Publications by authors named "Jens Bollerslev"

199 Publications

Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study.

Pediatr Rheumatol Online J 2021 Apr 26;19(1):56. Epub 2021 Apr 26.

Bjørknes University College, Oslo, Norway.

Background: Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD.

Methods: JDM patients (n = 59) were examined median 16.8y (range 6.6-27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored.

Results: Reduced BMD Z-scores (<-1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively.

Conclusion: In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12969-021-00543-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077908PMC
April 2021

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

J Endocr Soc 2021 Mar 9;5(3):bvaa205. Epub 2021 Feb 9.

Royal Veterinary College, University of London, London, UK.

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jendso/bvaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874572PMC
March 2021

TGFBR3L-An Uncharacterised Pituitary Specific Membrane Protein Detected in the Gonadotroph Cells in Non-Neoplastic and Tumour Tissue.

Cancers (Basel) 2020 Dec 31;13(1). Epub 2020 Dec 31.

Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjöldsväg 20, 752 37 Uppsala, Sweden.

Here, we report the investigation of transforming growth factor beta-receptor 3 like (TGFBR3L), an uncharacterised pituitary specific membrane protein, in non-neoplastic anterior pituitary gland and pituitary neuroendocrine tumours. A polyclonal antibody produced within the Human Protein Atlas project (HPA074356) was used for TGFBR3L staining and combined with SF1 and FSH for a 3-plex fluorescent protocol, providing more details about the cell lineage specificity of TGFBR3L expression. A cohort of 230 pituitary neuroendocrine tumours were analysed. In a subgroup of previously characterised gonadotroph tumours, correlation with expression of FSH/LH, E-cadherin, oestrogen (ER) and somatostatin receptors (SSTR) was explored. TGFBR3L showed membranous immunolabeling and was found to be gonadotroph cell lineage-specific, verified by co-expression with SF1 and FSH/LH staining in both tumour and non-neoplastic anterior pituitary tissues. TGFBR3L immunoreactivity was observed in gonadotroph tumours only and demonstrated intra-tumour heterogeneity with a perivascular location. TGFBR3L immunostaining correlated positively to both FSH ( = 0.290) and LH ( = 0.390) immunostaining, and SSTR3 ( = 0.315). TGFBR3L correlated inversely to membranous E-cadherin staining ( = -0.351) and oestrogen receptor β mRNA ( = -0.274). In conclusion, TGFBR3L is a novel pituitary gland specific protein, located in the membrane of gonadotroph cells in non-neoplastic anterior pituitary gland and in a subset of gonadotroph pituitary tumours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13010114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795056PMC
December 2020

Controversies in Vitamin D: A Statement From the Third International Conference.

JBMR Plus 2020 Dec 10;4(12):e10417. Epub 2020 Nov 10.

Department of Medicine, Endocrinology Division, College of Physicians and Surgeons Columbia University New York NY USA.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10-13, 2019. The conference was held as a follow-up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm4.10417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745884PMC
December 2020

Assessing Periprosthetic Bone in Total Wrist Arthroplasty: The Validity of DXA.

J Clin Densitom 2020 Oct 18. Epub 2020 Oct 18.

Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Introduction: Dual-energy X-ray absorptiometry (DXA) can measure bone mineral density (BMD) around joint arthroplasties. DXA has never been used in total wrist arthroplasties (TWA). We investigated (1) whether BMD differs between 2 TWAs implanted in the same cadaver forearm, (2) the effect of forearm rotation and wrist extension on measured BMD around TWA in a cadaver, and (3) the precision of DXA in a cadaver and patients.

Methodology: One ROI around the distal and 1 and 3 ROIs (ROI1-3) around the proximal component were used. Ten DXA scans were performed on forearm and femur mode convertible to orthopedic knee mode without arthroplasty, with ReMotion, and with Motec TWA in one cadaver forearm. Ten scans with 5° increments from 90°-70° pronation and 0°-20° extension, were performed with Motec. Precision was calculated as coefficient of variation (CV%) and least significant change (LSC%) from cadaver scans and double examinations with femur mode converted to orthopedic knee mode in 40 patients (20 ReMotion, 20 Motec).

Results: BMD was higher in all Motec than corresponding ReMotion ROIs (p < 0.05). BMD changed with 10° supination in the distal ROI and ROI1, and with 5° extension in the distal ROI (p < 0.05). In the cadaver the orthopedic knee mode was more precise than the forearm mode in 3 Motec ROIs (p < 0.05). In patients CV was 2.21%-3.08% in the distal ROI, 1.66%-2.01% in the proximal ROI, and 1.98%-2.87% with 3 ROIs.

Conclusions: DXA is feasible for BMD measurement around the proximal component using the orthopedic knee mode, but not the distal component of TWA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocd.2020.10.006DOI Listing
October 2020

Effects of Parathyroidectomy on Quality of Life: 10 Years of Data From a Prospective Randomized Controlled Trial on Primary Hyperparathyroidism (the SIPH-Study).

J Bone Miner Res 2021 Jan 22;36(1):3-11. Epub 2020 Nov 22.

Section of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway.

