Despite extensive research on miR-642a-5p, its specific function in pancreatic β-cells and its contribution to the pathogenesis of type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the regulatory role of miR-642a-5p in pancreatic β-cells (EndoC-βH1) and its association with the transcription factor Mef2d. Differentially expressed miRNAs related to T2DM were identified through analysis of the GSE70318 dataset. Based on predictions from the TargetScan, miRDB, miWalk, and miRTarBase databases, the interaction between miR-642a-5p and Mef2d was validated using dual-luciferase reporter assays and gene interference experiments. In EndoC-βH1 cells treated with high glucose and palmitic acid, cell apoptosis, insulin secretion, and the expression of related genes were evaluated. The functional impact of co-transfection with miR-642a-5p and Mef2d on EndoC-βH1 cells was also analyzed. Results indicated that miR-642a-5p was abnormally expressed in the GSE70318 dataset, and Mef2d was confirmed as its target gene. Overexpression of miR-642a-5p promoted insulin secretion, upregulated insulin secretion-related genes, enhanced cell viability, inhibited cell apoptosis, reduced malondialdehyde (MDA) levels, suppressed Bax and Nox4 expression, and upregulated Bcl-2 and Sod2. These effects were reversed by Mef2d overexpression. Conversely, inhibition of miR-642a-5p impaired insulin secretion, downregulated Ins1 and Pdx1, reduced cell viability, promoted cell apoptosis, increased MDA levels, promoted Bax and Nox4 expression, and suppressed Bcl-2 and Sod2. These effects were reversed upon Mef2d silencing. In summary, miR-642a-5p protects EndoC-βH1 cells from apoptosis by targeting Mef2d and regulating cellular function and oxidative stress levels.

The purpose of this study was to clarify how parental willingness to allow child participation in thyroid ultrasound examinations (TUE) changed after reading about the merits and demerits of TUE. This study was a cross-sectional questionnaire survey. A total of 2,200 parents and guardians, who had children <18 years old, were included in the final analysis. First, basic characteristics of parental participants and willingness to allow child participation in TUE were assessed (pre-survey). Second, parental participants read an explanation about the merits and demerits of TUE. Third, the understandability of the explanation and intention regarding child participation in TUE were assessed (post-survey). The primary outcome was the change in willingness for child participation in TUE after reading the explanation about the merits and demerits. After reading the explanation, the number of parents in both the “yes” and “no” groups decreased, while the numbers in the “up to the child” and “undecidable” groups increased. This trend was especially prominent among parental participants who were previously unaware of the merits and demerits. Among those who changed their willingness from “yes” to “up to the child” or “undecidable,” the proportion was higher in the group that had not known about the merits and demerits than the group that had known (odds ratio (95% confidence interval): 1.76 (1.32–2.34) and 2.97 (1.87–4.71), respectively). Repeated dissemination of information about the merits and demerits of TUE is necessary to support appropriate decision-making.

The purpose of the present study was to investigate how the intention to participate in thyroid ultrasound examination (TUE) changed after reading an explanation of its merits and demerits among adolescents in Fukushima Prefecture following the nuclear disaster in a cross-sectional questionnaire study with a pre-post design. The study was conducted among adolescents eligible for TUE. In the pre-survey, data were collected on participants’ background characteristics, history of TUE participation, willingness to participate in TUE, and prior knowledge of the merits and demerits of TUE. Next, participants were provided with a written explanation of the merits and demerits of TUE. Following this, they were surveyed again regarding the understandability of the explanation and their willingness to participate in TUE after reading it. The primary outcome was the change in intention to participate in TUE between the pre- and post-surveys. The overall proportion of willingness to participate in TUE did not change dramatically after reading the explanation. However, 77.8% (367/472) of participants in the group that already knew the merits and demerits did not change their intention to participate in TUE, whereas only 70.5% (537/762) in the previously unaware group did not change their intention. The highest proportion of change was observed among those who initially responded as “undecided” regarding participation in TUE. Providing information on the merits and demerits of TUE was especially important for undecided individuals, as this group showed the greatest change in intention following the explanation.

We review the recent remarkable progress of the molecular mechanisms of action of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) regarding their beneficial effects on older people and adrenal regenerative therapy by looking back on our research extending over 50 years since 1971. DHEAS is the most abundant circulating steroid hormone in humans and apes. DHEAS is essential for brain development in adrenarche and for anti-aging in adrenopause as shown by the evolutionary process in primates. The molecular mechanisms of action of DHEA and DHEAS have been clarified by the discovery of many membrane receptors and by the concept of intracrinological action, which is especially important in menopausal women. The genes associated with serum DHEAS concentrations were identified by genome-wide association study meta-analysis of cohort studies. Recent advances in aging research have shown that DHEA and DHEAS have anti-aging action via antioxidants, anti-inflammation, telomere protection, p38MAPK inhibition, anti-cortisol effects, and chaperone induction. DHEA has beneficial effects on the prevention of atherosclerosis based on visceral obesity-induced metabolic syndrome in middle-aged people. DHEA also prevents infection, frailty via reverse metabolism, sarcopenia, and osteoporosis in older people, with a marked decrease in serum DHEAS concentrations. This review discusses adrenal regenerative therapy using steroid-producing cell replacement by overexpressing Ad4BP/steroidogenic factor 1 in mouse or human bone marrow mesenchymal stem cells. This therapy replaces cortisol and DHEAS treatment for the prevention of sudden death by adrenal crisis and severe infection in primary adrenal insufficiency (Addison’s disease).

