Endocrine最新文献

Purpose: Adrenal crisis (AC) is the most severe manifestation of primary adrenal insufficiency (PAI) and is associated with high mortality. Its insidious presentation often leads to a delayed diagnosis and treatment. In this study, we aim to determine the incidence, characteristics, precipitating and predisposing factors for AC.

Methods: A total of 132 patients with PAI were evaluated retrospectively. Patients' features and information on their previous AC were collected through a structured interview and clinical documentation, supplied by patients or retrieved from archives of the Hospitals of Padova and Venice-Mestre.

Results: Among enrolled patients, 95 (71.9%) were females, the mean age was 48.8 ± 13.5 years, and the mean PAI duration was 14.9 ± 11.8 years. The most frequent cause of PAI was autoimmune adrenalitis (92.4%), mainly associated with other autoimmune comorbidities. The 65.9% of patients experienced at least one AC, with an incidence of 10.5/100 patient-years. A significant number of AC (116/206) occurred in patients already undergoing glucocorticoid therapy. The most frequent features of AC were fatigue (96%), gastrointestinal symptoms (85%), and hyponatremia (77%). The most frequent triggers were vomiting and/or diarrhoea (65%), infections (38%), and emotional stress (29%). Patients with more autoimmune comorbidities and those with premature ovarian insufficiency (POI) were at higher risk of AC (p < 0.02).

Conclusions: AC is still a frequent complication of patients with PAI, particularly in those with additional autoimmune comorbidities or with POI. Awareness of AC among clinicians, patients, and care-givers is crucial for the prevention, recognition, and proper treatment of this life-threatening complication.

Background: Although type 2 diabetes mellitus (T2DM) is common among elderly patients, there are no large studies examining the geriatric status of patients with T2DM.

Aim: To study the characteristics of geriatric status in patients with T2DM aged ≥ 65 years.

Materials and methods: The multicenter EVKALIPT study conducted in 11 constituent entities of the Russian Federation included 4308 patients aged 65-107 years (mean age 78 ± 8 years), who were divided into two groups: with T2DM (n = 935) and without T2DM (n = 3360). All participants underwent a comprehensive geriatric assessment: a survey (step 1) and a physical examination (step 2).

Results: The prevalence of type 2 diabetes was 21.8% (n = 935), predominantly in patients aged 65-74 years. The comprehensive geriatric assessment showed that changes in the geriatric status are more pronounced in T2DM, namely: lower basic activity in everyday life and a lower total score on the Short Physical Performance Battery (SPPB); slower walking speed; lower handgrip strength in women; worse health self-assessment score, higher total score on the geriatric depression scale (GDS-15) and on the questionnaire "Age is not a hindrance;" more pronounced pain syndrome; and the use of a greater number of assistive devices per patient was noted. Geriatric syndromes (GS), which were detected more often in the group with T2DM in comparison without T2DM were: chronic pain syndrome (91 vs 86%, p < 0.001), frailty (67 vs 62%, p = 0.005), basic dependence in everyday life (67 vs 60%, p < 0.001), depression (52 vs 47%, p = 0.004), urinary incontinence (51 vs 44%, p < 0.001), falls (34 vs 30%, p = 0.004%), and pressure ulcers (3.3 vs 2%, p = 0014). Regression analysis demonstrated that T2DM is associated with an increased risk of developing such GS as basic dependence of patients in everyday life, frailty syndrome, pressure ulcers, chronic pain, depression (odds ratio from 1.19-1.78).

Conclusion: Geriatric status was worse in patients with T2DM than in those without T2DM. It has been demonstrated that T2DM adversely affects the physical performance of patients aged 65 years and older.

Highlights: To study the characteristics of geriatric status in patients with T2DM aged ≥ 65 years. T2DM was associated with geriatric syndromes due to worse performance status in patients aged ≥ 65 years. In routine clinical practice, it is necessary to identify geriatric syndromes in patients with T2DM. This will foster patient-centered approach, which undoubtedly contributes to improving the quality of life of elderly patients with T2DM.

Purpose: Postoperative remission in pituitary adenoma (PA) patients significantly affects treatment outcomes and quality of life. Accurate prediction of remission is crucial for neurosurgeons and oncologists as it aids in personalizing treatment plans, optimizing follow-up care, and preventing unnecessary interventions. Unlike diagnostic classification, this review specifically focuses on remission prediction as a distinct prognostic application of AI. This systematic review and meta-analysis aim to evaluate the performance of machine learning (ML) algorithms in predicting remission outcomes in PA patients.

Methods: A comprehensive search of PubMed, Scopus, Embase, Web of Science, and the google scholar was conducted to identify eligible studies until Dec 2024. Data on sensitivity, specificity, accuracy, precision, F1-score, and area under the curve (AUC) were extracted from the included studies.

Results: Out of 1530 studies screened, 10 met our eligibility criteria involving ML approaches in patients with confirmed PA. ML algorithms, particularly artificial neural networks (ANN), offer promising performance for predicting remission outcomes in PA patients. Meta-analysis of 10 studies resulted in a pooled sensitivity of 0.84 (95% CI: 0.74-0.91), specificity of 0.84 (95% CI: 0.74-0.91), positive diagnostic likelihood ratio (DLR) of 0.19 (95% CI: 0.11-0.32), negative DLR of 15.26 (95% CI: 8.23-28.26), diagnostic odds ratio (DOR) of 28.25 (95% CI: 10.85-73.57), the diagnostic score was 3.34 (95% CI: 2.38-4.3) and an AUC of 0.91 (95% CI: 0.88-0.93).

Conclusion: ML-based models demonstrate moderate to high diagnostic accuracy in predicting remission outcomes in PA patients. While these models show promise in enhancing clinical decision-making post-surgery, further prospective validation and larger studies are necessary before their routine clinical integration.

