Journal of Endocrinological Investigation最新文献

Purpose: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and central precocious puberty (CPP) in children, with emphasis on sex-specific threshold effects and mediation pathways.

Methods: This cross-sectional study enrolled 494 CPP patients (female: 413; male: 81) and 2,259 age-matched healthy controls who underwent ​liquid chromatography-tandem mass spectrometry (LC-MS/MS) based 25(OH)D quantification, Tanner-Whitehouse 3 bone age assessment, and hormonal profiling. Dose-response relationships were analyzed via restricted cubic splines (RCS), and causal mediation analysis with 1,000 bootstrap resamples were quantified using structural equation models.

Results: CPP patients exhibited significantly lower 25(OH)D levels than controls (median (IQR): females, 20.00 (14.00-24.20) vs. 23.40 (18.10-29.22) ng/mL, P < 0.001; males, 21.60 (16.00-27.10) vs. 23.30 (18.30-28.83) ng/mL, P = 0.033), with higher deficiency rates (females: 49.6% vs. 33.0%; males: 43.2% vs. 32.8%). RCS analysis revealed inverse 25(OH)D-CPP associations, with threshold concentrations at 35.4 ng/mL (females) and 19.5 ng/mL (males).​ Each 1 ng/mL increment in serum 25(OH)D was associated with 3.6% reduced risk of advanced pubic hair maturation (adjusted OR = 0.964, P = 0.009). Sex-stratified logistic regression showed elevated CPP risks in vitamin D-insufficient/deficient groups versus sufficient counterparts: females (OR = 2.13, P = 0.037; OR = 2.26, P = 0.030) and males (OR = 3.89, P = 0.059; OR = 4.71, P = 0.034). Mediation analysis identified bone age acceleration (64.6% mediation) and gonadotropin activation (14.6%) dominated pathways in females.

Conclusion: Vitamin D demonstrated sex-dimorphic associations with CPP risk, requiring higher protective thresholds in females. Bone age acceleration and gonadotropin activation emerged as primary mediators in females. These findings advocated sex-specific vitamin D supplementation strategies for CPP prevention.

Exercise associated hyponatremia (EAH) is a medical condition that can occur during physical exertion. Initially, EAH was considered to be restricted to extreme endurance activities, such as ultramarathons and Ironman triathlons. However, it has been more recently recognized in a variety of sports, including team sports and in shorter-duration events. The pathophysiology of EAH is multifactorial and includes excessive fluid intake and non-osmotic arginine vasopressin secretion, which is induced by physical activity. Sodium loss through sweat appears to play a less important role in contributing to EAH. The clinical presentation may vary, depending on the degree of serum sodium reduction. Symptoms, which are due to increased intracranial pressure, may vary from nausea, vomiting, headache, confusion to severe alterations in cognitive functions, decorticate posturing, respiratory distress, coma and even death. It is of pivotal importance to differentiate EAH from other conditions that may present with similar signs/symptoms, such as for instance hypoglycemia, orthostatic hypotension, vasovagal syncope, heat stroke. The treatment of EAH depends on the severity of symptoms. In life-threatening situations intravenous infusion of hypertonic saline solution (3%NaCl) is recommended. In less severe situations oral hypertonic saline solutions can be administered, as an alternative to intravenous hypertonic saline, when tolerated by patients. When symptoms are negligible, the treatment can be limited to fluid restriction. Effective strategies to prevent EAH would be important to reduce the risk of incurring in potentially life-threatening situations. In particular, recommendations to drink in anticipation of thirst during physical exertions should be replaced by the "drinking when thirsty" strategy.

Purpose: The clinical use of artificial intelligence (AI) is expanding in endocrinology, yet the performance of large language models (LLMs) in managing adrenal incidentalomas remains uncertain. To compare the performance of four LLMs-ChatGPT-4o, ChatGPT-o1, Google Gemini 2.0, and Claude 3.5-on guideline-based queries and clinical scenarios involving adrenal incidentalomas.

Methods: In this cross-sectional study, 34 guideline-derived questions and four case scenarios were presented to the LLMs, covering diagnosis, treatment and follow-up, patient questions, and clinical cases. Six endocrinologists evaluated responses using Likert scales assessing hallucination tendency, quality, usability, reliability, and accuracy. Readability metrics and word counts were also analyzed.

Results: No significant differences were found between models in diagnosis (p = 0.86-0.72), treatment and follow-up (p = 0.46-0.10), and patient question (p = 0.78-0.10) categories. However, in complex cases, ChatGPT-4o outperformed ChatGPT-o1 with higher scores in hallucination control (6.5 ± 0.8 vs. 4.8 ± 0.8), quality (6.2 ± 0.8 vs. 5.0 ± 0.6), and usability (4.5 ± 0.8 vs. 3.3 ± 0.5) (all p < 0.05). Readability analysis revealed high text complexity (Flesch-Kincaid Grade Level: 10.6-17.4), and inter-rater reliability was excellent (intraclass correlation coefficient: 0.876-0.961, p < 0.001).

