Endocrine最新文献

Purpose: To investigate the aberrant distribution and clinical relevance of regulatory B cells (Bregs) subsets in the peripheral blood of individuals with different levels of insulin resistance (IR).

Methods: A cohort of 124 subjects were divided into five groups according to their insulin resistance index (HOMA-IR) and diabetes diagnosis. The groups comprised Group 1 (IR^- with good glycemic control) and Group 2 (IR^- with poor glycemic control) at HOMA-IR < 3, Group 3 (IR⁺ without T2DM) and Group 4 (IR⁺ with T2DM), at 3 ≤ HOMA-IR < 6, and Group 5 (IR⁺⁺ with T2DM) at HOMA-IR ≥ 6. Peripheral blood samples were collected from each group, the percentages of CD19⁺CD24⁺CD27⁺ and CD19⁺CD24⁺CD38⁺ Bregs and the levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ were detected by flow cytometry and flow microsphere matrix method. Additionally, the cytokines levels were validated through ELISA. The activation of Bregs and the production of IL-10 among different groups were analyzed. Spearman correlation analysis was used to analyze the correlation between Bregs activation rate and IR degree.

Results: The results showed that the levels of CD19⁺CD24⁺CD27⁺ and CD19⁺CD24⁺CD38⁺ cells were increased whether in IR⁺ without or with type 2 diabetes mellitus (T2DM) groups compared to the IR^- groups, with the most significant increase observed in Group 5. Moreover, the plasma levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ in the IR⁺ group were higher than those in the IR^- group. The expression and activation level of Bregs were positively correlated with the severity of IR in T2DM.

Conclusion: These results suggest that the increase level of Bregs is closely related to the severity of IR, highlighting the potential significance of Bregs in the clinical progression of T2DM and its associated insulin resistance.

Purpose: This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC).

Methods: This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021.

Results: From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023).

Conclusion: Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.

Background: Cardiometabolic index (CMI) is a novel marker of diabetes mellitus. However, few studies have examined its association with gestational diabetes mellitus (GDM) risk. This study aimed to explore the association between CMI and GDM risk among pregnant women in the United States.

Methods: We performed a cross-sectional study utilizing data recorded in the National Health and Nutrition Examination Survey database from 1999 to 2018. Univariate and multivariate logistic regression, restricted cubic splines (RCS), sensitivity, and subgroup analyses were performed to clarify the relationship between CMI and GDM risk.

Results: A total of 710 pregnant women were recruited, among whom 113 were diagnosed with GDM based on established criteria. This population showed a significant association between a higher CMI value and GDM (odds ratio: 1.75, 95% confidence interval: 1.03-2.99, P = 0.038). RCS regression analysis identified a linear relationship between CMI and GDM (P-value < 0.001, P-nonlinear = 0.702). Sensitivity analysis further confirmed the validity of this relationship. Subgroup analysis indicated a positive association between CMI and GDM among women who drink or smoke and Mexican Americans.

Conclusion: This study demonstrates a significant positive association between CMI and GDM risk, suggesting that a higher CMI predicts GDM incidence during pregnancy. Further research is required to investigate the CMI index as an early predictor of GDM.

Purpose

Data regarding [18^F]FDG-PET/CT for the characterization of adrenal lesions are limited. Most of the studies proposed the tumor-to-liver maximum standardized uptake values (SUVratio) > 1.5 as the best cut off to predict malignancy. The aim of the study was to calculate the optimum cut off in a heterogeneous population with adrenal lesions and evaluate the diagnostic performance SUVratio >1.5.

Patients and methods

Retrospective analysis of adrenal lesions undergoing [18^F]FDG-PET/CT (2013–2022) for different reasons (atypical adrenal incidentalomas, extra adrenal tumor staging). The diagnosis of benignity was assessed by: (i) histology; (ii) stability or minimal diameter increase (<20%/<5 mm) on 12-months follow-up for non-operated patients. The optimal SUVratio and performance of SUVratio >1.5 were calculated by ROC curves.

