Endocrine journal最新文献

The consumption of a high-fat, high-sucrose diet (HFHSD) promotes obesity. Although dietary sugars are obesogenic, they activates a negative feedback mechanism between hepatic fibroblast growth factor 21 (FGF21) and oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVH^Oxt), thereby suppressing sugar appetite. We previously reported that the low-calorie rare sugars d-allulose, d-tagatose, and d-sorbitol induce FGF21, activate PVH^Oxt neurons, and reduce sugar intake. In this study, we evaluated the anti-obesity effects of these rare sugars in male BL/6 mice. The mice were fed with HFHSD, along with ad libitum access to FGF21-inducing rare sugar solutions for 1 month. Body weight, feed intake, fluid intake, and total caloric intake were recorded every 3 days. At the end of the treatment, obesity-associated parameters-including insulin resistance, glucose intolerance, and adiposity-were assessed. Rare sugar supplementation reduced body weight gain and total caloric intake without increasing energy expenditure. These interventions improved obesity-associated phenotypes to varying degrees, suggesting that these rare sugars ameliorated the overall state of diet-induced obesity. In contrast, these sugars did not reverse established obesity or insulin resistance, as prolonged HFHSD feeding desensitized mice to their effects. Therefore, rare sugars appear effective for the prevention, but not the treatment, of diet-induced obesity.

Soluble T-cadherin (sT-cad), which is a circulating form of membrane T-cadherin, is present in human serum. We examined the relationships among sT-cad levels, adiponectin (APN) levels, and the number of metabolic risk factors in individuals undergoing medical health checkups. A total of 1,144 Japanese individuals (811 males and 333 females, average age: 56.3 ± 9.9 years in males and 53.7 ± 10.1 years in females) were analyzed. Serum levels of sT-cad and APN were measured by enzyme-linked immunosorbent assay (ELISA). Associations of sT-cad and APN levels with the number of metabolic risk factors (abdominal obesity, diabetes, hypertension, and dyslipidemia) were evaluated. Serum 130-kDa sT-cad levels were significantly lower in males than in females, and were positively correlated with APN levels. Individuals with low APN levels exhibited more metabolic risk factors. Notably, among males with high APN levels, those with low 130-kDa sT-cad levels had a greater number of metabolic risk factors than those with high 130-kDa sT-cad levels. Serum 130-kDa sT-cad levels were significantly correlated with APN levels in individuals undergoing medical health checkups. Even among males with high APN levels, low sT-cad levels were indicative of the presence of more metabolic risk factors.

The impact of autonomous cortisol secretion (ACS) on adrenal venous sampling (AVS) in patients with primary aldosteronism (PA) remains uncertain. This study aimed to evaluate the effects of ACS on success and lateralization of AVS. From the Japan Primary Aldosteronism Study-II, 872 PA patients with adrenal nodular lesions on computed tomography (CT) who underwent a 1-mg dexamethasone suppression test (DST) were included. ACS was defined as a post-DST cortisol level ≥1.8 μg/dL. AVS success was assessed using selectivity index (cutoff value 2 without, 5 with ACTH-stimulation), and lateralization was determined using lateralization index (cutoff value 2 without, 4 with ACTH-stimulation). Among 872 patients, 283 (32.4%) had ACS. After ACTH-stimulation, AVS success rate was significantly lower in ACS group than in non-ACS group (84.8% vs. 91.0%, p < 0.01), while no significant difference was observed before ACTH-stimulation. Among 524 patients with successful AVS both before and after ACTH-stimulation, 161 (30.7%) had ACS. The proportion of unilateral results did not differ significantly between ACS and non-ACS groups either with or without ACTH. Concordance between AVS and CT laterality was significantly lower in ACS group only without ACTH-stimulation (44.1% vs. 61.7%, p < 0.01). In patients with post-DST cortisol ≥5 μg/dL, reverse AVS-CT laterality was significantly more frequent than in those with cortisol <1.8 μg/dL both with and without ACTH-stimulation. In conclusion, ACS was associated with a lower AVS success rate with ACTH-stimulation, had no impact on rate of unilateral results, but reduced AVS-CT concordance, especially in patients with higher post-DST cortisol levels.

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.

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.

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.

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 magnetic resonance imaging (MRI); b.) rapid (occurring during the first 12 months after surgery/diagnosis), persisting (for 24 months after surgery), and clinically significant increase in body mass index (BMI) (≥5% BMI increase in adult; ≥1.0 standard deviation score (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 standard deviations (SD) in pediatric; BMI ≥25 kg/m² or BMI ≥30 kg/m² in adult patients), depending on racial and ethnic characteristics.

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.

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.