Jens Bollerslev

• Ueland, Thor; Michelsen, Annika Elisabet; Qvigstad, Elisabeth; Roland, Marie Cecilie; Westerberg, Ane Cecilie & Michelsen, Trond Melbye [Vis alle 9 forfattere av denne artikkelen] (2026). Secreted frizzled-related protein 3 is associated with metabolic disturbances in gestational diabetes. Frontiers in Endocrinology. 17. doi: 10.3389/fendo.2026.1905877. Fulltekst i vitenarkiv
• Kvammen, Janne Anita; Thomassen, Rut Anne; Godang, Kristin; Buchner, Jochen; Bollerslev, Jens & Bentsen, Beint Sigmund [Vis alle 8 forfattere av denne artikkelen] (2026). Body Composition, Bone Health, and Dietary Intake in Children After Allogeneic Hematopoietic Stem Cell Transplantation. Nutrients. 18(13). doi: 10.3390/nu18132193. Fulltekst i vitenarkiv
• Godang, Kristin; Wessel, Maren Ileby; Khan, Yusuf; Ueland, Thor; Lekva, Tove & Berg, Jens Petter [Vis alle 8 forfattere av denne artikkelen] (2026). Targeted proteomics reveals novel biomarkers of disease activity and inflammation in acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 194(5), s. 732–743. doi: 10.1093/ejendo/lvag083. Fulltekst i vitenarkiv
• Melmed, Shlomo; Filippo, Luigi di; Fleseriu, Maria; Mercado, Moisés; Karavitaki, Niki & Gurnell, Mark [Vis alle 52 forfattere av denne artikkelen] (2025). Consensus on acromegaly therapeutic outcomes: an update. Nature Reviews Endocrinology. ISSN 1759-5029. 21(11), s. 737–737. doi: 10.1038/s41574-025-01148-2. Fulltekst i vitenarkiv
• Arlien-Søborg, M. C.; Radovick, S.; Boguszewski, M. C.S.; Bidlingmaier, M.; Johannsson, G. & Grimberg, A. [Vis alle 44 forfattere av denne artikkelen] (2025). Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society. Pituitary. ISSN 1386-341X. 28(3). doi: 10.1007/s11102-025-01526-z. Fulltekst i vitenarkiv
• Cardoso, Luís Miguel; Rolighed, Lars; Amrein, Karin; Pilz, Stefan; Underbjerg, Line & Pretorius, Mikkel [Vis alle 16 forfattere av denne artikkelen] (2025). Advances in the clinical management of parathyroid disorders: report from the 2024 workshop by the ESE educational program on parathyroid disorders. European Journal of Endocrinology (EJE). ISSN 0804-4643. 193(6), s. R65–R88. doi: 10.1093/ejendo/lvaf204. Fulltekst i vitenarkiv
• Atai, Shahriar; Wiedmann, Markus; Dahlberg, Daniel; Bollerslev, Jens & Heck, Ansgar (2025). Management of acromegaly beyond primary surgery: efficacy and safety of repeat surgery and radiotherapy. Acta Neurochirurgica. ISSN 0001-6268. 167(1). doi: 10.1007/s00701-025-06640-2. Fulltekst i vitenarkiv Vis sammendrag

  Introduction and purpose Re-intervention, either transsphenoidal surgery or radiotherapy, is suggested in patients who are not in remission after primary surgery for acromegaly; however, the evidence is weak. We aimed to assess the remission rate after re-intervention, and complications compared to a comparison group who had undergone primary interventions only. Methods Patients diagnosed with acromegaly between 2005–2021 at Oslo University Hospital were screened for inclusion. The study cohort included patients with two or more interventions. The comparison group included patients not in remission after primary surgery. Results Of 223 patients with acromegaly, 42 underwent re-interventions (study cohort). At diagnosis, median age was 38 (IQR 29–48) years and 41 patients (98%) had a macroadenoma. The comparison group consisted of 49 patients, median age 54 (IQR 44–60) years and 37 (76%) had a macroadenoma at diagnosis. Re-interventions in the study cohort consisted of surgery, radiotherapy and a combination of these (22, 12 and eight patients). After re-interventions, 22 patients (52%) were in remission and 12 (29%) had reduced disease activity. Seven patients (17%) acquired new hormone deficiencies, two of them corticotroph deficiency. One patient in remission developed spinal fluid leakage and meningitis. There was no significant difference in complications after surgery between the study cohort and the comparison group. Conclusion Re-interventions were safe and resulted in remission or substantial improvement in most patients. Re-intervention should be considered for patients who would otherwise require lifelong medical treatment.