Results

Forty-two consecutive lesions (diameter 36.1 ± 20.3 mm, 6 bilateral) underwent [18^F]FDG-PET/CT (19F, age 61.2 ± 11.7 years). Twenty-nine lesions were benign, 11 malignant [8 metastases (2 bilateral) and 1 adrenocortical carcinoma (ACC)] and 2 pheochromocytomas. The SUVratio cut-off in our population was 1.55 (Sn 100%, Sp 73.7%, AUC 0.868), with similar values excluding pheochromocytomas and metastases (SUVratio cut-off 1.49, Sn 100%, Sp 96.3%, AUC 0.988). The SUVratio cut-off of 1.5 showed 100% Sn, 87% Sp, 73% PPV, and 100% NPV.

Conclusion

[18^F]FDG-PET/CT could help in decision making process avoiding unnecessary surgery. The SUVratio cut-off of 1.5 has a good performance in a heterogenous population.

Background

In nondiabetic people, the long-term effects of insulin resistance (IR) on heart failure (HF) and all-cause mortality have not been studied.

Objectives

To examine the association between IR trajectories and incident HF and all-cause mortality in a nondiabetic population.

Methods

We studied 7835 nondiabetic participants from the Atherosclerosis Risk in Communities (ARIC) Study. We estimated IR with several methods: Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride glucose Index (TyG Index), and metabolic score for insulin resistance (METS-IR). The latent class analysis identified two trajectories for HOMA-IR (‘low level’ and ‘high level’), and three trajectories for TG/HDL-C, TyG index, and METS-IR (‘low level’, ‘moderate level’, and ‘high level’). Cox proportional hazard models were employed to examine the association.

Results

Participants in the ‘high level’ group of HOMA-IR trajectory patterns were more likely to have incident HF and all-cause mortality with HRs (95% CIs) of 1.29 (1.11–1.50) and 1.31(1.19–1.44), respectively, compared to the ‘low level’ group. Similarly, participants in the ‘moderate level’ and ‘high level’ groups of TG/HDL-C, TyG index, and METS-IR trajectories had elevated risks of incident HF and all-cause mortality. However, no increased risk was found for all-cause mortality for men in the ‘moderate level’ and ‘high level’ group of TG/HDL-C, TyG index, and METS-IR relative to the ‘low level’ group.

Conclusions

Long-term moderate and high IR levels were positively associated with increased risks of incident HF for both males and females. For all-cause mortality, however, consistent associations were found only in women.

Graphical Abstract

Bone is the second most common site of metastasis for differentiated thyroid carcinoma (DTC). Bone metastasis (BMs) occur in about 10% of patients with DTC and is observed more often in follicular thyroid carcinoma (FTC) (7–28%) than papillary thyroid carcinoma (PTC) (1–7%). Bone metastasis is associated with unfavorable clinical outcomes mainly including skeletal-related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions, and hypercalcemia, which negatively impact the quality of life of patients and reduce their life expectancy. Patients with BMs from DTC require comprehensive and multimodal treatment approaches, including radioiodine (RAI) therapy, palliative care, surgery, external beam radiotherapy, and targeted drug therapy. RAI therapy is the first-line treatment, despite being rather ineffective, especially in large BMs. The response to RAI therapy, either alone or in combination with BM focal treatment depends on iodine avidity. This study reports a rare case of metachronous skull bone metastasis from FTC in a 72-year-old female patient 15 years after initial treatment. The patient had an excellent response to RAI therapy, which resulted in the abnormal uptake disappearing. Following treatment, the patient has been disease-free for six years. This case confirms that a complete response to RAI treatment for BM depends on the degree of dedifferentiation of cancer cells, which highlights the need for long-term follow-up, especially for FTC patients.

Background/objective

Primary hyperparathyroidism (PHPT) may be asymptomatic or present with renal calculi, secondary osteoporosis, fractures and neuropsychiatric manifestations. Posterior reversible encephalopathy syndrome (PRES) and parkinsonism are atypical manifestations that may be rarely associated with PHPT. We report two patients who presented with the conditions mentioned above.

