Endocrine Research最新文献

Objectives/introduction: To evaluate the presence and concentration of antithyroid peroxidase (TPOAb) and antithyroglobulin (TGAb) antibodies at the onset of Hashimoto's Thyroiditis (HT) and their association with disease characteristics and reproductive parameters before and after diagnosis.

Methods: This is a cross-sectional study with 65 women with HT followed in an outpatient clinic. The data was collected by interviews and review of medical records. The variables were characteristics of the disease; TPOAb and TGAb measurements; pregnancies; live children; premature births; pregnancy losses and infertility. We used the chi-square or Fisher's exact tests, the Mann-Whitney test and the Spearman correlation. The significance level was set at 5%.

Results: The mean age at diagnosis was 38 (SD ± 11.1) years and the duration of the disease was 7.5 (SD ± 5.3) years; 46% of the women reported infertility periods. 59/65 (90.7%) women had TPOAb and 42 (64.6%) had TGAb antibodies. Comparison between the groups with and without TPOAb or TGAb showed no differences between all variables studied. We found positive correlations between TPOAb concentration and preterm births and thyroid volume; and TGAb concentration was positively correlated with age.

Conclusion: The presence of autoantibodies did not influence reproductive parameters; TPOAb concentration was correlated with premature births and thyroid volume.

Background: While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC.

Methods: In this retrospective study, we included 18 patients median age 49 years (42-62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor.

Results: The median time from the initial surgery to ACC recurrence was 29 months (IQR 18-50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25-53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapy±mitotane (n = 4) and locoregional therapy ±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8-26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03).

Conclusion: A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

Background: Monogenic diabetes often occurs as a result of single-gene mutations. The illness is minimally affected by environmental and behavioral factors, and it constitutes around one to five percent of all cases of diabetes.

Methods: Newborn diabetes mellitus (NDM) and maturity-onset diabetes of the young (MODY) are the predominant causes of monogenic diabetes, accounting for a larger proportion of cases, while syndromic diabetes represents a smaller percentage. MODY, a group of inherited non-autoimmune diabetes mellitus disorders, is quite common. However, it remains frequently misdiagnosed despite increasing public awareness. The condition is characterized by insulin resistance, the development of diabetes at a young age (before 25 years), mild high blood sugar levels, inheritance in an autosomal dominant pattern, and the preservation of natural insulin production.

Results: Currently, there are 14 distinct subtypes of MODY that have been identified. Each subtype possesses distinct characteristics in terms of their frequency, clinical symptoms, severity of diabetes, related complications, and response to medicinal interventions. Due to the clinical similarities, lack of awareness, and high expense of genetic testing, distinguishing between type I (T1D) and type II diabetes mellitus (T2D) can be challenging, resulting in misdiagnosis of this type of diabetes. As a consequence, a significant number of individuals are being deprived of adequate medical attention. Accurate diagnosis enables the utilization of novel therapeutic strategies and enhances the management of therapy in comparison to type II and type I diabetes.

Conclusion: This article offers a concise overview of the clinical subtypes and characteristics of monogenic diabetes. Furthermore, this article discusses the various subtypes of MODY, as well as the process of diagnosing, managing, and treating the condition. It also addresses the difficulties encountered in detecting and treating MODY.

Objective: The hallmarks of Hashimoto's thyroiditis (HT) include the destruction of thyroid cells by leading to insulin resistance (IR), hypothyroidism, and metabolic abnormalities. Kisspeptin, spexin, and galanin control appetite and body weight (BW) to regulate metabolisms. Here, we sought to determine if galanin, kisspeptin, and spexin are linked to the pathophysiology of HT in euthyroid female individuals.

Methods: Forty-five women with HT and 45 healthy control women of the same age participated in the current study. The enzyme-linked immunosorbent assay (ELISA) method was used to measure the serum levels of galanin, spexin, and kisspeptin.

Results: In comparison to the controls, HT patients had significantly higher levels of kisspeptin (p < 0.01), galanin (p < 0.01), anti-thyroid peroxidase (anti-TPO) (p < 0.001), anti-thyroglobulin (anti-Tg) (p < 0.001), and body mass index (BMI) (p < 0.05). The two groups were comparable in terms of spexin, free triiodothyronine-3 (fT3), fT4, thyroid-stimulating hormone (TSH) levels, and homeostatic model assessment for insulin resistance (HOMA-IR). Galanin and kisspeptin were seen to have a positive correlation (p < 0.01; r = 0.786).

Conclusions: Euthyroid women with HT were found to have higher levels of kisspeptin and galanin. These results imply that kisspeptin and galanin may be linked to the pathogenesis of hypothyroidism, and as a result, we believe that these markers may be beneficial in the early detection and treatment of HT patients.

Objective: The aim of this study was to investigate changes in heart rate variability (HRV) and QT dispersion (QTd) in patients with differentiated thyroid cancer at different TSH suppression levels.

Methods: The study included 125 DTC patients, who had been on TSH suppression treatment (TSHST) for at least 1 year. The patients were categorized into three groups: patients with TSH < 0.1 mIU/L (n:30), those with TSH 0.1 to 0.5 mIU/L (n:56), and those with TSH 0.5 to 2 mIU/L (n:39). The first two groups were classified as suppression groups, and the last as replacement (control) group. All patients underwent 12-lead electrocardiogram (ECG) recording and 24-hour rhythm holter echocardiography analysis.

