Cushing’s disease is a rare endocrine disorder that presents many systemic complications, and its initial phase management can be difficult in atypical and severe cases or at institutes with limited experience. It is a disease in which several complications may have already progressed at the time of diagnosis, and complications may become more severe during the initial management phase, potentially becoming life-threatening. In addition, many patients are young, and depending on this phase management, their quality of life will significantly decline later on. Therefore, this review summarizes the evidence accumulated to date and outlines strategies for disease management, focusing on the initial stages from detection, diagnosis, and referral of patients to surgery.

Limited real-world data are available on persistence to growth hormone replacement therapy (GHRT) in Japan. Therefore, we used the Japan Medical Data Center claims database to retrospectively investigate persistence with GHRT in patients with pediatric growth hormone deficiency (pGHD). We identified 1,020 patients with pGHD treated with GHRT. The mean age at initial diagnosis was 7.5 ± 3.8 years, and we found a bimodal pattern in age, with peaks at 3 and 12 to 13 years of age; the peaks were more pronounced in male patients. After excluding patients with early withdrawal, 1,016 patients were eligible for persistence analysis. The time to initial treatment discontinuation, i.e., the first prescription-free period of 182 days (6 months) or more, for 50% of the patients was 2,526 days, which was similar to that of treatment completion (2,626 days). Most patients persisted with GHRT until they completed treatment, but 24 out of 1,016 (2.4%) had a treatment discontinuation. The mean proportion of days covered was 89.8%. Being female (hazard ratio [95% CI]: 1.85 [1.36–2.51]) and older age at diagnosis (1.50 [1.41–1.60]) were associated with shorter time to discontinuation. This finding suggests that most patients persist with GHRT until puberty. In conclusion, although most Japanese patients with pGHD appear to persist well with GHRT, some complete GHRT before puberty. Additionally, there are patients diagnosed and starting treatment just before puberty. Therefore, continued efforts towards early referral and diagnosis are important.

We investigated the association between a 500 MBq dose of radioactive iodine treatment (RAIT) and both thyroid nodule volume and thyroid function in patients with a single autonomous functioning thyroid nodule (AFTN). We retrospectively studied 201 patients with an AFTN who received RAIT at a dose of 500 MBq and were followed up for more than 2 years. Thyroid function at diagnosis, thyroid antibody positivity, treatment with antithyroid drugs before RAIT, cystic components of the nodule, and ¹³¹I uptake outside the nodule were assessed. Nodule enlargement was observed in 18 patients (9%), persistent hyperthyroidism in 13 patients (6.5%), and hypothyroidism in 45 patients (22.3%). Nodule volume before RAIT was significantly larger in the nodule enlargement group compared to the non-enlargement group. The risk factors for persistent hyperthyroidism were larger nodule volume and absence of a cystic component in multivariate analysis. The cutoff nodule volume before RAIT for predicting nodule enlargement was 15.5 mL, and for predicting persistent hyperthyroidism was 16.6 mL. Nodule volume decreased to 47% in the first year and continued to gradually decrease thereafter. This study provided long-term outcome data regarding nodule volume change and thyroid function in AFTN patients following single fixed-dose RAIT, and it identified risk factors for nodule enlargement and persistent hyperthyroidism after RAIT. Nodule volume before treatment was a good predictor of treatment response.

This study investigated the role of scutellarin (Scu) and Nrf2 in diabetic atherosclerosis, focusing on their effects on FBXL2 and NLRP3 ubiquitination. Human umbilical vein endothelial cells were treated with high glucose (HG) to model diabetic atherosclerosis in vitro. Cell viability, cytotoxicity, pyroptosis, and inflammatory cytokine levels were assessed, and gene interactions were examined by dual-luciferase reporter assays. Ubiquitination and protein levels were analyzed through immunoprecipitation and western blotting. The results revealed that HG treatment decreased Nrf2 and FBXL2 levels and enhanced NLRP3-mediated pyroptosis. However, Scu treatment increased Nrf2 expression, improved cell viability, and inhibited pyroptosis. Nrf2 knockdown downregulated FBXL2 and reversed the protective effects of Scu. Additionally, FBXL2 promoted the ubiquitination-mediated degradation of NLRP3 and suppressed pyroptosis. The activation of NLRP3 reversed the protective effects of Scu on diabetic atherosclerosis. These findings suggest that Scu alleviated diabetic atherosclerosis by increasing Nrf2 and FBXL2 expression, promoting NLRP3 ubiquitination-mediated degradation, and suppressing pyroptosis.