Primary hyperparathyroidism (PHPT) was previously considered a disease presenting with multiorgan involvement and a wide range of symptoms. Today, the disease presents with no symptoms or mild symptomatology in most patients. Data regarding nonspecific symptoms such as pain, fatigue, memory loss, depression, and other neuropsychiatric signs have been ambiguous, and results from prospective long-term randomized control trials are lacking. The Scandinavian Investigation on Primary Hyperparathyroidism (SIPH) is a prospective randomized controlled trial (RCT) with 10-year follow up, comparing parathyroidectomy (PTX) to observation without any treatment (OBS). From 1998 to 2005, 191 patients with mild PHPT were included from Sweden, Norway, and Denmark. A total of 95 patients were randomized to PTX and 96 to OBS. The generic Short Form-36 survey (SF-36) and the Comprehensive Psychopathological Rating Scale (CPRS) were studied at baseline, 2, 5, and 10 years after randomization. After 10 years, the PTX group scored significantly better on vitality (PTX 65.1 ± 20.2 versus OBS 57.4 ± 22.7; p = .017) compared to the OBS group in SF-36. We found no differences between the groups in the physical subscales. The OBS group had no significant change in any of the SF-36 scores throughout the study. The CPRS showed an improvement of symptoms in both groups for single items and sum scores after 10 years compared to baseline. There were, however, no significant differences between the two groups in the CPRS data. The results of this large and long-term RCT indicate improvement in some of the mental domains of SF-36 following PTX. However, the treatment effects between the groups were subtle with uncertain clinical significance. The observation group had stable SF-36 values and improvement in CPRS symptom-scores. Thus, in considering only quality of life (QoL) and in the absence of declines in renal and skeletal parameters, it may be safe to observe patients with mild PHPT for a decade. © 2020 American Society for Bone and Mineral Research (ASBMR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4199DOI Listing
January 2021

Distinct Pattern of Endoplasmic Reticulum Protein Processing and Extracellular Matrix Proteins in Functioning and Silent Corticotroph Pituitary Adenomas.

Cancers (Basel) 2020 Oct 14;12(10). Epub 2020 Oct 14.

Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital (OUS), 0424 Oslo, Norway.

Functioning (FCA) and silent corticotroph (SCA) pituitary adenomas act differently from a clinical perspective, despite both subtypes showing positive TBX19 (TPIT) and/or adrenocorticotropic hormone (ACTH) staining by immunohistochemistry. They are challenging to treat, the former due to functional ACTH production and consequently hypercortisolemia, and the latter due to invasive and recurrent behavior. Moreover, the molecular mechanisms behind their distinct behavior are not clear. We investigated global transcriptome and proteome changes in order to identify signaling pathways that can explain FCA and SCA differences (e.g., hormone production vs. aggressive growth). In the transcriptomic study, cluster analyses of differentially expressed genes revealed two distinct groups in accordance with clinical and histological classification. However, in the proteomic study, a greater degree of heterogeneity within the SCA group was found. Genes and proteins related to protein synthesis and vesicular transport were expressed by both adenoma groups, although different types and a distinct pattern of collagen/extracellular matrix proteins were presented by each group. Moreover, several genes related to endoplasmic reticulum protein processing were overexpressed in the FCA group. Together, our findings shed light on the different repertoires of activated signaling pathways in corticotroph adenomas, namely, the increased protein processing capacity of FCA and a specific pattern of adhesion molecules that may play a role in the aggressiveness of SCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12102980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650558PMC
October 2020

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Medical Research Unit in Endcrine Diseases, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, IMSS, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Bone mineral density and vitamin D in paediatric intestinal failure patients receiving home parenteral nutrition.

Clin Nutr ESPEN 2020 10 14;39:234-241. Epub 2020 Jul 14.

University of Oslo, Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, Oslo, Norway.

Background & Aims: Patients with intestinal failure (IF) are dependent on long-term home parenteral nutrition (HPN) to ensure growth and development. The primary aim of the present study was to assess bone mineral density (BMD) and vitamin D status in paediatric IF patients on HPN and a group of healthy children aged 2-18 years. Secondary aims were to assess growth, body composition, nutrient provision and physical activity.

Methods: An observational cross-sectional study was performed at Oslo University Hospital and at the Department of Nutrition, University of Oslo, from January to September 2017. Dual energy x-ray absorptiometry (DXA; Lunar Prodigy in IF patients and Lunar iDXA in healthy subjects) was performed to assess BMD and body composition. BMD z-score (BMDz) was calculated for total body and lumbar spine L2-L4 based on the integrated reference population in the software. Weight and height were measured for growth assessment. Nutrient provision was assessed by a 4-day food record. Blood samples were analysed for 25-hydroxy-vitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D). Physical activity was reported by a questionnaire.