Results: The HRV results derived from a 24-hour rhythm holter did not exhibit any significant difference (p < 0.05). In dispersion evaluations, the QTd was significantly longer in the suppression groups (groups 1 and 2), than in the replacement group (group 3) (p < 0.001 and p:0.002, respectively). The same was found for corrected QT dispersion (QTcd) (p < 0.001 and p: 0.008, respectively). In multivariate linear regression analysis, TSH was found to affect QTd (β = -0.299; p = 0.002) and QTcd (β = -0.300; p = 0.002) values independently.

Conclusion: In this study, it was shown that in patients with DTC receiving TSHST, QT dispersion prolonged as the TSH suppression level increased. Especially in high-risk DTC patients, evaluation of QTd may be useful in terms of evaluating cardiovascular risk and regulating TSHST level.

Background: Progastrin-releasing peptide (ProGRP) is the precursor of the gastrin-releasing peptide, a neuropeptide secreted by cells of neural and endocrine origin. Recently, ProGRP has emerged as a circulating biomarker for small cell lung cancer (SCLC), a subtype of aggressive and poorly differentiated neuroendocrine neoplasm (NEN). Given the ability of the neuroendocrine SCLC cells to secrete this peptide, we performed an in-depth narrative review aimed at collecting, summarizing, and critically analyzing the available literature about the possible value of ProGRP as a biomarker for pulmonary NENs other than SCLC, and for NENs of non-pulmonary origin.

Methods: We conducted an extensive search on international databases (PubMed, Web of Science, and Scopus).

Results: We selected 21 pertinent published articles (12 original studies and 9 case reports). Overall, the original studies included 1,711 patients, and the case reports described the clinical course of 10 patients.

Conclusion: The data analyzed suggest a potential role for ProGRP as a diagnostic biomarker for typical and atypical lung carcinoids, pulmonary large cell neuroendocrine carcinoma, medullary thyroid carcinoma, non-pulmonary neuroendocrine carcinomas, prostate cancer with neuroendocrine differentiation, and the pancreatobiliary neuroendocrine carcinoma. Despite these promising results, additional studies are needed, to clarify the role of ProGRP as the diagnostic biomarker for specific NENs.

Background: Cushing's syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing's syndrome, Cushing's disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination.

Methods: Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels.

Results: Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9-77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol).

Conclusion: The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.

Objective: Type 1 diabetes mellitus (T1DM) is an autoimmune disease where immune cells attack insulin-producing beta cells. Islet transplantation is a promising treatment for T1DM. This study aims to evaluate the effects of adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with pancreatic islet transplantation using hydrogel.

Methods: T1DM mouse model was established using streptozotocin (STZ). Islets and AT-MSCs were co-embedded in a hydrogel and transplanted into diabetic mice. Five groups with six animals in each (control, hydrogel alone, AT-MSCs embedded hydrogel, islet embedded in hydrogel, and islet + AT-MSCs co-imbedded into a hydrogel) were evaluated in terms of blood glucose, insulin levels and serum and lavage cytokine production.

Results: During 32 days, blood glucose levels decreased from over 400 mg/dl to less than 150 mg/dl in the transplanted mice. Analysis showed increased transformation growth factor beta (TGF-β1) and IL-4 levels, while IL-17 and IFN-γ levels significantly decreased in the MSC-treated groups.

Conclusion: These findings suggest that using AT-MSCs with hydrogel could be a beneficial alternative for enhancing pancreatic islet engraftment and function.

Background: The existence of a functional relationship between a certain thyroid hormone analogue and cancer cell radioresistance has been shown by Leith and coworkers. The hormone analogue with relevance to malignant cells' radioresistance is tetraiodothyroacetic acid (tetrac). Tetrac is the deaminated derivative of L-thyroxine (T4), the principal product of the thyroid gland. Preclinical studies demonstrated that tetrac and chemically modified tetrac (CMT), e.g. a fluorobenzyl-conjugated tetrac analogue, restores radiosensitivity in certain radioresistant tumor cells. Due to their molecular, physico-chemical, and biological properties, actions of CMT analogues are believed to be initiated at the thyroid hormone analogue receptor site on plasma membrane integrin αvβ3.

Objective: To explore possible molecular mechanisms of the potentially therapeutically beneficial effect of CMT on cancer cells' sensitivity to radiation, we analyzed actions of CMT analogues on expression of selected sets of genes that have been previously implicated in radioresistance of malignant cells.

Discussion and conclusions: In the current study, we report that genome-wide gene expression profiling analysis of human glioblastoma (GBM) and acute myelocytic leukemia (AML) cell lines exposed in vitro to noncytotoxic doses of CMT has identified decreased expression of discrete trios of genes each of which was previously linked to cancer cells' radioresistance. Following the CMT treatment in AML cells, expression of PARP9, PARP15 and STAT3 genes was significantly reduced, while in GBM cells, expression of PRKDC, EGFR and CCNDI was significantly decreased by the drug. Notably, a broader spectrum of genes implicated in cancer cells' radioresistance was observed in primary patient-derived GBM cells after the CMT treatment. Extensive additional experimental and clinical studies are indicated, including analyses of individual patient tumor genomics and of an array of different tumor types to define the sub-sets of tumors manifesting radioresistance in which tetrac-based agents may be expected to enhance therapeutic effects of radiation.