Case report

The first patient involved a 38-year-old woman who presented with diminution of vision, seizures, altered behavior and hypertension over eight months. An MRI of the brain done had shown vasogenic edema involving the parieto-occipital regions, suggestive of PRES. A metabolic screen revealed PTH-dependent hypercalcemia that was localized to the left inferior parathyroid gland. Following focused parathyroidectomy, there was improvement in sensorium, vision and normalization of blood pressure. The second patient was of a 74-year-old man who presented with progressive extrapyramidal symptoms of gait abnormalities and rigidity since the past eight months. He was initiated on Selegeline and Levodopa for the same purpose, and subsequently reported minimal improvement in symptoms. Investigations revealed PHPT associated with a right inferior parathyroid adenoma. Within two weeks following surgery, there was an improvement in rigidity and gait and he was able to ambulate without support.

Discussion

PRES has been reported to occur in the context of preeclampsia, hypertension, infection, sepsis and autoimmune conditions. PRES associated with hypercalcemia is rarely reported. While extra-pyramidally related manifestations are described in hypoparathyroidism, PHPT related parkinsonism is not commonly encountered. Identifying the underlying aetiology and initiation of corrective measures may lead to amelioration of patient symptomatology.

Conclusion

The occurrence of PRES and parkinsonism is rare in primary hyperparathyroidism; the two patients described above highlight the importance of screening for hypercalcemia in the setting of neurological manifestations.

Purpose

Multitarget kinase inhibitors (MKIs) are effective options in the treatment of cancer, significantly increasing the progression-free survival (PFS) of many tumors. Data about severity and prevalence of metabolic adverse events is scarce and may be significant in patients with a better survival. The aim of this study was to investigate glucose and lipids values of patients treated with lenvatinib. Secondary aims included evaluating changes in the estimated risk of cardiovascular disease and the relationship between metabolic alterations and tumor response to therapy.

Methods

A retrospective pilot study on 29 patients with advanced differentiated thyroid cancer was conducted. Clinical and biochemical characteristics were collected at the day of therapy initiation and follow up. The 10-year risk of cardiovascular disease was estimated with the SCORE2 and SCORE2-OP algorithms. Tumor burden change was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Results

No differences in glucose values were observed. A significant increase in total cholesterol (208 ± 41 versus 245 ± 67 mg/dl), triglycerides (112 [interquartile range, 58–326] versus 157 [78–296] mg/dl), calculated LDL cholesterol (128 [66–204] versus 140 [81–308] mg/dl) and cardiovascular risk was observed from baseline to follow up. Furthermore, these parameters increase progressively with increasing tumor response to therapy.

Conclusions

Despite limitations, this study shows an association between the use of lenvatinib and the development of lipid alterations in patients with advanced thyroid cancer. However, further investigation is necessary for a more comprehensive understanding of the adverse metabolic profile of MKIs.

Type 2 Diabetes (T2D) is a chronic disease with increasing incidence and prevalence and serious chronic complications, especially from cardiovascular system. However, other organs can be affected too. Several studies have associated T2D, especially when poorly controlled, with multiple pulmonary diseases. T2D is a common comorbidity among patients with asthma, Chronic Obstructive Pulmonary Disease (COPD), and Obstructive Sleep Apnea Syndrome (OSAS), and it is related to higher respiratory infection incidence, prevalence and severity. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are novel antihyperglycaemic agents with established cardiovascular benefits. There are also limited studies indicating their potential benefit in respiratory function. The aim of this article is to review data on the impact of GLP-1RA and SGLT-2i on respiratory function and describe the possible clinical benefits. Key findings indicate that GLP-1RA significantly improve lung function in patients with COPD, evidenced by improvements in spirometry measurements. Additionally, both GLP-1RA and SGLT-2i are associated with a decreased risk of severe and moderate exacerbations in COPD patients and have shown potential in reducing the incidence of respiratory disorders, including asthma and pneumonia. The mechanisms underlying these benefits are not yet fully understood and include multiple effects, such as anti-inflammatory action and oxidative stress reduction.

Objective

To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing’s syndrome (ECS) by sex.

Methods

Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated.

Results

28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar.

Conclusion

While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.