In Japan, the guidelines for gestational weight gain (GWG) were revised in 2021. Under the new guidelines, pregnant women are recommended to increase their GWG. The aim of this study was to compare the incidence of adverse pregnancy outcomes (APOs), large for gestational age (LGA), and postpartum glucose tolerance in gestational diabetes mellitus (GDM) patients before and after the revised GWG standards. This retrospective cohort study enrolled 1,021 GDM patients who underwent prenatal glycemic control and a postpartum 75-g oral glucose tolerance test. The endpoint was the incidence of APOs, LGA, and postpartum impaired glucose tolerance (IGT) and diabetes mellitus (DM). There was no significant difference in the incidence of APOs and postpartum IGT and DM in GDM patients before and after the revised GWG standards. On the other hand, when the new GWG standards were applied to GDM patients, the incidence of LGA increased (adjusted odds ratio [aOR]; 1.764, 95% confidence interval [CI]; 1.180–2.637). In particular, when classified by pre-pregnancy body mass index, the incidence of LGA increased in the obese group (aOR; 5.944, 95% CI; 1.847–19.129). Future prospective cohort studies are needed to verify the efficacy and safety of appropriate GWG in Japanese GDM patients.

The prevalence of obesity is increasing rapidly worldwide, particularly in Asia. Visceral obesity, characterized by intra-abdominal fat accumulation, is a precursor to metabolic syndrome, encompassing hyperglycemia, dyslipidemia, and hypertension, which elevate the risk of atherosclerosis and cardiovascular disease. A visceral fat area (VFA) of ≥100 cm² is a recognized threshold for diagnosing obesity-related metabolic syndrome. This study aimed to identify independent risk factors for VFA ≥100 cm² in middle-aged Chinese individuals from the general population. We analyzed data from 148 participants (mean age: 49.3 ± 10.8 years; 54% male) who underwent health check-ups. VFA and subcutaneous fat area were assessed using computed tomography, while arterial stiffness and fatty liver were evaluated via brachial-ankle pulse wave velocity (baPWV) and abdominal ultrasonography, respectively. Between-group comparisons (VFA ≥100 cm² vs. VFA <100 cm²) were conducted using unpaired t-tests and Mann-Whitney U tests, and logistic regression analysis identified risk factors. Multivariable regression analysis revealed that baPWV ≥1,400 cm/s (odds ratio [OR] = 5.71, p = 0.011), waist circumference ≥85 cm (OR = 5.46, p = 0.026), fasting blood glucose (FBG) ≥100 mg/dL (OR = 5.69, p = 0.030), male sex (OR = 12.79, p = 0.029), and fatty liver (OR = 3.99, p = 0.042) were significant independent risk factors for VFA ≥100 cm². Among these, baPWV ≥1,400 cm/s was the most significant, showing a positive correlation with VFA (r = 0.365, p < 0.001). Visceral obesity (VFA ≥100 cm²) is a critical target for interventions addressing metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and cardiovascular disease, particularly in males.

