Endocrine Connections最新文献

Objective: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare syndrome manifesting in childhood. Diagnosis of ROHHAD syndrome remains challenging due to the diversity of symptoms that may be missed easily, especially for autonomic dysfunction, and partly develop later in time. The 2023 hypothalamic syndrome (HS) diagnostic criteria are a novel tool for recognizing symptoms of hypothalamic dysfunction. However, symptoms of autonomic dysregulation are lacking in these criteria. They are therefore insufficient for use in ROHHAD patients. No other scoring system for autonomic dysfunction in ROHHAD syndrome exists. We aim to improve the diagnostic criteria for HS by including a score for autonomic dysregulation, supporting early diagnosis of ROHHAD syndrome.

Methods: A score for autonomic dysregulation in ROHHAD syndrome supplementary to the 2023 HS diagnostic criteria was developed based on existing instruments to assess autonomic dysfunction symptoms adjusted for specific symptoms in ROHHAD syndrome, with a score ranging from 0 to 10. The diagnostic criteria for HS including our add-on were tested retrospectively in four ROHHAD patients.

Results: Four ROHHAD patients, median age 9.4 years (range 4.6-25.7), were assessed regarding signs and symptoms of HS and autonomic dysfunction. All patients had HS and scored on at least three different domains of autonomic dysregulation. Median score was 9 out of 10 (range 4-9).

Conclusions: The 2023 HS diagnostic criteria are not sufficient to recognize autonomic dysfunction due to hypothalamic dysfunction in ROHHAD syndrome. Our add-on score is clinically easy to use and may help in early recognition and follow-up in ROHHAD syndrome and other causes of HS.

Significance statement: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare cause of HS in childhood. In the recently developed diagnostic criteria for HS, the autonomic manifestations of hypothalamic dysfunction, which are common in ROHHAD syndrome, are not represented sufficiently. Children with ROHHAD may, for example, experience ophthalmological problems (strabismus or oculomotor apraxia), altered pain threshold, increased or impaired sweating, cold extremities, and/or heart rate dysregulation. Many of these symptoms are mostly unnoticed by the clinician or caregivers, leading to a delay in diagnosis and treatment. An add-on to the diagnostic criteria for HS including parameters of autonomic dysregulation will support early recognition of ROHHAD syndrome, follow-up during treatment and research purposes.

Surufatinib, an oral vascular immune kinase inhibitor targeting angiogenesis and immune escape, is approved in China for the treatment of unresectable locally advanced or metastatic neuroendocrine tumors (NETs). This real-world study aimed to evaluate its efficacy and safety in neuroendocrine neoplasms (NENs), including neuroendocrine carcinomas (NECs). From 2022 to 2024, 21 patients (12 with NET and 9 with NEC) at Nanjing Drum Tower Hospital received surufatinib-based therapy. The median follow-up period was 690 days. The primary endpoint, the disease control rate, was 81% (95% confidence interval (CI): 58.1-94.6), and the objective response rate (ORR) was 14% (95% CI: 3.0-36.3). The ORR was 8.3% (95% CI: 0.2-38.5) in NET and 44.4% (95% CI: 13.7-78.8) in NEC, with no significant difference by Fisher's exact test (P = 0.119). The median progression-free survival (mPFS) was 9.7 months (95% CI: 2.5-15.9), while the median overall survival (mOS) had not been reached. For first-line treatment, the mPFS was 9.7 months (95% CI: 3.5-15.9) in NET patients and 15.1 months (95% CI: 3.8-26.5) in NEC patients; for second-line treatment, it was 6.7 months (95% CI: 0.9-12.4) in NET patients and 4.6 months (95% CI: 1.7-7.6) in NEC patients. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 28% of patients, and no treatment-related deaths were reported. Patients with TRAEs ≥1 (hazard ratio 0.349, P = 0.048) had longer PFS. This study supported the activity of surufatinib in advanced NENs; subgroup findings, including those for NEC, were exploratory and required confirmation.

Background: Gestational diabetes mellitus (GDM) affects 7-14% of pregnancies, increasing maternal and neonatal complications. Phytochemical-rich diets, abundant in plant-based foods, may improve glucose metabolism and reduce inflammation. The phytochemical dietary index (PDI) measures intake of such foods, but prospective data on GDM risk are scarce. This study aimed to examine early-pregnancy PDI in relation to subsequent GDM risk in a large birth cohort.

Methods: A total of 2,770 pregnant women (mean age 29.61 ± 4.55 years; mean pre-pregnancy BMI 23.96 ± 1.19 kg/m2) from the Women's Health Center of Shanxi were included. Dietary intake was assessed using a validated food frequency questionnaire. The plant-based diet index (PDI) was calculated as the proportion of daily energy intake from whole grains, fruits, vegetables, legumes, nuts, seeds, and olive oil. Participants were divided into PDI quartiles. GDM was diagnosed at 24-28 weeks' gestation using a 75 g oral glucose tolerance test based on IADPSG criteria. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for confounders.

Results: GDM occurred in 377 women (13.6%). Higher PDI was inversely associated with GDM risk (P-trend <0.001). Each 10% increase in PDI was associated with a 14% lower odds of GDM (OR 0.86; 95% CI: 0.82-0.91). Higher PDI was associated with lower risk of neonatal hypoglycemia (OR 0.93; 95% CI: 0.92-0.95) and better maternal biochemical profiles, including lower fasting glucose, HbA1c, post-load glucose, triglycerides, total cholesterol, and higher HDL cholesterol.

Conclusions: Higher early-pregnancy PDI was associated with substantially lower risk of GDM, reduced neonatal hypoglycemia, and improved maternal metabolic profiles. Our findings support the integration of phytochemical-rich dietary guidance into early prenatal care.

