Endocrine Research最新文献

Background: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities.

Objective: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly.

Methods: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models.

Results: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025).

Conclusions: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN, or dyslipidemia in this study.

Abbreviations: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Background: Epithelial-mesenchymal transition (EMT) of tumor cells is a prerequisite to cancer cell invasion and metastasis. This process involves a network of molecular alterations. Androgen receptor (AR) plays an important role in the biology of breast cancers, particularly those dependent on AR expression like luminal AR (LAR) breast cancer subtype. We have recently reported that the AR agonist, dihydrotestosterone (DHT), induces a mesenchymal transition of MDA-MB-453 cells, concomitant with transcriptional up-regulation of Slug and regulator of G protein signaling 2 (RGS2).

Objective: The role of Slug and RGS2 in mediating the DHT-induced effects in these cells was investigated.

Methods: MDA-MB-453 cells were used as a model system of LAR breast cancer. Immunofluorescence was used to examine cell morphology and protein localization. Protein expression was analyzed by immunoblotting. Protein localization was confirmed by cell fractionation followed by immunoblotting. Protein-protein interaction was confirmed by co-immunoprecipitation followed by immunoblotting. Transwell membranes were used to assess cell migration. Transfection of cells with siRNA molecules that target Slug and RGS2 mRNA was utilized to delineate the modes of action of these two molecules.

Results: Treatment of MDA-MB-453 cells with DHT induced the expression of both proteins. In addition, AR-Slug, AR-RGS2, and Slug-RGS2 interactions were observed shortly after AR activation. Knocking down Slug abrogated the basal, but not the DHT-induced, cell migration and blocked DHT-induced mesenchymal transition. On the other hand, RGS2 knocked-down cells had an increased level of Slug protein and assumed mesenchymal cell morphology with induced migration, and the addition of DHT further elongated cell morphology and stimulated their migration. Inhibition of AR or β-catenin reverted the RGS2 knocked-down cells to the epithelial phenotype, but only inhibition of AR blocked their DHT-induced migration.

Conclusions: These results suggest the involvement of RGS2 and Slug in a complex molecular network regulating the DHT-induced mesenchymal features in MDA-MB-453 cells. The study may offer a better understanding of the biological role of AR in breast cancer toward devising AR-based therapeutic strategies.

Background: Coronavirus disease 2019 (COVID-19) is a severe infectious illness. It has been reported that COVID-19 has an effect on thyroid function. However, the association between thyroid function and prognosis of COVID-19 is still unclear.Methods: This retrospective study included patients with COVID-19 admitted to Tongji Hospital in Wuhan from January 28 to April 4, 2020. Demographic, epidemiological, clinical, laboratory, treatment, and outcome data were collected from patients with laboratory-confirmed COVID-19. Patients without history of thyroid disease who had a thyroid function test at admission were enrolled in the final analysis. Risk factors of in-hospital death were explored using univariable and multivariable Cox regression analyses. Survival differences were assessed with Kaplan-Meier curves and log-rank test.Results: A total of 127 patients were included in this study, with 116 survivors and 11 non-survivors. The serum levels of thyroid stimulating hormone (TSH) [0.8 (0.5-1.7) vs. 1.9 (1.0-3.1) μIU/mL, P = .031] and free triiodothyronine (FT₃) [2.9 (2.8-3.1) vs. 4.2 (3.5-4.7) pmol/L, P < .001] were lower in non-survivors than in survivors, and a low FT₃ state (defined as FT₃ < 3.1 pmol/L) at admission accounted for a higher proportion in non-survivors than in survivors (72.7% vs. 11.2%, P < .001). Univariate Cox regression analysis showed that FT₃ level (HR 0.213, 95% CI: 0.101-0.451, P < .001) and the low FT₃ state (HR 14.607, 95% CI: 3.873-55.081, P < .001) were negatively and positively associated with the risk of in-hospital death, respectively. Furthermore, multivariate Cox regression analysis revealed that a low FT₃ state was associated with an increased risk of in-hospital death after adjusting for confounding factors (HR 13.288, 95% CI: 1.089-162.110, P = .043). Moreover, Kaplan-Meier curves indicated a lower survival probability in COVID-19 patients with a low FT₃ status.Conclusion: Serum FT₃ level is lower in non-survivors among moderate-to-critical patients with COVID-19, and the low FT₃ state is associated with an increased risk of in-hospital mortality of COVID-19.

Aims: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations  C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS.Methods: Patients with MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically.Results: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios.Conclusions: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.

