Endocrine journal最新文献

This study aimed to investigate the association between body composition and lung function. Metabolic body composition can independently predict the risk of poor lung function. Accordingly, this cross-sectional observational study included adults aged ≥18 years who attended annual health examinations at Xiamen Chang-Gung Hospital from 2013 to 2016. The study evaluated the association between lung function and metabolic body composition, after correcting for possible influencing factors. Males had a higher body mass index and waist-to-hip ratio and a higher prevalence of smoking and drinking histories. Additionally, men showed significantly higher mean arterial pressure, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, insulin, and homeostasis model assessment for insulin resistance values than those of women (all p < 0.001). The proportion of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) was also higher in men than in women (17.91% vs. 25.20% and 11.28% vs. 13.67%, respectively). However, female participants demonstrated better pulmonary function. The prevalence of restrictive lung disease (RLD) was substantially higher in men than in women. The study findings suggest that MUO, and to a lesser extent, metabolic obesity with normal weight (MONW), are independent risk factors for RLD. These results imply that MUO, and to a lesser extent, MONW, may serve as potential screening markers for preclinical RLD in annual health checkups.

Medullary thyroid carcinoma (MTC) can occur sporadically or as a hereditary disease. The latter often presents with a multiple endocrine neoplasia type 2 (MEN2) phenotype and is caused by germline-activating pathogenic variants in the RET proto-oncogene, whereas the former may harbor somatic-activating RET pathogenic variants. Here, we report a family with a germline RET V778I pathogenic variant. The proband was a 72-year-old woman with bilateral multifocal MTCs but without other MEN2 features. Germline RET analysis revealed a homozygous V778I pathogenic variant. Postoperative histopathological examination confirmed bilateral multifocal MTC with lymph node metastasis. The patient's parents were cousins. The patient had no family history of MTC or MEN2. Her three middle-aged children were heterozygous for the V778I pathogenic variant, had no symptoms or signs of MTC, and had normal serum calcitonin and CEA levels. The proband died of cardiac and pulmonary diseases at the age of 86, 15 years after surgery, without MTC recurrence. Unlike other dominant RET pathogenic variants, in which a single mutated allele is sufficient for tumor development, V778I may have weak oncogenic activity, requiring homozygosity to develop MTC. Therefore, prophylactic thyroidectomy is not recommended for heterozygous carriers. To the best of our knowledge, this is the second report of a family with MTC exclusively associated with a homozygous RET pathogenic variant. This is also the first report of a germline RET V778I pathogenic variant associated with MTC under homozygous conditions.

East Asians are known to develop diabetes mellitus at a lower body weight than Caucasians, potentially because of the different mechanisms underlying disease development. This study aimed to evaluate the variation in weight transition leading to diabetes onset in two subtypes of individuals (obese and non-obese) in a Japanese population. We conducted a retrospective, observational, longitudinal cohort study using health checkup data from 9, 260 participants in Japan. Individuals who developed diabetes within three years of the start of the observation period were excluded. Among the participants, 61.4% were men, and 259 developed diabetes. In the obesity group (body mass index [BMI] ≥25 kg/m²), the average BMI increased prior to the diabetes onset and subsequently decreased. Conversely, in the non-obesity group (BMI <25 kg/m²), the average BMI decreased and then stabilized before the onset of diabetes. Notably, a greater number of participants in the non-obesity group exhibited a BMI change of ≤-0.15 kg/m² per year compared with those with a BMI change of ≥0.15 kg/m² per year before diabetes onset (p = 0.003). Our findings indicate that body weight loss precedes the onset of diabetes in the non-obesity group. We recommend that non-obese individuals with elevated blood glucose levels who do not meet the criteria for diabetes should be considered a high-risk group for diabetes development. Therefore, it is imperative to identify these individuals and provide lifestyle guidance that does not focus on weight loss to prevent the onset of diabetes.

