Endocrine Connections最新文献

Objective: This study aimed to assess the latent threat of depression and suicide/self-injury associated with the combination of glucagon-like peptide-1 agonists (GLP-1RAs) and metformin versus GLP-1RAs monotherapy, through analyzing the data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: We systematically searched the FAERS database for reports on the concomitant use of GLP-1RAs and metformin compared with the GLP-1RAs monotherapy in diabetic or obese patients. Reports were categorized on the basis of the Medical Dictionary for Regulatory Activities (MedDRA) terminology. The signal was considered to be significant when the reporting odds ratio (ROR) and lower limit of 95% CI > 1, and information component (IC)025 > 0, in no less than three patients.

Results: The addition of metformin increased the risk of death (38.5 vs 12.4%, P < 0.001) and hospitalization - initial or prolonged (13.5 vs 7.2%, P = 0.035) attributed to suicide/self-injury in patients who received GLP-1RAs. Furthermore, the combination of GLP-1RAs with metformin was disproportionately linked to a higher incidence of suicide/self-injury (ROR = 50.89, 95% CI: 40.79-63.48, IC025 = 5) and depression (except suicide and self-injury) (ROR = 17.28, 95% CI: 13.65-21.87, IC025 = 3.64) when compared with the GLP-1RAs monotherapy. The addition of metformin was confirmed to have shorter intervals to time-to-onset (TTO) than the GLP-1RAs monotherapy.

Conclusions: The combination of GLP-1RAs and metformin is linked to a higher risk of depression and suicide/self-injury compared with the GLP-1RAs monotherapy.

Objective: Statins are low-density lipoprotein cholesterol-lowering drugs that are highly effective in the prevention of cardiovascular disease and death. Evidence that statin therapy increases the risk of type 2 diabetes is accumulating, but the mechanism behind this phenomenon remains obscure.

Design: A clinical, randomised, placebo-controlled, double-blind, crossover study.

Methods: Here, we investigated the effect of atorvastatin on fasting and postprandial circulating concentrations of glucose, gluco-regulatory hormones, bile acid profiles as well as gut microbiota composition. Fifteen healthy men came in for a mixed meal test following 14 days of treatment with atorvastatin (40 mg once-daily during week one and 80 mg once-daily during week two) or placebo.

Results: Treatment with atorvastatin did not affect postprandial plasma glucose or insulin concentrations, but basal as well as postprandial concentrations of glucagon were increased compared with placebo. Postprandial plasma concentrations of the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were increased after atorvastatin treatment compared with placebo. Also, postprandial concentrations of taurine-conjugated primary bile acids increased, whereas glycine-conjugated secondary bile acids decreased. Microbiota composition was not affected by atorvastatin treatment.

Conclusions: Atorvastatin treatment did not alter glucose or insulin concentrations, nor did it alter gut microbiota composition. However, we found that atorvastatin treatment increased fasting and postprandial glucagon concentrations, which may point to hyperglucagonaemia as a possible link between statin treatment and type 2 diabetes.

Clinicaltrials.gov: NCT03018444.

Significance statement: This randomised, placebo-controlled, double-blind, crossover study reveals that short-term high-dose atorvastatin treatment increases fasting and postprandial glucagon levels and alters amino acid and bile acid profiles without affecting glucose, insulin, or gut microbiota in healthy men. These findings suggest hyperglucagonaemia as a potential mechanistic contributor to the increased risk of type 2 diabetes associated with statin therapy.

A better understanding of the benefit of burosumab for treating tumor-induced osteomalacia (TIO) in Chinese patients is needed. The objective of this open-label, multicenter, single-cohort, post-marketing Phase 4 study was to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of burosumab after repeated administration in Chinese adults with TIO. Burosumab was administered subcutaneously every 4 weeks for up to 48 weeks at an initial 0.3 mg/kg dose. We investigated the change from baseline in mean serum phosphorus level over time, and changes in serum and urinary phosphorus levels, bone turnover biomarkers, patient-reported outcomes, and other parameters after repeated burosumab administration. Nine patients were treated. Serum phosphorus levels increased and remained above baseline and lower limit of normal at the end of the dosing cycles (averaged over Weeks 20 to 48) (mean [standard deviation] change, 1.5 [0.86] mg/dL). Tubular reabsorption of phosphate and the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate level ratio increased and remained above baseline values. Alkaline phosphatase (ALP), bone-specific ALP, carboxy-terminal cross-linked telopeptide of type I collagen, and procollagen type 1 N propeptide levels increased, reaching maximums at Weeks 16 or 24. The distance walked in 6 minutes nearly doubled from baseline by Week 48. Patients reported improvements in pain and quality of life over time. There were no serious adverse events and only five treatment-related adverse events (all mild in severity) in three patients. In Chinese patients with TIO, continued treatment with burosumab can provide sustained clinical benefit and a favorable safety profile.