• Bollerslev, Jens; Buch, Ottilia; Cardoso, Luís Miguel; Gittoes, Neil; Houillier, Pascal & Hulsteijn, Leonie Van [Vis alle 13 forfattere av denne artikkelen] (2025). Revised European Society of Endocrinology Clinical Practice Guideline: Treatment of Chronic Hypoparathyroidism in Adults. European Journal of Endocrinology (EJE). ISSN 0804-4643. 193(5), s. G49–G78. doi: 10.1093/ejendo/lvaf222. Fulltekst i vitenarkiv Vis sammendrag

  In the present European Society of Endocrinology (ESE) clinical guideline, we present recommendations for the diagnosis, management, and monitoring of chronic hypoparathyroidism (HypoPT) in adults. Management of HypoPT has changed since the first ESE clinical guideline was published in 2015, as has the knowledge on patient burden of the disease, and the understanding of associated morbidities. In line with the ESE policy, the 2015 guidelines were updated based on up-to-date scientific evidence. As HypoPT is an orphan disease, strong evidence for most outcomes is scarce and recommendations were based on careful synthesis of the literature and expert opinion. Postsurgical HypoPT should be defined as persisting more than 12 months following surgery; recovery could be expected even thereafter (clinical question I [Q I]). For Q II (optimal treatment of chronic HypoPT), relevant data regarding conventional treatment are lacking for clinically relevant endpoints and long-term effects. PTH replacement therapy reduces the pill burden of conventional therapy, improves various biochemical parameters, and potentially improves QoL. We cannot recommend a substantial role for parathyroid allotransplantation in the treatment of chronic HypoPT (Q III). In conclusion, we present recommendations for the diagnosis, management, and monitoring of chronic HypoPT in adults, to give health care providers practical clinical guidance on the management of this condition. The guideline can serve as a source for preparation of educational materials to empower patients and clinicians.

• Giustina, Andrea; Filippo, Luigi di; Aleksova, Aneta; Bollerslev, Jens; Colao, Anna Maria & Dawson-Hughes, Bess [Vis alle 21 forfattere av denne artikkelen] (2025). Consensus statement on vitamin D role in metabolic health. Metabolism: Clinical and Experimental. ISSN 0026-0495. 176. doi: 10.1016/j.metabol.2025.156484. Fulltekst i vitenarkiv Vis sammendrag

  The 8th International Conference Controversies in Vitamin D, held in September 2024, convened leading experts to address the multifaceted role of vitamin D in human health. Key discussions focused on its influence on metabolic health, including effects on sarcopenia, muscle function, and energy metabolism, as well as its role in obesity, cardiovascular health, and diabetes. Preclinical evidence was presented, suggesting a pivotal role of vitamin D in regulating muscle function and repair, potentially preventing sarcopenia. A relationship between low vitamin D (25[OH]D) concentrations and increased risk of cardiovascular diseases and diabetes was supported by several preclinical and clinical studies. Vitamin D supplementation was recently demonstrated to help improve glycemia and reduce the progression to diabetes and increase the likelihood of regression to normal glucose regulation in adults with prediabetes. Despite mixed outcomes from large, population-based randomized clinical trials, the conference underscored the critical need for personalized research, through disease-specific clinical trials, to fully elucidate the therapeutic potential of vitamin D supplementation, particularly in chronic conditions such as cardiovascular diseases and diabetes. In conclusion, while vitamin D demonstrates considerable promise in modifying a wide array of metabolic health concerns, rigorous scientific inquiry is essential to deepen our understanding of its mechanisms as well as potential protective effects and establish evidence-based guidelines for supplementation. This growing body of work has the potential to significantly enhance clinical outcomes and improve public health strategies, calling for continued exploration and collaboration in the field of vitamin D research.

• Olarescu, Nicoleta Cristina; Jørgensen, Anders Palmstrøm; Atai, Shahriar; Wiedmann, Markus; Dahlberg, Daniel & Bollerslev, Jens [Vis alle 7 forfattere av denne artikkelen] (2025). Pasireotide as first line medical therapy for selected patients with acromegaly. Pituitary. ISSN 1386-341X. 28(3). doi: 10.1007/s11102-025-01514-3. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background and purpose In acromegaly, growth hormone (GH) excess and pituitary tumours are typically managed through transsphenoidal surgery, often in combination with somatostatin receptor ligands (SRLs) given either before or following surgery. Although first-generation SRLs (lanreotide and octreotide) are efficacious in many patients, some exhibit resistance. Methods We present the efficacy of the second-generation SRL, pasireotide, in six patients anticipated to be resistant to first-generation SRLs. The patients had large, hyperintense tumors on T2-weighted MRI and sparse granulation pattern by histology. Results Over three to eight months, pasireotide reduced tumour volume in all patients and improved GH and IGF-1 levels. Visual field defects normalised. Despite hyperglycemia, requiring antidiabetic treatment in two patients, pasireotide proved effective as a first pharmacological therapy. Conclusion This series supports the use of pasireotide for rapid tumour control and GH reduction, in selected patients with complex and large tumours, likely to be resistant to first-generation SRLs. This approach expands the therapeutic options for managing the most challenging cases enhancing the potential for other subsequent treatment modalities.

