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Natasha Bergmann Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Søren Ballegaard Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Pernille Holmager Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Per Bech Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Åke Hjalmarson Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Finn Gyntelberg Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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Jens Faber Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark
Department of Endocrinology, Ull Care A/S, Psychiatric Research Unit, The Cardiovascular Institute, The National Research Center for the Working Environment, Faculty of Health and Medical Sciences, Herlev University Hospital, Herlev, Denmark

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The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two chronic diseases results in an elevation in specific elements of the chronic stress concept. A total of 361 participants with IHD were included, of whom 47 suffered from concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and by the following questionnaires: the Major Depression Inventory (MDI), the SF-36 Quality of Life questionnaire (SF-36 QOL), the WHO-5 Well-being Index, and the clinical stress signs (CSSs) scale. Participants with diabetes and IHD had a higher MDI score, a lower SF-36 physical component summary score, and a lower score of several sub-measurements of the SF-36 mental component score when compared with patients with IHD without diabetes. No significant differences were observed regarding stress measured by the PPS measure, the WHO-5 Well-being Index, or the number of CSSs. In conclusion, the combination of diabetes and IHD seems to be associated with increased depressive symptoms, lower overall physical QOL, and reduced mental QOL on several sub-elements of the questionnaire. This should be recognized in the management of patients with double diagnoses.

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S U Jayasinghe
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S J Torres
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C A Nowson
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A J Tilbrook Centre for Physical Activity and Nutrition Research, Livestock and Farming Systems, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Melbourne, Victoria 3125, Australia

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A I Turner
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We tested the hypothesis that overweight/obese men aged 50–70 years will have a greater salivary cortisol, salivary alpha amylase and heart rate (HR) responses to psychological stress compared with age matched lean men. Lean (BMI=20–25 kg/m2; n=19) and overweight/obese (BMI=27–35 kg/m2; n=17) men (50–70 years) were subjected to a well-characterised psychological stress (Trier Social Stress Test, TSST) at 1500 h. Concentrations of cortisol and alpha amylase were measured in saliva samples collected every 7–15 min from 1400 to 1700 h. HR was recorded using electrocardiogram. Body weight, BMI, percentage body fat, resting systolic and diastolic blood pressure and mean arterial pressure were significantly higher (P<0.05) in overweight/obese men compared with lean men. Both groups responded to the TSST with a substantial elevation in salivary cortisol (372%), salivary alpha amylase (123%) and HR (22%). These responses did not differ significantly between the groups (time×treatment interaction for salivary cortisol, salivary alpha amylase and HR; P=0.187, P=0.288, P=0.550, respectively). There were no significant differences between the groups for pretreatment values, peak height, difference between pretreatment values and peak height (reactivity) or area under the curve for salivary cortisol, salivary alpha amylase or HR (P>0.05 for all). The results showed that, for men with a moderate level of overweight/obesity who were otherwise healthy, the response of salivary cortisol, salivary alpha amylase and HR to acute psychological stress was not impaired.

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Hongyan Wang Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Bin Wu Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Zichuan Yao Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Xianqing Zhu Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Yunzhong Jiang Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Song Bai Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

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Purpose

Although resection is the primary treatment strategy for pheochromocytoma, surgery is associated with a high risk of morbidity. At present, there is no nomogram for prediction of severe morbidity after pheochromocytoma surgery, thus the aim of the present study was to develop and validate a nomogram for prediction of severe morbidity after pheochromocytoma surgery.

Methods

The development cohort consisted of 262 patients who underwent unilateral laparoscopic or open pheochromocytoma surgery at our center between 1 January 2007 and 31 December 2016. The patients’ clinicopathological characters were recorded. The least absolute shrinkage and selection operator (LASSO) binary logistic regression model was used for data dimension reduction and feature selection, then multivariable logistic regression analysis was used to develop the predictive model. An independent validation cohort consisted of 128 consecutive patients from 1 January 2017 and 31 December 2018. The performance of the predictive model was assessed in regards to discrimination, calibration, and clinical usefulness.

Results

Predictors of this model included sex, BMI, coronary heart disease, arrhythmia, tumor size, intraoperative hemodynamic instability, and surgical duration. For the validation cohort, the model showed good discrimination with an AUROC of 0.818 (95% CI, 0.745, 0.891) and good calibration (Unreliability test, P = 0.440). Decision curve analysis demonstrated that the model was also clinically useful.

Conclusions

A nomogram was developed to facilitate the individualized prediction of severe morbidity after pheochromocytoma surgery and may help to improve the perioperative strategy and treatment outcome.

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Kimberly Kuiper Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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Hanna Swaab Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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Nicole Tartaglia eXtraordinarY Kids Clinic, Developmental Pediatrics, Children’s Hospital Colorado, Aurora, Colorado
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado

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Sophie van Rijn Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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The presence of an additional X or Y chromosome (sex chromosome trisomies, SCT) is associated with an increased risk for neurodevelopmental difficulties, including socio-emotional problems, across the life span. Studying emotion regulation in young children with SCT could signal deviations in emotional development that serve as risk markers to guide clinical care. This study explored the presence and variety of emotion regulation strategies in 75 SCT children and 81 population-based controls, aged 1–7 years, during a frustration-inducing event in which physiological (heart rate) and observational data (behavioral responses) were collected. Children with SCT were equally physiologically aroused by the event as compared to controls. However, they showed more emotion regulation difficulties in terms of behavior compared to controls that were not explicable in terms of differences in general intellectual functioning. Specifically, they had a more limited range of behavioral alternatives and tended to rely longer on inefficient strategies with increasing age. The field of practice should be made aware of these early risk findings regarding emotion regulation in SCT, which may potentially lay the foundation for later socio-emotional problems, given the significant impact of emotion regulation on child and adult mental health outcomes. The current results may help to design tailored interventions to reduce the impact of the additional sex chromosome on adaptive functioning, psychopathology, and quality of life.

