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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 toward 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

Teodoro Durá-Travé, Fidel Gallinas-Victoriano, María Malumbres-Chacon, Lotfi Ahmed-Mohamed, María Jesús Chueca Guindulain, and Sara Berrade-Zubiri


The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.


Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- to 8- years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.


There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (p<0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89% and 82% respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.


Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, eliminating the need for GnRH stimulation testing.

Open access

Liubov G. Yanevskaya, Tatiana Karonova, Ilya V Sleptsov, Marina Evgenevna Boriskova, Aluza Ramilevna Bakhtiyarova, Roman A Chernikov, Karina Alexandrovna Pogosian, Alena Timurovna Andreeva, Denis Andreevich Lebedev, Elena Nikolaevna Grineva, and John P. Bilezikian

Objective. The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy.

Materials and methods. Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and  iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed.

Results. Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2 % being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/ml, p=0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r= -0.294, p=0.005), iCa (r= -0.268, p=0.010) and total Ca (r= -0.284, p=0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7% and 63.4%, p=0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, p<0.0001; 30.4 vs 26.0 kg/m2, p<0.0001, respectively).

Conclusions. This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Open access

Franca Genest, Michael Schneider, Andreas Zehnder, Dominik Lieberoth-Leden, and Lothar Seefried

Purpose: Aging and concurrent constitutional changes as sarcopenia, osteoporosis and obesity are associated with progressive functional decline. Coincidence and mutual interference of this risk factors require further evaluation.

Methods: Cross-sectional evaluation of musculoskeletal health in a community-dwelling cohort of men aged 65-90 years. Objectives included descriptive analysis of age-related decline in physical performance, prevalence of osteoporosis (FRAX-Score), sarcopenia (EWGSOP criteria) and obesity (BMI>30kg/m²) and their coincidence/interference.

Results: Based on 507 participants assessed, aging was associated with progressive functional deterioration, regarding power (Chair Rise Test -1.54% per year), performance (Usual Gait Speed -1.38 % per year) and muscle force (Grip Strength -1.52 % per year) while muscle mass declined only marginally (Skeletal Muscle Index -0.29% per year). Prevalence of osteoporosis was 41.8% (n=212) while only 22.9% (n=116) of the participants met the criteria for sarcopenia and 23.7% (n=120) were obese. Osteosarcopenia was found in n=79 (15.6%), sarcopenic obesity was present in 14 men (2.8%). A combination of all three conditions could be confirmed in n=8 (1.6%). There was an inverse correlation of BMI with physical performance whereas osteoporosis and sarcopenia did not interfere with functional outcomes.

Conclusion: Based on current definitions there is considerable overlap in the prevalence of osteoporosis and sarcopenia, while obesity appears to be a distinct problem. Functional decline appears to be associated with obesity rather than osteoporosis or sarcopenia. It remains to be determined to what extend obesity itself causes performance deficits or if obesity is merely an indicator of insufficient activity eventually predisposing to functional decline.

Open access

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


More than 30% 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.


We performed a comprehensive cost analysis.


We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to the absence of work in 2018. 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.


Annual average costs per case in the year of diagnosis were € 211 for goiter/thyroid nodules; € 308 for hyperthyroidism; and € 274 for hypothyroidism. Average one-time costs for thyroidectomy were € 4184 and € 3118 for radioiodine therapy. Average costs for one case of spontaneous abortion were € 916. Annual costs of intellectual disability were € 14,202. 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.


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-Jäntti, Petra Bruegmann, Manuela Broesamle, Natasa Bratina, Vallo Tillmann, Olaf Hiort, and Alberto M Pereira


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.


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 their own material in the national language (81%); referred to advocacy groups (68%), and relevant online sources (50%). Respondents believed the European Commission should fund education through Endo-ERN.


