Endocrine Research

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ISSN / EISSN : 0743-5800 / 1532-4206
Published by: Informa UK Limited (10.1080)
Total articles ≅ 1,581
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Wenjiang Sun, Guanghui Liu,
Published: 4 December 2021
Adiponectin (APN) is reported to be correlated closely with autonomic nervous function in different clinical settings. Heart rate recovery (HRR) is a noninvasive and readily obtainable indicator, which reflects the coordinated interplay between parasympathetic reactivation and sympathetic withdrawal. This study aimed to investigate the relationship between serum APN and HRR in polycystic ovarian syndrome (PCOS) women. Eighty-nine PCOS women were enrolled and divided into two groups. Women with HRR values slower than 12 beats were defined as Blunted HRR Group. APN levels were compared between Blunted HRR Group and Normal HRR Group. Multivariate logistic regression analysis and multiple linear regression analysis were performed to determine which clinical variables were independently associated with HRR and APN levels, respectively. Twenty-three women were categorized into Blunted HRR Group, in which APN level was significantly lower than Normal HRR Group. Age, body mass index, hypertension, and APN were independent factors of attenuated HRR in PCOS women. Meanwhile, multiple linear regression analysis showed age, dyslipidemia, and homeostasis model assessment-insulin resistance (HOMA-IR) were closely associated with APN levels in PCOS women. Our findings suggested that decreased APN concentration was closely associated with HRR blunt in PCOS women. Further studies are needed to explore the underlying interactions between APN and autonomic nervous function.
Jessica M. Toothaker, Kristen Roosa, Alexandra Voss, Suzanne M. Getman,
Published: 4 December 2021
Endocrine Research pp 1-11; https://doi.org/10.1080/07435800.2021.2011907

