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Jesper Krogh Department of Endocrinology & Metabolism, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Peter Plomgaard Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Ruth Frikke-Schmidt Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Sten Velschow Fluisense ApS, Lillerød, Denmark

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Jesper Johannesen Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Department of Pediatrics, Copenhagen University Hospital - Herlev & Gentofte, Copenhagen, Denmark

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Linda Maria Hilsted Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Malene Schrøder Fluisense ApS, Lillerød, Denmark

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Ulla Feldt-Rasmussen Department of Endocrinology & Metabolism, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Repeated blood sampling is required in certain clinical and research settings, which is currently performed by drawing blood from venous catheters requiring manual handling of each sample at the time of collection. A novel body-worn device for repeated serial samples, Fluispotter®, with automated extraction, collection, and storage of up to 20 venous dried blood spot samples over the course of 20 h may overcome problems with current methods for serial sampling. The purpose of this study was to assess the performance and safety of Fluispotter for the first time in healthy subjects. Fluispotter consists of a cartridge with tubing, a reservoir for flushing solution, pumps and filterpaper, and a multi-lumen catheter placed in the brachial vein. We recruited healthy subjects for testing in an in-hospital setting. Fluispotter was attached by an anesthesiologist to 22 healthy subjects of which 9/22 (40.9%) participants had all 20 samples taken, which was lower than the goal of complete sampling in 80% of the subjects (P = 0.02). The main reason for sample failure was clogging of blood flow which was observed in 11/22 (50%) of the participants. No serious adverse events occurred, and the participants rated the pain from the insertion and the removal of catheter as very low. A cortisol profile showed nadir values at midnight and highest values at 05:00 h. Although full sampling was not successful in all participants, the Fluispotter technology proved safe and highly acceptable to the participants producing the expected cortisol profile without the requirement of staff during sample collection.

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Tomaž Kocjan Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Gaj Vidmar Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
University Rehabilitation Institute, Ljubljana, Slovenia
FAMNIT, University of Primorska, Koper, Slovenia

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Peter Popović Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Milenko Stanković Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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The 20-point clinical prediction SPACE score, the aldosterone-to-lowest potassium ratio (APR), aldosterone concentration (AC) and the AC relative reduction rate after saline infusion test (SIT) have recently been proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). To validate those claims, we performed a retrospective cross-sectional study that included all patients at our center who had positive SIT to confirm PA and were diagnosed with either bilateral disease (BPA) according to AVS or with lateralized disease (LPA) if biochemically cured after adrenalectomy from November 2004 to the end of 2019. Final diagnoses were used to evaluate the diagnostic performance of proposed clinical prediction tools. Our cohort included 144 patients (40 females), aged 32–72 years (mean 54 years); 59 with LPA and 85 with BPA. The originally suggested SPACE score ≤8 and SPACE score >16 rules yielded about 80% positive predictive value (PPV) for BPA and LPA, respectively. Multivariate analyses with the predictors constituting the SPACE score highlighted post-SIT AC as the most important predictor of PA subtype for our cohort. APR-based tool of <5 for BPA and >15 for LPA yielded about 75% PPV for LPA and BPA. The proposed post-SIT AC <8.79 ng/dL criterion yielded 41% sensitivity and 90% specificity, while the relative post-SIT AC reduction rate of >33.8% criterion yielded 80% sensitivity and 51% specificity for BPA prediction. The application of any of the validated clinical prediction tools to our cohort did not predict the PA subtype with the high diagnostic performance originally reported.

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Isabel M Abreu Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal

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Eva Lau Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Alameda Professor Hernâni Monteiro, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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Bernardo de Sousa Pinto Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal

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Davide Carvalho Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Alameda Professor Hernâni Monteiro, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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Previous studies suggested that subclinical hypothyroidism has a detrimental effect on cardiovascular risk factors, and that its effective treatment may have a beneficial impact on overall health. The main purpose of this review and meta-analysis was to assess whether subclinical hypothyroidism treatment is of clinical relevance, based on cardiovascular risk parameters correction. A systemic research of the literature using MEDLINE tool was performed to identify the relevant studies. Only placebo-controlled randomized control trials were included. A quantitative analysis was also performed. This systematic review and meta-analysis of randomized placebo-controlled trials assess the different impact of levothyroxine vs placebo treatment. A significant decrease in serum thyroid-stimulating hormone and total and low-density lipoprotein cholesterol was obtained with levothyroxine therapy (66, 9 and 14%, respectively) and, although modest, this could be significant in terms of reduction of the incidence of coronary artery disease. Other significant results of lipid parameters were not obtained. This systematic review provides a strong evidence-based data in favour of specific changes and beneficial effects of levothyroxine treatment.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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Peiwen Zheng School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Fan Wang Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China

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Hui Li Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, China

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Hanlu Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Mengtong Li School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haozheng Ma School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Jue He School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Li Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Yanlong Liu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haiyun Xu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Objective

This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism.

Methods

A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed.

Results

Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers.

Conclusion

These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

Open access
Esben Thyssen Vestergaard Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Morten B Krag Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Morten M Poulsen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Steen B Pedersen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Niels Moller Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Jens Otto Lunde Jorgensen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Niels Jessen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Objective

Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.

Materials and methods

To study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.

Results

Ghrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.

Conclusions

i) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

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I Azzam Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel

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S Gilad Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel

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R Limor Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel

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N Stern Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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Y Greenman Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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Ghrelin plasma concentration increases in parallel to cortisol after a standardized psychological stress in humans, but the physiological basis of this interaction is unknown. We aimed to elucidate this question by studying the ghrelin response to pharmacological manipulation of the hypothalamic–pituitary–adrenal (HPA) axis. Six lean, healthy male volunteers were examined under four experimental conditions. Blood samples were collected every 30 min for two sequential periods of two hours. Initially, a baseline period was followed by intravenous injection of a synthetic analog of ACTH (250 μg). Subsequently, a single dose of metyrapone was administered at midnight and in the following morning, blood samples were collected for 2 h, followed by an intravenous injection of hydrocortisone (100 mg) with continued sampling. We show that increased cortisol serum levels secondary to ACTH stimulation or hydrocortisone administration are positively associated with plasma ghrelin levels, whereas central stimulation of the HPA axis by blocking cortisol synthesis with metyrapone is associated with decreased plasma ghrelin levels. Collectively, this suggests that HPA-axis-mediated elevations in ghrelin plasma concentration require increased peripheral cortisol levels, independent of central elevation of ACTH and possibly CRH levels.

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Satoshi Higuchi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hideki Ota Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Advanced MRI Collaboration Research, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Yuta Tezuka Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Kazumasa Seiji Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Hidenobu Takagi Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Jongmin Lee Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Korea

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Yi-Wei Lee Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Kei Omata Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Yoshikiyo Ono Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Department of Radiology, The University of British Columbia, Vancouver, Canada

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Ryo Morimoto Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Masataka Kudo Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

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Fumitoshi Satoh Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Kei Takase Department of Diagnostic Radiology, Tohoku University Hospital, Sendai, Miyagi, Japan

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Objectives

This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.

Design

A retrospective, single-center, observational study.

Methods

We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.

Results

PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).

Conclusions

APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

Open access
Roxanne C S van Adrichem Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands

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Aart Jan van der Lely Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

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Martin Huisman Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

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Piet Kramer Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

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Richard A Feelders Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands

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Patric J D Delhanty Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

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Wouter W de Herder Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands

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To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

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Metin Guclu Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Sinem Kiyici Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Zulfiye Gul Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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Sinan Cavun Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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Aim

In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus.

Methods

Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35 kg/m2 and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000 mg per day. Exenatide treatment was initiated at 5 µg per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10 µg twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment.

Results

Thirty-eight patients (male/female = 7/31) entered the study. The mean age of patients was 50.5 ± 8.8 years with a mean diabetes duration of 8.5 ± 4.9 years. The mean BMI was 41.6 ± 6.3 kg/m2 and the mean HbA1c of patients was 8.9 ± 1.4%. The mean change in the weight of patients was −5.6 kg and the percentage change in weight was −5.2 ± 3.7% following 12 weeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (P < 0.001 and P < 0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4 ± 166.8 vs 245.3 ± 164.8 pg/mL) (P = 0.024).

Conclusion

These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.

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