• Kvammen, Janne Anita; Thomassen, Rut Anne; Buechner, Jochen; Myklebust, Tor Åge; Thorsby, Per Medbøe & Bollerslev, Jens [Vis alle 9 forfattere av denne artikkelen] (2025). Vitamin D status in children undergoing allogeneic hematopoietic stem cell transplantation: A prospective exploratory study. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 80(6), s. 1007–1017. doi: 10.1002/jpn3.70028. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with nutritional risks. This study describes vitamin D status and intake in children undergoing HSCT and compares results to healthy children. Methods In a prospective observational study, vitamin 25(OH)D and 1,25(OH)2D were assessed at hospital admission before HSCT (baseline), at 3-month and 1-year post-transplant. Vitamin D deficiency was defined as 25(OH)D < 50 nmol/L. A 4-day diet record assessed vitamin D intake at 3-months and 1-year. Healthy children were assessed once. Results Twenty-eight HSCT patients (mean age: 10.3-years, standard deviation [SD]: 4.0) and 50 healthy children (mean age: 10.0-years, SD: 3.6) were included. Vitamin D deficiency was more prevalent in patients at baseline (36%, p < 0.001) and 3-months (24%, p = 0.007) but not at 1-year (14%, p = 0.084) than in healthy children (2%). Median 1,25(OH)2D was significantly lower than in healthy children at the two first visits (p < 0.001) but not at 1-year (p = 0.198). Median vitamin D provision was higher at 3-months (18.1 µg/day) and 1-year (25 µg/day) compared to healthy children (5.3 µg/day, p < 0.001). Conclusions Children undergoing HSCT were at a high risk of vitamin D deficiency at baseline and 3-month post-transplant, but not at 1-year compared to healthy children. Vitamin D intake was higher after transplantation than in healthy children. These findings indicate that vitamin D requirements are elevated in HSCT patients, emphasizing the need for monitoring and adequate supplementation.

• Risum, Kristine; Olarescu, Nicoleta Cristina; Godang, Kristin; Marstein, Henriette Schermacher; Bollerslev, Jens & Sanner, Helga (2025). Visceral adipose tissue is related to interleukin 6 and resistin in juvenile idiopathic arthritis - a case-control study. Rheumatology International. ISSN 0172-8172. 45(3). doi: 10.1007/s00296-025-05820-8. Fulltekst i vitenarkiv Vis sammendrag

  To compare visceral adipose tissue (VAT) mass, lipid profile, and selected adipokines/cytokines in patients with juvenile idiopathic arthritis (JIA) with controls, and to explore associations between these markers and VAT. We included 60 JIA patients (30 oligoarticular,30 polyarticular), aged 10–16 years, and 60 age-and sex-matched controls. VAT (g) was estimated by dual-energy x-ray absorptiometry. Lipid profile and selected adipokines/cytokines were analyzed by standard methods and ELISA, respectively. VAT (g) was comparable between patients and controls [median (25th-75th percentile): 64 (23–149) g vs. 66 (30–99) g, p = 0.98] and between oligoarticular and polyarticular disease courses [46 (22–123) g vs. 80 (23–167) g, p = 0.32]. Patients had lower serum levels of apolipoprotein A1 (APOA1) and elevated levels of interleukin- 6 (IL-6) and progranulin compared to controls. As compared to oligoarticular disease course, patients with polyarticular disease had lower serum levels of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), interleukin 1 receptor antagonist (IL-1RA) and progranulin, and elevated levels of interleukin-1 beta (IL-1b) and IL-1b/IL-1RA ratio. In patients (B, 95% CI), higher IL-6 (48.7, 25.1 to72.2, p < 0.001), resistin (8.5, 5.1 to 11.8, p < 0.001), and leptin (2.5, 0.9 to 4.0, p = 0.002) were associated with higher VAT. In controls, higher leptin (5.3, 3.7 to 6.9), p < 0.001) was associated with higher VAT. Despite similar VAT mass between patients and controls, VAT was related to IL-6 and resistin in patients only, suggesting an active metabolic role in JIA. Several pro-inflammatory adipokines/cytokines were increased in JIA, with differences in Lp(a) between oligoarticular and polyarticular disease courses.