Purpose: This study investigated the impact of sex differences on the relationship of subclinical hypothyroidism (SCH) with the prevalence of metabolic syndrome (MetS) and its components in an older Chinese population.Methods: The study included 1842 older Chinese individuals aged 65 years or older who received annual health checkups. The impact of sex differences on the relationship of SCH with the prevalence of MetS and its components was investigated by multivariate logistic regression analysis. Interaction effect between sex and SCH on the prevalence of MetS and its components were evaluated using a multivariate logistic regression model which includes interaction terms (sex-SCH).Results: The study comprised 1701 (92.3%) individuals with euthyroidism and 141 (7.7%) with SCH. In men, SCH was not associated with MetS or any components of the MetS. In women, the SCH group had higher prevalence of MetS [odds ratio (OR), 1.870; 95% confidence interval (CI), 1.136-3.079], abdominal obesity (OR, 1.693; 95% CI, 1.043-2.748), hypertriglyceridemia (OR, 1.711; 95% CI, 1.054-2.775) and low high-density lipoprotein cholesterol (HDL-C) (OR, 3.039; 95% CI, 1.576-5.861). There was an interaction between sex and SCH in terms of the effect on the prevalence of MetS and its components, including abdominal obesity and hypertriglyceridemia (P < .01 for all), and with a trend for low HDL-C (P = .098).Conclusion: There were sex differences in the correlation of SCH with the prevalence of MetS and its components in the older Chinese population. An interaction effect between sex and SCH on the prevalence of MetS and its components was found.

Background: Sexual dimorphism in specific biochemical pathways and immune response, underlies the heterogeneity of type 1 diabetes mellitus (T1DM) and affects the outcome of immunotherapy. Arginase and nitric oxide (NO) synthase (NOS) metabolize L-arginine and play opposite roles in the immune response and autoimmune processes.Objective: We hypothesized that the above mentioned enzymes can be involved in sex and age differences in T1DM and its treatment. Based on this, the enzymes have been studied in peripheral blood leukocytes (PBL) and plasma of young people with T1DM.Methods: Patients were recruited from Muratsan University Hospital (Yerevan, Armenia) and were divided into groups: girls and boys by age, from children to adolescents and adolescents/young adults with recent-onset T1DM (RO-T1DM) (0.1-1 years) and long-term T1DM (LT-T1DM) (1.6-9.9 years). Arginase activity was assessed by L-arginine-dependent production of L-ornithine, and the NOS activity was assessed by NO/nitrite production. Glycemic control was assessed using hemoglobin A1c test. Plasma HbA1c concentration below 7.5% (median (range) 6.7 [6.2-7.5]) was taken as good glycemic control (+) and above 7.5% (median (range) 10.5 [7.6-13]) as poor glycemic control (-). Healthy volunteers with corresponding sex and age were used as the control group.Results: All the patients with RO-T1DM, with poor glycemic control, had increased arginase activity in the cytoplasm (cARG) and mitochondria (mARG) in PBL. In girls with RO-T1DM, with good glycemic control, the subcellular arginase activity decreased, and normalized in LT-T1DM, regardless of age. In contrast, boys from both age groups showed high arginase activity, regardless of glycemic control and duration of T1DM along with insulin therapy. At the same time, a significant decrease in the subcellular production of bioavailable NO was observed in children/preadolescents, regardless of glycemic control and duration of diabetes. In adolescents/young adult boys with RO-T1DM, with (-), the subcellular production of NO decreased significantly, and with LT-T1DM, the decrease was attenuated, but even with (+) remained lower than in healthy people. In contrast, in the group of same age girls with RO-T1DM, NO production increased above normal in both cellular compartments, while with LT-T1DM it normalized in the cytoplasm. In adolescents/young adults with LT-T1DM, NO production in PBL mitochondria decreased by almost a half, regardless of glycemic control and gender. Changes in the metabolic pathways of L-arginine in plasma differed and were less substantial than in the PBL cellular compartments in T1DM.Conclusions: Glycemic status and duration of T1DM along with insulin therapy affect the activity of arginase and NOS-dependent production of bioavailable NO in the cytoplasm and mitochondria in PBL of young patients with T1DM, depending on sex and age. Arginase and NOS can directly affect the processes occurr