Results: Nineteen IF patients and 50 healthy children were included. The mean age of participants was 10.0 years. The aetiology of IF patients was paediatric intestinal pseudo-obstruction (58%), short bowel syndrome (26%), and intestinal enteropathy (16%). Lower median BMDz for total body (-0.4 vs 1.1, P < 0.001) and lumbar spine L2-L4 (-0.9 vs 0.2, P = 0.01) were found in the IF group compared with the healthy children. Vitamin D provision was significantly higher in IF patients (17 μg/d vs 5.3 μg/d, P < 0.001). Both groups were sufficient in 25(OH)D (IF patients 71 nmol/L vs healthy 81 nmol/L). Nevertheless, IF patients had significantly lower 1,25(OH)D than healthy children (71 pmol/L vs 138 pmol/L, P < 0.001). The IF group was significantly shorter (height for age z-score -1,5 vs 0,1, P = 0.001) and lighter (weight for age z-score -1,0 vs 0,1, P = 0.009) compared with the healthy subjects. BMIz did not differ; however, body fat percentage was significantly higher in IF patients compared with healthy children (34% vs 25%, P = 0.02). A lower frequency of physical activity was found in the IF group compared with the healthy group (P = 0.001).

Conclusions: Paediatric IF patients on HPN had lower BMD, impaired growth, and higher body fat percentage in comparison with the healthy children. Despite a higher total supply of vitamin D in the IF group, the levels of 25(OH)D did not differ. Nevertheless, a significantly lower level of 1,25(OH)D was found in IF patients. The results raise questions regarding differences between oral and parenteral vitamin D provision and whether intestinal function is important for the metabolism of vitamin D.

Trial Identification Number: Clinical Trials AEV2017/1. 2016/391/REK sør-øst B REVISION NUMBER: CLNESP-D-20-00022.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnesp.2020.06.006DOI Listing
October 2020

Changes in maternal blood glucose and lipid concentrations during pregnancy differ by maternal body mass index and are related to birthweight: A prospective, longitudinal study of healthy pregnancies.

PLoS One 2020 23;15(6):e0232749. Epub 2020 Jun 23.

Department of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: Maternal obesity is increasing worldwide but the consequences for maternal physiology and fetal growth are not fully understood.

Objective: To study whether changes in glucose and lipid metabolism during pregnancy differ between women with normal weight and overweight/obesity, and investigate which of these metabolic factors are associated with birthweight.

Design: Prospective, longitudinal study.

Setting: Department of Obstetrics, Oslo University Hospital, Rikshospitalet.

Population: 1031 healthy pregnant women with singleton pregnancies.

Methods: Blood samples from early and late pregnancy were analyzed for fasting glucose, insulin and lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Associations between metabolic factors and birthweight (z-scores) were explored by linear regression models. Main Outcome Measures: Group-dependent longitudinal changes in glucose and lipids and their association with birthweight (z-scores).

Results: Compared to women with normal weight (BMI < 25), women with overweight (BMI 25-29.9) and obesity (BMI > 30) had significantly higher fasting glucose (4.54, 4.68 and 4.84 mmol/l), insulin (23, 33 and 50 pmol/l), total cholesterol (4.85, 4.99 and 5.14 mmol/l), LDL-C (2.49, 2.66 and 2.88 mmol/l) and triglycerides (1.10, 1.28 and 1.57 mmol/l), but lower HDL-C (1.86, 1.75 and 1.55 mmol/l). BMI (B 0.05, 95% CI 0.03-0.06, p<0.001), gestational weight gain (GWG) (B 0.06, 0.05-0.08, p<0.001) and an increase in fasting glucose (B 0.30, 0.16-0.43, p<0.001) were positively associated with birthweight, whereas a decrease in HDL-C (B -0.72, -0.96- -0.53, p<0.001) had a negative association with birthweight.

Conclusions: Overweight/obesity was associated with an unfavorable metabolic profile in early pregnancy which was associated with increased birthweight. However, modifiable factors like gestational weight gain and an increase in fasting glucose were identified and can be targeted for interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232749PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310681PMC
August 2020

FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors.

J Clin Endocrinol Metab 2020 08;105(8)

Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.

Context: Gonadotroph pituitary neuroendocrine tumors (PitNETs) can express follicle-stimulating hormone (FSH) and luteinizing hormone (LH) or be hormone negative, but they rarely secrete hormones. During tumor development, epithelial cells develop a mesenchymal phenotype. This process is characterized by decreased membranous E-cadherin and translocation of E-cadherin to the nucleus. Estrogen receptors (ERs) regulate both E-cadherin and FSH expression and secretion. Whether the hormone status of patients with gonadotroph PitNETs is regulated by epithelial-to-mesenchymal transition (EMT) and ERs is unknown.

Objectives: To study the effect of EMT on hormone expression in gonadotroph nonfunctioning (NF)-PitNETs.

Design: Molecular and clinical analyses of 105 gonadotroph PitNETs. Immunohistochemical studies and real-time quantitative polymerase chain reaction were performed for FSH, LH, E-cadherin, and ERα. Further analyses included blood samples, clinical data, and radiological images.

Setting: All patients were operated on in the same tertiary referral center.

Results: NF-PitNET with high FSH expression had decreased immunohistochemical staining for membranous E-cadherin (P < .0001) and increased staining for nuclear E-cadherin (P < .0001). Furthermore, high FSH expression was associated with increased ERα staining (P = .0002) and ERα mRNA (P = .0039). Circulating levels of plasma-FSH (P-FSH) correlated with FSH staining in gonadotroph NF-PitNET (P = .0025). Tumor size and invasiveness was not related to FSH staining, E-cadherin, or ERα. LH expression was not associated with E-cadherin or ERα.

