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Open access

Shih-Rong Lin, Shih-Fen Chen, Yu-Cih Yang, Chung-Y Hsu, and Yu-Chih Shen

Hyperthyroidism contributes to many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hyperthyroidism. A total of 8788 patients with hyperthyroidism and 8788 controls (without hyperthyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000-2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of PD incidence rate between patients with hyperthyroidism and unaffected controls. Patients with hyperthyroidism had a significantly increased risk of PD compared with unaffected controls (1.21 versus 0.45 per 1000 person-years, HR: 2.69, 95% CI: 1.08-6.66) after adjusting for age, gender, CCI score, comorbidities, and antithyroid therapy. Hyperthyroidism and PD may share common manifestations. After excluding the first year of observation, a similar result is obtained (HR: 2.57, 95% CI: 1.61-4.01). Also, this study found that older age (HR: 3.74-8.53), more comorbidities (HR: 1.58-1.63), and specific comorbidities [brain injury (HR: 1.57) and cerebrovascular disease (HR: 3.44)] were associated with an increased risk of developing PD. Patients with hyperthyroidism have an increased risk of developing PD. Additional prospective clinical studies are warranted to examine the relationship between hyperthyroidism and PD and determine if there is an intervention that could reduce PD risk.

Open access

Ju-shuang Li, Tao Wang, Jing-jing Zuo, Cheng-nan Guo, Fang Peng, Shu-zhen Zhao, Hui-hui Li, Xiang-qing Hou, Yuan Lan, Ya-ping Wei, Chao Zheng, and Guang-yun Mao

Diabetic retinopathy (DR), the most common microvascular complication of diabetes and leading cause of visual impairment in adults worldwide, is suggested to be linked to abnormal lipid metabolism. The present study aims to comprehensively investigate the relationship between n-6 polyunsaturated fatty acids (PUFAs) and DR. This was a propensity score matching based case–control study, including 69 pairs of DR patients and type 2 diabetic patients without DR with mean age of 56.7 ± 9.2 years. Five n-6 PUFAs were determined by UPLC-ESI-MS/MS system. Principle component regression (PCR) and multiple conditional logistic regression models were used to investigate the association of DR risk with n-6 PUFAs depending on independent training and testing sets, respectively. According to locally weighted regression model, we observed obvious negative correlation between levels of five n-6 PUFAs (linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid and arachidonicacid) and DR. Based on multiple PCR model, we also observed significant negative association between the five n-6 PUFAs and DR with adjusted OR (95% CI) as 0.62 (0.43,0.87). When being evaluated depending on the testing set, the association was still existed, and PCR model had excellent classification performance, in which area under the curve (AUC) was 0.88 (95% CI: 0.78, 0.99). In addition, the model also had valid calibration with a non-significant Hosmer–Lemeshow Chi-square of 9.44 (P = 0.307) in the testing set. n-6 PUFAs were inversely associated with the presence of DR, and the principle component could be potential indicator in distinguishing DR from other T2D patients.

Open access

Xingrong Tan, Wenjing Hu, Shan Yang, Han Dai, Shangcheng Xu, Gangyi Yang, Ling Li, Shiguo Tang, and Yi Wang

Background: The purpose of this study was to investigate the relationship between circulating zinc α 2-glycoprotein (ZAG), Irisin, betatrophin and adiponectin concentrations and metabolic syndrome (MetS) components and to analyze the effects of blood glucose and insulin on these cytokine concentrations in vivo.

Methods: A total of 196 young women, including 78 healthy women and 118 women with MetS components, were recruited for this cross-sectional study. An oral glucose tolerance test and euglycemic-hyperinsulinemic clamp (EHC) were performed in healthy subjects and women with MetS components. An enzyme-linked immunosorbent assay kit was used to measure serum ZAG, irisin, betatrophin, and adiponectin levels, and their relationship with the MetS components was analyzed.

Results: In women with MetS components, circulating irisin and betatrophin levels were significantly higher than those in the healthy women, but circulating ZAG and adiponectin levels were significantly lower . FBG, WC, and Triglyceride were significantly correlated with the circulating levels of these four cytokines (p < 0.001 or < 0.05). All four cytokines were associated with MetS and its components. In response to increasing insulin levels, circulating ZAG concentrations were markedly increased in both healthy subjects and women with MetS components during the EHC. However, serum irisin, betatrophin, and adiponectin levels in both healthy subjects and women with MetS components were significantly reduced compared with baseline.

Conclusion: Serum ZAG, Irisin, betatrophin and adiponectin were associated with MetS and might be biomarkers for screening MetS components.