• Abusdal, Merisa; Markussen, Kjersti Normann; Nyman, Tuula A; Øystese, Kristin Astrid Berland; Sundaram, Arvind & Dahlberg, Daniel [Vis alle 10 forfattere av denne artikkelen] (2024). PCSK1N as a Tumor Size Marker and an ER Stress Response Protein in Corticotroph Pituitary Adenomas. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 110(4), s. 1065–1075. doi: 10.1210/clinem/dgae643. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Context Silent corticotroph adenoma (SCA) exhibits more tumor aggressiveness features than functioning adenomas (FCAs). Objective We aimed to investigate proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N) expression in CA and examine if endoplasmic reticulum (ER) stress-induced responses affect cell survival in a corticotroph tumor cell model. Methods Clinical and imaging characteristics were recorded in 33 patients with FCA (20 women, 11 macroadenomas) and 18 SCAs (8 women, all macroadenomas). Gene expression of pro-opiomelanocortin (POMC), T-box transcription factor 19(TBX19)/TPIT, proprotein convertase subtilisin/kexin type 1 (PCSK1)/PC1/3, and its inhibitor PCSK1N, was measured by reverse transcription–quantitative polymerase chain reaction in adenoma tissue. Mouse pituitary corticotroph tumor (AtT-20) cells were treated with tanespimycin (17-AAG), an HSP90 chaperone inhibitor, to induce ER stress, followed by gene and protein analyses. Results POMC, TPIT, and PCSK1 expression were higher, whereas PCSK1N was lower in FCA compared to SCA. PCSK1N correlated with POMC (rs = −0.514; P &lt; .001), TPIT (rs = −0.386; P = .005), PCSK1 (rs = −0.3691; P = .008), and tumor largest diameter (rs = 0.645; P &lt; .001), in all CA. Induction of ER stress by 17-AAG in AtT-20 cells led to a decrease of Pomc and an increase of Pcsk1n gene expression at 24 hours. Moreover, a downregulation of cell cycle, apoptosis, and senescence pathways, and alterations in cell adhesion and cytoskeleton, were observed at the protein level. Conclusion PCSK1N is higher in SCA compared with FCA, and associated with corticotroph cell markers and tumor size. PCSK1N is likely to be part of the adaptive response to ER stress, potentially conferring a survival advantage to the corticotroph tumor cell in conjunction with other proteins.

• Atai, Shahriar; Andersen, Martin Knudtzon; Wiedmann, Markus; Dahlberg, Daniel; Øystese, Kristin Astrid Berland & Bollerslev, Jens [Vis alle 8 forfattere av denne artikkelen] (2024). Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment. Acta Radiologica. ISSN 0284-1851. 65(7), s. 753–758. doi: 10.1177/02841851241246107. Fulltekst i vitenarkiv
• Falch, Camilla Maria; Godang, Kristin; Lekva, Tove; Ueland, Thor; Heck, Ansgar & Bollerslev, Jens [Vis alle 7 forfattere av denne artikkelen] (2024). Long-term depot specific changes in adipose tissue after treatment of acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 190(3), s. K37–K42. doi: 10.1093/ejendo/lvae016. Fulltekst i vitenarkiv Vis sammendrag

  Context Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that treatment leads to AT depot-specific gain. However, it remains unclear if the increase is persistent in the long-term perspective and/or is sex-dependent. Design To characterize the depot-specific changes of AT after treatment of acromegaly and identify contributing factors. Methods Adipose tissue, including visceral (VAT), subcutaneous (SAT), and total (TAT), and android to gynoid ratio (A/G ratio) were measured by dual energy X-ray absorptiometry at diagnosis (n = 62), and after treatment at short-term (median (IQR) 1.9 (1.5-2.3)) and long-term 5.5 (3.9-9.5) years, and correlated to clinical and biochemical measurements. Growth hormone (GH), insulin-like growth factor 1 (IGF-1), glucose and HbA1c levels, gonadal status, and the presence of diabetes mellitus were recorded. Remission status was assessed at the long-term visit (IGF-1/ULN ≤ 1.3). Differences in the temporal course of AT from baseline to short- and long-term follow-up according to sex, diabetes, gonadal, and remission status were evaluated by mixed model analysis, adjusted for age. Results Despite a stable body mass index, VAT and A/G ratio increased at both time points, whereas SAT mainly increased at short-term, plateauing afterwards (P < .05 for all). Visceral adipose tissue and A/G ratio were higher in men (P = .035 and P < .001), and the A/G ratio increased more than in women (P = .003). Glucose and HbA1c decreased short-term (P < .05) and remained stable at long-term. The increase in AT depots correlated with the decrease of disease activity at long-term. Remission status had no effect on changes in AT mass during follow-up. Conclusion Treatment of acromegaly leads to an increase in AT mass in a depot- and sex-specific manner both at short-term and long-term follow-up. Glucose metabolism improves rapidly after disease control and persists.