Objective: To investigate the correlation between insulin receptor (IR) expression and patients' preoperative blood glucose level, and to analyze the correlation between IR expression level (IR percentage) and well-differentiated pancreatic neuroendocrine neoplasms (pNENs) cell proliferation and recurrence, and to explore whether it can be used as a potential biomarker for predicting tumor recurrence and metastasis.

Methods: A retrospective evaluation of the clinical data of 81 patients with well-differentiated pNENs who underwent surgical treatment at five different centers between January 2015 and September 2024 was performed. A subset of patients' pathological sections was collected for analysis.

Results: Multivariate linear regression analysis revealed that blood glucose (P = 0.024) was the only risk factor for increased Ki-67 expression. Preoperative blood glucose was significantly associated with IR percentage (P = 0.001). There was a significant positive correlation between Ki-67 and IR percentage in patients with G1-2 pNENs (P = 0.003). Cox regression analysis showed that IR percentage >12.5% was a good predictor of tumor recurrence (HR = 9.12, P = 0.004).

Conclusions: In patients with G1-2 pNENs, IR percentage could effectively predict tumor recurrence and metastasis, indicating that it can be used as a potential biomarker to predict pNEN recurrence and metastasis.

Objectives: To elucidate the expression dynamics of serum BMP1 during pubertal development and in central precocious puberty (CPP), and to evaluate its correlation with puberty-related clinical indicators and diagnostic potential for CPP.

Animals and patients: Female SD rats at different developmental stages and rats with CPP models. Seventy-five girls with CPP and 55 age-matched prepubertal control girls.

Measurements: Serum BMP1 levels were determined by ELISA. Spearman correlation and multivariate linear regression analyses were used to evaluate associations between BMP1 and puberty-related parameters. Receiver operating characteristic curves were plotted to evaluate the diagnostic efficacy of BMP1 for CPP.

Results: Serum BMP1 levels in normal female SD rats peaked during the neonatal period and early adolescence then decreased significantly upon sexual maturity and adulthood. Markedly elevated serum BMP1 levels were observed in both CPP model rats and Tanner stage 2 girls with CPP compared to age-matched controls (P < 0.01). Serum BMP1 correlated positively with E2 and negatively with bone age and BA/CA ratio (P < 0.05). Multivariate analysis identified no independent determinants of serum BMP1 (all P > 0.05). For CPP diagnosis, BMP1 alone achieved an AUC of 0.692 with 76.0% sensitivity and 61.82% specificity, while the BMP1/IGF-1 combination showed superior performance (AUC = 0.832, sensitivity 84.78%, specificity 72.73%).

Conclusions: Serum BMP1 demonstrates potential as a biomarker for pubertal growth but lacks sufficient diagnostic accuracy for CPP when used alone. Its combination with IGF-1 significantly improves diagnostic performance.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, with over 20% of patients progressing to metabolic dysfunction-associated steatohepatitis (MASH), which carries a high risk of cirrhosis and hepatocellular carcinoma. While liver biopsy remains the gold standard for MASH diagnosis, its invasiveness and limitations necessitate reliable noninvasive alternatives. This study aimed to develop a cost-effective biomarker panel using routine laboratory tests to distinguish MASLD severity stages.

Methods: We conducted a single-center, retrospective study of 209 biopsy-proven MASLD patients, stratified by NAS: simple steatosis (NAS <3, n = 40), borderline (NAS 3-4, n = 120), and definitive MASH (NAS ≥5, n = 49). Clinical, biochemical, hematologic parameters and metabolic markers were analyzed. Logistic regression and ROC curves assessed diagnostic performance.

Results: Key findings revealed progressive increases in BMI, ALT, AST, and transferrin (Tf) levels with disease severity. Multivariate logistic regression identified ALT and Tf as independent predictors for borderline and MASH. Notably, ALT showed superior diagnostic performance for distinguishing simple MASLD with borderline (AUC 0.763), while Tf was most effective for MASH detection (AUC 0.723). A combined model integrating BMI, ALT, and Tf demonstrated excellent diagnostic accuracy for borderline (AUC 0.840) and MASH (AUC 0.805).

Conclusion: Our study highlights that a simple, cost-effective panel of routinely available biomarkers (BMI, ALT, and Tf) can effectively stratify MASLD progression, offering a practical alternative to invasive diagnostics. This approach enhances early MASH detection, facilitating timely clinical intervention.

Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels and normal FT4, and is associated with an increased risk of cardiovascular diseases, but its specific impacts on the right ventricle and underlying mechanisms remain unclear. This study aimed to investigate the direct role of TSH signaling through its receptor in right ventricular hypertrophy and energy metabolism remodeling. A model of pulmonary arterial hypertension-induced right ventricular injury was created in male cardiomyocyte-specific TSH receptor knockout mice and control mice using Sugen5416 combined with hypoxia (10% O2). Cardiac function was assessed via echocardiography, while histological and molecular changes were examined through staining techniques, quantitative PCR, and Western blot. Metabolic alterations were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Results demonstrated that pulmonary hypertension induced right ventricular dysfunction, hypertrophy, and metabolic dysregulation in control mice, characterized by impaired systolic and diastolic function, increased glycolytic enzyme expression, lactate accumulation, and reduced ATP levels. These pathological changes were significantly attenuated in TSH receptor knockout mice. In vitro, TSH treatment promoted hypertrophic marker expression and shifted metabolic activity toward glycolysis in H9c2 cardiomyocytes. In conclusion, our in vivo and in vitro experiments demonstrate that TSH promotes cardiomyocyte hypertrophy and upregulates the glycolytic pathway. These findings reveal a direct contribution of elevated TSH to right ventricular injury and may offer novel mechanistic insights into right ventricular impairment associated with subclinical hypothyroidism.