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Randi Ugleholdt Department of Endocrinology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Åse Krogh Rasmussen Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

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Pernille A H Haderslev Department of Anaesthesiology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark

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Bjarne Kromann-Andersen Department of Urology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark

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Claus Larsen Feltoft Department of Endocrinology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark

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Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood pressure targets differ between institutions. We retrospectively compared per- and postoperative hemodynamics in 30 patients with PPGL that were pretreated with phenoxybenzamine aiming at different blood pressure targets at two separate endocrine departments. All patients were subsequently undergoing laparoscopic surgery at Department of Urology, Herlev University hospital. Fourteen patients were treated targeting to symptomatic and significant orthostatic hypotension and 16 patients to a seated blood pressure below 130/80 mmHg. As a control group, we included 34 patients undergoing laparoscopic adrenalectomy for other reasons. The group titrated to orthostatic hypotension required a higher dose of phenoxybenzamine to achieve the blood pressure target. This group had less intraoperative systolic and diastolic blood pressure fluctuation (Mann–Whitney U test; P  < 0.05) and less periods with heart rate above 100 b.p.m. (Mann–Whitney U test; P = 0.04) as compared to the group with a preoperative blood pressure target below 130/80 mmHg. Peroperative use of intravenous fluids were similar between the two groups, but postoperatively more intravenous fluids were administered in the group with a target of ortostatism. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. We conclude that phenoxybenzamine pretreatment targeting ortostatic hypotension may improve peroperative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.

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Jindong Wan J Wan, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, China

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Sen Liu S Liu, Department of Cardiology, Chengdu Medical College, Chengdu, China

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Tao Luo T Luo, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, China

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Yi Yang Y Yang, Department of Cardiology, Chengdu Medical College, Chengdu, 610083, China

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Dan Wang D Wang, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, China

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Xinquan Wang X Wang, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, China

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Peng Zhou P Zhou, Department of Cardiology, Chengdu Medical College, Chengdu, 610083, China

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Jixin Hou J Hou, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, China

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Peijian Wang P Wang, Department of Cardiology, Chengdu Medical College The First Affiliated Hospital, Chengdu, 610500, China

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Background: Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant, and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF.

Methods: Datasets were obtained from the Gene Expression Omnibus (GEO) database. Hub genes were identified by enrichment and protein‒protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 and GSE41177. Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples.

Results: The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF.

Conclusion: Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.

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Ashley N Reeb Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Andrea Ziegler Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Reigh-Yi Lin Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

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H A Booij Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands

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W D C Gaykema Roessingh Rehabilitation Center, Enschede, the Netherlands

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K A J Kuijpers Roessingh Rehabilitation Center, Enschede, the Netherlands

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M J M Pouwels Department of Endocrinology, Medisch Spectrum Twente, Enschede, the Netherlands

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H M den Hertog Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands

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Background

Poststroke fatigue (PSF) is a highly prevalent and debilitating condition. However, the etiology remains incompletely understood. Literature suggests the co-prevalence of pituitary dysfunction (PD) with stroke, and the question raises whether this could be a contributing factor to the development of PSF. This study reviews the prevalence of PD after stroke and other acquired brain injuries and its association with fatigue.

Summary

We performed a bibliographic literature search of MEDLINE and EMBASE databases for English language studies on PD in adult patients with stroke, traumatic brain injury (TBI) or aneurysmatic subarachnoid hemorrhage (aSAH). Forty-two articles were selected for review. Up to 82% of patients were found to have any degree of PD after stroke. Growth hormone deficiency was most commonly found. In aSAH and TBI, prevalences up to 49.3% were reported. However, data differed widely between studies, mostly due to methodological differences including the diagnostic methods used to define PD and the focus on the acute or chronic phase. Data on PD and outcome after stroke, aSAH and TBI are conflicting. No studies were found investigating the association between PD and PSF. Data on the association between PD and fatigue after aSAH and TBI were scarce and conflicting, and fatigue is rarely been investigated as a primary end point.

Key messages

Data according to the prevalence of PD after stroke and other acquired brain injury suggest a high prevalence of PD after these conditions. However, the clinical relevance and especially the association with fatigue need to be established.

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Ermina Bach Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Niels Møller Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto L Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Mads Buhl The Neonatal Intensive Care Unit, Aarhus University Hospital, Aarhus, Denmark

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Holger Jon Møller Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

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Aims/hypothesis

The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner.

Methods

We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively.

Results:

Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163.

Conclusion:

Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

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Richard W Carroll Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand

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Brian Corley Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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Joe Feltham Department of Radiology, Wellington Regional Hospital, New Zealand

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Patricia Whitfield Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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William Park University of Otago, Wellington, New Zealand

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Rowena Howard Diabetes and Endocrinology Service, Hutt Hospital, New Zealand

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Melissa Yssel Department of Biochemistry & Endocrinology, Awanui Labs, New Zealand

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Ian Phillips Department of Biochemistry, Awanui Labs, Dunedin, New Zealand

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Simon Harper Department of Surgery & Anaesethesia, University of Otago, Wellington, New Zealand
Department of General Surgery, Wellington Regional Hospital, New Zealand

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Jun Yang Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Medicine, Monash University, Clayton, Victoria, Australia

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Objective

The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS.

Design

This is a diagnostic accuracy study in a tertiary referral endocrinology department.

Methods

Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS.

Results

There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet–PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet–AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%).

Conclusions

Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy.

Significance statement

Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

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