Endocrine Research[JOURNAL]
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200 papers
Serologic Testing for Celiac Disease in Graves' Hyperthyroidism: Should We Act Early?
Demirdere H, Caklili OT, Yarman S
Endocr Res · 2022 Feb · PMID 34374618 · Publisher ↗
BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet....
BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. MATERIALS AND METHODS: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG - AGA and IgA - AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. RESULTS: Screening 35 patients with GD revealed positive results for IgA-AGA ( = 6/35, 17%), IgG-AGA ( = 9/35, 26%), IgA-EmA ( = 2/35, 6%) and IgA-tTG ( = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. CONCLUSION: Due to possibility of false seropositivity of celiac antibodies in patients with Graves' thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.
Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma.
de Jong MC, Patel N, Hassan-Smith Z … +2 more , Mihai R, Khan S
Endocr Res · 2022 Feb · PMID 34340645 · Publisher ↗
AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been...
AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm/m for males and <38.5cm/m for females. RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age ( < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69]; = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.
Post-treatment heterogeneity of cardiometabolic risk in patients with acromegaly: The impact of GH and IGF-1.
Heydari M, Hashemi-Madani N, Emami Z … +5 more , Khajavi A, Ghorbani M, Malek M, Ataei Kachuee M, Khamseh ME
Endocr Res · 2022 Feb · PMID 34102938 · Publisher ↗
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...
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, = .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 , 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.
The Ratios of Triglycerides and C-reactive protein to High density-lipoprotein -cholesterol as valid biochemical markers of the Nascent Metabolic Syndrome.
Jialal I, Adams-Huet B
Endocr Res · 2021 Nov · PMID 34080928 · Publisher ↗
: 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-rea...
: 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.: Patients with MetS ( = 58) and matched controls ( = 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.: 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.: 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.
AST-120 Treatment Alters the Gut Microbiota Composition and Suppresses Hepatic Triglyceride Levels in Obese Mice.
Hiraga Y, Kubota T, Katoh M … +5 more , Horai Y, Suzuki H, Yamashita Y, Hirata R, Moroi M
Endocr Res · 2021 Nov · PMID 34060951 · Publisher ↗
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....
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. AST-120 (5% w/w) was administrated to 6-week-old male 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. Significant decreases of the hepatic weight and hepatic TG levels were observed in the AST-120-treated 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 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 mice. These data suggest that AST-120 treatment alters the composition of the fecal microbiota and suppresses hepatic TG levels in the mice.
Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy of Radioactive Iodine Monotherapy versus Radioactive Iodine Therapy and Adjunctive Lithium for the Treatment of Hyperthyroidism.
Ahmed FW, Kirresh OZ, Majeed MS … +2 more , Iftikhar M, Sajid MS
Endocr Res · 2021 Nov · PMID 34028325 · Publisher ↗
: 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.: A sys...
: 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.: 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.: 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.: 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.
Women with Subclinical Hypothyroidism are at Higher Prevalence of Metabolic Syndrome and Its Components Compared to Men in an Older Chinese Population.
Deng L, Wang L, Zheng X … +2 more , Shuai P, Liu Y
Endocr Res · 2021 Nov · PMID 34028317 · Publisher ↗
: 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.: The stu...
: 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.: 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).: 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 ( < .01 for all), and with a trend for low HDL-C ( = .098).: 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.
Association between Thyroid Function and Prognosis of COVID-19: A Retrospective Observational Study.
Lang S, Liu Y, Qu X … +5 more , Lu R, Fu W, Zhang W, Wang H, Hong T
Endocr Res · 2021 Nov · PMID 34014139 · Publisher ↗
: 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 s...