High-mobility group AT-hook 2 (HMGA2) is a nuclear protein involved in the differentiation and proliferation of epithelial-derived tumors and also considered to be involved in the growth and differentiation of various malignant tumors, including thyroid cancer. Immunohistochemistry (IHC) for HMGA2 has been reported to show diffuse positivity in several follicular thyroid carcinoma (FTC) cases. This study aimed to investigate whether positive immunohistochemical staining for HMGA2 in primary tumors can be used to predict the prognosis and detect prognostic factors in malignant thyroid tumors associated with metastatic recurrence in FTC. Formalin-fixed, paraffin-embedded (FFPE) resected specimens used for the IHC for HMGA2. The association of positive HMGA2 staining with metastasis and recurrence, along with the potential of HMGA2 as a prognostic marker of metastatic recurrence, was statistically determined. HMGA2 staining was positive in most malignant tissues, whereas benign tissues were unstained. HMGA2 staining of the marginal and invasive regions was observed in FTC tissues. The association of HMGA2 staining with metastasis and recurrence was significant (p = 0.018). Kaplan-Meier curves showed an association of negative HMGA2 staining with metastasis and disease-free survival (p = 0.090). Tumor size (>4 cm) and wide invasion were also significant factors (p = 0.043, p < 0.001). The risk ratio without HMGA2 was significantly reduced by 30% compared to that with HMGA2. In primary tumors, positive HMGA2 staining can be used to predict prognosis in malignant thyroid tumors associated with metastatic recurrence in FTC and negative HMGA2 staining may indicate longer disease-free survival after surgery.

The Japan Association of Endocrine Surgery published the first edition of the “Clinical guidelines on the management of thyroid tumors” in 2010 and the revised edition in 2018. The guideline presented herein is the English translation of the revised third edition, issued in 2024. The aim is to enhance health outcomes for patients suffering from thyroid tumors by facilitating evidence-based shared decision-making between healthcare providers and patients, as well as standardizing the management of thyroid tumors. The focus is on adult patients with thyroid tumors, addressing clinically significant issues categorized into areas such as an overview of the diagnosis and treatment of thyroid nodules, treatment strategies by histological type, radioactive iodine therapy, treatment of advanced differentiated carcinoma, pharmacotherapy, and complications and safety management associated with thyroid surgery. Thirty-two clinical questions were established in these areas. Following a comprehensive search of the literature and systematic review to evaluate the overall evidence, we aimed to present optimal recommendations by considering the balance of benefits and harms from the patient’s perspective. We integrated evidence and clinical experience to determine the “Certainty of evidence” and “Strength of recommendations”. Based on these, we illustrated overall flows of care as “Clinical algorithms”. Necessary background knowledge of diseases and established clinical procedures for understanding the recommendations are presented in “Notes”, while information that may be clinically useful but for which evidence remains insufficient is included in “Columns”, based on the current state of evidence. Finally, future challenges for the next revision are presented as “Future research questions”.

Serum thyroglobulin (Tg) levels are highly sensitive and specific tumor markers in patients with thyroid cancer who have undergone total thyroidectomy and radioiodine (RAI) therapy. Recently, we reported a case wherein serum Tg levels fluctuated according to hemoglobin A1c (HbA1c) levels, demonstrating a strong correlation between serum Tg and HbA1c levels. However, whether this association exists broadly in other patients with thyroid cancer remains unclear. Therefore, we retrospectively investigated this association in six patients with thyroid cancer and diabetes who underwent total thyroidectomy and RAI therapy at our institution. Two patients exhibited a significant correlation between serum Tg and HbA1c levels (r = 0.53, p < 0.01 and r = 0.66, p = 0.01). In these patients, a gradual decrease in serum Tg levels was observed, along with improved glycemic control. Two other patients showed a non-significant correlation between serum Tg and HbA1c levels (r = 0.72, p = 0.11 and r = 0.54, p = 0.17). In these patients, a rapid increase in serum Tg levels was observed, with HbA1c levels showing only small fluctuations. In the remaining two patients, no correlation was found; in these patients, the fluctuations in serum Tg levels were only small, despite fluctuations in HbA1c levels. In conclusion, serum Tg levels may be associated with HbA1c levels in some patients with thyroid cancer and diabetes. The correlation between serum Tg and HbA1c levels was more evident in patients with gradual fluctuations in Tg levels. Future studies with larger cohorts are necessary to clarify the underlying mechanism by which glycemic control influences Tg levels and establish appropriate monitoring methods.