Endocrine Connections最新文献

Graphical abstract:

Abstract: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. The GnRH stimulation test remains the diagnostic gold standard, especially in girls with undetectable basal LH levels. However, native GnRH is expensive and often unavailable. Rapid-acting subcutaneous triptorelin has been proposed as a reliable alternative. This retrospective study evaluated the diagnostic accuracy of subcutaneous triptorelin compared with intravenous gonadorelin and investigated the optimal timing for LH peak assessment. A total of 341 girls referred for suspected precocious puberty were evaluated: 102 underwent the triptorelin test and 239 the gonadorelin test, with gonadotropins measured by electrochemiluminescence assay at baseline and after stimulation. Based on clinical, radiological, and laboratory criteria, 143 girls were diagnosed with CPP and 198 with non-progressive thelarche (NPT). Triptorelin elicited significantly higher FSH peaks than gonadorelin, while LH peaks were comparable; consequently, FSH/LH ratios were higher after triptorelin. ROC analysis identified an optimal diagnostic LH peak cut-off of 7.14 IU/L following triptorelin administration (sensitivity 94%, specificity 96%; AUC 0.985), while a threshold of 4.7 IU/L was observed after gonadorelin (sensitivity 100%, specificity 87%; AUC 0.982). Peak LH occurred predominantly at 180 min after triptorelin in both CPP and NPT groups (78 and 90%, respectively). Despite the limitations of its retrospective and non-parallel design, this large cohort study demonstrates that subcutaneous triptorelin provides excellent diagnostic accuracy, comparable to gonadorelin. These findings support triptorelin as a reliable and accessible alternative for CPP diagnosis and contribute to the standardization of diagnostic protocols in clinical practice.

Plain language summary: This study tested triptorelin stimulation as an alternative to the standard gonadorelin test to diagnose precocious puberty in girls. Triptorelin proved equally accurate and reliable, especially when hormone levels are measured 3 h after injection, offering a practical diagnostic tool in clinical practice.

This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA adverse event reporting system (FAERS) data (Q1 2004 to Q3 2024) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. In addition, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.

Pituitary neuroendocrine tumors (PitNETs) cause hormonal hypersecretion, which can disrupt cardiovascular homeostasis and lead to both overt and subclinical cardiac dysfunction. This study retrospectively examined 198 hospitalized PitNET patients (n = 91 male, n = 107 female) from March 2019 to December 2022. Two-dimensional speckle-tracking echocardiography (2D-STE) was used to determine the absolute left ventricular global longitudinal strain (GLS) values. Comprehensive clinical information was gathered, including endocrine axis status, symptoms, surgery history, and demographics. Standard transthoracic echocardiography parameters were also recorded. Multiple linear regression analysis and intergroup comparisons were used to identify factors affecting GLS. Pre-planned subgroup analyses were conducted for the acromegaly cohort and by surgical status. Clinical presentations overlapped across tumor subtypes. Cranial imaging was the primary method for detecting cases with atypical symptoms. Female patients were older and sought treatment more frequently than males. The mean patient age was 43.7 years, with most diagnoses occurring between 30 and 50 years. GLS showed a significant positive correlation with EF (62.64 ± 5.04%; P = 0.00) and E/e' ratio (7.10 ± 1.96; P = 0.01), and a significant negative correlation with BMI (25.20 ± 3.92 kg/m2; P = 0.00). Significant differences in GLS were observed based on gender (t = 2.47, P = 0.01) and operator (t = 2.52, P = 0.01). Regression analysis identified baseline predictors (BMI), EF, LV function, and gender as independent predictors of GLS. A key finding from a dedicated acromegaly subgroup analysis was that disease activity (IGF-1) independently predicted impaired GLS. 2D-STE is a sensitive tool for detecting subclinical myocardial dysfunction in PitNET patients. GLS is significantly influenced by BMI, EF, left ventricular dimensions, and gender, underscoring the need to integrate metabolic and cardiac profiles into the cardiovascular assessment of this population. Furthermore, the identification of IGF-1 as a predictor in acromegaly highlights the value of disease-specific cardiac risk stratification.

Introduction: Circular RNAs (circRNAs) have garnered attention as potential biomarkers for diabetes mellitus (DM) and its complications due to their stability and presence in various tissues and plasma. The objective of this study was to perform a systematic review of the available literature to better understand the involvement of circRNAs in DM and its chronic complications.

Methods: PubMed and Embase repositories were searched to identify all studies that evaluated the expression of one or more circRNAs in samples from individuals with DM and without DM. Studies comparing circRNA expression between DM patients with or without chronic complications were also included.

Results: In total, 2990 articles were found in the databases and, after excluding articles that did not meet the eligibility criteria, 130 articles were included in this systematic review. In these 130 studies, we identified over 3000 circRNAs differentially expressed between cases and controls. Among these, eight circRNAs were reported as altered in samples from three or more studies, which were selected for additional evaluations. Five of them were consistently dysregulated between DM patients and controls. The circRNAs hsa_circ_0000324 and hsa_circ_0060450 were increased, while the hsa_cic_0080325 was decreased in type 1 DM patients vs. controls. Moreover, hsa_circ_0054633 was increased in type 2 DM patients vs. controls, and hsa_circ_0003218 was decreased in gestational DM patients vs. controls. Regarding chronic DM complications, three circRNAs were identified as dysregulated: hsa_circ_0037128 and hsa_circ_0003928 in diabetic kidney disease and hsa_circ_0006057 in diabetic retinopathy.

Conclusion: Eight circRNAs are dysregulated in DM and its chronic complications.