Conclusion: In gonadotroph PitNETs, FSH staining is related to E-cadherin, ERα expression, and circulating levels of P-FSH. There was no association between FSH staining and invasiveness. The clinical significance of these findings will be investigated in ongoing prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758833PMC
August 2020

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of calcium metabolic disorders and osteoporosis.

Eur J Endocrinol 2020 Aug;183(2):G57-G65

Department of Endocrinology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6-9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-20-0385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938011PMC
August 2020

Cardiovascular consequences of parathyroid disorders in adults.

Ann Endocrinol (Paris) 2020 Feb 28. Epub 2020 Feb 28.

Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

PTH is a metabolic active hormone primarily regulating calcium and phosphate homeostasis in a very tight and short term-manner. Parathyroid disorders in adult patients reflect a variety of different conditions related either to the parathyroid glands itself or to the effects of the secreted hormone. The clinical spectrum varies from the common disease primary hyperparathyroidism (PHPT) to the orphan conditions pseudohypoparathyroidism (Ps-HypoPT) and chronic hypoparathyroidism (HypoPT). The purpose of this review is to describe the consequences of disturbances in levels or action of PTH for cardiac function and cardiovascular risk in adult patients with these disorders. Most patients with PHPT achieve the diagnose by chance and have minor or no specific symptoms. Still, these patients with mild PHPT do possess cardiovascular (CV) morbidity, however so far not proven ameliorated by surgery in controlled trials. In severe cases, the CV risk is increased and with a potential reversibility by treatment. Patients with Ps-HypoPT have resistance to PTH action, but not necessarily total resistance in all tissues. So far, no clear CV morbidity or risk has been demonstrated, but there are several aspects of interest for further studies. Most patients with HypoPT do get their hormonal deficiency syndrome following neck surgery. These patients do experience multiple symptoms and do have an increased CV-risk before the primary surgery. Based on existing data, their CV mortality do not deviate from the expected when adjusting for the preexisting increased risk. Patients with nonsurgical (NS-) HypoPT do demonstrate increased CV-risk also associated with exposure time. Endocrine disorders with alterations in PTH function have major impact on the cardiovascular system of importance for morbidity and mortality, wherefore management of these specific diseases should be optimized currently, as new data become available, however also avoiding over-treating asymptomatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ando.2020.02.003DOI Listing
February 2020

Content and system development of a digital patient-provider communication tool to support shared decision making in chronic health care: InvolveMe.

BMC Med Inform Decis Mak 2020 03 4;20(1):46. Epub 2020 Mar 4.

Department of Digital Health Research, Division of Medicine, Oslo University Hospital, Oslo, Norway.

Background: Chronic conditions present major health problems, affecting an increasing number of individuals who experience a variety of symptoms that impact their health related quality of life. Digital tools can be of support in chronic conditions, potentially improving patient-provider communication, promoting shared decision making for treatment and care, and possibly even improving patient outcomes. This study aimed to develop a digital tool for patient-provider communication in chronic health care settings and describes the data collection and subsequent content and software development of the InvolveMe tool. InvolveMe will provide patients with the opportunity to report symptoms and preferences to their health care providers (HCP), and to use secure messaging to interact with the HCPs.

Method: The study employed a combination of interviews with patients with chronic conditions and focus groups with HCPs, examining experiences with chronic conditions and the potential use of a digital tool for support. Participants were recruited from two outpatient clinics at a university hospital. Data collected from interviews and focus groups were analysed using thematic analysis. Content and software development was informed by the data collection and by tool development workshops.

Results: Analyses from interviews with patients (n = 14) and focus groups with HCPs (n = 11) generated three main themes: 1) Making symptoms and challenges visible, 2) Mastering a new life, and 3) Digital opportunities for follow-up. Each main theme generated separate subthemes. Theme 1 and 2 gave input for content development of the symptom and needs assessment part of the tool, while theme 3 provided ideas for the software development of the InvolveMe tool. Tool development workshops with patients (n = 6) and HCPs (n = 6) supplemented the development.

Conclusions: A digital tool such as InvolveMe has the potential to support shared decision making for patients with chronic health conditions. Through integration with an existing patient portal such a tool can provide opportunities for meaningful interactions and communication between patients and HCP's, particularly with regards to symptoms, needs and preferences for care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12911-020-1065-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057594PMC
March 2020

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies.

J Hypertens 2020 07;38(7):1347-1354

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet.

Objective: Preeclampsia is a syndrome characterized by hypertension and poor placental development. The developmental wingless (Wnt) pathway plays an important role in placental development and we hypothesized that Wnt signaling would be dysregulated in preeclampsia.

Methods: To elucidate aberrations in the Wnt signaling pathway we conducted a pathway analysis on placental mRNA in late-onset preeclampsia and normal pregnancy from the STORK study [n = 10 in each group, RNA sequencing (RNAseq)] to identify differentially expressed genes. In addition, we compared circulating levels of secreted Wnt agonists and antagonists at term pregnancy and 6 months postpartum from an acute preeclampsia study (preeclampsia n = 34, normal pregnancy n = 61).