Open access

Thera P. Links, Trynke van der Boom, Wouter T. Zandee, and Joop D Lefrandt

Thyroid hormone stimulates cardiac inotropy and chronotropy via direct genomic and non-genomic mechanisms. Hyperthyroidism magnifies these effects, resulting in an increase in heart rate, ejection fraction and blood volume. Hyperthyroidism also affects thrombogenesis and this may be linked to a probable tendency towards thrombosis in patients with hyperthyroidism. Patients with hyperthyroidism are therefore at higher risk for atrial fibrillation, heart failure and cardiovascular mortality. Similarly, TSH suppressive therapy for differentiated thyroid cancer is associated with increased cardiovascular risk.

In this review, we present the latest insights on the cardiac effects of thyroid suppression therapy for the treatment of thyroid cancer. Finally, we will show new clinical data on how to implement this knowledge into the clinical practice of preventive medicine.

Open access

Malgorzata Oczko-Wojciechowska, Agnieszka Czarniecka, Tomasz Gawlik, Barbara Jarzab, and Jolanta Krajewska

Medullary thyroid cancer (MTC) is a rare thyroid malignancy, which arises from parafollicular C-cells. It occurs in the hereditary or sporadic form. Hereditary type is a consequence of activation of the RET proto-oncogene by germline mutations, whereas about 80% of sporadic MTC tumors harbor somatic, mainly RET or rarely RAS mutations. According to the current ATA guidelines, a postoperative MTC risk stratification and long-term follow-up are mainly based on histopathological data, including tumor stage, the presence of lymph node and/or distant metastases (TNM classification), and serum concentration of two biomarkers: calcitonin (Ctn) and carcinoembryonic antigen (CEA). The type of RET germline mutation also correlates with MTC clinical characteristics. The most common and the best known RET mutation in sporadic MTC, localized at codon 918, is related to a more aggressive MTC course and poorer survival. However, even if histopathological or clinical features allow to predict a long-term prognosis, they are not sufficient to select the patients showing aggressive MTC courses requiring immediate treatment or those, who are refractory to different therapeutic methods. Besides the RET gene mutations, there are currently no other reliable molecular prognostic markers. This review summarizes the present data of genomic investigation on molecular prognostic factors in medullary thyroid cancer.

Open access

Jing Zhang, Zhiyong Zhao, Li Dong, Tao Han, Guojin Zhang, Yuntai Cao, and Junlin Zhou

Introduction and aim

It is difficult to distinguish between non-functioning pituitary macroadenomas (NFPMAs) and sellar meningiomas because of their overlapping imaging manifestations on routine MRI, especially in cases of meningiomas growing into the saddle. Here, we aimed to differentiate between these two tumors using apparent diffusion coefficient (ADC) values and MRI characteristics.


A total of 60 NFPMA and 52 sellar meningioma cases confirmed by the pathological analysis were retrospectively reviewed. All patients were examined via routine MRI and diffusion-weighted imaging (DWI) before undergoing surgery. The clinical characteristics, MRI characteristics, and max ADC (ADCmax), average ADC (ADCmean), and minimum ADC (ADCmin) values were compared between the two tumors via Chi-square test and two sample t-tests. Receiver operating characteristic (ROC) curve and binary logistic regression analyses were conducted to determine the discrimination ability.


The ADCmax, ADCmean, and ADCmin values were significantly higher in NFPMAs compared to sellar meningiomas (P < 0.001 for all). Among ADC values, ADCmax demonstrated good performance with an AUC of 0.896 (95% CI, 0.823–0.969) and accuracy of 88.7%. A cut-off value of 0.97 × 10−3 mm2/s was used for ADCmax for differentiation between tumors. A combination of ADCmax values and clinicoradiological features showed the best discrimination ability for differential diagnosis between the two tumors, with an AUC of 0.981 (95% CI, 0.958–1.000) and accuracy of 96.9%.


A combination of ADCmax and clinicoradiological features demonstrates good discrimination ability and high accuracy for differentiation between NFPMAs and sellar meningiomas, and is a potential quantitative tool to aid in the selection of surgical techniques.

Open access

Monika Schaffner, Ursula Rochau, Nikolai Mühlberger, Annette Conrads-Frank, Vjollca Qerimi-Rushaj, Gaby Sroczynski, Eftychia Koukkou, Betina Heinsbaek, Henry Volzke, Wilhelm Oberaigner, and Uwe Siebert

Objective: More than 30 percent of the German population suffers from mild to moderate iodine deficiency causing goiter and other iodine deficiency disorders (IDDs). The economic burden of iodine deficiency is still unclear. We aimed to assess costs for prevention, monitoring and treatment of IDDs in Germany.

Design: We performed a comprehensive cost analysis.

Methods: We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to absence of work in 2018 Euro. Additionally, we calculated total costs for an IDD prevention program comprising universal salt iodization (USI). We performed threshold analyses projecting how many cases of IDDs or related treatments would need to be avoided for USI to be cost saving.