The combination of methimazole (MMI) and potassium iodide (KI) is often used to improve the thyroid function more quickly in the initial medical treatment of Graves’ disease when the levels of free T4 are ≥5.0 ng/dL. However, deterioration in the levels of free T3 and T4 was observed immediately after the cessation of KI. To avoid deterioration following cessation of KI, we investigated 150 drug-naïve patients with Graves’ disease treated with a combination of MMI and KI. Patients administered KI for 3–17 weeks (median, 9 weeks) during the initial period were selected for this study. Levels of free T3 and T4 were determined before treatment, at the time of cessation of KI, and at 2–8 weeks (median, 4 weeks after cessation). In 35 of 150 patients (23.3%), the levels of free T3 and/or free T4 were elevated beyond the upper limit of each reference range after cessation of KI. In a multivariate regression analysis, the levels of free T3 and the ratio of the daily dose of KI (mg) to MMI (mg) at the cessation of KI were significantly lower (p < 0.0001, p = 0.0007) in patients without deterioration than in those with deterioration. The odds ratios were 0.175 (95% confidence interval [CI]: 0.072–0.381) and 0.675 (95% CI: 0.533–0.846), respectively. When the ratio of the dose of KI to MMI at cessation was ≤1.7, and the level of free T3 was ≤3.2 pg/mL, deterioration was avoided in 97.8% of patients.

The skeletal muscle plays a key role in thermogenesis and energy homeostasis in endotherms. Therefore, reduced skeletal muscle mass and function are closely associated with health disorders such as obesity and hypothermia. In humans, inactivity and nutritional deficiencies can lead to skeletal muscle atrophy. However, hibernating mammals, which can greatly suppress their metabolic rate, can maintain significant skeletal muscle mass even during prolonged periods of inactivity and nutritional restriction. This review focuses on how skeletal muscle contributes to maintaining body temperature as the organ that consumes the most energy, while also contributing to whole-organism homeostasis through its high metabolic flexibility in a self-sacrificing manner. Particularly, we reconceptualized muscle atrophy associated with the thermoregulatory process in terms of inter-organ metabolic interaction, proposing that sarcopenia is an integral component of systemic energy metabolism regulation. By deepening our understanding of the functional metabolic flexibility of skeletal muscle and its regulatory mechanisms, we can redefine sarcopenia as an adaptive response that contributes to maintaining metabolic homeostasis. This perspective could provide new insights into the pathophysiology of sarcopenia and metabolic disorders, and inform the development of more effective prevention and treatment strategies.

The biological clock enables organisms to align their intrinsic rhythms with daily environmental cycles thereby maintaining homeostasis and imparting resilience against metabolic derangements. Endocrine hormones and neural networks are key mediators of temporal coordination across remote tissues. The potential impact of maternal-fetal synchronization during pregnancy has been extensively studied, as alterations in maternal circadian rhythms because of mistimed food intake, sleep disturbances, and jet-lagged conditions appear to influence organ development, maturation, and behavior, leading to enduring metabolic consequences in offspring. In support, the in utero environment and maternal nutritional state influence long-term health outcomes, as proposed in the developmental origins of health and disease. While the molecular mechanisms connecting maternal circadian disruption to sustained alterations in progeny are still under investigation, endocrine hormones and metabolites may engage in temporal communication between the mother and fetus and induce epigenetic changes. This review outlines recent discoveries on maternal circadian rhythms as an external input for the fetus and discusses future strategies to strengthen metabolic fitness in subsequent generations.

The National Health Insurance Bureau in Taiwan introduced several initiatives to slow the progression of diabetic kidney disease (DKD) through early interventions and comprehensive patient education. This study evaluates the association of a multidisciplinary care and education model for patients with type 2 diabetes mellitus and early-stage DKD in Taiwan. A total of 355 participants enrolled in an integrated care program from May 2022 to September 2023 and followed up until April 2024 were analyzed. The intervention included personalized education, exercise management, dietary counseling, and multimedia tools aimed at improving disease self-management. The results demonstrated that compared to baseline, the patients with second follow-up data had lower systolic blood pressure (p < 0.001), lower diastolic blood pressure (p < 0.001), lower glycosylated hemoglobin A_1c (HbA_1c) (7.51% vs. 7.10%, p < 0.001), lower total cholesterol (p = 0.047), lower high-density lipoprotein cholesterol (p = 0.047), lower low-density lipoprotein (LDL) cholesterol (p = 0.009), lower estimated glomerular filtration rate (p < 0.001), lower log urine albumin to creatinine ratio (p < 0.001), used fewer types of antihypertensive agents (p < 0.001), more types of oral hypoglycemic agents (p = 0.045), more insulin (p < 0.001), and more statins (p = 0.029). These findings showed that the multidisciplinary care model significantly improved glycemic control, blood pressure, lipid profiles, and albuminuria in patients with type 2 diabetes and early-stage DKD. Specifically, reductions in HbA_1c, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, and albuminuria were achieved, underscoring the importance of a comprehensive team-based approach.