Results: We found circulating and placental mRNA levels of the secreted Wnt agonist R-spondin 3 (RSPO3) at term elevated in preeclampsia. Increased plasma RSPO3 was associated with high mean arterial pressure. Further, pathway analysis of placental tissue revealed elevated mRNA levels of upstream ligands WNT6 and WNT10A and frizzled receptors 2 and 4 in preeclampsia and downstream activation of the noncanonical Ca/NFAT pathway. Finally, plasma dickkopf 3 was decreased in preeclampsia 6 months postpartum.

Conclusion: We identify a potential role for RSPO3 and activation of noncanonical Wnt signaling in preeclampsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002362DOI Listing
July 2020

Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma.

Acta Neurochir (Wien) 2020 04 6;162(4):845-852. Epub 2020 Jan 6.

Section of Specialized Endocrinology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.

Objective: The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-μg Short Synacthen Test after surgery.

Design: Longitudinal cohort study.

Methods: One hundred seventeen patients (52/65 females/males, age 59 years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed.

Results: All tumours were macroadenomas (mean size 26.9 mm, range 13-61 mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3 months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172 nmol/l (6.2 μg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320 nmol/l (11.6 μg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500 nmol/l (18.1 μg/dl) during Short Synacthen Test in 48% of patient.

Conclusion: Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6 μg/dl) Short Synacthen Test indicates a sufficient response, while < 309 nmol/l (11.2 μg/dl) indicates secondary adrenal insufficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-019-04068-zDOI Listing
April 2020

Hip Structure Analyses in Acromegaly: Decrease of Cortical Bone Thickness After Treatment: A Longitudinal Cohort Study.

JBMR Plus 2019 Dec 23;3(12):e10240. Epub 2019 Oct 23.

Section of Specialized Endocrinology Oslo University Hospital Oslo Norway.

Long-standing growth hormone (GH) excess causes the skeletal clinical signs of acromegaly with typical changes in bone geometry, including increased cortical bone thickness (CBT). However, a high prevalence and incidence of vertebral fractures has been reported. The aim of this study was to assess the course of cortical bone dimensions in the hip by comparing patients with acromegaly and clinically nonfunctioning pituitary adenomas (NFPAs) at baseline and 1 year after pituitary surgery (1-year PO) in a longitudinal cohort study. DXA was performed in patients with acromegaly ( = 56) and NFPA ( = 47). CBT in the femoral neck (CBTneck), calcar (CBTcalcar), and shaft (CBTshaft) were determined by hip structural analysis (HSA). CBT at baseline and the change to 1-year PO were compared. Test results were adjusted for differences in gender distribution, age, and gonadal status. Cortical thickness analyses showed higher values [mm] at baseline in patients with acromegaly compared with NFPA: CBTneck median [25th; 75th] 6.2 [4.7; 8.0] versus 5.1 [4.1; 6.4] ( = 0.006), CBTcalcar 4.8 [4.2, 5.7] versus 4.0 [3.2, 4.5] ( < 0.001), CBTshaft 6.2 [5.1, 7.2] versus 5.2 [4.6, 6.0], ( = 0.003). In acromegaly, GH was correlated with CBTneck ( = 0.31, = 0.020), whereas IGF-1 was correlated with CBTcalcar ( = 0.39, = 0.003) at baseline. In acromegaly, CBTneck decreased by 11.2%, = 0.002 during follow-up. Finally, the decrease in CBTneck and CBTcalcar in acromegaly was significant compared with NFPA ( = 0.023 and = 0.017, respectively). Previous observations of increased CBT in acromegaly were confirmed with DXA-derived HSA in a large, well-defined cohort. The decline in CBT in acromegaly could contribute to the increased fracture risk in acromegaly despite increased bone dimensions and disease control. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm4.10240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894724PMC
December 2019

Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey.

Clin Endocrinol (Oxf) 2020 02 11;92(2):159-168. Epub 2019 Dec 11.

Section of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway.

Objective: To address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism.

Design: Global patient and caregiver survey.

Study Populations: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers.

Measurements: Health-related quality of life (HRQoL) and health status were evaluated using the 36-item Short Form version 2 (SF-36 v2.0) and Five-Level EuroQoL 5 Dimensions (EQ-5D-5L) instruments, respectively. Hypoparathyroidism-associated symptoms were assessed by a disease-specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI).

Results: Data were obtained from 398 patients and 207 caregivers. Patients' self-rated hypoparathyroidism-related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7-day recall period. Impacts (rated 'somewhat' or 'very much') were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self-rated overall symptom severity and HRQoL and health status assessment scores-the greater the symptom severity, the lower the SF-36 and EQ-5D-5L scores. Caregiver burden increased with patient self-rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI.

Conclusion: Patients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cen.14128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027891PMC
February 2020

Elevated Cholesteryl Ester Transfer Protein Activity Early in Pregnancy Predicts Prediabetes 5 Years Later.

