Journal of Endocrinological Investigation最新文献

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.

Purpose: The genetic background and catecholamine phenotype of pheochromocytomas and paragangliomas (PPGLs) influence the age at diagnosis. However, few studies have systematically investigated clinical features of older patients with PPGLs. This study was based on one of the largest PPGL cohorts in China and aimed to summarize the clinical and genetic characteristics of older PPGL patients, especially concerning intraoperative hemodynamics and genetic background.

Methods: This retrospective study involved 897 patients with abdominal PPGLs from two Chinese centers. DNA from tumor samples was sequenced using next-generation sequencing. Clinical information, intraoperative hemodynamic data, and pathogenic variants were collected and compared between younger (≤ 50 years) and older (> 50 years) patients.

Results: Older patients had a higher rate of incidental tumors (40.5% vs. 48.2%, P = 0.022), fewer typical catecholamine-related symptoms (49.8% vs. 42.4%, P = 0.032), lower plasma normetanephrine levels (7.61 vs. 5.17, P = 0.003) and higher proportion exceeding the normal glycemic range (21.7% vs. 34.4%, P = 0.01) compared to younger patients. The proportion of older patients receiving α-adrenergic receptor blockers for preoperative preparation decreased to 74% compared to 82.4% in younger patients (P = 0.003). During surgery, older patients showed hemodynamic changes indicative of vascular and cardiac aging. Specifically, older patients had lower minSBP, DBP, minMAP, and heart rate, while the SBP fluctuation was higher (P = 0.008). Additionally, younger patients have significantly higher mutation rates for SDHB (5.5% vs. 1.0%, P < 0.001) and VHL (13.3% vs. 7.3%, P = 0.003). HRAS mutations are more prevalent in older patients (10.5% vs. 21.3%, P < 0.001). IDH1 mutations occurred exclusively in older patients (0.56%, 5/887).

Conclusion: Older patients with PPGLs have unique clinical and genetic characteristics. These differences highlight the importance of personalized diagnosis and treatment for various age groups, particularly in developing preoperative preparation strategies to improve vascular and cardiac function in older patients.

Purpose: Subtotal parathyroidectomy (STP) is the preferred surgery for MEN1-related primary hyperparathyroidism (PHPT), balancing recurrence and complication risks. MEN1-negative patients show a milder disease course, supporting the hypothesis that post-operative outcomes may also differ between MEN1-positive and MEN1-negative patients.

Methods: We conducted a retrospective study of 101 MEN1 patients undergoing parathyroidectomy to compare PHPT outcomes by genetic status and surgical approach. MEN1-positive patients mainly received total parathyroidectomy (TP) or STP, while MEN1-negative patients underwent less than subtotal parathyroidectomy (LSTP).

Results: No significant differences were found between MEN1-positive and MEN1-negative patients in remission (p = 0.423), recurrence (p = 0.509) or persistence (p = 0.814) rates, regardless of surgical approach. Chronic postsurgical hypoparathyroidism occurred only in MEN1-positive patients (12.7%). In a sub-analysis of LSTP cases, MEN1-negative patients showed significantly better outcomes, with higher remission (47.6% vs. 16.6%, p = 0.01), and lower recurrence and persistence. Among MEN1-positive patients, TP or STP led to better outcomes compared to LSTP, with higher remission (60.5% vs. 16.7%, p = 0.00005), and lower recurrence and persistence. Recurrence occurred earlier after LSTP (84.0 vs. 160.0 months, p = 0.032).

Conclusions: MEN1 genetic status and surgical strategy both shape PHPT outcomes. MEN1-positive patients benefit from more extensive surgery, performed at high-volume centers, whereas MEN1-negative patients have more favorable outcomes with limited resections, though their remission still trails that of sporadic PHPT. These differences underscore the need for individualized surgical planning.

Purposes: Controversy has emerged regarding the impact of non-nutritive sweeteners (NNS) on body weight. This systematic review and meta-analysis of randomized controlled trials aims to assess the effect of NNS intake on body weight change.

Results: Of the 3327 studies retrieved, 19 met the eligibility criteria for inclusion in the meta-analysis. Compared to the control group, the experimental group that replaced daily caloric sugars with NNS showed significant weight change (MD = -0.79 kg; 95% CI: [-1.55, -0.04]; P = 0.04; I² = 84) When grouped by study duration, the effect of NNS intervention on weight change was significant in studies lasting less than 18 weeks (MD = -0.91 kg; 95% CI: [-1.70, -0.12]; P = 0.02), but minimal in studies longer than 18 weeks (P = 0.51). According to the weight status of the participants, the effect of NNS on body weight was statistically significant only in the normal weight group (MD = -0.97 kg; 95% CI: [-1.40, -0.54]; P < 0.01) and the mixed weight group (comprising normal and overweight individuals) (MD= -1.59 kg, 95% CI: [-2.62, -0.57]; P < 0.01), not in the obese group (MD = -0.646 kg; 95% CI: [-1.839, 0.546]; P = 0.29). In the comparator group, NNS had a greater effect only when compared with caloric sugars (MD= -0.94 kg, P = 0.04). Significant weight differences were also observed in the population with diabetes (MD = -1.56 kg, P < 0.01), but not in the nondiabetic population.

Conclusion: Our study indicates that replacing sugar with NNS leads to weight loss, particularly in normal-weight participants who received the intervention for less than 18 weeks and those with diabetes. For the overweight, it is still advisable to focus on active weight intervention strategies, using NNS only as an auxiliary measure to replace the caloric sugars in the daily diet during weight intervention. This information can inform evidence-based clinical decision-making.