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

Yu Lin, Yingying Zhang, Lei Xu, Wei Long, Chunjian Shan, Hongjuan Ding, Lianghui You, Chun Zhao, and Zhonghua Shi

Aims: Gestational diabetes mellitus (GDM)-induced macrosomia is predominantly characterized by fat accumulation, which is closely related to adipocyte differentiation. An unknown long noncoding RNA RP11-290L1.3, referred to as RP11, was identified to be dramatically upregulated in the umbilical cord blood of women with GDM-induced macrosomia in our previous study. We conducted this study to identify the function of RP11 in GDM-induced macrosomia.

Methods: The effects of RP11 gain- and loss-of-function on HPA-v (human preadipocytes-visceral) adipogenesis were determined with lentivirus mediated cell transduction. The mRNA and protein expression levels of adipogenesis makers were evaluated by qPCR/western blot. Then, we performed the Microarray and pathway analysis to explore the possible mechanisms by which RP11 regulates adipogenesis.

Results: Overexpression of RP11 significantly enhanced adipocyte differentiation and increased the mRNA and protein expression levels of adipogenesis makers, such as PPAR-γ, SREBP1c, and FASN by qPCR/western blot. Knockdown of RP11 showed opposite effects. Microarray and pathway analysis showed, after RP11 knockdown, 1,612 genes were upregulated and 583 genes were downregulated which were found to be mainly involved in metabolic pathways, insulin signaling pathway and MAPK signaling pathway.

Conclusion: In conclusion, the unknown lncRNA RP11 serves a positive factor on preadipocyte differentiation which could shed light on fetal fat accumulation in GDM.

Open access

Jan Roar Mellembakken, Azita Mahmoudan, Lars Mørkrid, Inger Sundström-Poromaa, Laure Morin-Papunen, Juha S. Tapanainen, Terhi Piltonen, Angelica Linden Hirschberg, Elisabeth Stener-Victorin, Eszter Vanky, Pernille Ravn, Richard Christian Jensen, Marianne Skovsager Andersen, and Dorte Glintborg


Objective: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI?

Methods: From a Nordic cross-sectional base of 2,615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI<25 kg/m2 (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurements of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles).

Results: The median age for women with PCOS were 28 (25; 32) years, and median BMI was 22.2 (20.7; 23.4) kg/m2. Systolic BP was 118 (109; 128) mmHg in women with PCOS compared to 110 (105; 120) mmHg in controls, and diastolic BP was 74 (67; 81) vs. 70 (64; 75) mmHg, both p<0.001. The prevalence of women with BP ≥140/90 mmHg was 11.1% (57/512) in women with PCOS vs. 1.8% (5/281) in controls, p<0.001. In women ≥ 35 years the prevalence of BP ≥140/90 mmHg was comparable in women with PCOS and controls (12.7% vs. 9.8%, p=0.6). Using multiple regression analyses, the strongest association with BP was found for waist circumference, fasting BG and total cholesterol in women with PCOS.

Conclusions: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.

Open access

Alexander V Amram, Stephen Cutie, and Guo N Huang

Research conducted across phylogeny on cardiac regenerative responses following heart injury implicates endocrine signaling as a pivotal regulator of both cardiomyocyte proliferation and heart regeneration. Three prominently studied endocrine factors are thyroid hormone, vitamin D, and glucocorticoids, which canonically regulate gene expression through their respective nuclear receptors thyroid hormone receptor, vitamin D receptor, and glucocorticoid receptor. The main animal model systems of interest include humans, mice, and zebrafish, which vary in cardiac regenerative responses possibly due to the differential onsets and intensities of endocrine signaling levels throughout their embryonic to postnatal organismal development. Zebrafish and lower vertebrates tend to retain robust cardiac regenerative capacity into adulthood while mice and other higher vertebrates experience greatly diminished cardiac regenerative potential in their initial postnatal period that is sustained throughout adulthood. Here, we review recent progress in understanding how these three endocrine signaling pathways regulate cardiomyocyte proliferation and heart regeneration with a particular focus on the controversial findings that may arise from different assays, cellular-context, age, and species. Further investigating the role of each endocrine nuclear receptor in cardiac regeneration from an evolutionary perspective enables comparative studies between species in hopes of extrapolating the findings to novel therapies for human cardiovascular disease.