The incidence of immune checkpoint inhibitor (ICI)-induced type 1 diabetes mellitus (ICI-T1DM) has increased as the use of ICIs has increased. Autoimmune ICI-T1DM often presents as diabetic ketoacidosis, resulting from insulin deficiency, among which insulin resistance is extremely rare. Here, we describe a patient with advanced myxoid liposarcoma who developed sintilimab-induced fulminant autoimmune diabetes associated with insulin resistance and metabolic disorders. The patient eventually required the combined use of insulin, metformin, liraglutide, and dapagliflozin to reduce blood glucose due to erratic glycaemic excursions and high insulin requirements during his duration of hospital stay. Metformin, dapagliflozin and liraglutide were discontinued because of weight loss half a year after discharge, and intensive insulin therapy was continued. The patient's blood glucose control was poor, and liraglutide and metformin were then added again, half a year later. Together, metformin, dapagliflozin and liraglutide in combination with insulin may help control blood glucose in ICI-induced DM patients with insulin resistance.

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.

Some patients with Graves' disease (GD) develop hypothyroidism after antithyroid drug (ATD) treatment and are found to be positive for thyroid stimulation-blocking antibody (TSBAb). However, thyroid volume (TV) changes throughout this process remain unclear. Therefore, we aimed to quantify TV changes before and after hypothyroidism onset in patients with GD harboring TSBAb and compare them with those in patients with GD who developed hypothyroidism without TSBAb or achieved remission with ATD. This retrospective study evaluated TV changes using ultrasonography in three groups: 10 patients with GD who developed hypothyroidism with TSBAb (TSBAb(+)-hypo group), nine without TSBAb (TSBAb(-)-hypo group), and 91 who achieved remission after ATD treatment (Remission group). In the TSBAb(+)-hypo group, TV significantly decreased from the hyperthyroid to hypothyroid phase (median: 33.3 mL [range: 14.2-52.0] vs. 13.6 mL [4.3-23.3], respectively; p = 0.001). In the TSBAb(-)-hypo group, TV significantly decreased from the hyperthyroid to hypothyroid phase (26.6 mL [11.9-49.2] vs. 20.9 mL [7.4-34.2], respectively; p = 0.037). In the Remission group, TV also decreased significantly from the hyperthyroid to remission phase (29.8 mL [8.2-88.4] vs. 25.1 mL [9.5-72.0], respectively; p = 0.0002). The decrease in TV was significantly higher in the TSBAb(+)-hypo group than in the TSBAb(-)-hypo and Remission groups (53.9% [37.9-74.5] vs. 30.9% [-22.3 to 63.0] and 10.7% [-100.7 to 52.0], respectively; p = 0.027 and <0.0001). This study documents the first precise measurement of TV reduction using ultrasonography in patients with GD who developed hypothyroidism with TSBAb, showing a markedly greater decrease than in those without TSBAb or in remission after ATD treatment.

Somatrogon is a long-acting recombinant human growth hormone approved in several countries, including Japan, for the treatment of children with growth hormone deficiency (GHD). In this study (Clinicaltrials.gov:NCT03874013) Japanese patients with GHD initially received once-weekly somatrogon or once-daily somatropin (0.175 mg/kg/week) for 12 months in the main study period; those who completed the main study were eligible to enroll in a single-arm, 3-year open-label extension (OLE) and receive once-weekly somatrogon (0.66 mg/kg/week). The primary endpoints of the OLE included annualized height velocity (HV), change in height standard deviation score (SDS), and safety. Of 43 patients who completed the main study, 42 continued into the OLE and 40 completed the OLE. Patients were analyzed by treatment received (somatrogon vs. somatropin) during the main study. Mean (SD) HV at OLE baseline was higher in patients originally randomized to somatrogon vs. somatropin (9.78 [1.59] vs. 7.70 [1.10] cm/year); mean HV was similar between original treatment groups for all other OLE timepoints. Mean height SDS increased from main study baseline through the end of the OLE in both treatment groups. During the OLE, 22 (100%) somatrogon-treated patients and 18 (90%) somatropin-treated patients reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild or moderate in severity and no patients discontinued from the OLE or required dose reductions due to TEAEs. Up to 4 years of treatment with once-weekly somatrogon resulted in improved growth response and was well tolerated in Japanese patients with pediatric GHD, including patients who switched to somatrogon from once-daily somatropin.Clinialtrials.gov:NCT03874013.

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).