In order to explore if γ-secretase inhibitor can regulate γδT17 cells by blockading Notch1 signaling pathway and then affect thyroid autoimmune damage in experimental autoimmune thyroiditis (EAT) mice. Twenty-four female C57BL/6 mice, 6 to 8-week-old, were randomly divided into NC and EAT groups, and EAT group included EAT-A (pTg treated) and EAT-B (treated with DAPT before pTg) subgroups. HE staining was conducted to observe the pathological changes of thyroid tissue. ELISA was adopted to measure the concentrations of thyroglobulin antibody (TgAb) and interleukin 17A (IL-17A) in serum. The proportions of γδT17 cells were analysed by flow cytometry. The mRNA expressions of Notch1, hairy and split 1 (Hes1) and IL-17A were measured by RT-qPCR and the protein levels of Notch intracellular domain (NICD), Hes1 and IL-17A were examined by Western Blot. The titers of TgAb and IL-17A in serum, the proportions of γδT17 cells in spleen mononuclear cells (SMCs) and thyroid mononuclear cells (TMCs), the Notch1, Hes1, IL-17A mRNA and protein expressions in EAT-A mice were all increased significantly compared with NC group (all p < 0.001). However, in EAT-B group, the above indexes were all reduced significantly than those in EAT-A group (all p < 0.05), as well as the degrees of lymphocyte infiltration in thyroid were alleviated remarkably compared with EAT-A group. Additionally, γδT17 cells percentages of EAT mice were positively correlated with TgAb titers, IL-17A concentrations and Notch1 mRNA expressions. γ-secretase inhibitor is speculated to alleviate thyroid autoimmune injury in EAT by downregulating γδT17 cells via inhibition of the Notch1/Hes1 signaling pathway.

Anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis is an acquired autoimmune disorder characterized by selective deficiencies of growth hormone (GH), prolactin (PRL), and thyrotropin (TSH). It is typically driven by ectopic PIT-1 expression in thymomas or other malignancies, and in previously reported cases, thymectomy has been shown to attenuate autoimmunity. In contrast, we report a novel case that developed after thymectomy. A 42-year-old woman with normal preoperative thyroid function underwent resection of a WHO type B2 thymoma. Eleven months later, she developed specific deficiencies of GH, PRL, and TSH. The diagnosis of anti-PIT-1 hypophysitis was confirmed by the presence of serum anti-PIT-1 antibodies and PIT-1-reactive cytotoxic T lymphocytes. Immunohistochemistry revealed ectopic PIT-1 expression in the resected tumor. Replacement therapy with levothyroxine and recombinant human GH was initiated. Serum FT4 and IGF-1 levels subsequently improved to normal. Two-year post-thymectomy chest computed tomography revealed no tumor recurrence. This unique clinical course challenges the conventional view that the presence of the tumor alone is sufficient to drive autoimmunity. Instead, it suggests a multifactorial pathogenesis requiring the convergence of ectopic antigen expression, genetic predisposition, and a potential trigger. We hypothesize that thymectomy itself acted as the trigger disrupting immune tolerance, potentially through immunogenic cell death or alterations in the immune milieu. This case highlights anti-PIT-1 hypophysitis as a potential post-thymectomy autoimmune complication and that central hypothyroidism should be considered in patients presenting with nonspecific symptoms after thymectomy. Further research is needed to delineate risk factors for susceptibility and to develop preventive strategies.

Sarcoidosis is a granulomatous disease that affects multiple organs; however, pituitary involvement is extremely rare. Although autoimmune diseases, such as Sjögren's disease (SjD), may coexist, overlapping cases presenting with hypopituitarism are exceedingly rare. A 76-year-old man was admitted with hyponatremia and altered consciousness as chief complaints. Endocrine testing revealed panhypopituitarism, and magnetic resonance imaging showed pituitary gland and pituitary stalk enlargement with homogeneous enhancement. Whole-body imaging revealed extensive lymphadenopathy. Histological examination of lymph node and lung biopsy specimens revealed non-necrotizing granulomas, indicative of sarcoidosis. Salivary gland biopsy and autoantibody testing confirmed the presence of concomitant SjD. Hormone replacement therapy markedly improved pituitary enlargement and pituitary hormone secretion, allowing the discontinuation of replacement therapy after 137 days. However, despite the improvement in pituitary and lymph node lesions, interstitial pneumonia subsequently developed due to SjD, necessitating systemic immunosuppressive therapy. In conclusion, this case demonstrates a rare overlap between sarcoidosis presenting with hypopituitarism and SjD, in which pituitary lesions improved, but immune activity progressed in other organs. Thus, immune-mediated disease activity may differ between organs in overlapping syndromes, and pituitary lesions in sarcoidosis do not necessarily parallel systemic disease activity.