Background: The objective of this article is to evaluate the outcomes in patients undergoing radioactive iodine (RAI) with adjunctive lithium (Li) therapy versus (vs.) RAI therapy alone for the treatment of hyperthyroidism.Methods: A systematic review of the literature was undertaken to analyze clinical trials comparing RAI with adjunctive Li therapy vs. RAI therapy alone for the treatment of hyperthyroidism.Results: Six randomized-controlled trials (RCT) involving 755 patients were analyzed. RAI with adjunctive Li was associated with a significantly higher cure rate for hyperthyroidism when compared to RAI alone. Furthermore, a significantly higher cure rate for hyperthyroidism at 12 months was achieved with RAI and adjunctive Li. Adjuvant Li with RAI for ≤ 7 days showed significantly higher cure rate compared to RAI alone, whereas > 7 days of adjuvant Li with RAI did not show any difference in cure rate compared to RAI alone. RAI with adjunctive Li was associated with a significantly higher cure rate for patients with Graves' disease compared to RAI alone. There was no significant difference between RAI with adjunctive Li and RAI alone for toxic nodular thyroid disorder (toxic nodule and toxic multinodular goiter) and thyroid volume >40 grams and ≤40 grams.Conclusions: RAI with adjunctive Li therapy demonstrated superiority over RAI therapy alone with regards to both curing hyperthyroidism and, reduced time till cure, with a limited side effect profile. A large multicenter RCT is required, and if this confirms the data from these smaller trials, then this could change current practice.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. The existence of a relationship between the microbiota and the pathology of hepatic steatosis is also becoming increasingly clear. AST-120, an oral spherical carbon adsorbent, has been shown to be useful for delaying dialysis initiation and improving uremic symptoms in patients with chronic kidney disease. However, little is known about the effect of AST-120 on fatty liver.Methods: AST-120 (5% w/w) was administrated to 6-week-old male db/db mice for 8 weeks. The body weight, blood glucose and food consumption were examined. Hepatic triglyceride (TG) levels, lipid droplets and epididymal fat cell size were measured. The gut microbiota compositions were investigated in feces and cecum.Results: Significant decreases of the hepatic weight and hepatic TG levels were observed in the AST-120-treated db/db mice. Furthermore, AST-120 treatment was also associated with a decrease of Bacteroidetes, increase of Firmicutes, and a reduced ratio of Bacteroidetes to Firmicutes (B/F ratio) in the feces in the db/db mice. The B/F ratio in the feces was correlated with the liver weight and area of the liver occupied by lipid droplets in the db/db mice.Conclusions: These data suggest that AST-120 treatment alters the composition of the fecal microbiota and suppresses hepatic TG levels in the db/db mice.

Background. Given the numerous gaps in our knowledge about the biological interactions of lipoprotein(a) [Lp(a)], we determined whether Lp(a) was associated with hyperinsulinemia in healthy normal-weight, prepubertal children.Methods. A total of 131 healthy normal-weight Mexican children aged 6 to 9 years at Tanner stage 1 who were born appropriate for gestational age were enrolled in a case-control study. Children with hyperinsulinemia were allocated into the case group (n = 32), and children with normal insulin levels were allocated into the control group (n = 99). Birth weight, age, and body mass index were matching criteria. Multivariate logistic regression analysis was used to compute the odds ratio (OR) between Lp(a) and both hyperinsulinemia and insulin resistance. Furthermore, a multivariate linear regression analysis was performed to evaluate the association between Lp(a) and both insulin levels and HOMA-IR. Both models were adjusted by sex, age, birth weight, and body mass index.Results. The median (25-75 percentile) serum levels of Lp(a) [20.0 (13.7-29.6) versus 14.6 (10.6-26.7) mg/dL, p = .003] and insulin [24.5 (6.0-30) versus 7.9 (4.3-9.0) µU/L, p < .0005] were higher in the case group than in the control group. The logistic regression analysis showed that Lp(a) was associated with hyperinsulinemia (OR 5.86; 95%CI 2.5-13.6, p < .0005) and insulin resistance (OR 2.01; 95%CI 1.1-9.9, p = .004). In addition, the linear regression analysis showed a significant association between serum Lp(a) and insulin levels (β 11.1; 95%CI 1.8-10.9, p < .0001) and the HOMA-IR index (β 2.606; 95%CI 2.3-2.9, p < .0005).Conclusion. Lp(a) was associated with hyperinsulinemia and insulin resistance in healthy normal-weight, prepubertal children.

Background: In patients with growth hormone (GH) deficiency, the prediction of adult height before initiation of GH treatment can be helpful to guide clinicians and families. However, data regarding the effectiveness of prediction methods in such patients are limited.Objective: We aimed to investigate the accuracy of the three most used adult height prediction methods [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their results with the near-adult height (NAH) data of children treated with GH.Methods: A single-center retrospective study was conducted including patients treated with somatotropin due to GH deficiency. Bone age radiographs were reread by three authors. Adult height predictions were made using BP, RWT, and TW2 methods for each patient.Results: Forty-nine patients with GH deficiency [median age at diagnosis 10.8 (9.2-12.0) years, 63.3% girls, 69.4% prepubertal] were included. Median differences between predicted adult height (PAH) and NAH standard deviation (SD) scores were -0.5, 0.0, and 0.3 for BP, RWT, and TW2 methods, respectively. The rates of PAH within ±1 SD score of NAH were 54.7%, 62.3%, and 77.4% for BP, TW2, and RWT methods, respectively. RWT was the most accurate method in girls, however, it showed a similar efficiency with TW2 in prepubertal patients or those with delayed bone age between 1-2 years, independent of gender.Conclusions: We found that RWT and TW2 methods may be preferable rather than the BP method for predicting adult height in patients with a diagnosis of GH deficiency.