Results: Annual average costs per case in the year of diagnosis were EUR 211 for goiter/thyroid nodules; EUR 308 for hyperthyroidism; and EUR 274 for hypothyroidism. Average one-time costs for thyroidectomy were EUR 4,184 and EUR 3,118 for radioiodine therapy. Average costs for one case of spontaneous abortion were EUR 916. Annual costs of intellectual disability were 14,202 Euro. In the German population, total annual costs for USI would amount to 8 million Euro. To be cost saving, USI would need to prevent, for example, 37,900 cases of goiter/thyroid nodules.

Conclusion: USI potentially saves costs, if a minimum amount of IDDs per year could be avoided. In order to recommend the implementation of USI, a full health-economic evaluation including a comprehensive benefit-harm assessment is needed.

Open access

Violeta Iotova, Camilla Schalin-Jantti, Petra Bruegman, Manuela Broesamle, Natasa Bratina, Vallo Tillmann, Olaf Hiort, and Alberto M Pereira

Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN), operational since 2017, consists of 71 health care providers (HCPs) in 19 EU member states. Our objective was to assess education and knowledge on rare endocrine conditions.

Design and Methods: A survey was developed and sent through the DIGIT-EUROSURVEY system to all Endo-ERN HCPs.

Results: Response rate was 55% (n=146), 95% physicians, 58% >20 years of experience, 96% academics. Largest knowledge gaps were reported for the transition and neonatal ages, and for the GPs. Less than 50% of HCPs had structured educational rare diseases (RD) plans, while 86% used RD specific guidelines. HCPs would share educational materials within Endo-ERN (74%), and participate in an accreditation model (85%). E-learning portals of the endocrine scientific societies used 58% (ESPE) and 64% (ESE). Most participants (90%) regarded Endo-ERN coordinated educational activities (annual meetings slots, webinars, etc.) as highly important and supported a common educational platform. Social media was perceived as important for educating patients (86%) but not for physicians (36%). Seventy-five % had developed patient education materials; only 31% had specific children’s materials, and by-country availability varied from 0% to 100%. Respondents provided newly diagnosed patients with own material in the national language (81%); referred to advocacy groups (68%), and relevant on-line sources (50%). Respondents believed European Commission should fund education through Endo-ERN.

Conclusion: Identified knowledge gaps in rare endocrine disorders set the basis for fast catch-up through collaboration, alignment with patients’ needs, and further development of existing and newly developed educational resources.

Open access

Jasmin Asberger, Thalia Erbes, Markus Jaeger, Gerta Rücker, Claudia Nöthling, Andrea Ritter, Kai Berner, Ingolf Juhasz-Böss, and Marc Hirschfeld

Breast cancer (BC) represents the most common type of cancer in females worldwide. Endocrine therapy evolved as one of the main concepts in treatment of hormone-receptor positive BC. Current research focuses on the elucidation of tumour resistance mechanisms against endocrine therapy. In a translational in vitro approach, potential regulatory effects of clinically implemented BC anti-oestrogens on ERα, its coactivators DDX5, DDX17 and other DEADbox proteins as well as on the proliferation markers cyclin D1 and Ki67 were investigated on both the RNA and protein level. BC in vitro models for hormone-receptor positive (MCF-7, T-47D) and hormone-receptor negative cells (BT-20) were subjected to endocrine therapy. Anti-oestrogen-dependent expression regulation of target genes on the transcriptional and translational level was quantified and statistically assessed. Endocrine therapy decreases the expression levels of Ki67, cyclin D1 and ERα in hormone-receptor positive cells. In the hormone-receptor negative cells, the three parameters remained stable after endocrine therapy. Endoxifen triggers a downregulation of DDX5 and DDX23 in MCF-7 cells. Fulvestrant treatment downregulates the expression levels of all investigated DEADbox proteins in MCF-7 cells. In T-47D cells, endoxifen and fulvestrant lead to a decrease of all target gene expression levels. Interestingly, endocrine therapy affects DEADbox RNA expression levels in BT-20 cells, too. However, this result could only be confirmed for DDX1, immunocytologically. The investigated DEADbox proteins appear to correlate with the oestrogen-dependent tumourigenesis in hormone-receptor positive BC and show expression alterations after endocrine treatment.

Open access

Emanuelle Nunes-Souza, Mônica Evelise Silveira, Monalisa Castilho Mendes, Seigo Nagashima, Caroline Busatta Vaz de Paula, Guilherme Guilherme Vieira Cavalcante da Silva, Giovanna Silva Barbosa, Julia Belgrowicz Martins, Lúcia de Noronha, Luana Lenzi, José Renato Sales Barbosa, Rayssa Danilow Fachin Donin, Juliana Ferreira de Moura, Gislaine Custódio, Cleber Machado-Souza, Enzo Lalli, and Bonald Cavalcante de Figueiredo


Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR.

Materials and methods

DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9–83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands.


We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis.


The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.