• Arlien-Søborg, Mai C.; Dal, Jakob; Heck, Ansgar; Stochholm, Kirstine; Husted, Eigil & Feltoft, Claus Larsen [Vis alle 48 forfattere av denne artikkelen] (2024). Acromegaly management in the Nordic countries: A Delphi consensus survey. Clinical Endocrinology. ISSN 0300-0664. 101(3), s. 263–273. doi: 10.1111/cen.15095. Fulltekst i vitenarkiv
• Giustina, Andrea; Bilezikian, John P; Adler, Robert A; Banfi, Giuseppe; Bikle, Daniel D & Binkley, Neil C [Vis alle 27 forfattere av denne artikkelen] (2024). Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows. Endocrine reviews. ISSN 0163-769X. 45(5), s. 625–654. doi: 10.1210/endrev/bnae009. Fulltekst i vitenarkiv Vis sammendrag

  The 6th International Conference, “Controversies in Vitamin D,” was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

• Strømmen, Ruth Cecilie; Godang, Kristin; Hovd, Markus; Finnes, Trine Elisabeth; Smerud, Knut Terje & Hartmann, Anders [Vis alle 9 forfattere av denne artikkelen] (2024). Hip geometry and strength remain stable the first year after kidney transplantation—an ibandronate/placebo post hoc analysis. Journal of Bone and Mineral Research. ISSN 0884-0431. 8(12). doi: 10.1093/jbmrpl/ziae130. Fulltekst i vitenarkiv Vis sammendrag

  The sensitivity of bone mineral density (BMD) to identify patients with high fracture risk after kidney transplantation is low, therefore alternative tools are needed. Hip Structure Analysis (HSA) provides an estimation of hip structural geometry and strength based on conventional DXA scans for hip analyses. We aimed to investigate the effect of antiresorptive therapy on hip geometrical and strength parameters by HSA. In a post hoc analysis of a 12-month randomized, double-blind, placebo-controlled trial evaluating the effect of ibandronate in addition to active vitamin D and calcium in kidney transplant recipients (KTR), we re-analyzed dual total hip and femoral neck DXA scans to measure cortical bone thickness (CBT) in the femoral neck (CBTNECK), calcar (CBTCALCAR), and shaft (CBTSHAFT), along with femur neck width, hip axis length, and to estimate buckling ratio and strength index. DXA measurements were performed within 5 weeks after transplantation and repeated at 10 weeks and 1-year post-transplant. The study included a total of 127 de novo KTR with estimated glomerular filtration rate >30 mL/min at baseline. The 5 geometrical and the strength and stability hip parameters remained stable over the first post-transplant year irrespective of antiresorptive therapy. We detected no statistically significant between-group differences in any of the HSA measures. Change in geometrical hip parameters and buckling ratio over the study duration was not correlated with change in plasma parathyroid hormone or change in dual total hip BMD. In this study, the so far largest of HSA in KTR, antiresorptive therapy with ibandronate for 12 months did not affect measures of hip geometry or strength.

• Heck, Ansgar; Pretorius, Mikkel; Lundstam, Karolina; Godang, Kristin; Hellström, Mikael & Ueland, Thor [Vis alle 7 forfattere av denne artikkelen] (2024). No effect of surgery on kidney and cardiovascular risk factors in mild primary hyperparathyroidism: secondary analyses from a 10-year randomized controlled trial. European Journal of Endocrinology (EJE). ISSN 0804-4643. 191(3), s. 354–360. doi: 10.1093/ejendo/lvae109. Fulltekst i vitenarkiv Vis sammendrag

  Objective Renal function and the skeleton are classic target organs in primary hyperparathyroidism (PHPT), affected by the chronic course of the disease. Most patients diagnosed today exhibit mild PHPT, characterized by slight hypercalcemia and no or unspecific symptoms. Concerns have been raised that PHPT could promote deteriorating kidney function and increase cardiovascular risk directly. To examine the effect of parathyroidectomy (PTX) on mild PHPT on renal function and markers for bone turnover, cardiovascular disease (CVD), and vascular inflammation. Design Prospective randomized controlled trial. ClinicalTrials.gov: NCT00522028. Setting Eight Scandinavian referral centers. Participants From 1998 to 2005, 191 patients with mild PHPT were included in Sweden, Norway, and Denmark. Of these 150 were included in the present analyses. Intervention Seventy patients were randomized to PTX and 80 to observation without intervention (OBS). Measures e-GFR was calculated based on creatinine and cystatin C. Markers of CVD and systemic inflammation: osteoprotegerin, vascular cell adhesion molecule 1, soluble CD40 ligand, interleukin-1 receptor antagonist, von Willebrand factor. Bone turnover markers: C-terminal telopeptide of type 1 collagen (CTX-1) and serum Procollagen type 1 N-terminal propeptide. Results No differences in the development of renal function or vascular and systemic inflammation were detected. CTX-1 was lower in PTX after 10 years. Limitations Secondary analyses of a randomized controlled trial. Conclusion PTX does not appear to affect renal function or markers of CVD and vascular inflammation in mild PHPT in a ten-year perspective.

