high worldwide, which is not necessarily in accord with pertinent society guidelines.

Obese pregnant women are more likely to develop hypertensive disorders of pregnancy (HDP), which puts them at risk for future cardiovascular events and type 2 diabetes. This study aimed to investigate the relationship between body weight and HDP in nondiabetic singleton-pregnant women. We examined the KODMO database, which included 5,120 pregnant women who gave birth at NHO Kokura Medical Center between January 2009 and December 2019, excluding those with pre-existing diabetes mellitus, hypertension, or multiple pregnancies. A multivariate logistic regression analysis of potential HDP risk factors revealed that both pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were independent risk factors. The estimated impact was considerably greater in women with higher pre-pregnancy BMI, with odds ratios of 1.60 (95% CI: 1.18-2.18, p = 0.0025) for obesity degree 1 (25 ≤ BMI < 30 kg/m²) and 3.42 (95% CI: 2.35-5.01, p < 0.0001) for obesity degree ≥2 (BMI ≥ 30 kg/m²) (reference: normal weight [18.5 ≤ BMI < 25 kg/m²]). GWG was further investigated by stratifying BMI categories, which revealed that obese pregnant women have a risk of developing HDP even with the normal GWG defined by current guidelines. The odds ratio of HDP in pregnant women with normal GWG was 1.79 (95% CI: 1.02-3.41, p = 0.0436) in obesity degree 1 and 3.25 (95% CI: 1.57-6.74, p < 0.0001) in obesity degree ≥2. The impact of GWG as a modifiable factor of HDP varies with pre-pregnancy BMI, highlighting the importance of weight management before and during pregnancy.

To elucidate the clinicopathological features of follicular thyroid carcinoma (FTC) coexisting with papillary thyroid carcinoma (PTC) (FTC + PTC). We collected a total of 55 FTC + PTC patients (including 12 males [21.8%] and 43 females [78.2%]), with an average age of 47.6 years. In the FTC alone group, the average age was 52.3 years, and the proportion of females was 71.3%. The median age was 43.5 years, with an average age of 45 years in the PTC alone group. Compared with the tumors in the FTC alone group, FTC in the FTC + PTC group exhibited a smaller maximum diameter (49.1% measuring ≤2 cm), a younger patient age (70.9% younger than 55 years), an earlier tumor stage (94.5% in stages I-II), a lower incidence of recurrent cancer (n = 2, 3.6%), a lower frequency of distant metastasis (6.1%), and a lower proportion of "extensively invasive" subtype (12.7%) (all p < 0.05). Compared with the PTC alone group (n = 289), the FTC + PTC group had a higher proportion of PTC with a maximum diameter of ≤1 cm (72.5%), and the degree of invasion of thyroid extracellular tissue was less severe (all p < 0.05). No statistically significant differences were found in overall survival (OS), cancer-specific survival (CSS), and RFS between these two groups (the FTC or PTC alone group versus FTC + PTC group). In sum, FTC + PTC has some clinicopathological features.