: 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.: 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.: 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) . 1.9 (1.0-3.1) μIU/mL, = .031] and free triiodothyronine (FT) [2.9 (2.8-3.1) . 4.2 (3.5-4.7) pmol/L, < .001] were lower in non-survivors than in survivors, and a low FT state (defined as FT < 3.1 pmol/L) at admission accounted for a higher proportion in non-survivors than in survivors (72.7% . 11.2%, < .001). Univariate Cox regression analysis showed that FT level (HR 0.213, 95% CI: 0.101-0.451, < .001) and the low FT state (HR 14.607, 95% CI: 3.873-55.081, < .001) were negatively and positively associated with the risk of in-hospital death, respectively. Furthermore, multivariate Cox regression analysis revealed that a low FT 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, = .043). Moreover, Kaplan-Meier curves indicated a lower survival probability in COVID-19 patients with a low FT status.: Serum FT level is lower in non-survivors among moderate-to-critical patients with COVID-19, and the low FT state is associated with an increased risk of in-hospital mortality of COVID-19.
Sexual Dimorphism in Alternative Metabolic Pathways of L-Arginine in Circulating Leukocytes in Young People with Type 1 Diabetes Mellitus.
Alchujyan N, Hovhannisyan M, Movsesyan N … +5 more , Melkonyan A, Shaboyan V, Aghajanova Y, Minasyan G, Kevorkian G
Endocr Res · 2021 Nov · PMID 33944639 · Publisher ↗
: 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 (...
: 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. 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. 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. 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. 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 occurring in the pancreas and the outcome of therapy through infiltrated leukocytes. Obtained data can be useful for understanding the heterogeneity of T1DM and using it to develop available criteria for assessing the severity and treatment of autoimmune diabetes.
Comparison of the Effectiveness of Adult Height Prediction Methods in Children with Growth Hormone Deficiency.
Erbaş İM, Ölmez Z, Paketçi A … +3 more , Demir K, Böber E, Abacı A
Endocr Res · 2021 Aug · PMID 33900130 · Publisher ↗
: 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...
: 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.: 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.: 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.: 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.: 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.
Relationship between Functional Cluster Variants and Susceptibility to Type 2 Diabetes Mellitus: A Preliminary Case-Control Study and Bioinformatics Analyses.
Jahantigh D, Mirani Sargazi F, Sargazi S … +4 more , Saravani R, Ghazaey Zidanloo S, Heidari Nia M, Piri M
Endocr Res · 2021 Aug · PMID 33870836 · Publisher ↗
To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the cluster with Type 2 diabetes mellitus (T2DM) risk. A total of 1200 subjects were genotyped using the ARMS-PCR method. The rs...
To investigate the link between two variants (rs4705342 and rs4705343) in the promoter of the cluster with Type 2 diabetes mellitus (T2DM) risk. A total of 1200 subjects were genotyped using the ARMS-PCR method. The rs4705342 variant enhanced the risk of T2DM under codominant CC (OR = 3.24; 95% CI: 1.89-5.60), recessive TT+TC (OR = 3.02; 95% CI: 1.77-5.17), and dominant TC+CC (OR = 1.35; 95% CI: 1.08-1.71) genetic models. Individuals carrying the C allele of rs4705342 conferred a 1.43 fold increased risk of T2DM. As regards rs4705343, decreased risk of T2DM was observed under codominant TC (OR = 0.53; 95% CI: 0.42-0.67), over-dominant TT+CC (OR = 0.51; 95% CI: 0.40-0.64), and dominant TC+CC (OR = 0.59; 95% CI: 0.48-0.75) models. Haplotype analysis of the variants showed a 1.941-fold increased risk of T2DM regarding the C T combination. Significant associations were noticed between different haplotypes and lipid indices of T2DM patients. There were no notable changes in -values after adjustment for BMI. Computational analysis revealed that miR143 and/or miR145 target important genes involved in glucose and lipid metabolism. Functional miR-143/145 variants might influence the risk of T2DM. Hence, clarifying the precise regulatory mechanisms of gene expression in the development of T2DM will significantly guide researchers to find a novel target for therapeutic intervention.
Editor's Comment. Caution: The Intersection of Diabetes and COVID-19.
