Hypokalemia is a common and potentially life-threatening complication of continuous intravenous insulin infusion (CII) in patients with hyperglycemic crises. However, no simple quantitative indicator can estimate the risk of hypokalemia at treatment initiation. This multicenter retrospective cohort study enrolled patients hospitalized for hyperglycemic crises who received CII. Clinical data available at CII initiation were collected. Machine-learning techniques were primarily employed for feature selection and model comparison to develop a simple, clinically interpretable prediction model. A logistic regression-based indicator was constructed using the most contributory variables and validated internally and externally. Hypokalemia was defined as a serum potassium level <3.5 mmol/L. The model-building and external validation cohorts included 99 and 55 patients, respectively. Among multiple candidate models, a lightweight logistic regression model using only two variables, serum potassium level and insulin infusion rate per body weight, was selected for clinical applicability. In internal validation, the model demonstrated good discriminative performance (receiver operating characteristic-area under the curve [ROC-AUC] 0.821). When applied to the external validation cohort, the ROC-AUC was 0.655, and accuracy decreased slightly. A lower threshold may increase sensitivity in screening, whereas a higher threshold may improve specificity. In conclusion, this study presents a simple and clinically applicable indicator for predicting CII-related hypokalemia using only two routinely available variables at treatment initiation. This model supports individualized electrolyte monitoring during the acute management of hyperglycemic crises. Additionally, it may facilitate safer and more efficient clinical decision-making without reliance on complex algorithms.

Renal dysfunction is an important complication of primary hyperparathyroidism (pHPT). However, the factors associated with a decline in estimated glomerular filtration rate (eGFR) in patients with pHPT have not been fully investigated. This study aimed to identify the factors associated with reduced eGFR at diagnosis in patients with pHPT, and the determinants of longitudinal eGFR decline among those with follow-up data. Eighty-nine patients with pHPT were categorized by renal function at diagnosis. In addition, the annual eGFR decline rate was assessed in 47 patients with more than one year of follow-up. Clinical and biochemical variables were analyzed to determine their association with renal function. Compared with the normal renal function group, the reduced renal function group (eGFR <60 mL/min/1.73 m2) had higher age, and uric acid levels, lower diastolic blood pressure, daily urinary calcium (Ca) excretion, and % tubular reabsorption of phosphate (%TRP). In the multivariable logistic regression analysis, a low %TRP remained significantly associated with reduced renal function at diagnosis. Patients with an eGFR decline faster than -3 mL/min/1.73 m2 per year had significantly higher serum chloride and 25-hydroxyvitamin D levels, and lower HbA1c levels than those with a slower decline. Logistic regression analysis showed, that higher serum chloride levels were associated with a faster annual decline in eGFR. In conclusion, reduced eGFR at pHPT diagnosis was associated with lower %TRP, whereas a faster annual eGFR decline was associated with higher serum chloride levels.

Malignant transformation in multiple endocrine neoplasia type 2 (MEN2)-associated pheochromocytoma is rare, and there have been few reports of treatment with 131I-metaiodobenzylguanidine (MIBG) therapy. Here, we describe a 47-year-old woman diagnosed as having bilateral pheochromocytoma with medullary thyroid carcinoma. Genetic testing confirmed the MEN2A subtype with the pathogenic variant p.C634Y in the RET oncogene. She underwent total thyroidectomy due to medullary thyroid carcinoma with elevated calcitonin levels as high as 1,380 pg/mL, classified as pT2N0M0, stage I. Plasma noradrenaline levels were significantly elevated, and abdominal computed tomography showed bilateral tumors of up to 6 and 2 cm in the right and left adrenal glands, respectively. She underwent right adrenalectomy and left partial adrenalectomy. Pathological examination confirmed bilateral pheochromocytoma, with Ki-67 indices of 2% and 12% in the left and right adrenal tumors, respectively. Calcitonin and catecholamine levels decreased after surgery. Seven years later, elevated plasma-free normetanephrine levels along with multiple metastases in the liver, spine, and pelvis on MIBG scintigraphy were indicative of metastatic pheochromocytoma. She underwent 131I-MIBG therapy with a dose of 7.6 GBq. Despite no significant change in metastatic or left adrenal tumor size, normetanephrine levels decreased from 1,210 to 437 pg/mL, and the patient has remained stable for more than 2 years after treatment without tumor growth. The malignant potential of MEN2A-associated pheochromocytoma emphasizes the need for accurate informed consent, especially when performing partial adrenalectomy. While 131I-MIBG therapy appears promising, its efficacy requires further assessment due to the limited number of reported cases of MEN2A-associated metastatic pheochromocytoma.