• Isand, Kristina; Feelders, Richard; Brue, Thierry; Toth, Miklos; Deutschbein, Timo & Reincke, Martin [Vis alle 21 forfattere av denne artikkelen] (2024). High prevalence of venous thrombotic events in Cushing’s syndrome: data from ERCUSYN and details in relation to surgery. European Journal of Endocrinology (EJE). ISSN 0804-4643. 190(1), s. 75–85. doi: 10.1093/ejendo/lvad176. Fulltekst i vitenarkiv Vis sammendrag

  Objective The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. Design A retrospective observational cohort study. Methods Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. Results Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. Conclusion Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.

• Øystese, Kristin Astrid Berland; Olarescu, Nicoleta Cristina; Lindskog, Cecilia; Xheka, Fabjola; Berg-Johnsen, Jon & Berg, Jens Petter [Vis alle 8 forfattere av denne artikkelen] (2024). Stem cell-associated transcription factors in non-functioning pituitary neuroendocrine tumours. Free Neuropathology. 5. doi: 10.17879/freeneuropathology-2024-5396. Fulltekst i vitenarkiv Vis sammendrag

  Background: Cells with stem cell features have been described in pituitary neuroendocrine tumours (PitNETs). Transcription factors SOX2 and SOX9 are stem cell-associated markers while the pituitary progenitor marker PROP1 is involved in anterior pituitary development. We characterised the presence of these markers known to be present in the human pituitary in non-functioning (NF) PitNETs. Methods: We investigated the pituitary transcription factors SOX2, SOX9 and PROP1 by immunohistochemistry (IHC) (N = 125) and RT-qPCR (N = 78) in a retrospective cohort of clinically NF-PitNETs. The markers were scored based on the percentage of immunolabeled cells. IHC staining scores were compared to reintervention rates for the whole cohort, and to expression of FSH, LH or ER in gonadotroph NF-PitNETs. Results: Most tumours showed no or few cells positive for SOX2, SOX9 and PROP1. More patients with SOX2-negative tumours went through reintervention (40 % vs 19 %, p = 0.03). SOX2, SOX9 and PROP1 staining correlated positively to each other (SOX2 and SOX9 rs = 0.666, SOX2 and PROP1 rs = 0.704, SOX9 and PROP1 rs = 0.570, and p < 0.001 for all). In gonadotroph NF-PitNETs, staining for SOX2 and PROP1 was positively associated to FSHβ staining (p < 0.001 for both). Staining for SOX2, SOX9 and PROP1 was positively associated with gene expression of Estrogen Receptor 1 (ESR1) (p < 0.001, p = 0.004 and p < 0.001) and IHC staining for ERα (p = 0.001, p = 0.03 and p = 0.05, respectively). Conclusion: SOX2, SOX9 and PROP1 were present at low levels in NF-PitNETs. Absence of SOX2 staining was associated with a higher reintervention rate. The stem cell markers correlated positively with markers of gonadotroph differentiation in gonadotroph NF-PitNETs. SOX2 and SOX9 were frequently coexpressed and showed positivity in intratumoural cells with epithelial features, however without coexpression of pituitary transcription factors.

• Marstein, Henriette; NOMELAND, BIRGIT; Godang, Kristin; Olarescu, Nicoleta Cristina; Schwartz, Thomas & Flatø, Berit [Vis alle 10 forfattere av denne artikkelen] (2023). Adipokine profile in long-term juvenile dermatomyositis, and associations with adipose tissue distribution and cardiac function: a cross-sectional study. RMD Open. 9:e002815(1), s. 1–9. doi: 10.1136/rmdopen-2022-002815. Fulltekst i vitenarkiv Vis sammendrag