J Clin Endocrinol Metab 2020 03;105(3)

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Context: Cholesteryl ester transfer protein (CETP) regulates high-density lipoprotein (HDL) cholesterol levels and interaction between glucose, and HDL metabolism is central in the development of diabetes.

Objective: We hypothesized that CETP levels would be regulated in diabetic pregnancies. We tested the hypothesis by evaluating CETP activity measured multiple times during pregnancy and at 5 years' follow-up in a prospective cohort (STORK) and investigated its association with gestational diabetes mellitus (GDM) during pregnancy or development of prediabetes 5 years after pregnancy. We also evaluated the strongest correlation of CETP activity among measures of adipocity and glucose metabolism, lipoproteins, adipokines, and monocyte/macrophage activation markers.

Design: A population-based longitudinal cohort study was conducted from 2001 to 2013.

Setting: The study setting was Oslo University Hospital.

Patients Or Other Participants: A total of 300 women during pregnancy and at 5 years postpartum participated in this study.

Main Outcome Measures: CETP activity was measured at 14 to 16, 22 to 24, 30 to 32, and 36 to 38 weeks' gestation, and at 5 years' follow-up.

Results: We found higher CETP activity in pregnancy in women developing prediabetes but no association with GDM. CETP activity decreased throughout pregnancy and remained low at follow-up. High CETP activity was associated with sCD14 levels, in particular in women who developed prediabetes. These data show that enhanced CETP activity during pregnancy is associated with systemic indices of monocyte/macrophage activation, in particular in women who develop prediabetes later in life.

Conclusions: CETP activity during pregnancy identifies women at risk for later diabetes development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz119DOI Listing
March 2020

Progressive loss of bone mass in children with Fontan circulation.

Congenit Heart Dis 2019 Nov 10;14(6):996-1004. Epub 2019 Oct 10.

Department of Pediatric Cardiology, Oslo University Hospital, Oslo, Norway.

Objective: We investigated bone mineral density (BMD) at different ages after the Fontan completion, and we evaluated the relationship between BMD, vitamin D levels, and pertinent patient variables.

Methods: A cross-sectional sample of 64 patients was examined with dual-energy X-ray absorptiometry (DXA) scans to determine BMD. Of these patients, 24 were also examined with BoneXpert software to determine bone mass density (BMX), expressed as the bone health index (BHI). Blood samples from all patients were analyzed. Patients were divided into three different age groups; A: 4-9 years old (n = 22), B: 10-15 years old (n = 21), and C: 16-18 years old (n = 21).

Results: Overall, BMD z scores were (mean ± SD): -1.0 ± 1.3 for the lumbar spine and -0.2 ± 1.2 for the total body. Groups B and C had significantly lower z score values compared to group A. Of patients in group C, 35% had z score values ≤-2 SD of the mean of the healthy population. There was no difference related to systemic ventricular anatomy (left or right); however, patients with lateral tunnels had lower BMD than patients with extra cardiac conduits. Overall, the BHI z score was (mean ± SD): -1.2 ± 0.9, but low BMX did not correlate with low BMD. The 25-hydroxy vitamin D level was 58 ± 30 nmol/L. Vitamin D levels decreased with age: in group C, 33.3% of patients exhibited vitamin D deficiencies. Vitamin D levels were not correlated with bone mineral densities.

Conclusion: BMD levels decreased with age in patients with Fontan circulation. Different bone components were involved. Vitamin D levels also decreased with age, but they were not consistently associated with bone mineral densities. The single factor most predictive of low BMD was a lateral tunnel Fontan, compared to an extra cardiac Fontan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/chd.12848DOI Listing
November 2019

Association Between Abdominal Aortic Calcification, Bone Mineral Density, and Fracture in Older Women.

J Bone Miner Res 2019 11 9;34(11):2052-2060. Epub 2019 Oct 9.

Medical School, The University of Western Australia, Perth, WA, Australia.

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score >6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r = -0.077, p = 0.013), heel broadband ultrasound attenuation ( r = -0.074, p = 0.020), and the Stiffness Index ( r = -0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3830DOI Listing
November 2019

Bone Matrix Levels of Dickkopf and Sclerostin are Positively Correlated with Bone Mass and Strength in Postmenopausal Osteoporosis.

Int J Mol Sci 2019 Jun 14;20(12). Epub 2019 Jun 14.

Section of Specialized Endocrinology, Oslo University Hospital; Faculty of Medicine, University of Oslo, 0027 Oslo, Norway.

Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, bone mass, and strength in postmenopausal osteoporosis. We measured cortical and trabecular bone contents of SOST and Dickkopf-1 (DKK1) in combined extracts obtained after ethylenediaminetetraacetic acid and guanidine hydrochloride extraction in 56 postmenopausal women aged 47-74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. Our findings were (i) SOST and DKK1 protein levels were higher in trabecular bone, (ii) cortical and trabecular DKK1 and trabecular SOST correlated positively with bone matrix levels of osteocalcin ( between 0.28 and 0.45, < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) ( = 0.32, < 0.05) and femoral neck BMD ( = 0.41, < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength ( between 0.34 and 0.51, < 0.01). In conclusion, cortical bone matrix levels of DKK1 and SOST were positively correlated with bone mass and bone strength in postmenopausal osteoporotic women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20122896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627473PMC
June 2019

MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.