Objective: Preclinical data suggest nitazoxanide (NTZ) as a potential PPAR-γ agonist with potential benefits in type 2 diabetes. This pilot trial aimed to explore the tolerability and preliminary effects of NTZ as an add-on therapy to the existing metformin-vildagliptin combination on glycemic control and inflammatory biomarkers in type 2 diabetes patients.

Methods: Eighty-eight patients were analyzed in the control and NTZ groups (44 per group). All patients were treated with metformin-vildagliptin combination. The NTZ group received 500 mg nitazoxanide orally twice daily. The primary outcome was glycemic control, assessed by glycated hemoglobin (HbA1c) and fasting blood glucose. Secondary outcomes included fasting insulin, serum interleukin-6 (IL-6), high mobility group box 1 (HMGB-1), asprosin, and malondialdehyde (MDA). All outcomes were measured at baseline and after three months.

Results: A between-groups comparison revealed significantly lower inflammatory markers with NTZ compared to control [IL-6: 23.64 ng/L (21.00-32.71) vs. 32.52 ng/L (29.63-36.13) and HMGB-1: 10.46 ng/mL (6.37-14.61) vs. 22.60 ng/mL (20.18-27.37), P < 0.001 for both]. HbA1c, fasting blood glucose, insulin, asprosin, and MDA were not considerably different between the two groups. Markedly lower levels of IL-6 (P = 0.009), HMGB-1 (P < 0.001), asprosin, (P = 0.002), and MDA (P < 0.001) were observed following NTZ treatment. Conversely, IL-6 and HMGB-1 increased significantly in the control group (P < 0.001 for both). Other biomarkers did not change significantly in both groups.

Conclusion: NTZ may alleviate oxidative stress and inflammation in type 2 diabetes despite no improvement in glycemic parameters.

Trial registration: This trial is registered on ClinicalTrials.gov under the name: Nitazoxanide as Adjuvant Therapy in Type 2 Diabetes Mellitus with the identifier: NCT06010992. Registration date: 8-2023.

Background: Papillary thyroid cancer (PTC) is the most common endocrine malignancy, demonstrating the most rapid incidence growth among solid tumors in the past decades. Notably, aggressive variants frequently manifest metastatic potential and therapeutic resistance, substantially compromising poor prognosis. Circular RNAs (circRNAs) have been recognized as pivotal regulators in diverse biological processes across multiple cancer types. However, the molecular mechanism underlying circ_0003997 (circCLMP) in PTC remains largely unexplored.

Methods: The expression levels of circ_0003997, miR-370-3p, and HMGA2 were assessed using real-time quantitative polymerase chain reaction (RT-qPCR). The functions of circ_0003997 were evaluated through CCK-8 assays, wound healing assays, and Transwell assays in PTC cells. Western blotting was used to analyze the expression of key epithelial-mesenchymal transition (EMT) proteins. Tumor development in vivo was assessed using xenograft tumor models. The expression of Ki67 and HMGA2 in tumor tissues was evaluated by immunohistochemical (IHC) assay. Dual-luciferase reporter assays were performed to validate the interactions among circ_0003997, HMGA2, and miR-370-3p.

Results: Circ_0003997 demonstrated significant upregulation in PTC tissues and cells. Functional validation experiments revealed that knockdown of circ_0003997 inhibited cell proliferation, migration, invasion, and EMT, while its overexpression promoted PTC progression. Mechanistically, circ_0003997 modulated HMGA2 expression by sponging miR-370-3p. Rescue experiments demonstrated that the oncogenic effects of circ_0003997 could be reversed by miR-370-3p. In vivo data showed that the decreased expression of circ_0003997 significantly suppressed tumor growth of PTC.

Conclusions: We identified a novel biomarker panel consisting of the circ_0003997/miR-370-3p/HMGA2 axis, offering potential diagnostic and therapeutic avenues for PTC.

Purpose: Randomized clinical trials (RCTs) have shown no benefit of levothyroxine for subclinical hypothyroidism (SCH) in improving well-being, cardiovascular outcomes, or mortality. We aimed to evaluate study procedures' feasibility, safety, and preliminary effects of levothyroxine discontinuation in adults with SCH.

Methods: We conducted a pilot, double-blind, placebo-controlled RCT with 6-month follow-up at a Veterans Affairs Medical Center. Adults with SCH on levothyroxine ≤75 mcg daily were randomized to continue levothyroxine or switch to placebo. The primary outcome was feasibility.

Results: Fifty participants were randomized (32% enrollment rate); five were excluded post-randomization due to unconfirmed SCH, yielding 45 participants (21 levothyroxine, 24 placebo). One patient in the placebo group withdrew for personal reasons (98% completion rate). Participants' mean age was 68.2 years (SD 9.7); 80% were male, and 86.7% were White. At 6 months, there was no statistically significant difference between the placebo and levothyroxine groups in ThyPRO-Hypothyroid Symptoms [28.3 (22.8) vs. 22.9 (19.5)], Tiredness [27.6 (22.8) vs. 32.8 (22.1)], and EQ-5D score [0.750 (0.232) vs. 0.741 (0.180)]. The only notable adverse event was rib fractures in a placebo group participant (TSH 3.04 mIU/L at 6 months). Two participants in the placebo group restarted levothyroxine (n = 1, TSH > 10 mIU/L; n = 1, fatigue).

Conclusion: We demonstrated feasibility of study procedures for discontinuing levothyroxine in patients with SCH and obtained preliminary effects on well-being. The low occurrence of adverse events suggests that levothyroxine discontinuation may be well-tolerated. These findings support conducting a larger multi-site RCT to comprehensively assess the effects of levothyroxine discontinuation.

Clinical trial registration number: NCT04288115.