The meibomian glands play a central role in maintaining ocular surface homeostasis by producing meibum, which is the lipid layer of the tear film that suppresses tear evaporation. Dysregulation of the secretion of this lipid leads to meibomian gland dysfunction (MGD), the most common cause of evaporative dry eye disease. Accumulating evidence indicates that androgen signaling is a critical regulator of meibomian gland structure and function. In contrast to classical endocrine mechanisms, androgen action in this tissue is largely mediated by intracrine steroid metabolism, whereby circulating adrenal precursors are locally converted to active androgens within the gland. Key steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), are expressed in the meibomian acinar cells, thereby enabling local testosterone production. Simultaneously, the gland exhibits robust metabolic pathways that convert testosterone to downstream androstane derivatives, providing a mechanism for the spatially restricted control of androgen signaling. Recent study has revealed that the intracrine steroidogenic system is affected by circadian rhythms. In particular, 3β-HSD activity exhibits daily rhythmicity that parallels fluctuations in nicotinamide adenine dinucleotide (NAD⁺), suggesting that NAD⁺-dependent metabolic processes contribute to temporal control of local androgen production. Importantly, administration of NAD⁺ precursors improves meibomian gland morphology in experimental models of aging-associated MGD. This review summarizes the current knowledge on intracrine androgen metabolism in the meibomian gland and highlights emerging metabolic and circadian mechanisms that may provide novel therapeutic targets for dry eye disease.

Differentiating painless thyroiditis (PT) from Graves’ disease (GD) is important for appropriate management. This study evaluated whether thyroid-stimulating hormone (TSH) receptor antibody (TRAb)-positive PT can be differentiated from GD using biochemical and ultrasound findings. This retrospective study included 1,924 patients with thyrotoxicosis associated with PT or GD who visited Kuma Hospital between November 2020 and September 2023. TRAb titers and radioactive iodine uptake (RAIU) or technetium-99m pertechnetate (^99mTc) uptake were measured in all patients. Patients were classified into TRAb-positive PT (n = 16), TRAb-negative PT (n = 222), and GD (n = 1,686). Serum alkaline phosphatase (ALP), TSH, free triiodothyronine (FT3)/free thyroxine (FT4) ratio, and thyroid blood flow were analyzed. No significant differences were observed between TRAb-positive and TRAb-negative PT in any single parameter. TRAb-positive PT significantly differed from GD in ALP (mean: 74.6 vs. 111.5 IU/L, p < 0.05), TSH (median: 0.037 vs. 0.007 μIU/mL, p < 0.001), FT3/FT4 ratio (mean: 2.54 vs. 3.30, p < 0.001), and blood flow (mean: 2.11% vs. 11.60%, p < 0.05). A scoring system assigned one point to each parameter—ALP above the upper limit, TSH below the detection limit, FT3/FT4 ratio >3.00, and blood flow >4.00%. None of the patients with TRAb-positive PT scored ≥3, compared with 65.7% of patients with GD. TRAb-positive PT can be differentiated from GD using combined biochemical and ultrasound markers. Our practical scoring system supports clinical decision-making when RAIU is not readily available or contraindicated and may help avoid unnecessary antithyroid therapy.

Telomeres maintain genomic integrity during cell replication by preventing chromosomal fusions. Beside genetic influences, telomere length is affected by environmental factors such as oxidative stress and inflammation. These mechanisms also contribute to metabolic syndrome components linked to cellular aging. We aim to evaluate whether telomere length is shortened in patients with non-functional adrenal incidentaloma (NFAI) compared to the control group. This study was designed as a prospective, single-center study. The total of 88 participants included were 44 patients aged between 40 and 60 years with NFAI in our endocrinology clinic and 44 control subjects. An Absolute Human Telomere Lengths Quantification qPCR Assay kit (Nucleotestbio, Budapest, Hungary) was used for analyses. There was no significant difference between the NFAI and control groups regarding age and sex distribution. Telomere length was significantly shorter in the NFAI group (NFAI group: 3.680 ± 1.970 kb; control group: 4.469 ± 1.672 kb; p = 0.046). While no significant difference was found in telomere lengths in subgroup analyses, patients with basal adrenocorticotropic hormone (ACTH) levels <15 pg/mL had significantly shorter telomeres than those with basal ACTH levels ≥15 pg/mL (p = 0.034). A strong positive correlation was observed only between telomere length and ACTH level (p = 0.001). This study demonstrated that telomere length is significantly shortened in NFAI patients. Here, we propose that the underlying cause of telomere length shortening in the NFAI group may be related to increased cardiovascular risk and an elevated inflammatory state, even in the presence of cortisol levels within the normal range.

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.

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.