Chernoff A
Endocr Res · 2021 · PMID 33730984 · Publisher ↗
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Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells.
Ahram M, Bawadi R, Abdullah MS … +4 more , Alsafadi DB, Abaza H, Abdallah S, Mustafa E
Endocr Res · 2021 Aug · PMID 33703980 · Publisher ↗
The cellular and molecular dynamics of DHT-induced EMT in MDA-MB-453 cells were investigated.:PCR arrays were used to examine the expression of EMT-regulatory genes. Immunoblotting was used to detect protein levels and c...
The cellular and molecular dynamics of DHT-induced EMT in MDA-MB-453 cells were investigated.:PCR arrays were used to examine the expression of EMT-regulatory genes. Immunoblotting was used to detect protein levels and confirm protein-protein interaction following immunoprecipitation. Immunofluorescence was used to observe rearrangement of the actin cytoskeleton and cell morphology. Cell migration was assessed by transwell assay Change of cell morphology was concomitant with increased cell migration after treating cells with DHT. Exposure of cells to DHT for one hour was sufficient to induce changes in cell morphology and actin cytoskeleton after 72 hours indicating altered gene expression. A long-term lasting nuclear translocation of AR was observed after a short exposure of cells to DHT. Investigating the expression of 84 EMT-related genes revealed down-expression of β-catenin, N-cadherin, and TCF-4 and increased expression of Slug, all of which were confirmed at the protein level. Yet, not only early interaction of AR and β-catenin was observed following AR activation, inhibition of β-catenin blocked DHT-induced mesenchymal transition and migration. Wnt signaling was found to be partially important in DHT-induced morphological alteration. The mesenchymal transition of cells could be induced by treating cells with an inhibitor of glycogen synthase kinase-3β, an enzyme that inhibits β-catenin; this morphological transition could be reversed by antagonizing AR suggesting that AR functions downstream of β-catenin. These results suggest that MDA-MB-453 cells undergo partial EMT induced by DHT, β-catenin is critical for this phenotypic change, and AR probably reciprocally mediates the mesenchymal transition of these cells upon activation of GSK-3 β.
Insulin Use and Poor COVID-19 Outcomes among Diabetes Patients: Association Not Necessarily Causation.
Riahi S, Lo KB, Anastasopoulou C … +1 more , Rangaswami J
Endocr Res · 2021 · PMID 33684317 · Publisher ↗
Our study looked at the relationship between insulin use and clinical outcomes in COVID-19. A response to our article, written by Dr. Chia Sing Kow and Dr. Syed Shahzad Hasan raised a few questions. They mentioned our us...
Our study looked at the relationship between insulin use and clinical outcomes in COVID-19. A response to our article, written by Dr. Chia Sing Kow and Dr. Syed Shahzad Hasan raised a few questions. They mentioned our use of hemoglobin A1c may be inaccurate as the patients in our study had high rates of CKD or ESRD which could alter the hemoglobin A1c levels. However due to the limitations of our patient population and perhaps in a lot of other sample populations in the real-world setting, it was the most feasible way to represent glucose control.The writers also suggested that the use of metformin, a potential confounder, was also not adjusted for. This should be considered in future research but addition of too many variables in a regression model may lead to less reliability of results for our study.The letter writers also suggested that the results of our paper may lead to misinterpretation by readers and may influence providers to not use insulin therapy for their patients when necessary due to fear of worse outcomes in the setting of COVID-19. We reiterated that it is very important that the data not be misinterpreted, and that nowhere in our paper did we imply or suggest that patients who need insulin therapy to treat their diabetes should not receive proper therapy due to the association we delineated in our paper. Instead, more careful surveillance of patients with advanced diabetes is needed especially when admitted with COVID-19.
Insulin Treatment May Not Be Associated with Increased Mortality in Patients with COVID-19 and Concurrent Diabetes.