Pancreatic α-cells secrete glucagon, a hormone that elevates blood glucose levels. In type 2 diabetes, high plasma glucagon levels are associated with hyperglycemia. However, the underlying mechanisms of increasing glucagon secretion remain unclear. We focused on the intrinsic regulatory mechanisms of glucagon secretion in α-cells, in particular sodium–glucose cotransporter 1 (SGLT1), which is involved in the early steps of glucose sensing. We previously demonstrated that SGLT1 is expressed in α-cells and is significantly upregulated in diabetic mice compared with non-diabetic mice. In isolated islets from diabetic mice, SGLT1 knockdown attenuated glucagon hypersecretion, and in αTC1 cells, SGLT-specific substrates promoted glucagon secretion by raising intracellular calcium. On the basis of these findings, we hypothesized that SGLT1 upregulation in α-cells under diabetic conditions impairs the suppression of glucagon secretion, thereby contributing to hyperglycemia. However, a previous study showed that systemic SGLT1 knockout (KO) mice exhibit a higher proportion of α-cells in the islets and atypically high plasma glucagon levels. To clarify the roles of SGLT1 specifically in α-cells, we generated α-cell–specific SGLT1 KO mice using a tamoxifen-inducible Cre-loxP system and analyzed these mice fed a high-fat, high-sucrose diet. The results clearly showed that, inconsistent with the results from the systemic SGLT1 KO mice, SGLT1 deficiency specifically in α-cells did not affect glucagon secretion, glucose tolerance, or α-cell proportion in the islets under diabetic conditions. Thus, though SGLT1 is upregulated in diabetic α-cells, this does not appear to contribute to hyperglucagonemia and impaired glucose tolerance in diabetic mice.

Thyroid hormones play a crucial role in regulating mood and cognitive function. However, the effect of thyroid function on psychiatric symptoms remains unclear. In this study, we investigated the association between psychiatric symptoms and thyroid hormone levels in patients with depression and mania. In this retrospective cross-sectional study, we enrolled patients with depression or mania admitted to the Department of Psychiatry of the National Kohnodai Medical Center from April 2014 to March 2023. We examined the association between thyroid function at admission and psychiatric symptoms using the Global Assessment of Functioning (GAF) score. A total of 309 patients with depression (199 females, mean age = 62 ± 15 years) and 91 patients with mania (60 females, mean age = 50 ± 16 years) were included. In the depression group, the median TSH level was 1.05 μIU/mL, the median free T3 level was 2.76 pg/mL, and the median free T4 level was 0.95 ng/dL. In the mania group, the median TSH level was 1.09 μIU/mL, the median free T3 level was 3.28 pg/mL, and the median free T4 level was 1.06 ng/dL. In patients with depression, the GAF score showed a weak but significant negative correlation with the free T4 level (r = –0.212, p < 0.001) and with the free T3 level (r = –0.253, p = 0.008). In patients with mania, the GAF score was negatively correlated with the free T4 level (r = –0.225, p = 0.033) and positively correlated with the TSH level (r = 0.226, p = 0.031). These findings suggest that higher thyroid hormone levels may be associated with more severe psychiatric symptoms. Our study presents possible associations between thyroid hormone levels and psychiatric symptoms.

Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, and anatomical sex characteristics are discordant with typical male or female development. These clinical practice guidelines provide evidence-based recommendations for the diagnosis and management of individuals with DSD across the lifespan. The guidelines were developed by a multidisciplinary committee of specialists representing pediatric endocrinology, adult endocrinology, urology, gynecology, psychiatry, and psychology. The committee employed a systematic review of the literature and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to assess the strength of recommendations and the quality of evidence. Key areas addressed include the initial management of infants with atypical genitalia, diagnostic approaches, hormonal treatment, surgical interventions, gonadal tumor risk assessment, fertility preservation, and the transition from pediatric to adult care. The guidelines integrate international best practices with Japan’s unique sociocultural, healthcare, and legal contexts for optimal DSD management and aim to improve clinical care for individuals with DSD while acknowledging the limited high-quality evidence in many aspects of DSD management.