Eur J Endocrinol 2019 09 1;181(3):P1-P19. Epub 2019 Jun 1.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations, or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas Quality of Life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with an increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity, and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function, and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-19-0316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598862PMC
September 2019

MANAGEMENT OF ENDOCRINE DISEASE: Individualised management of acromegaly.

Eur J Endocrinol 2019 Aug;181(2):R57-R71

Section of Specialized Endocrinology, Department of Endocrinology, Medical Clinic, Oslo University Hospital.

Acromegaly is a rare and challenging disease calling for management in highly specialised multidisciplinary teams (MDTs). Untreated disease has severe morbidity and a clearly increased mortality. Major attainments have been gained over the latest decades, and therefore, the aim of this review is to discuss recent achievements in modern multimodal therapy of acromegaly performed by MDTs, with an emphasis on an individualised, proactive management from the time of diagnosis to long-term outcome. Treatment by surgery is the only potential curative treatment, however, even with modern techniques still with modest cure rates, leaving the patients to often long-term medical treatment. Treatment strategies have changed dramatically in the Western world over recent years, implying a more proactive treatment algorithm often with a shorter or longer pre-surgical treatment period with somatostatin receptor ligands (SRLs). Not all patients will however respond to primary treatment with conventional SRLs and there has recently been a development of potential biomarkers for response that has been implemented in the clinical routine. By today, multimodal treatment can bring every patient in remission, but still almost a third of all patients are undertreated according to large, international registries. On the other hand, it might be a challenge not to over treat thereby bringing the patient into a state of relative or absolute growth hormone deficiency. Clinical series published during the last decade on treatment of patients with acromegaly have indicated a normalisation of mortality, most probably reflecting the proactive and individualised modern treatment. In conclusion, modern, multimodal treatment seems to have normalised mortality, but still the patients suffer from a high multi-organ morbidity and often multi-pharmacy. Every patient should receive an individualised, proactive treatment in order to improve long-term outcome and to reduce costs for the society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-19-0124DOI Listing
August 2019

Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission.

Eur J Endocrinol 2019 May;180(5):329-338

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objective Cushing's syndrome is associated with long-term cognitive deficits and affective symptoms such as depression and anxiety. The alterations in brain function underlying these deficits after Cushing's syndrome are unclear and therefore we aimed to explore alterations in resting-state functional connectivity in patients with Cushing's syndrome in remission. Design Cross-sectional case-control study. Methods Nineteen women with Cushing's syndrome in remission for a median time of 7 years (IQR: 6-10) and a mean age of 45 years were included at three university clinics. These patients and 38 age-matched female controls underwent brain imaging at a single center. The main outcome measure was functional connectivity at rest, measured with functional magnetic resonance imaging. Results The medial temporal lobe (MTL) and prefrontal cortex networks, exhibited elevated functional connectivity among patients compared to controls. The degree of elevated functional connectivity in the MTL was negatively associated with time in remission. Conclusions Resting-state functional connectivity within glucocorticoid receptor-rich regions, particularly the MTL and medial prefrontal cortex, was increased in patients. These differences in connectivity may provide a neural basis for the cognitive deficits and affective symptoms commonly experienced by patients with Cushing's syndrome in remission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-19-0028DOI Listing
May 2019

Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus.

Diabetes Care 2019 06 12;42(6):1067-1074. Epub 2019 Mar 12.

Section of Nephrology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have lately become the recommended treatment in patients with type 2 diabetes and high cardiovascular risk. Patients with posttransplant diabetes mellitus (PTDM) also have high cardiovascular risk. The aim of this study was to investigate the safety and efficacy of empagliflozin in renal transplant recipients with PTDM.

Research Design And Methods: Forty-nine renal transplant recipients were included in an investigator-initiated, single-center, prospective, double-blind study and randomized to receive either 10 mg empagliflozin or placebo once daily for 24 weeks. Patients transplanted >1 year ago, diagnosed with PTDM, with stable renal function (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m), and with stable immunosuppressive therapy were studied.

Results: Forty-four renal transplant recipients (22 empagliflozin/22 placebo, 34 males) completed the study. Median (interquartile range) change in glycated hemoglobin (HbA) was significantly reduced with empagliflozin compared with placebo: -0.2% (-0.6, -0.1) (-2.0 mmol/mol [-6.5, -1.0]) vs. 0.1% (-0.1, 0.4) (1.0 mmol/mol [-0.75, 3.8]) ( = 0.025). The magnitude of glucose reduction was dependent on GFR and baseline HbA. The treatment also resulted in a significant reduction in body weight of -2.5 kg (-4.0, -0.05) compared with an increase of 1.0 kg (0.0, 2.0) in the placebo group ( = 0.014). There were no significant differences between the groups in adverse events, immunosuppressive drug levels, or eGFR.

Conclusions: Empagliflozin appeared safe and improved glycemic control in renal transplant recipients with PTDM compared with placebo. A concomitant reduction in body weight was seen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc19-0093DOI Listing
June 2019

Serum Omega-6 Fatty Acids and Immunology-Related Gene Expression in Peripheral Blood Mononuclear Cells: A Cross-Sectional Analysis in Healthy Children.