This study aimed to investigate the clinical efficacy and safety of dabrafenib plus trametinib for BRAFV600E-mutated advanced thyroid carcinoma in a Japanese real-world setting. We analyzed 37 BRAFV600E-mutated advanced thyroid carcinoma patients treated with dabrafenib plus trametinib between November 2023 and July 2025. Thirty-one patients (84%) had papillary thyroid carcinoma (PTC) histology, one (3%) had poorly differentiated thyroid carcinoma (PDTC) histology, and 5 (13%) had anaplastic thyroid carcinoma (ATC) histology. Among 31 PTC patients, dabrafenib plus trametinib was initiated as first-line treatment in 16 patients. The most common previous systemic therapy was lenvatinib (n = 16, 43%). The most common sites of target lesion were the lung (n = 23, 62%) and lymph node (n = 23, 62%). The median sum of the diameters of the target lesion was 40 mm (range, 8-166 mm). The objective response and disease control rates were 29% and 74% in patients with PTC, and 50% and 83% in patients with non-PTC (PDTC and ATC), respectively. The 12-month progression-free survival rates in patients with PTC and non-PTC (PDTC and ATC) were 73.2% (95% confidence interval [CI], 48.7-87.4%) and 60.0% (95% CI, 12.6-88.2%) (hazard ratio, 2.769; 95% CI, 0.691-11.1; p = 0.134), respectively. Dabrafenib plus trametinib treatment showed a response rate similar to that observed in clinical trials for BRAFV600E-mutated advanced thyroid carcinoma in this real-world study. However, long-term follow-up is required to determine the efficacy of dabrafenib plus trametinib treatment.

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.

Familial partial lipodystrophy (FPLD) is a rare inherited disorder characterized by limb adipose tissue atrophy and metabolic abnormalities, including severe insulin resistance. However, diagnosis is often delayed because the characteristic physique can be difficult to recognize without a high index of suspicion. We present the case of a 19-year-old Japanese woman diagnosed with FPLD type 2 (FPLD2). She had a history of irregular menses and hirsutism since adolescence. The FPLD2 diagnosis was prompted by her concerns about axillary and inguinal pigmentation. Her mother's online search first suggested acanthosis nigricans (AN). After including "muscular limb" as an additional search term, they suspected lipodystrophy, prompting a consultation with an endocrinologist. Clinical examination revealed impaired glucose tolerance, severe insulin resistance, dyslipidemia, fatty liver, and polycystic ovary syndrome. Genetic testing identified a heterozygous LMNA p.R482Q variant, confirming the diagnosis. This case demonstrates that AN, a skin manifestation of insulin resistance, is an important diagnostic clue for FPLD. Although women with FPLD frequently present with menstrual irregularities and hirsutism in their late teens, their insulin levels are rarely measured before diabetes onset. Consequently, the underlying severe insulin resistance is frequently overlooked. Although reported cases of FPLD2 in Japan are limited, many cases may remain undiagnosed. Therefore, clinicians should examine the friction-prone areas in non-severely obese individuals with metabolic or menstrual irregularities. The absence of AN does not rule out insulin resistance. Therefore, even without AN, the presence of other features of insulin resistance warrant consideration of FPLD and careful evaluation for limb fat loss, facilitating early diagnosis.

This report describes the case of a 44-year-old woman without structural heart disease who developed ventricular fibrillation (VF) during preoperative management of multiple pancreatic neuroendocrine tumors (NETs) associated with multiple endocrine neoplasia type 1. She had an insulinoma in the uncinate process and a non-functioning NET in the pancreatic tail. Immediately after intravenous glucose administration for recurrent hypoglycemia, VF occurred. An electrocardiogram obtained immediately before VF onset showed repolarization abnormalities with marked QTc prolongation, terminal T-wave bulging, and U waves. Laboratory testing revealed concomitant mild hypokalemia. No coronary artery disease was detected. The severe repolarization abnormalities improved after resection of the insulinoma. The presumed mechanism was that mild hypokalemia and recurrent hypoglycemia, together with hypoglycemia-induced epinephrine surge and extracellular-to-intracellular potassium shift, synergistically prolonged the action potential duration and induced early afterdepolarizations, which progressed from torsades de pointes to VF. This case highlights that unstable glycemic control in insulinoma can precipitate life-threatening arrhythmias, even in the absence of structural heart disease. Particularly when surgery is delayed, maintaining serum potassium as 4.5-5.0 mmol/L and preventing recurrent hypoglycemia are crucially important. Early recognition and intervention might help reduce arrhythmic risk in such patients.

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.

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.