Diabetes mellitus (DM) is a key global public health issue with rising incidence. The triglyceride-glucose (TyG) index has been widely applied to assess insulin resistance and metabolic abnormalities in recent years. However, the relation of the TyG index with DM is elusive when combined with central obesity indicators. This research was conducted to probe into the relationship between TyG-derived indices and DM. A total of 10,729 participants from the NHANES database were enrolled, of whom 1,984 had DM. The linkage of five TyG-derived indices with DM was examined using a weighted logistic regression model. At the same time, stratified analysis was undertaken on different gender and age subgroups. To evaluate the predictive performance of each indicator, ROC curve analysis was undertaken to examine the predictive capability of different indicators. The findings indicated that all TyG-derived indices were greatly positively linked with the risk of DM. The AUC values of TyG-CI and TyG-WWI were considerably higher than those of the TyG index and other indicators, demonstrating a stronger capability to predict the risk of DM. In subgroup analyses, both TyG-CI and TyG-WWI exhibited high robustness across different populations regardless of gender or age. The indices with the TyG index combined with indicators related to central obesity, especially TyG-CI and TyG-WWI, are effective tools for predicting the risk of DM.

Proptosis, a key clinical manifestation of thyroid eye disease (TED), serves as an objective indicator of this disease’s severity. Although body compositions and the prevalences of myopia and tobacco smoking have changed in Japan, no updated reference exophthalmometry values have been reported since the 1980s. To determine normal values for exophthalmometry in a contemporary Japanese general population and identify factors associated with exophthalmos in people with/without Graves’ disease (GD), we conducted a cross-sectional study using a general population cohort and a GD cohort, from October 2023 to October 2024. We used a Hertel exophthalmometer to measure the exophthalmometry values in both cohorts, and we obtained clinical data from medical records and/or questionnaires. Eighty-six patients with GD and 502 general population controls were included. The GD cohort’s mean exophthalmometry value (17.0 ± 3.3 mm) was significantly higher than the general population (15.6 ± 2.8 mm), which was larger than the upper limit of the normal references (15.0 mm) defined by the Japan Thyroid Association based on a 1970s’ report. Multiple regression analyses revealed that age, BMI, myopia, and dyslipidemia remained independently associated with exophthalmometry values in the general population cohort, whereas height, smoking, and anti-thyroglobulin autoantibody negativity were associated with the GD cohort’s exophthalmometry values. Our findings suggest a possible increase in mean exophthalmometry values in the contemporary Japanese general population. They highlight the need to update normative exophthalmometry values, accounting for body-composition including metabolic profiles and myopia, which could lead to accurate assessments of proptosis severity and appropriate therapeutic strategies for patients with TED. Clinical Trials Registry (CTR) registration: UMIN-CTR no. 000051753

Reports on long-term safety and effectiveness of daily GH replacement therapy in Japanese children with short stature due to Noonan syndrome (NS) are limited. This post-marketing, prospective, non-interventional study (ClinicalTrials.gov NCT03435627) evaluated the long‑term safety and effectiveness of daily GH therapy in this patient population. The study took place at 22 sites in Japan during November 2017–January 2022. Seventy participants were enrolled and received Norditropin^® at least once during the study as per routine clinical practice: new patients (n = 35) received Norditropin^® (somatropin) after study initiation and existing patients (n = 35) were previously enrolled in a 4-year trial of Norditropin^® for NS (ClinicalTrials.gov NCT01927861). The main outcome measures were adverse drug reactions (ADRs) and serious adverse events (SAEs). Improvements in height were also measured. In total, four new patients experienced five ADRs and one new patient experienced one SAE. Five existing patients experienced one ADR each and three existing patients experienced one SAE each. One existing patient with pre-existing cardiomyopathy who experienced an SAE (arrhythmia) died during the study; Norditropin^® causality was judged ‘unlikely.’ Change from baseline in mean (SD) height standard deviation score (SDS), according to Japanese and NS standards, was 1.01 (0.5) and 0.92 (0.3) for new patients and 1.01 (1.0) and 1.31 (0.8) for existing patients, respectively. Our results show that Norditropin^® effectively improved height outcomes in Japanese children with NS and was well tolerated with no new safety issues identified. For patients with NS and cardiomyopathy receiving GH therapy, careful monitoring is advised.