Liddle syndrome is a rare monogenic form of hypertension that can be misdiagnosed as essential hypertension or, in the context of obesity, be mistaken for metabolic syndrome. This case report describes a 19-year-old Chinese male with obesity, hypertension, insulin resistance, impaired glucose tolerance, dyslipidemia, and hyperuricemia-a classic presentation of metabolic syndrome. However, the early onset of severe hypertension and a strong family history prompted further investigation. Laboratory evaluation revealed mild hypokalemia, suppressed plasma renin activity and normal aldosterone levels, raising suspicion for Liddle syndrome. Whole exome sequencing was performed to explore monogenic causes of hypertension, which identified a novel heterozygous frameshift variant in the SCNN1B gene (NM_000336.3:c.1711_1713delinsAA). This variant leads to the loss of the PY motif-a functionally critical and indispensable structural element of the epithelial sodium channel (ENaC) β-subunit-and was classified as likely pathogenic in accordance with the ACMG/AMP guidelines. The patient was initiated on targeted therapy with amiloride, which rapidly normalized his blood pressure and hypokalemia, thereby confirming the diagnosis. This case highlights the diagnostic challenge of distinguishing monogenic hypertension from metabolic syndrome in young, obese individuals. It emphasizes the necessity of systematically investigating for secondary causes in this population. Key steps include obtaining a family history, screening for hypokalemia, evaluating renin and aldosterone levels, and assessing the response to standard therapy. Identifying a rare disorder like Liddle syndrome allows for a paradigm shift in management from empiric to targeted treatment, which is essential for preventing the debilitating long-term sequelae of chronic hypertension.

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 (PVHOxt), thereby suppressing sugar appetite. We previously reported that the low-calorie rare sugars d-allulose, d-tagatose, and d-sorbitol induce FGF21, activate PVHOxt 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.

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.

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.

Osilodrostat is an oral steroidogenesis inhibitor used in the treatment of hypercortisolism. It works by inhibiting 11-beta-hydroxylase, a key enzyme in cortisol synthesis. As a consequence of drug action, adrenal insufficiency can be observed in about 40% of patients. Although this effect has been accepted as a consequence of therapy, recent reports suggest adrenal insufficiency can persist even after discontinuation of osilodrostat. We present the case of a 74-year-old female patient who developed prolonged adrenal insufficiency after withdrawal of osilodrostat. The patient was diagnosed with ectopic ACTH-dependent Cushing’s syndrome and underwent radiotherapy for a primary lesion located in the anterior mediastinum. During treatment, osilodrostat was introduced (2 to 4 mg/d), and adrenal insufficiency developed within four weeks. Hydrocortisone (intermittently dexamethasone) replacement therapy was initiated, and over time, undetectable morning cortisol levels continued. After de-escalating the osilodrostat dose, the drug was withdrawn 15 months after initiation. Despite being off the drug for 11 months, the patient with adrenal insufficiency (morning serum cortisol: 37.2 nmol/L), still requires hydrocortisone substitution. The underlying mechanism of prolonged adrenal insufficiency after osilodrostat discontinuation remains unclear. It is unknown whether this is due to permanent inhibition of 11-beta-hydroxylase or interference at another step in steroidogenesis. Factors such as treatment duration, dose, or individual sensitivity may play a role, but other mechanisms, such as an adrenolytic effect, should also be considered. We expect an increase of similar cases, which we believe will lead to further research to better understand the mechanisms behind prolonged adrenocortical blockade after osilodrostat discontinuation.

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.

Obesity resulting from long-term sedentary a significant threat to human health. This study explores the effects of exercise snack intervention on body composition and plasma metabolomics in sedentary obese adults. Participants in the snack group were subjected to 4 days of sprint exercises by stair-climbing per week for 12 weeks. Systemic and regional fat mass, epicardial adipose tissue (EAT), abdominal visceral (AVFA) and subcutaneous (ASFA) fat area and plasma metabolomics data were measured before and after intervention. A higher improvement of EAT, AVFA and ASFA in the snack group compared to that in the control group, with a significant interaction effect (p < 0.05). The key differential metabolites between the two groups include isoleucine, glycine and serine. The proposed exercise snack effectively reduced the amount of AVFA and EAT. The change in body composition may be associated with the altered pathways of isoleucine, glycine, and serine metabolism.