Background: Assembly of oocytes into primordial follicles is essential for establishing the ovarian reserve required for female fertility. In mice, this process begins during embryonic development. Primordial germ cells form cysts by incomplete mitosis until 13.5 days post coitum (dpc). These cysts break apart just before birth. Some oocytes undergo apoptosis while surviving oocytes are enclosed by granulosa cells to form primordial follicles. Cyst breakdown and primordial follicle formation were previously shown to be inhibited by estradiol and estrogenic compounds in vitro, suggesting that estrogen is important for regulation of this process. Methods: To determine the role of fetal estrogen in cyst breakdown and follicle formation these processes were quantified in aromatase deficient (ArKO) mice between 17.5 dpc and postnatal day (PND) 9. Ovaries of ArKO mice were also examined at 2-week intervals to determine if folliculogenesis is affected by lack of estrogen and the age at which the typical ArKO ovarian phenotype first appears. Results: Oocyte number, follicle assembly, and follicle development in ArKO mice did not differ from controls between 17.5 dpc and PND 9. At 2 weeks, ArKO ovaries still had oocytes in cysts while all oocytes were enclosed in follicles in wild type ovaries. From 2 to 8 weeks oocyte numbers were similar in all genotypes with a significant reduction at 10 weeks in ovaries from homozygous mutants. Abnormal hemorrhagic follicles were observed starting at 6 weeks, earlier than previously reported and hemosiderin deposits were found starting at 8 weeks. Conclusions: These results suggest that a lack of fetal estrogen does not affect oocyte survival or the rate of primordial follicle formation perinatally, and maternal estrogen or other signals are the chief regulators. The appearance of abnormal hemorrhagic follicles observed as early as 6 weeks suggests that the lack of estrogen becomes problematic at this time.
, , Aleck Hercbergs, Kelly A. Keating, Shaker A. Mousa
Published: 14 November 2021
Integrin αvβ3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)—when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction—may enhance cellular uptke of SARS-CoV-2 and its receptor. Because T4 also acts nongenomically via the integrin to promote platelet aggregation and angiogenesis, we suggest here that T4 may contribute to the coagulopathy and endothelial abnormalities that can develop in COVID-19 infections, particularly when the lung is primary affected. Elevated FT4 has been described in the NTIS of COVID-19 patients and may be associated with increased illness severity, but the finding of FT4 elevation is inconsistent in the NTIS literature. Circulating 3,5’,3’-triiodo-L-thyronine (reverse T3, rT3) are frequently elevated in NTIS. Thought to be biologically inactive, rT3in fact stimulates cancer cell proliferation via avb3 and also may increase actin polymerization. We propose here that rT3 in the NTIS complicating systemic COVIF-19 infection may support coagulation and disordered blood vessel formation via actin polymerization.
Jiasheng Wang,
Published: 30 August 2021
Glucagon-like peptide 1 receptor agonists (GLP1Ra) are commonly used in type 2 diabetes mellitus (T2DM). However, differential risk of various cancers among GLP1Ra recipients is unknown. We inquired an aggregated electronic health record database, Explorys, and compared the adjusted odds ratio (aOR) of cancers between GLP1Ra and metformin users. Findings were validated in the FDA Adverse Event Reporting System (FDA FAERS). From 1/2005 to 6/2019, we identified 619 340 and 64 230 patients in the metformin and GLP1Ra group, respectively. Within 5 years of starting antidiabetic medications, GLP1Ra was associated with significantly lower incident risk of prostate (aOR 0.81, p = .03), lung (aOR 0.81, p = .05), and colon cancer (aOR 0.85, p = .03), while the risk of thyroid cancer was significantly higher (aOR 1.65, p < .01). Similar findings were seen in the FDA FAERS database, where GLP1Ra was associated with lower risk of prostate (aOR 0.72, p = .08), lung (aOR 0.52, p < .01), colon cancer (aOR 0.82, p = .31), and higher risk of thyroid cancer (aOR 4.33, p < .01). In addition, with longer duration of GLP1Ra use, the risk of prostate, lung, and colon cancer further decreased, suggesting an exposure duration–response relationship. GLP1Ra is associated with lower risks of prostate, lung, and colon cancer, but higher risk of thyroid cancer.
Wanteng Wang, Yu Sun, Shuai Wang,
Published: 19 August 2021
The purpose of this study is to review observational studies on the effect of insulin use and mortality in patients with COVID-19 and diabetes. A systematic literature search was performed using the PubMed, Medline, EMBASE, and Cochrane Library databases. The meta-analysis was performed using a random effects model, and I2 was applied to evaluate heterogeneity. Sensitivity and subgroup analyses were also performed. Overall, 1,338 patients over six studies were ultimately included. Insulin use was related to a higher risk of death in diabetic patients with COVID-19 compared to those who did not use insulin (odds ratio: 2.59, 95% confidence interval: 1.66–4.05; P < .0001; I2: 57%). This meta-analysis revealed a correlation between insulin usage and increased mortality in diabetic patients with COVID-19. These results showed that insulin requirement in patients with COVID-19 and diabetes might indicate a poor prognosis.
Hande Demirdere, , Sema Yarman
Published: 10 August 2021
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 (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 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.
Published: 3 August 2021
Endocrine Research pp 1-10; https://doi.org/10.1080/07435800.2021.1954942

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. 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 <52.4cm2/m2 for males and <38.5cm2/m2 for females. 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 (p < .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];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. 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.
Mahshid Heydari, , Zahra Emami, , Mohammad Ghorbani, Mojtaba Malek, Manizhe Ataei Kachuee, Mohammad E. Khamseh
Published: 9 June 2021
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
Published: 3 June 2021
Endocrine Research, Volume 46, pp 196-202; https://doi.org/10.1080/07435800.2021.1930039

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.
Yuki Hiraga, , Makoto Katoh, Yasushi Horai, Hiroyuki Suzuki, Yusuke Yamashita, Rieko Hirata,
Published: 1 June 2021
Endocrine Research, Volume 46, pp 178-185; https://doi.org/10.1080/07435800.2021.1927074

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.
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