X-linked adrenal hypoplasia congenita (AHC) is a rare, life-threatening disorder caused by pathogenic variants in NR0B1 (DAX1), leading to adrenal insufficiency and hypogonadotropic hypogonadism. AHC is often associated with Xp21 contiguous gene deletion syndrome, which involves the deletion of multiple genes, including NR0B1, GK, DMD, and IL1RAPL1, resulting in a spectrum of phenotypic manifestations, such as glycerol kinase deficiency (GKD), Duchenne muscular dystrophy (DMD), and neurodevelopmental disorders. We report two cases of AHC with neurodevelopmental delays due to contiguous Xp21 deletions involving NR0B1 and IL1RAPL1, each diagnosed through distinct clinical pathways. Case 1 involved a neonate with adrenal insufficiency, persistent hyperCKemia, and excessive urinary glycerol excretion, leading to a diagnosis of Xp21 deletion syndrome with DMD and GKD. The patient’s sister, an asymptomatic carrier, exhibited elevated CK levels and mild developmental delays. Array comparative genomic hybridization identified a novel complex structural variation, including duplication-deletion-duplication rearrangement, which may have modified clinical manifestations. Case 2 involved a 10-year-old boy with AHC and developmental delay that was initially considered a consequence of adrenal crises. Genetic analysis confirmed an Xp21 deletion, including IL1RAPL1, implicating it in his intellectual disability. A literature review reveals that Xp21 deletions involving IL1RAPL1 are strongly associated with neurodevelopmental delays, suggesting a distinct phenotype within Xp21 deletion syndromes. Early genetic diagnosis via chromosomal microarray analysis facilitates precise delineation of deletion regions, aiding in clinical management, genetic counseling, and early intervention strategies. Further studies are needed to elucidate genotype-phenotype correlations in Xp21 deletion syndromes and optimize individualized medical care.

Males and females show significant differences in body structure, typical behavior, average life expectancy, and disease susceptibility. This review article introduces the current understanding and recent findings on the factors that lead to sexual dimorphism. First, recent studies have shown that sex chromosomes underlie male- and female-specific phenotypes through various mechanisms. For example, X chromosome inactivation exerts both positive and negative effects on female health, independent of sex hormone actions. Furthermore, differences in the frequency and clinical consequences of the mosaic loss of X and Y chromosomes have been implicated in sex differences in disease susceptibility and average life expectancy. In addition, sex-specific epigenetic regulation of the pseudoautosomal gene SHOX has been linked to the relative short stature of females. Second, an alternative steroidogenic pathway and novel non-aromatizable androgens have been specified in humans. These factors, together with classical sex hormones, likely contribute to the phenotypic differences between males and females. Elucidating the molecular basis of sexual dimorphism helps us understand the factors involved in human diversity.

PaTHway Japan is an ongoing, phase 3, multicenter, single-arm, open-label trial comprised of a 26-week efficacy period with an extension period through week 182 designed to demonstrate the efficacy, safety, and tolerability of palopegteriparatide in Japanese individuals with hypoparathyroidism. Japanese men and women (≥18 years of age) with hypoparathyroidism of any etiology (≥26 weeks) taking stable doses of active vitamin D were enrolled across five sites in Japan. Once-daily palopegteriparatide was self-administered subcutaneously via a pre-filled pen injector. Titration of palopegteriparatide and conventional therapy was performed according to a protocol-specified algorithm. The main outcomes measures included the proportion of participants at week 26 who achieved albumin-adjusted serum calcium in the normal reference range, independence from active vitamin D, and independence from therapeutic doses of elemental calcium. Thirteen participants were enrolled. Hypoparathyroidism etiology was most commonly idiopathic, followed by postsurgical and genetic causes. After 26 weeks of treatment with palopegteriparatide, 92% (12/13) of participants achieved the primary multi-component endpoint. Of the participants who entered the extension period, 92% (11/12) met the multi-component endpoint at week 52. Adverse events were mild to moderate in severity; none led to discontinuation of palopegteriparatide treatment. These findings in Japanese adults are consistent with results of the pivotal phase 3 and phase 2 North American/European trials and demonstrate the reproducibility of the palopegteriparatide treatment benefit in diverse populations and geographies. Japan Registry of Clinical Trials ID: jRCT2051210058.

Children born small for gestational age (SGA) who fail to experience catch-up growth often remain short-statured with heterogeneous etiologies, including genetic factors. This study aimed to investigate Insulin-like Growth Factor 1 Receptor (IGF1R) gene alterations and their clinical relevance in 66 Korean children born SGA with persistent short stature. All the subjects underwent detailed phenotyping and molecular analyses. Two patients carried heterozygous deletions encompassing the entire IGF1R gene, as confirmed by chromosomal microarray analysis. Both patients exhibited advanced bone age, with one showing a favorable response to growth hormone therapy. Additionally, 14 variants of uncertain significance were identified, with one rare missense variant (c.158C>T, p.Thr53Met) showing a high predicted pathogenicity. Subgroup analysis showed that severe SGA was associated with lower mid-parental height, and those with an insulin-like growth factor 1 standard deviation score of ≥0 had less bone age delay, but no clear auxological differences were observed between subgroups. These patterns, although not definitive, may help to identify SGA-short children who warrant further evaluation for IGF1R-related growth impairment. Exploratory clustering revealed two subgroups but failed to show distinct phenotypic separation. Although no strong genotype–phenotype correlations were observed, this study highlights the potential clinical value of identifying IGF1R deletions and suggests that molecular and phenotypic profiling may offer hypothesis-generating insights into SGA-related growth disorders. Our findings underscore the importance of integrating genetic screening into the diagnostic workup for children born SGA with unexplained growth failure, and the need for future studies to functionally characterize rare IGF1R variants.