  Objectives In long-term juvenile dermatomyositis (JDM), altered adipose tissue distribution and subclinical cardiac dysfunction have been described. Our aims were to compare adipokine levels in patients with JDM after long-term disease with controls, and explore associations between adipokines and (1) adipose tissue distribution and (2) cardiac function. Methods The study cohort included 59 patients with JDM (60% female, mean age 25.2 years, mean disease duration 16.9 years), and 59 age/sex-matched controls. Updated Pediatric Rheumatology International Trials Organization criteria for clinically inactive JDM were used to stratify patients into active (JDM-active) or inactive (JDM-inactive) disease groups. Lipodystrophy was clinically assessed in all patients. In all study participants, we measured adipose tissue distribution by dual-energy X-ray absorptiometry and cardiac function by echocardiography. Serum adipokines (adiponectin, apelin-12, lipocalin-2, leptin, visfatin and resistin) were analysed using ELISA. Results Patients with JDM had higher leptin levels compared with controls (p≤0.01). In JDM-active, apelin-12 and visfatin were higher compared with JDM-inactive (p≤0.05). In JDM-total and JDM-active, lower adiponectin correlated with lipodystrophy and total fat mass. Also, systolic dysfunction correlated with: lower adiponectin in JDM-total, JDM-inactive and JDM-active, and with lower apelin-12 in JDM-total and JDM-active and resistin in JDM-active (all p≤0.05). Lower adiponectin correlated with diastolic dysfunction in JDM-total and JDM-active. Conclusion After long-term disease, leptin levels were unfavourably regulated in patients with JDM compared with controls, and apelin-12 and visfatin in JDM-active versus JDM-inactive. We found associations between adipokines and both adipose tissue distribution and cardiac systolic function in all patients with JDM, which was most prominent in patients with active disease.

• Lekva, Tove; Michelsen, Annika Elisabet; Roland, Marie Cecilie; Norwitz, Errol R.; Estensen, Mette-Elise & Olstad, Ole Kristoffer [Vis alle 11 forfattere av denne artikkelen] (2023). Increased ferroptosis in leukocytes from preeclamptic women involving the long non-coding taurine upregulated gene 1 (TUG1). Journal of Internal Medicine. ISSN 0954-6820. 295(2), s. 181–195. doi: 10.1111/joim.13732. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Ferroptosis plays a key role in placental development and physiology, and abnormal ferroptosis has been implicated in trophoblast injury leading to preeclampsia (PE). We hypothesize that leukocytes isolated from PE exhibit increased ferroptosis and that extracellular vesicles contain long non‐coding (lnc) RNA/mRNAs that modulate oxidative stress and iron toxicity in vascular endothelial cells. Methods We measured the expression of key regulators of ferroptosis in leukocytes and extracellular vesicles as well as circulating biomarkers of iron homeostasis and oxidative stress in plasma from women with/without PE at different timepoints during pregnancy. For markers that were dysregulated, we assessed their temporal correlation with established markers of disease activity and marker of endothelial activation. For markers dysregulated in early pregnancy, we assessed their ability to predict the development of PE. Results We found decreased lncRNA/mRNAs in leukocytes, but not extracellular vesicles, in PE that may modulate oxidative stress and iron toxicity. This decrease in anti‐ferroptotic markers does not appear to be related to maternal disease activity or plasma oxidative stress status but rather to attenuated anti‐inflammatory expression in these cells. Circulating ferritin was elevated in PE, supporting the hypothesis that PE represents a disbalance in iron homeostasis. Low lncRNA taurine upregulated gene 1 RNA levels in leukocytes at 22–24 weeks were strongly associated with the development of PE. Conclusions Our findings suggest that maternal leukocytes in PE show decreased anti‐ferroptotic activity that correlates with anti‐inflammatory expression. Moreover, some of these changes in ferroptotic activity appear to precede the development of PE.

• Falch, Camilla Maria; Dupont, Anne Kristine; Olarescu, Nicoleta Cristina; Wiedmann, Markus; Dahlberg, Daniel & Bollerslev, Jens [Vis alle 8 forfattere av denne artikkelen] (2023). Long-term control of acromegaly after pituitary surgery in South-Eastern Norway. Acta Neurochirurgica. ISSN 0001-6268. doi: 10.1007/s00701-023-05772-7. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. Methods Patients operated for GH-secreting pituitary adenomas between 2005–2020 were included from the local pituitary registry ( n  = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. Results A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38–59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p  = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas ( p  = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96–0.99), p  = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57–1.00), p = 0.053). Conclusion In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

• Heck, Ansgar; Godang, Kristin; Lekva, Tove; Markussen, Kjersti Normann; Vincentis, Sara De & Ueland, Thor [Vis alle 7 forfattere av denne artikkelen] (2023). Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk? JBMR Plus. 7(10). doi: 10.1002/jbm4.10787. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Growth hormone (GH) is nonphysiologically increased in acromegaly, stimulating target tissues directly and indirectly via insulin‐like growth factor type 1 (IGF‐1). Despite GH having anabolic effects on bone growth and renewal, the risk of vertebral fractures is paradoxically increased in acromegaly. We hypothesized that bone tissue compartments were differentially affected by hormonal alterations in active and controlled acromegaly. We aimed to study the effect of sex and gonadal status on long‐term outcome of bone mass and structure to understand the biomechanical competence of bone. We followed 62 patients with newly diagnosed acromegaly longitudinally (median 4.8 years after pituitary surgery) to investigate changes assessed by dual X‐ray absorptiometry (DXA), trabecular bone score (TBS), and hip structure analysis (HSA). At diagnosis, patients had increased bone mineral density (BMD) in most compartments compared with normative data (Z‐scores). Conversely, TBS Z‐score was decreased (Z = −0.64 (SD 1.73), p  = 0.028). Following treatment of acromegaly, BMD increased further in compartments containing predominantly trabecular bone, such as the lumbar spine, in eugonadal and male subjects, while compartments with predominantly cortical bone, such as the hip and femoral neck, were unchanged. Total body measurements showed further increase in BMD independent of sex and gonadal status. TBS did not change. HSA revealed a significant decrease in cortical thickness in both sexes independent of gonadal status, whereas the overall size of bone (hip axis length and neck width) did not change over time. In conclusion, patients with acromegaly had increased bone mass and dimensions by DXA. Following normalization of disease activity, BMD increased mainly in compartments rich in trabecular bone, reflecting a closure of the remodeling space. However, HSA revealed a significant decrease in cortical thickness, implying endocortical trabecularization, potentially explaining the increased risk for incident vertebral fractures following treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

