Endocrine journal最新文献

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.

Adrenal hormones are essential for maintaining physiological homeostasis; however, imbalances in their production can significantly impact bone metabolism. This review examines how adrenal hormone dysregulation affects bone health, focusing on the following three key pathological conditions: autonomous cortisol secretion, primary aldosteronism, and pheochromocytoma/paraganglioma. Each disorder exerts distinct effects on bone metabolism, contributing to reduced bone mass, deteriorated bone quality, and increased fracture risk. Recent advances in steroid profiling and single-cell transcriptome analysis have revealed that, in adrenocortical adenomas-such as cortisol-producing and aldosterone-producing adenomas-multiple steroid hormones contribute to these effects rather than a single hormone. Additionally, age-related changes in steroid hormones, particularly the progressive decline in dehydroepiandrosterone sulfate production and alterations in cortisol circadian rhythm, may contribute to age-associated bone fragility. This review summarizes the effects of adrenal hormone imbalances on bone metabolism in both pathological conditions and aging, which may contribute to understanding adrenal-related osteoporosis.

GPT-4o, a general-purpose large language model, has a Retrieval-Augmented Variant (GPT-4o-RAG) that can assist in dietary counseling. However, research on its application in this field remains lacking. To bridge this gap, we used the Japanese National Examination for Registered Dietitians as a standardized benchmark for evaluation. Three language models-GPT-4o, GPT-4o-mini, and GPT-4o-RAG-were assessed using 599 publicly available multiple-choice questions from the 2022-2024 national examinations. For each model, we generated answers to each question five times and based our evaluation on these multiple outputs to assess response variability and robustness. A custom pipeline was implemented for GPT-4o-RAG to retrieve guideline-based documents for integration with GPT-generated responses. Accuracy rates, variance, and response consistency were evaluated. Term Frequency-Inverse Document Frequency analysis was conducted to compare word characteristics in correctly and incorrectly answered questions. All three models achieved accuracy rates >60%, the passing threshold. GPT-4o-RAG demonstrated the highest accuracy (83.5% ± 0.3%), followed by GPT-4o (82.1% ± 1.0%), and GPT-4o-mini (70.0% ± 1.4%). While the accuracy improvement of GPT-4o-RAG over GPT-4o was not statistically significant (p = 0.12), it exhibited significantly lower variance and higher response consistency (97.3% vs. 91.2-95.2%, p < 0.001). GPT-4o-RAG outperformed other models in applied and clinical nutrition categories but showed limited performance on numerical questions. Term Frequency-Inverse Document Frequency analysis suggested that incorrect answers were more frequently associated with numerical terms. GPT-4o-RAG improved response consistency and domain-specific performance, suggesting utility in clinical nutrition. However, limitations in numerical reasoning and individualized guidance warrant further development and validation.

Comparative endocrinology is a research subfield in endocrinology that delves into deeper understanding of the endocrine system from an evolutionary or phylogenetic perspective. To date, this approach has contributed significantly to the development of endocrinology by elucidating the evolutionary history of hormone molecules and their functions from invertebrates to vertebrates. In this review, the author initially introduces how the comparative approach has expanded and enlightened the view in endocrinology using the concept of hormones as an example. The expansion of the hormone concept blurs boundaries between signaling molecules of the three homeostatic systems, namely, the endocrine, nervous, and immune systems. Subsequently, the evolutionary history of the endocrine system is introduced in terms of both molecules and functions using the insulin superfamily as a model. This hormone family is one of the most ancient hormonal systems in animal (metazoan) phylogeny and the homologous hormones are identified in the most ancient metazoans such as sponges and hydra. In addition, this hormonal system was chosen as a topic of this review, because insulin is one of the most focused research topics in modern medicine in relation to insulin resistance and metabolic syndrome. Finally, the ancestral molecule of the insulin superfamily and its original or essential function will be discussed with some speculations to illustrate the value and joy of comparative studies that can create an original concept of the endocrine system from the evolutionary viewpoint. The comparative approach certainly helps deeper understanding of the insulin superfamily of humans.

Hailey-Hailey disease (HHD), or familial benign chronic pemphigus, is a rare autosomal dominant disorder characterized by recurrent vesicles and erosions in intertriginous areas. Topical corticosteroids are the primary treatment, but their potential systemic side effects are often overlooked. Prolonged use on compromised skin can lead to excessive absorption, increasing the risk of iatrogenic Cushing's syndrome and adrenal insufficiency. Here, we report the case of a 50-year-old woman with HHD who had been using topical clobetasol or betamethasone for over 10 years, reaching doses up to 50 g/day. She developed Cushingoid features, metabolic abnormalities, and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. After tapering off topical corticosteroids, she developed adrenal insufficiency and associated withdrawal symptoms. Following the initiation of hydrocortisone replacement therapy, psychiatric symptoms, impaired glucose tolerance, and osteoporotic fractures emerged, suggesting exacerbation of iatrogenic Cushing's syndrome. This case highlights the risk of systemic complications from chronic topical corticosteroid use, particularly in high-absorption areas. Gradual dose reduction, close endocrine monitoring, and individualized tapering strategies are essential to prevent severe outcomes. Clinicians should be aware of potential adrenal suppression and consider endocrine evaluation in patients receiving prolonged, high-dose topical corticosteroid therapy.