Endocrine journal最新文献

Cushing's disease (CD) is a rare but serious endocrine disorder caused by excessive cortisol secretion due to adrenocorticotropic hormone-secreting pituitary tumors. Despite recent developments in diagnostic criteria and treatment options, CD remains associated with substantial comorbidities and mortality. Early and accurate diagnosis is thus essential. Both the Korean Endocrine Society (KES) and Japan Endocrine Society (JES) guidelines are intended to standardize diagnostic approaches to CD, and they share common principles; however, notable differences exist, particularly in biochemical testing thresholds and imaging recommendations. This consensus statement integrates clinical evidence and expert practice from both the KES and JES to establish harmonized recommendations for biochemical evaluation, imaging, and differential testing. This unified framework is intended to enhance diagnostic precision and improve clinical outcomes across East Asian populations.

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.

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.

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.

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.

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.

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.

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.

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.

Lenvatinib is a standard systemic therapy for radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Although pivotal trials such as SELECT demonstrated significant efficacy, real-world evidence remains limited, particularly regarding treatment timing and the role of planned drug holidays. We retrospectively analyzed 44 consecutive patients with RAI-R DTC treated with lenvatinib between 2015 and 2024. All patients initiated therapy at 24 mg/day, with dose reductions and treatment interruptions-including planned drug holidays-implemented according to toxicity. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and best tumor shrinkage. A subgroup analysis was conducted in patients with lung metastases. The median PFS was 36.0 months, and the median OS was 76.7 months. ORR was 52.3% and DCR was 95.5%. In the lung metastases-only subgroup (n = 25), outcomes were particularly favorable: PFS 58.1 months, unreached OS, ORR 64.0%, and DCR 100%. Univariate Cox analysis identified performance status, histological subtype, TV-DT, and tumor burden as significant prognostic factors. The most common adverse events were hypertension, proteinuria, fatigue, and palmar-plantar erythrodysesthesia; these were generally manageable with dose adjustments and individualized planned holidays. Clinically meaningful renal dysfunction was rare despite frequent proteinuria. Lenvatinib demonstrated durable efficacy and acceptable tolerability in real-world practice, especially in patients with lung metastases. Early treatment initiation and individualized toxicity management-including planned drug holidays-enabled sustained dose intensity and prolonged disease control. These findings support the clinical utility of personalized adverse event management strategies in routine care for RAI-R DTC.