Frontiers in Endocrinology最新文献

Endocrine malignancies constitute a heterogeneous tumour group with diverse biological characteristics. While typically indolent, they encompass aggressive types and presence of any metastatic sign indicates a high probability of recurrence and a diminished response to conventional therapies. Chimeric antigen receptor (CAR)-T cell immunotherapy has constituted a revolutionary advance in cancer treatment and exhibited significant potential for application in endocrine cancer. However, limited effectiveness was displayed in clinical application, which necessitates the exploration of novel modalities. Identification of specific and safe targets for endocrine cancer is the initial stage towards establishing a successful CAR-T treatment. Various therapies under investigation offer potential enhancements to CAR T cell efficacy through diverse mechanisms. Herein, we summarize recent advances in identifying targets of endocrine cancer for CAR therapy and provide an overview of combinatorial approaches.

Patients with duplicated pituitary often have severe neurodevelopmental abnormalities and craniofacial deformities. Till now, only eight patients diagnosed with duplicated pituitary showing barely central precocious puberty (CPP) are reported in the published literature. Herein, we report a 6-year-old and 3-month-old girl diagnosed with pituitary duplication presented with CPP. She has enlarged breasts for more than 1 year, accelerated height of linear growth, advanced bone age, increased hormone level, and increased volume of uterus and ovary. A duplicated pituitary gland was shown in the MRI. As the gonadotropin-releasing hormone analogue (GnRHa) stimulation test showed a positive result, the child was treated with GnRHa. After 2 years of follow-up, there was a delay in the progression of sexual development, a reduction in symptoms of precocious puberty, and an increase in predicted adult height.

Purpose: Adult body shape index (ABSI) is widely recognized as a reliable indicator for evaluating body fat distribution and dysfunction. However, the relationship between ABSI and Klotho protein, known for its anti-aging biological function, has not yet been investigated. Therefore, the aim of this study was to assess the correlation between ABSI and serum Klotho levels in adults residing in the United States.

Methods: A cross-sectional study of participants was conducted based on the 2007-2016 National Health and Nutrition Examination Survey. Visceral adiposity was determined using the ABSI score, and Klotho protein concentration was measured using an enzyme-linked immunosorbent assay kit. Multiple regression models were used to estimate the association between ABSI and Klotho protein after adjusting for several potential confounding variables. Subgroup analysis of ABSI and Klotho was performed using restricted cubic splines.

Result: A total of 11,070 adults were eligible for participation, with a mean ABSI of 8.28 ± 0.45 and a mean Klotho protein concentration of 853.33 ± 309.80 pg/mL. Multivariate regression analysis showed that participants with high ABSI scores had lower serum Klotho protein concentrations. When ABSI was divided into quartiles, after full adjustment, Klotho protein levels were lower in participants in the fourth fully adjusted ABSI quartile (Q4: -0.352 pg/ml) than in those in the lowest quartile (Q1) (P<0.0001).

Conclusion: There was a negative linear correlation between ABSI score and serum Klotho concentration. Higher ABSI was associated with lower serum Klotho concentrations; however, this association did not seem to be significant in subjects with BMI ≥30 kg/m2.Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

Purpose: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a crucial lipid marker associated with various cardiovascular diseases. However, its relationship with kidney injury, particularly albuminuria, remains poorly understood. This study aims to investigate the association between NHHR and macroalbuminuria in U.S. adults.

Patients and methods: This cross-sectional study utilized data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). NHHR was calculated as (Total cholesterol - HDL cholesterol)/HDL cholesterol. Macroalbuminuria was defined by an albumin-creatinine ratio (ACR) >300 mg/g. Logistic regression, smoothed curve fitting, subgroup analyses, and sensitivity analysis were employed to assess the relationship between NHHR and macroalbuminuria.

Results: A total of 41,225 participants were included in the analysis. Higher NHHR was significantly associated with an increased likelihood of macroalbuminuria (OR = 1.34, 95% CI: 1.13-1.59, p=0.0007). Subgroup analysis revealed a stronger association in participants with BMI ≥30 kg/m²(OR = 1.89, 95% CI: 1.44-2.47, p<0.01). Sensitivity analysis revealed that the association remained robust even after excluding participants taking medications that affect lipid metabolism.

Conclusion: In U.S. adults, an increased likelihood of incident NHHR levels of macroalbuminuria is positively associated and is more pronounced in those with a BMI ≥30kg/m².

Background: There are currently no biomarker-based prediction models for amlodipine therapeutic efficacy in pediatric hypertension. This study aimed to identify potential biomarkers and establish a biomarker-based model for predicting amlodipine therapeutic efficacy in pediatric primary hypertension (PH).