Conclusion: LLMs show potential as decision-support tools in adrenal incidentaloma management. While their performance is comparable in routine tasks, significant differences arise in complex cases, highlighting the need for model selection, human oversight, and attention to readability in endocrine practice.

Objective: Cushing Disease (CD) presents with typical clinical findings, even though, there is a wide spectrum of manifestations. Over the years, the sings and symptoms of Cushing's syndrome (CS) have become more subtle and atypical forms of CS have emerged. In this study, we aimed to investigate the changes in the clinical presentation of CD in recent years.

Materials and methods: In this study, CD patients followed by our center were examined. A total of 258 patients with CD were included in the study. The clinical findings at the time of presentation, laboratory and imaging findings, treatment modalities and remission status in the first year after treatment were evaluated.

Results: The mean age of the patients included in the study was 41.3 ±13.28 years. CD patients diagnosed between 2013 and 2023 were older than those diagnosed between 1990 and 2012 (p < 0.001). There was no difference between the groups in terms of gender. Moon face, purple striae, hirsutism, and menstrual irregularities were statistically significantly less frequent in the last 10 years than in previous years (p < 0.001; p = 0.004; p < 0.001; p < 0.001, respectively). In addition, patients who applied after 2013 had lower baseline cortisol and adrenocorticotropic hormone (ACTH) levels, and a smaller median size of the pituitary adenoma. Limitations of the study include its retrospective design and the subjectivity of clinical data.

Conclusion: As the clinical presentation of Cushing's disease changes over time, waiting for the typical Cushing's clinic can delay diagnosis. It is important that clinicians take this into account when they suspect CD.

Background: Acne, a chronic inflammatory disease, is influenced by insulin-like growth factor 1 (IGF-1). Acromegaly, characterized by excessive growth hormone (GH) and IGF-1, is associated with a higher prevalence of acne, though the underlying mechanisms remain unclear.

Objective: This study aims to explore the underlying mechanisms why patients with acromegaly are more susceptible to acne, especially refractory acne.

Methods: An acromegaly rat model was established via biweekly long-acting recombinant human GH (rhGH) injections for eight weeks. Serum levels of GH, IGF-1, and glucose were measured, and skin pathology was examined. Immunohistochemistry, transcriptomics, and proteomics were performed to explore molecular pathways, with RT-qPCR and western blot validation.

Results: Serum GH and IGF-1 levels significantly increased from week 3 and remained elevated throughout the study in the rhGH-treated group. Acneiform lesions, including epidermal hyperkeratosis, sebaceous gland hyperplasia, and dermal thickening, were observed. Immunohistochemical analysis revealed upregulation of IGF-1, IGF-1R, SREBP1, and IL-1β. Transcriptomic and proteomic analyses identified 1,112 differentially expressed genes and 440 differentially expressed proteins, underscoring the activation of inflammation, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), and cell proliferation through PI3K/Akt pathways. Significant upregulation of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) was observed in both transcriptomic and proteomic analyses.

Conclusion: Chronic GH stimulation leads to persistent IGF-1 elevation, promoting acne by increasing IGF-1R expression and disrupting ECM remodeling via PI3K/Akt-regulated MMPs and TIMP-1. These findings help clarify the link between acromegaly and acne and provide mechanistic insights into the role of IGF-1 in acne pathogenesis.

Purpose: Thyroid Eye Disease (TED) is the most common thyroid-related autoimmune inflammatory disorder. Despite a surge in TED-related publications over the past five years-matching the total output of the preceding sixteen years-a systematic bibliometric analysis remains absent. This study aims to systematically map the knowledge structure, research hotspots, and future trends in TED research.

Methods: Publications related to TED from 2004 to 2024 were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and the R package "Bibliometrix" were utilized for bibliometric analysis.

Results: A total of 4,306 publications from 91 countries, led by the United States and China, were included. The number of TED publications has shown a consistent upward trend. The leading research institution was the University of Pisa. Among scientific journals, the Journal of Clinical Endocrinology & Metabolism, THYROID, Journal of Endocrinological Investigation, and Ophthalmic Plastic and Reconstructive Surgery, had the highest number of publications. The 15,766 contributing authors were led by Smith, Kahaly, Marino, Yoon, and Marcocci in terms of publication volume. Bartalena was identified as the most frequently co-cited author. TED research focuses foremost on mechanisms (pathogenesis, immunity, autoantibodies), treatment (management, therapy, orbital complications), and epidemiology (prevalence, diagnosis, risk factors). Artificial intelligence, disease activity, hearing loss, teprotumumab, dysthyroid optic neuropathy, inflammation, and magnetic resonance imaging are the primary keywords of emerging research hotspots.

Conclusion: Our study represents the first comprehensive bibliometric analysis of TED, summarizing its knowledge mapping, research hotspots, and frontiers, while providing valuable insights for scholars in the field.