The physical and/or electrical properties of the peptide-binding pockets of Human Leukocyte Antigen (HLA) class II molecules vary depending on their amino acid sequence, influencing peptide-binding affinity. Previous studies have reported associations between HLA-DRB1 amino acid polymorphisms and susceptibility to Graves’ disease (GD) and Hashimoto’s disease (HD). We hypothesized that polymorphisms in the peptide-binding region of HLA-DRB1 contribute to disease development and prognosis. This study investigated associations between HLA-DRB1 amino acid polymorphisms and both the development and prognosis of autoimmune thyroid diseases. We analyzed HLA-DRB1 sequences in 136 GD patients, 132 HD patients, and 109 healthy Japanese controls. HLA-DRB1 typing was performed using polymerase chain reaction (PCR) with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). Glu9, His13, and Leu67 were more frequent in intractable GD than in GD remission or controls. Lys9, Phe13, Tyr26, and Val57 were associated with susceptibility to HD, whereas Trp9, Ser37, Phe47, and Asp57 were associated with resistance to HD. Structural modeling revealed that GD-susceptible pockets showed a positive electrostatic potential in pocket 7, while GD-resistant pockets showed a negative electrostatic potential. In pockets 4, 7, and 9, HD-susceptible pockets showed a positive electrostatic potential, whereas HD-resistant pockets showed neutral or negative electrostatic potential. Therefore, specific amino acids in pockets 4, 7, and 9 of HLA-DRB1 are associated with the development and prognosis of GD and HD in the Japanese population.

Acquired hypothalamic obesity (aHO) presents as rapid, clinically relevant, and persistent weight gain due to hypothalamic damage, and leads to significant morbidity/mortality and decreased quality of life. Causes include craniopharyngioma and other space-occupying lesions, neurosurgical intervention, irradiation, and traumatic brain injury. This review summarizes the evidence and provides expert opinion on diagnostic criteria for aHO. Eight experts in neuroendocrinology and neurosurgery from Japan and Europe participated in a multidisciplinary meeting at the 57^th Annual Meeting of the Japanese Society for Pediatric Endocrinology, Yokohama, Japan, 2024. Thereafter, three experts from Korea joined the discussion. Data were sourced from a search of the databases Web of Science, MEDLINE/PubMed, and Embase for reports published since 2000. Expert opinion of the authors was used substantially when no published data were available. The consensus on diagnostic criteria for aHO included: a.) traumatic event or (oncological) disease leading to hypothalamic lesions/damage detectable on MRI; b.) rapid (occurring during the first 12 months after surgery/diagnosis), persisting (for 24 months after surgery), and clinically significant increase in BMI (≥5% BMI increase in adult; ≥1.0 SDS BMI increase in pediatric patients) starting during the first 12 months following the onset of hypothalamic damage under clinical and anthropometric monitoring at 3 months intervals; c.) obesity of a certain level (BMI SDS ≥+2.0 SD in pediatric; BMI ≥25 kg/m² or BMI ≥30 kg/m² in adult patients), depending on racial and ethnic characteristics.

Thyroid hormone (TH) prescribing practices, particularly on hypothyroid and euthyroid patients, were compared between Japan Thyroid Association (JTA)-certified thyroid specialists and non-certified members. A nationwide questionnaire survey (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) was conducted among all 2,938 JTA members, including 874 certified specialists and 2,064 non-certified members, to assess self-reported TH prescription choices in various clinical scenarios. Responses from certified specialists and non-certified members were statistically compared. A total of 207 certified specialists (23.7%) and 129 non-certified members (6.3%) responded and completed the questionnaire. Although all certified specialists and non-certified members selected levothyroxine (LT4) as first-line therapy for hypothyroidism, certified specialists more often used liothyronine (LT3) plus LT4 combination therapy than non-certified members (28% vs. 12%, p < 0.001), particularly for LT4-treated patients with persistent hypothyroid-like symptoms (9% vs. 2%, p = 0.02). For euthyroid individuals, 71% of certified specialists and 60% of non-certified members considered TH treatment (p = 0.043). Non-certified members who see >100 hypothyroid patients per year were more inclined to use combination therapy for hypothyroid patients and TH for euthyroid patients than those of ≤100 patients (p < 0.049 and 0.001, respectively). In conclusion, JTA-certified thyroid specialists and non-certified members exhibit distinct TH prescribing patterns. Certified specialists are more open to combination therapy and treating selected euthyroid patients, whereas non-certified members favor guideline-based LT4 monotherapy. These differences underscore the impact of specialization on clinical practice and suggest a need for updated guidelines and targeted education to rationalize thyroid care.