Kow CS, Hasan SS
Endocr Res · 2021 · PMID 33635726 · Publisher ↗
Previous study reported that preadmission insulin treatment in patients with coronavirus disease 2019 (COVID-19) and concurrent diabetes was associated with a significantly increased odds of mortality. However, such asso...
Previous study reported that preadmission insulin treatment in patients with coronavirus disease 2019 (COVID-19) and concurrent diabetes was associated with a significantly increased odds of mortality. However, such association may be modified by possible baseline differences in glycemic control between insulin users and non-insulin users. Misinterpretation of the association between insulin treatment and mortality could lead to confusion in clinical practice and hospitalized patients with COVID-19 for whom insulin treatment is appropriately indicated may be omitted from such treatment. However, requirement for insulin during hospitalization for COVID-19 may be a marker of poor prognosis and as such could be used to identify patient population who require more aggressive treatments to prevent mortality.
The Influence of Glucocorticoid Receptor on Sex Differences of Gene Expression Profile in Skeletal Muscle.
Yoshikawa N, Oda A, Yamazaki H … +4 more , Yamamoto M, Kuribara-Souta A, Uehara M, Tanaka H
Endocr Res · 2021 Aug · PMID 33590778 · Publisher ↗
Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elus...
Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elusive. Glucocorticoids are adrenocortical hormones maintaining homeostasis, including regulating whole-body energy metabolism in addition to stress response. In skeletal muscle, glucocorticoids can reduce the synthesis of muscle proteins and simultaneously accelerate the breakdown of proteins to regulate skeletal muscle mass and energy metabolism via a transcription factor glucocorticoid receptor (GR). We herein evaluated the related contributions of the GR to sex differences of gene expression profiles in skeletal muscle using GR-floxed (GRf/f) and skeletal muscle-specific GR knockout (GRmKO) mice. There were no differences in GR mRNA and protein expression levels in gastrocnemius muscle between males and females. A DNA microarray analysis using gastrocnemius muscle from GRf/f and GRmKO mice revealed that, although most gene expression levels were identical in both sexes, genes related to cholesterol and apolipoprotein synthesis and fatty acid biosynthesis and the immunological system were predominantly expressed in males and females, respectively, in GRf/f but not in GRmKO mice. Moreover, many genes were up-regulated in response to starvation in GRf/f but not in GRmKO mice, many of which were sex-independent and functioned to maintain homeostasis, while genes that showed sex dominance related to a variety of functions. Although the genes expressed in skeletal muscle may be predominantly sex-independent, sex-dominant genes may relate to sex differences in energy metabolism and the immune system and could be controlled by the GR.
The association between insulin-like growth factor 1 levels within reference range and early postoperative remission rate in patients with Cushing's disease.
Gezer E, Çetinarslan B, Selek A … +6 more , Cantürk Z, Sözen M, Elen Ö, Baydemir C, Çabuk B, Ceylan S
Endocr Res · 2021 Aug · PMID 33560156 · Publisher ↗
INTRODUCTION: The relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) and glucocorticoids (GC) was examined in various studies. Long-term GC treatment was shown to decrease GH concentration and,...
INTRODUCTION: The relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) and glucocorticoids (GC) was examined in various studies. Long-term GC treatment was shown to decrease GH concentration and, interestingly, to increase IGF-1 concentration. We performed a retrospective study in order to examine how preoperative IGF-1 concentrations vary within the reference range and if tertiles of age- and sex-adjusted normal IGF-1 are predictive for early postoperative remission in the patients with Cushing's Disease (CD). PATIENTS AND METHODS: Patients diagnosed with CD were retrospectively evaluated. After the exclusion of 67 patients, a final cohort of 250 CD patients were included. Age- and sex-adjusted normal IGF-1 levels were divided into tertiles (T1, T2 and T3). Early postoperative remission was defined as a nadir morning cortisol concentration measured within the first 3 consecutive days following surgery of less than 5 µg/dL (138 nmol/L). RESULTS: Early postoperative remission rate was the lowest in T1 and highest in T3; 49.1% (n = 28) versus 77.3% (n = 75), = .001, respectively. Binary logistic regression analysis showed the remission rate in T3 was three times higher than that in T1 ( = .003). Cortisol and ACTH concentration were significantly higher and GH concentrations were significantly lower in T1 compared to those in the other two tertiles. CONCLUSIONS: As the first study evaluating the correlation between early postoperative remission rate in patients with CD and the tertiles of normal age- and sex-adjusted IGF-1 levels, we have shown that higher IGF-1 levels could predict better outcome in CD.