Methods: From January 2022 to December 2023, 165 children and adolescents with PH prescribed amlodipine were recruited at our department for a prospective observational study. Patients were grouped into Responders and Non-responders after one month treatment. The baseline data in the two groups were analyzed to identify variables associated with amlodipine treatment responsiveness; furthermore, a nomogram prediction model was established based on those potential predictors derived from multivariate regression analysis. This model's discrimination and calibration were evaluated by a series of statistical methods and internal validation was done using the bootstrap sampling method (1000 resamples).

Results: Eighty-nine patients responded to amlodipine while 76 did not. After statistical adjustment, 4 variables were found to be independently associated with therapeutic efficacy, including hyperinsulinemia (OR = 3.000, 95% CI: 1.409-6.386, p  = 0.004), insulin resistance (OR = 2.354, 95% CI: 1.032-5.370, p = 0.042), the baseline plasma Endothelin-1 level (OR = 0.627, 95% CI: 0.532-0.740, p < 0.001) and amlodipine dosages (OR = 1.743, 95% CI: 1.400-2.169, p <0.001). Compared to the baseline model, the full model with the four variables had a good calibration with an area under the curve (AUC) of 0.967 (95% CI: 0.945-0.990), yielding a sensitivity and a specificity of 91.0% and 92.1%, respectively; the clinical decision curve showed a positive net benefit. Additionally, a nomogram model was established based on the four variables and evaluated by bootstrap internal validation with the c-statistic of 0.865 and the calibration curve being close to the ideal line (p > 0.05).

Conclusion: A nomogram model with high predictive value for amlodipine therapeutic efficacy in pediatric PH was established. This model may be potentially applied to guide the selection of amlodipine for the treatment of pediatric PH.

The primary management in the care of patients with adrenal incidentalomas is to determine the oncologic risk, namely, the possibility of malignancy. The first place among adrenal incidentaloma lesions requiring diagnosis and treatment promptly is adrenocortical carcinoma (ACC). Similarly, in the case of pheochromocytoma, the lack of early diagnosis worsens the patient's prognosis. Even though both ACC and pheochromocytoma are among the less frequent adrenal lesions, neither should be excluded during differential diagnostics, especially in patients with an equivocal clinical presentation and non-typical adenoma radiological features. ACC presenting as pheochromocytoma is one of the few cases described in the literature, some of which could not collect exhaustive clinical data. Herein, in this article, we would like to provide an overview of reported ACC cases clinically manifesting as pheochromocytoma, based on the clinical image of a 59-year-old female patient with unintentional weight loss, non-specific abdominal pain, a diagnosis of hypertension, and significantly elevated excretion of 3-methoxytyramine in a 24-h urine collection, histopathologically diagnosed with ACC. The case presented emphasizes how crucial a comprehensive diagnostics and individual approach to the patient would be.

Background: Management of type 2 diabetes mellitus (T2DM) during Ramadan fasting presents unique challenges due to prolonged fasting periods, irregular meal schedules, and altered medication timing, potentially impacting glycemic control. Ertugliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been shown to improve glycemic control in T2DM effectively. However, the effectiveness of ertugliflozin during Ramadan fasting, a period with unique glycemic challenges, has not been studied extensively.

Methods: This study was a multicenter, real-life experience study involving 1373 adult patients with known T2DM for at least one year, an HbA1c level of less than 10%, and who intended to fast during Ramadan. Participants were divided into two groups: the Ertu group (n=703), consisting of patients who had been on a stable dose of ertugliflozin for at least three months before Ramadan, and the non-Ertu group (n=670), which included patients receiving other oral antihyperglycemic drugs (OADs) except ertugliflozin. Patients attended a baseline visit one month before the first day of Ramadan and a follow-up visit within one month after the last day of Ramadan. Both visits included history taking, physical examinations, and laboratory tests. The primary endpoints were changes in HbA1c levels, body weight, body mass index (BMI), and the incidence of hypoglycemia during Ramadan fasting.

Results: The mean age of the study participants was 50.37 ± 11.14 (SD) years, with 40.6% male and 58.7% female. Patients receiving ertugliflozin showed significant reduction in HbA1C (-0.65 ± 0.67% vs. -0.22 ± 0.64%, p<0.001), body weight (-1.24 ± 2.58 kg vs. -0.36 ± 3.41 kg, p<0.001), and BMI (-0.48 ± 1.03 kg/m² vs. -0.11 ± 1.33 kg/m², p<0.001) compared to the non-Ertu group. Hypoglycemia was reported in 0.3% of the ertugliflozin group and 0.7% of the other group, with comparable adverse events (p=.23; ≥0.05), indicating a favorable safety profile for ertugliflozin during fasting.

Conclusion: This study demonstrates that ertugliflozin is effective and safe for patients with T2DM during Ramadan fasting.