Mol Nutr Food Res 2019 04 11;63(7):e1800990. Epub 2019 Feb 11.

Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, 0317, Oslo, Norway.

Scope: Some studies suggest that a high dietary intake of omega-6 fatty acids is pro-inflammatory. However, whether omega-6 fatty acids actually cause pathogenic inflammation in humans is debated. Therefore, the associations between expression of immunology-related genes in peripheral blood mononuclear cells (PBMCs) and serum total omega-6 PUFA status are investigated.

Methods And Results: Serum fatty acid profile and expression of 460 immunology-related genes in PBMCs from 58 healthy children (6-13 years) is measured, and examined the expression differences between children with high or low total omega-6 PUFA status (upper vs lower tertile). Taken together, both univariate analyses and integrated omics analyses support that while high omega-6 PUFA level associated with higher expressing of genes related to innate immune responses, it also associated with lower expression of several genes related to adaptive immune responses.

Conclusion: Omega-6 PUFA status associated both positively and negatively with expression of specific immunology-related genes in PBMCs in healthy children. The results may suggest a nuanced role for omega-6 fatty acids in the interphase of lipids and inflammation, and warrants further examination in gene-environment studies and randomized controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.201800990DOI Listing
April 2019

Adipokines and macrophage markers during pregnancy-Possible role for sCD163 in prediction and progression of gestational diabetes mellitus.

Diabetes Metab Res Rev 2019 03 7;35(3):e3114. Epub 2019 Jan 7.

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Aims: The risk of gestational diabetes mellitus (GDM) is increased in overweight and obese women potentially involving secreted mediators from adipose tissue. Our main aim was to evaluate if circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and the influence body mass and indices of glucose metabolism had on this association. We further explored if early detection of these markers improved prediction of GDM and if they remained modified during long-term follow-up.

Materials And Methods: Population-based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5-year follow-up.

Results: sCD163 was higher (25% at 14-16 weeks, P < 0.001) and adiponectin lower (-17% at 14-16 weeks, P < 0.01) early in pregnancy and at 5-year follow-up in GDM women, independent of BMI, and other GDM risk factors. Leptin, adiponectin, and chemerin were robustly associated with glucose metabolism throughout pregnancy while sCD163 was inversely associated with β-cell function early in pregnancy in women with increased BMI. Finally, the markers at 14 to 16 weeks displayed modest discriminatory properties with regard to prediction of GDM (AUC < 0.7). Using a combination of fasting glucose and sCD163, 53% of GDM could be identified when 25% of the population scored positive suggesting some merit in a multimarker approach.

Conclusions: sCD163 and adiponectin were dysregulated in GDM, independent of body mass. None of the adipokines or monocyte/macrophage activation markers displayed clinically useful properties alone for early detection of GDM. Activation of monocytes/macrophages may be an important event in the early development of GDM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.3114DOI Listing
March 2019

Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus.

Eur J Endocrinol 2019 Mar;180(3):P1-P22

Mayo Clinic, Rochester, Minnesota, USA.

Purpose: To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults.

Methods: Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords 'hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy'. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism.

Results: Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults.

Main Conclusions: Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-18-0609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365672PMC
March 2019

Physical Fitness in Patients With Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis Diagnosed in the Era of Biologics: A Controlled Cross-Sectional Study.

Arthritis Care Res (Hoboken) 2019 12;71(12):1611-1620

Oslo University Hospital, Rikshospitalet and Bjørknes University College, Oslo, Norway.

Objective: To perform a comprehensive evaluation of and identify correlates for physical fitness in consecutive patients with juvenile idiopathic arthritis (JIA) who have been diagnosed in the era of biologics and to compare the results with those obtained in healthy controls.

Methods: The study cohort included 60 patients with JIA (50 girls) ages 10-16 years and 60 age- and sex-matched controls. The JIA group included 30 patients with persistent oligoarticular JIA and 30 patients with extended oligoarticular or polyarticular disease. Measures of physical fitness included cardiorespiratory fitness (CRF) by peak oxygen uptake (Vo ) during a continuous graded treadmill exercise test, muscle strength by isokinetic and isometric knee and hand grip evaluations, and bone mineral density (BMD) and body composition by dual-energy x-ray absorptiometry. Physical activity was assessed by accelerometry.

Results: Forty-two percent of the patients were being treated with biologic drugs. Patients with JIA demonstrated lower muscle strength and total body BMD compared to controls, but there were no differences in CRF and body composition. Physical fitness was comparable between the persistent oligoarticular and extended oligoarticular/polyarticular-JIA groups. In patients with JIA, we identified associations between higher vigorous physical activity and higher CRF and muscle strength, but did not find any association between physical fitness and disease variables.

Conclusion: In this cohort of patients with JIA, we found suboptimal muscle strength and BMD compared to controls, but no differences in CRF and body composition. Vigorous physical activities appeared important for optimizing muscle strength and CRF in patients with JIA; the importance of such activities should be highlighted in patient education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.23818DOI Listing
December 2019