Lipoprotein(a) and Hyperinsulinemia in Healthy Normal-weight, Prepubertal Mexican Children.
Rodríguez-Moran M, Gamboa-Gómez CI, Preza-Rodríguez L … +1 more , Guerrero-Romero F
Endocr Res · 2021 Aug · PMID 33554676 · Publisher ↗
. 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.. A...
. 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.. 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.. The median (25-75 percentile) serum levels of Lp(a) [20.0 (13.7-29.6) 14.6 (10.6-26.7) mg/dL, = .003] and insulin [24.5 (6.0-30) 7.9 (4.3-9.0) µU/L, < .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, < .0005) and insulin resistance (OR 2.01; 95%CI 1.1-9.9, = .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, < .0001) and the HOMA-IR index (β 2.606; 95%CI 2.3-2.9, < .0005).. Lp(a) was associated with hyperinsulinemia and insulin resistance in healthy normal-weight, prepubertal children.
MTHFR Polymorphisms in Girls with Anorexia Nervosa: Implications on Body Weight.
Augoulea A, Armeni E, Deligeoroglou E … +8 more , Paschou SA, Papadimitriou G, Stergioti E, Karountzos V, Tsitsika A, Panoulis K, Economou E, Lambrinoudaki I
Endocr Res · 2021 · PMID 33508999 · Publisher ↗
The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the met...
The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, -value = 0.041; CI 95% 1.057-6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076-22.579, -value = 0.040; A1298C, OR = 0.097, 95% CI 0.011-0.866, -value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism.
Effect of Vagotomy and Sympathectomy on the Feeding Responses Evoked by Intra-Aortic Cholecystokinin-8 in Adult Male Sprague Dawley Rats.
Mhalhal TR, Washington MC, Heath JC … +1 more , Sayegh AI
Endocr Res · 2021 · PMID 33426974 · Publisher ↗
The vagus nerve and the celiaco-mesenteric ganglia (CMG) are required for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by intraperitoneal (ip) sulfated cholecystokinin-8 (CCK-8). However,...
The vagus nerve and the celiaco-mesenteric ganglia (CMG) are required for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by intraperitoneal (ip) sulfated cholecystokinin-8 (CCK-8). However, recently we have shown that the gut regulates these responses. Therefore, reevaluating the role of the vagus and the CMG in the feeding responses evoked by CCK is necessary because the gut contains the highest concentration of enteric, vagal and splanchnic afferents and CCK-A receptors, which are required for reduction of food intake by this peptide, compared to other abdominal organs. To address this necessity, we injected sulfated CCK-8 (0, 0.1, 0.5, 1 and 3 nmol/kg) in the aorta, near the gastrointestinal sites of action of the peptide, in three groups of free-feeding rats (n = 10 rats per group), subdiaphragmatic vagotomy (VGX), celiaco-mesenteric ganglionectomy (CMGX) and sham-operated, and recorded seven feeding responses. In the sham group, CCK-8 reduced MS (normal chow), prolonged the intermeal interval (IMI, time between first and second meals), increased satiety ratio (SR, IMI/MS), shortened duration of first meal, reduced total (24 hrs) food intake and reduced number of meals relative to saline vehicle. Vagotomy attenuated all of the previous responses except IMI length and SR, and CMGX attenuated all of those responses. In conclusion, the feeding responses evoked by sulfated CCK-8 require, independently, the vagus nerve and the CMG.
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