To-and-fro puncture and to-and-fro whirling puncture are two common specimen acquisition methods of thyroid fine-needle capillary (FNC) biopsy. While both techniques are widely used, a direct comparison of their outcomes has been lacking. This prospective study enrolled 110 patients with 138 thyroid nodules. Each nodule underwent four punctures: two using the to-and-fro technique and two using the to-and-fro whirling technique. The primary outcome was specimen adequacy, while secondary outcomes included malignancy diagnosis rate, sensitivity, diagnostic accuracy, and procedure time. No significant difference was found in specimen adequacy between the two techniques (90.58% vs. 89.86%, p = 0.839). However, the to-and-fro technique demonstrated superior performance in terms of malignancy diagnosis rate (31.88% vs. 20.29%, p = 0.028), sensitivity (100.00% vs. 81.82%, p = 0.006), and diagnostic accuracy (97.78% vs. 83.33%, p = 0.041). Additionally, the to-and-fro technique required less procedure time (18.38 ± 8.34 seconds vs. 20.84 ± 10.54 seconds, p < 0.001). In conclusion, both the to-and-fro puncture technique FNC and the to-and-fro whirling puncture technique FNC demonstrated comparable specimen adequacy, and both can achieve good specimen adequacy. The to-and-fro puncture technique shows potential advantages in terms of operation time, reduction of the risk of missed diagnosis of malignant tumors, sensitivity, and diagnostic accuracy. Trial registration: Chinese Clinical Trial Registry, ChiCTR2400080882. Registered 14 February 2024.

Children with Down syndrome (DS) have a high prevalence of thyroid dysfunction; however, age-related changes in thyroid hormone profiles remain unclear. We investigated the age-related changes in thyroid function in children with DS. We retrospectively analyzed the thyroid function test results of 762 patients with DS aged 3–14 years without known thyroid disease, and compared them with those of 764 age-matched controls with idiopathic short stature. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and the FT3/FT4 ratio were compared between patients with DS with/without congenital heart disease (CHD) and gastrointestinal malformations. In each age group, the log-transformed TSH distribution exhibited similar standard deviation and kurtosis, but showed consistently higher mean values in patients with DS than in controls. Mean FT3 levels were slightly lower in the DS group, except at ages 11–12 years. Mean FT4 levels were slightly lower in the DS group after 9 years of age. The mean FT3/FT4 ratio was lower in the DS group at ages 3–8 years but normalized after 9 years of age. Patients with DS and CHD had higher TSH levels than those without CHD after 11 years of age, whereas FT3, FT4, and the FT3/FT4 ratio showed no significant differences. A rightward shift in serum TSH distribution was observed in patients with DS without thyroid disease, suggesting that TSH levels are generally high in patients with DS. These variations highlight the need for personalized management of thyroid function in patients with DS.

A meta-analysis of cohort studies found a positive association between white rice consumption and chronic disease risk, particularly in women. However, the association between rice intake and obesity remains inconsistent across populations. We aimed to examine the relationship between rice intake and obesity stratified by sex and age. This cross-sectional study used nationwide registry data from Japanese type 2 diabetes outpatients (2014–2019). Obesity was defined as BMI ≥25 kg/m². The study included 1,565 outpatients aged 30–89 years (mean age: 62.3 ± 11.6 years), with 63.1% being male. Rice intake was associated with a diet low in energy from protein, fiber density, and dairy products. In adjusted multivariate analysis, older women in the highest tertile of rice intake had a higher prevalence of obesity (95% CI = 1.104–4.260, p trend = 0.042); however, this association lost significance after adjusting for fiber density (95% CI = 0.864–3.558, p trend = 0.080). In younger women, an inverse association with obesity emerged after fiber density adjustment in the supplementary quartile analysis. No significant associations were found in men. These results suggest that the association between rice intake and obesity is influenced by overall dietary quality rather than rice consumption alone. Promoting greater dietary diversity while maintaining traditional staples like rice may be a practical strategy to improve diet quality in Japan. Prospective studies in Japanese and other populations are needed to confirm these associations.

This study examined the association of physical activity (PA) and sedentary time (ST) with the risk of non-alcoholic fatty liver disease (NAFLD) in adults with and without diabetes mellitus (DM). The study used data from the 2017–2020 National Health and Nutrition Examination Survey and conducted weighted logistic regression analysis to examine the association between PA, ST and NAFLD risk in individuals with and without DM. A total of 4,805 participants were included, with a weighted prevalence of NAFLD of 36% and a weighted prevalence of DM of 13.3%. Participants were divided into quartiles (Q1–Q4) based on PA levels (MET-min/week) and ST (min/day), with Q1 representing the lowest activity/shortest sitting time. In the total population, for PA, the risk of NAFLD in the Q2 and Q3 groups was reduced by 0.593 and 0.660 times, respectively, compared with the Q1 group. For ST, relative to the Q1 group, the NAFLD risk increased in the Q2, Q3 and Q4 groups by 1.420, 1.361 and 1.690 times, respectively. The dose–response analysis revealed that in the total population, NAFLD risk decreased when PA levels were between 1,553.4 and 30,402.3 metabolic equivalent of task (MET)-min/week (p_non-linear = 0.016). Among individuals without DM, for PA, the NAFLD risk in the Q2 and Q3 groups was 0.571 and 0.648 times lower, respectively, than that in the Q1 group. When PA was within the range of 1,775.3 to 24,410.6 MET-min/week, the risk of NAFLD was reduced (p_non-linear = 0.033). Patterns of association between PA, ST, and NAFLD appeared to differ between individuals with and without DM; however, multiplicative interaction terms were not statistically significant.