Gender equity has become an important issue in academic medicine, but data on gender distribution in subspecialty medical societies remain limited. We analyzed gender distribution in membership, leadership positions, and conference participation in the Japanese Society for Hypothalamic and Pituitary Tumors (JSHPT). Membership data as of March 2025 (n = 860) were examined, and gender distribution among speakers and session chairs at the 36th Annual Meeting of the JSHPT was evaluated using the publicly available abstract book. Among all members, 128 (14.9%) were women. Women accounted for 6.6% of councilors and 5.6% of board members and auditors, and only one woman has served as Annual Meeting president among the first 36 annual meetings. At the 36th Annual Meeting, women represented 18.6% of presenters in general oral sessions, but only 5.0% of session chairs in general oral sessions and 3.7% of chairs in other sessions. Women also accounted for 36.4% of members with less than 1 year of membership. These findings suggest that, although women remain underrepresented in leadership positions within the society, female participation may be increasing among newer members, and women are actively participating as conference presenters. Continued efforts to increase opportunities for women to serve as session chairs and to encourage qualified women to apply for councilor positions may contribute not only to a more equitable academic environment, but also to the vitality and future leadership of the field.

Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), may coexist with Type 1 diabetes mellitus (T1DM) as autoimmune polyglandular syndrome type 3 (APS3). Sialic acid-binding immunoglobulin-like lectin (SIGLEC) 1 is an interferon-inducible molecule implicated in autoimmune disorders, but its clinical significance across AITD, T1DM, and APS3 remains unclear. In this cross-sectional study, 219 patients with AITD, T1DM, or APS3 were enrolled. SIGLEC1 mRNA levels derived from peripheral blood cells were quantified using quantitative reverse transcription PCR. In the primary analysis, 213 patients with SIGLEC1 mRNA levels were included (AITD-only, n = 127; T1DM-only, n = 59; APS3, n = 27). SIGLEC1 mRNA levels differed significantly among the three groups (p = 0.00086). Holm-adjusted post hoc comparisons showed significantly higher SIGLEC1 mRNA levels in the T1DM-only group and APS3 group than in the AITD-only group (p = 0.0099 and p = 0.0099, respectively), whereas the T1DM-only and APS3 groups did not differ significantly (p = 0.289). Within the AITD-only cohort, thyroid autoantibody-positive patients had higher SIGLEC1 mRNA levels than antibody-negative patients (median 130.1 vs. 74.4 copies, p = 0.034). SIGLEC1 mRNA levels showed a modest positive correlation with HbA1c (r = 0.210, p = 0.0060) but not with thyroid function parameters. In multivariable models, APS3 remained independently associated with higher SIGLEC1 mRNA levels after adjustment for age, sex, and HbA1c. Elevated SIGLEC1 mRNA levels were associated with coexisting endocrine autoimmunity and thyroid autoantibody positivity in this cohort. Longitudinal studies are required to determine whether SIGLEC1 mRNA levels have prognostic or predictive utility.

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.

Amyloid spherule-containing prolactinomas are rare entities associated with dopamine agonist (DA) resistance and aggressive behaviour. We report a giant amyloid spherule-containing prolactinoma with a substantial tumour burden and markedly elevated prolactin levels, highlighting novel multimodal therapeutic strategies. A 49-year-old man presented with headache and visual disturbance. Imaging revealed a giant pituitary macroadenoma (63 × 84 × 46 mm) with Knosp grade 4 cavernous sinus invasion and clivus erosion. Laboratory investigations revealed marked hyperprolactinemia (prolactin (PRL): 30,969 ng/mL) and autonomous growth hormone (GH) hypersecretion. Histopathology confirmed a sparsely granulated lactotroph tumour with extensive amyloid spherules and dystrophic calcifications (Ki-67: 8%). Notably, immunohistochemistry demonstrated PRL positivity without GH immunoreactivity, suggesting tumour heterogeneity with sampling limitations. Comprehensive systemic amyloidosis screening, the first systematic evaluation reported for this entity, excluded systemic disease. Following surgical debulking with extensive residual disease, postoperative cabergoline treatment resulted in a reduction in the PRL (4,700→927 ng/mL). Given the presence of amyloid-associated dopamine resistance, cabergoline was discontinued, and radiotherapy (RT) (45 Gy) was initiated to control the amyloid burden, followed by temozolomide. Based on evidence from other malignancies suggesting RT-mediated amyloid reduction, cabergoline was reintroduced postradiotherapy without paradoxical tumour growth. Concurrent cabergoline-temozolomide therapy, a novel approach that differs from conventional sequential protocols, achieved a dramatic response: 93.4% prolactin reduction (10,320→677 ng/mL) and 52.4% tumour volume reduction. This superior outcome far exceeded that of initial postsurgical cabergoline monotherapy (80% reduction), suggesting that RT successfully modulated the amyloid burden and restored dopamine sensitivity. This case suggests that RT may restore dopamine agonist sensitivity in patients with amyloid-containing prolactinomas, potentially enabling concurrent dopamine agonist–temozolomide therapy in refractory cases, warranting further validation.