Purpose: This study aimed to compare the differences in kidney stone recurrence between typical primary hyperparathyroidism (TPHPT) and normocalcemic primary hyperparathyroidism (NPHPT) patients who did not receive parathyroidectomy (PTX) treatment.

Materials and methods: We conducted a retrospective analysis of patients hospitalized for surgical management of kidney stones between September 2015 and March 2023. Patients' demographic data, blood test parameters, stone parameters, and surgical interventions were collected. Based on serum calcium and parathyroid hormone (PTH) levels, patients were categorized into TPHPT, NPHPT, and control groups. Postoperative stone recurrence was assessed during follow-up.

Results: A total of 288 patients (139 males and 149 females) were analyzed, with 96 patients in each group. PTH and serum calcium levels were significantly higher in the TPHPT group than in both NPHPT and control groups (P < 0.001). The recurrence probability of kidney stones after surgery was higher in patients with both TPHPT and NPHPT than in the control group (42.7 vs 19.8% and 36.5 vs 19.8%, P < 0.05, respectively). However, no significant difference was found between TPHPT and NPHPT groups (P > 0.05). After adjusting for covariates, the Cox regression analysis revealed that NPHPT was a risk factor for kidney stone recurrence (HR: 2.31, 95% CI: 1.26-4.26, P = 0.007).

Conclusions: Patients with TPHPT and NPHPT who have not undergone PTX treatment both exhibit a higher recurrence rate of kidney stones, with no significant difference between the two groups. Nevertheless, clinicians should place more emphasis on the recurrence of kidney stones in patients with NPHPT.

Background: The biology of papillary thyroid carcinoma (PTC) is highly varied. However, the intraregional heterogeneity present in PTC with or without lymphatic metastasis (LM) is still not well understood.

Methods: Six tumor samples from patients with PTC were used for viable cell single-cell RNA sequencing (scRNA-seq) analysis. The cell types were identified using markers from the CellMarker database and published research. To perform functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene Set Enrichment Analysis (GSEA) were carried out using ClusterProfiler. The cell-chat package was used to analyze the cell-cell interaction.

Results: 13 cell types were identified in the scRNA-seq dataset by published cell markers. Enrichment pathway analyses of tumor cells found that PTC with LM was associated with pathways related to cell proliferation, migration, and survival. Cell-cell interaction analysis showed increased CD44-TYROBP-mediated and decreased PPIA-BSG and APP-SORL1-mediated cell communication between tumor cells and other cells. Specifically, CD8+ resident memory T cells emerged as pivotal regulators in LM of PTC, primarily through the expression of MHC-I, CD99, and LCK.

Conclusions: This study provides new insights into the heterogeneity of PTC and the basis for LM in PTC, which might provide potential therapeutic targets in future treatment.

Aims: Insulin resistance is increasingly recognized in type 1 diabetes as a risk factor for chronic complications and cardiovascular disease. Sudomotor dysfunction, reflecting small fiber neuropathy, can be assessed non-invasively by electrochemical skin conductance (ESC). This study evaluated the association between sudomotor function and insulin resistance in adults with type 1 diabetes.

Methods: The study included 476 adults with type 1 diabetes (247 men), aged 42 (IQR: 33-53) years, with a disease duration of 24 (IQR: 19-32) years, and HbA1c level of 7.9 (IQR: 7.2-8.9)%. Sudomotor function was evaluated using the SUDOSCAN device. Insulin resistance was assessed using the estimated glucose disposal rate formula (eGDR), which is based on HbA1c, waist-to-hip ratio, and the presence of hypertension. The study group was subdivided into three groups based on tertiles of eGDR (<5.5, 5.5-9.5, >9.5 mg/kg/min).

Results: Participants with lower eGDR (lower insulin sensitivity) had lower feet ESC 71 (IQR: 50-81) vs 79 (IQR: 63-85) vs 83 (IQR: 74-86) μS; P < 0.0001. We found a positive correlation between feet ESC and eGDR (Rs = 0.28, P < 0.001). In a multiple linear regression model, feet ESC was independently associated with eGDR (β = 0.16, P = 0.001).

Conclusion: Insulin resistance is associated with impaired sudomotor function in adults with type 1 diabetes.

Aim: Rare disease registries focusing on natural history provide an opportunity to understand the transition process for rare endocrine conditions, including pituitary diseases. This study aims to assess the feasibility of using the European Registry for Rare Endocrine & Bone Conditions (EuRREB) for transition research in pituitary disease and to establish basic clinical characteristics of transition-age pituitary patients managed at reference centers (RCs) within the European Reference Network for Rare Endocrine Conditions (Endo-ERN).

Methods: Patients in the Core Registry of EuRREB aged between 14 and 24 years with a pituitary diagnosis were eligible for inclusion. Physicians were asked to fill out a secondary survey evaluating transition aspects. Descriptive statistics and non-parametric analysis (Kruskal-Wallis, Mann-Whitney) were used.

Results: Of 106 eligible patients, 98 patients had a confirmed diagnosis. Secondary survey data were available for 79 patients (74%) across 6 RCs from 5 countries. 72/79 patients (91%) remained in active care, with a single patient lost or discharged from follow-up (each n = 1, 1.3%). 29/79 (36.7%) were already transferred to adult care. Transfer typically occurred at age 18 years and in a few patients up to 22 years. A documented transfer plan was reported for 11 patients (13.9%). Patient-reported outcomes were collected in ten patients (13.5%). Transition challenges were either care-related or patient-related.

Conclusion: This study provides initial characterization of transition of care in rare pituitary diseases in Endo-ERN RCs, showing high follow-up but inconsistent use of plans, patient-reported outcome measures (PROMs), and documentation. Rare disease registries can act as a tool to understand the process and identify barriers.

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.