Objective: CT attenuation value is useful in the differential diagnosis of adrenal masses, and values <10 Hounsfield units (HU) can exclude malignancy and pheochromocytoma. However, few reports have examined the reliability of CT attenuation measurements. We examined the reliability of CT attenuation measurements made by surgeons not specialized in image reading.

Design: A retrospective analysis of 313 patients (325 lesions) who underwent surgery at a single institution was performed.

Methods: One general surgeon and one endocrine surgeon independently measured CT attenuation values. The intraclass correlation coefficient and Cohen's kappa coefficient were used to analyze interobserver reliability. All cases were subjected for endocrine function tests and histopathologically diagnosed. Additional analyses included segmented regression for size-related measurement variability and multivariable analyses comparing aldosterone-producing adenomas (APAs) and cortisol-producing adenomas (CPAs).

Results: The intraclass correlation coefficient between observers was 0.938 (95% CI: 0.923-0.949), and Cohen's kappa coefficient was 0.851 (95% CI: 0.781-0.922). Both observers measured all malignant adrenal tumors (such as adrenocortical carcinoma, metastatic adrenal carcinoma, and malignant lymphoma) and pheochromocytomas as ≥ 10 HU. CT attenuation values were significantly higher in CPAs than in APAs, independent of mass size (P < 0.001 for both observers).

Conclusions: CT attenuation value was shown to be reliable enough for simple measurements that could be performed by non-radiologists and was useful for excluding malignancy and pheochromocytoma.

Significance statement: This study reinforced evidence for the reliability of CT attenuation value. Even with a simple method that can be performed by non-radiologists, CT attenuation values were highly reliable and useful for excluding malignancy and pheochromocytoma. In addition, all lesions in this study were evaluated both endocrinologically and pathologically, giving high validity to the reference standard. These findings complement and further substantiate the latest clinical practice guidelines of the European Society of Endocrinology.

Background: Type 2 diabetes increases the risk of cognitive decline and dementia. Data on ethnic differences in dementia prevalence among patients with diabetes remain limited.

Methods: We conducted a retrospective matched case-control study of Clalit Health Services members aged 60 or older. Matching (1:3) was based on age, sex, language, and socioeconomic status. Ethnicity was determined by spoken language or place of birth. Prescriptions and refills for antidiabetic medications were recorded for the two years preceding the index date. Clinical, anthropometric, and comorbidity data were analyzed.

Results: During follow-up, 39% of participants were diagnosed with dementia over a maximum observation period of 20 years (crude proportion). However, given a median follow-up of 9.6 years, dementia incidence was primarily evaluated using time-specific competing-risk analyses. When accounting for death as a competing event, the 10-year cumulative incidence of dementia was approximately 9-10%, varying across ethnic groups. However, in multivariable competing-risk models adjusting for age, sex, socioeconomic status, and comorbidities, ethnicity was no longer independently associated with dementia incidence. In matched analyses, the use of SGLT-2 inhibitors and DPP-4 inhibitors was associated with a lower probability of dementia. In time-to-event analyses of dementia-related mortality, treatment with SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors was associated with significantly reduced mortality risk.

Conclusion: Ethnic differences in dementia incidence were attenuated after adjustment for demographic and clinical factors. SGLT-2 and DPP-4 inhibitors were associated with a lower risk of dementia, whereas GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were associated with reduced dementia-related mortality.

Purpose: The transition of differentiated thyroid carcinoma (DTC) care from hospital to primary care remains controversial. Current studies suggest that low-risk patients with an excellent response to therapy are safely followed up by primary care professionals. Despite this, discharge practices among Portuguese thyroidologists remain heterogeneous and the success of this clinical transition is yet unknown. This study aims to evaluate primary care compliance to follow-up recommendations for DTC patients after tertiary care discharge.

Methods: A retrospective observational study was conducted including individuals with a history of DTC who were treated in a Portuguese tertiary care hospital and discharged to follow-up at primary care setting, during 2022. Data were collected from electronic records, including thyroglobulin and antithyroglobulin antibody levels.

Results: A total of 134 individuals were discharged. The majority (n = 105; 78.4%) were female, with a mean age at discharge of 64 ± 12 years. The most frequent diagnosis was papillary thyroid carcinoma (95.5%, n = 128). Regarding treatment, 52.2% (n = 70) only underwent thyroidectomy, 44.8% (n = 60) underwent thyroidectomy followed by iodine-131 ablation, and 3.0% (n = 4) underwent subtotal thyroidectomy. Most DTC cases (86.6%, n = 116) were classified as low risk and showed an excellent response to treatment (82.1%, n = 110) according to the ATA 2015 Guidelines. One year after discharge, biochemical response evaluated by thyroglobulin and antithyroglobulin levels were registered in 29.1% (n = 39) of individuals. Thirteen patients (9.7%) had records of either antithyroglobulin antibodies or thyroglobulin alone.