Vitamin D (VD) insufficiency in pregnant women is a serious health problem worldwide. To prevent VD insufficiency during pregnancy, several guidelines recommend 600 IU/day VD for all pregnant women. In Japan, no national guidelines for preventing VD insufficiency have been implemented, and no study has evaluated adequate VD intake in pregnant women; however, the number of pregnant women taking commercial dietary supplements containing VD has increased in recent years. This study aimed to examine the effects of maternal commercial supplementation of VD on 25-hydroxyvitamin D (25(OH)D) levels in newborns. We retrospectively analyzed the serum 25(OH)D levels in 279 four-days-old newborns born at the Saitama City Hospital from 2022 to 2023. Newborns were classified into a supplement group (mothers who took VD-containing commercial supplements regularly throughout pregnancy; n = 103) and a non-supplement group (mothers who did not take any supplements during pregnancy; n = 176). The study findings revealed that serum 25(OH)D levels in newborns in the supplement group were higher than those in the non-supplement group (median [interquartile range]: supplement group 17.2 [14.6, 22.9] vs. non-supplement group 14.3 [11.6, 16.7], p < 0.001). In the supplement group, approximately 70% of newborns still showed VD insufficiency. Although the maternal use of VD-containing commercial supplements during pregnancy increased the serum 25(OH)D levels in newborns at four days of age, additional measures, such as VD supplementation for newborns, are needed to improve neonatal VD status.

A high body mass index (BMI) is associated with the onset of diabetes mellitus (DM). However, evidence regarding the association between changes in BMI and DM onset is limited, and the effect of annual BMI (kg/m²/year) change on DM onset is unknown. Therefore, we assessed the effects of changes in BMI and annual BMI on DM onset. We enrolled 13,949 participants aged 21–81 years who underwent an annual health checkup at least twice between April 2003 and March 2021 and examined the effect of BMI change and annual BMI change on DM onset. In total, 462 individuals newly developed DM. Compared with a BMI change of –0.25–<0.25, univariate and multivariate analyses—adjusted for age, sex, BMI, systolic blood pressure, creatinine, total cholesterol, triglycerides, alanine aminotransferase, hemoglobin A1c, and family history of DM—showed that a BMI change <–2 was associated with a lower risk, while 2 ≤ BMI change < 4 and 4 ≤ BMI change were associated with a higher risk of DM onset. In contrast, compared with –0.05 ≤ BMI change per year < 0.05, univariate and multivariate analyses showed a significant association between DM onset and 0.3 ≤ BMI change per year. In the age-stratified analysis, these associations were significant among younger and middle-aged participants but not in older adults. In conclusion, changes in BMI affect DM onset. Therefore, clinicians can prevent DM onset by providing guidance based on BMI and focusing on a ≥2 increase in BMI and a ≥0.3 increase per year of BMI in young and middle-aged individuals.

β3-Adrenoceptors (β3ARs) are expressed in the adipose tissue, the brain, and the bladder. In rodents, selective β3AR agonists have been shown to reduce normal chow intake through central and peripheral mechanisms. However, the impact of β3AR agonists on nutritional balance, as well as the relative contribution of each organ system to this effect, remains elusive. In this study, we aimed to determine whether the peripheral effect of β3AR agonists on food intake is nutrient-specific or energy in general using food choice experiments that allow for independent analysis of energy and nutrients. Mice were presented with two different diet options (normal diet [ND] vs. high-sucrose diet [HSD], high-fat diet [HFD], or high-protein diet [HPD]), and the effects of the β3AR agonist CL316,243 on the intake of these diets were examined. Treatment with CL316,243 reduced total energy intake, primarily through decreased consumption of HSD, HFD, and HPD. Accordingly, CL316,243 reduced food intake in a non-nutrient-specific manner, resulting in decreased caloric intake. In addition, CL316,243 increased plasma levels of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). In the ND vs. HSD food choice test, CL316,243 reduced HSD intake, even in liver-specific Fgf21 knockout mice. Furthermore, CL316,243 reduced food intake in mice with diet-induced obesity. These findings suggest that the CL316,243-mediated reduction in HSD intake occurs independently of liver-derived FGF21. Moreover, elevated plasma GDF15 levels were positively associated with reduced food intake induced by CL316,243.