Conclusion: Patients with low-risk DTC receive suboptimal monitoring after transition to primary care, emphasizing the need to enhance follow-up practices to ensure adequate long-term surveillance.

Background: Patients with adrenal insufficiency require glucocorticoid replacement therapy either as hydrocortisone in multiple-daily doses or as low-dose prednisolone once daily. Data on the long-term safety, cardiovascular risk, and quality-of-life (QoL) outcomes of prednisolone remain limited.

Methods: In this prospective longitudinal cohort study, patients with adrenal insufficiency underwent a pre-specified switch from multiple-daily dose hydrocortisone to once-daily low-dose prednisolone (2-4 mg) as part of routine clinical care and followed up for at least four months. Cardiovascular risk was assessed using anthropometric and biochemical markers (lipid profile, HbA1c, C-reactive protein, blood pressure, and waist and hip circumference). QoL was evaluated using a modified SF-36 questionnaire. Baseline and follow-up measures were compared using paired t-tests or non-parametric equivalents.

Results: Of the 62 enrolled patients, 48 completed follow-up. The mean age was 54.5 ± 13 years; 56% were female; and 83% had secondary adrenal insufficiency. After at least four months on prednisolone, weight decreased significantly (90.6-89.6 kg, P = 0.007), accompanied by a reduction in systolic blood pressure (-5 mmHg, P = 0.032). Lipid parameters, HbA1c, and CRP remained unchanged (P > 0.05). Energy scores improved significantly (+9 points, P = 0.003), and patients reported increased treatment convenience (P = 0.002).

Conclusion: Low-dose once-daily prednisolone offers comparable cardiovascular risk to hydrocortisone while improving treatment convenience, systolic blood pressure, and SF-36 subjective energy scores. These findings support the use of prednisolone as a potentially preferable alternative in patients with adrenal insufficiency.

Objective: This study aimed to investigate the association between fasting glucagon levels and the risk of comorbid stroke in hospitalized patients with type 2 diabetes mellitus (T2DM).

Methods: This study included 1,745 T2DM patients hospitalized at Tianjin Medical University General Hospital from September 1, 2022, to September 30, 2025. Patients were divided into a T2DM group and a T2DM with stroke group based on the presence of stroke. Fasting glucagon levels and other clinical data were collected. Binary logistic regression models were used to analyze the relationship between fasting glucagon and stroke risk.

Results: Among female T2DM patients, fasting glucagon levels were significantly higher in the T2DM with stroke group compared to the T2DM group (13.38 vs 11.56 pmol/L, P = 0.011). Multivariable logistic regression analysis showed that after adjusting for multiple confounding factors, including age, diabetes duration, BMI, hypertension, eGFR, HbA1c, dyslipidemia, and medication use, higher fasting glucagon levels are independently associated with the presence of comorbid stroke in female T2DM patients (model 3: Q4 vs Q1: OR = 2.396, 95% CI: 1.075-5.339, P = 0.037). In addition, the prevalence of stroke increased with ascending quartiles of glucagon levels in female patients (P = 0.023). However, no significant association was observed between fasting glucagon levels and stroke risk in male patients.

Conclusion: This study demonstrates that among hospitalized female patients with T2DM, higher fasting glucagon levels are independently associated with the presence of comorbid stroke. This association suggests a potential link between glucagon and cerebrovascular diseases in this population, warranting further investigation to explore its role.

Objective: To identify factors independently associated with quality-of-life (QoL) impairment in Graves' hyperthyroidism (GH) patients and develop a clinically applicable nomogram for outpatient settings.

Methods: A total of 402 GH patients were recruited from the outpatient clinic of Endocrinology Department of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, from January 2024 to June 2025. Participants were surveyed using a general information questionnaire, the Thyroid-specific Patient-Reported Outcome Short-Form (ThyPRO-39), the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Depression Scale (HAMD), and the Hamilton Anxiety Scale (HAMA). Univariate and multivariate analyses identified independent predictors of QoL impairment. A nomogram was developed and validated using the area under the receiver operating characteristic curve (AUC), bootstrap-calibrated plots, and decision curve analysis (DCA). An online dynamic calculator (dynnom) was also developed to facilitate clinical application.

Results: Multivariate analysis revealed that thyroid eye disease (TED), goiter, sleep disturbances, anxiety, and depressive symptoms were independent predictors of QoL impairment. The nomogram demonstrated an excellent discriminative ability: AUC was 0.886 in the training group and 0.844 in the validation group. Bootstrap calibration showed good consistency between predicted and observed probabilities. DCA revealed favorable net clinical benefit across a 0.2-0.6 threshold range. The associated online calculator further improved clinical usability.

Conclusions: The nomogram integrating TED, goiter, sleep, and emotional factors provides a reliable tool for early identification of GH patients at high risk of QoL impairment in outpatient settings. Future external multicenter validation is needed to improve its generalizability.