• Strømmen, Ruth Cecilie; Godang, Kristin; Finnes, Trine Elisabeth; Smerud, Knut Terje; Reisæter, Anna Varberg & Hartmann, Anders [Vis alle 9 forfattere av denne artikkelen] (2023). Trabecular Bone Score Improves Early After Successful Kidney Transplantation Irrespective of Antiresorptive Therapy and Changes in Bone Mineral Density. Transplantation direct. 10(1), s. e1566–e1566. doi: 10.1097/TXD.0000000000001566. Fulltekst i vitenarkiv Vis sammendrag

  Background. Trabecular bone score (TBS) is a new tool to assess trabecular bone microarchitecture based on standard dual-energy x-ray absorptiometry (DXA) of lumbar spine images. TBS may be important to assess bone quality and fracture susceptibility in kidney transplant recipients (KTRs). This study aimed to investigate the effect of different bone therapies on TBS in KTRs. Methods. We reanalyzed DXA scans to assess TBS in 121 de novo KTRs at baseline, 10 wk, and 1 y. This cohort, between 2007 and 2009, participated in a randomized, placebo-controlled trial evaluating the effect of ibandronate versus placebo in addition to vitamin D and calcium. Results. Although bone mineral density (BMD) Z scores showed a subtle decrease in the first weeks, TBS Z scores increased from baseline to 10 wk for both treatment groups, followed by a slight decline at 12 mo. When comparing treatment groups and adjusting for baseline TBS, there were no differences found in TBS at 12 mo (P = 0.419). Correlation between TBS and BMD at baseline was weak (Spearman’s ρ = 0.234, P = 0.010), and change in TBS was not correlated with changes in lumbar spine BMD in either of the groups (ρ = 0.003, P = 0.973). Conclusions. Treatment with ibandronate or vitamin D and calcium did not affect bone quality as measured by TBS in de novo KTRs, but TBS increased early, irrespective of intervention. Changes in TBS and BMD during the study period were not correlated, indicating that these measurements reflect different aspects of bone integrity. TBS may complement BMD assessment in identifying KTRs with a high fracture risk.

• Giustina, Andrea; Filippo, Luigi di; Facciorusso, Antonio; Adler, Robert A.; Binkley, Neil & Bollerslev, Jens [Vis alle 29 forfattere av denne artikkelen] (2023). Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis. Reviews in endocrine and metabolic disorders (Print). ISSN 1389-9155. doi: 10.1007/s11154-023-09831-3. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D &lt; 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D &lt; 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (&lt; 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

• Lundstam, Karolina; Pretorius, Mikkel; Bollerslev, Jens; Godang, Kristin; Fagerland, Morten & Mollerup, Charlotte [Vis alle 15 forfattere av denne artikkelen] (2023). Positive Effect of Parathyroidectomy Compared to Observation on BMD in a Randomized Controlled Trial of Mild Primary Hyperparathyroidism. Journal of Bone and Mineral Research. ISSN 0884-0431. 38(3), s. 372–380. doi: 10.1002/jbmr.4763. Fulltekst i vitenarkiv Vis sammendrag

  Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years to the end of study (EOS). BMD was measured with dual-energy X-ray absorptiometry (DXA), peripheral fractures were noted, and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD compared with OBS for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (p < 0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33, and ultradistal radius (UDR) (p < 0.001). Even though there was a significant treatment effect of PTX compared with OBS, there was only a significant increase in BMD over time for LS (p < 0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention-to-treat (mITT) analysis nor per protocol analysis. Because BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective.

• Kolnes, Anders Jensen; Øystese, Kristin Astrid Berland; Sjöstedt, Evelina; Olarescu, Nicoleta Cristina; Heck, Ansgar & Pahnke, Jens [Vis alle 12 forfattere av denne artikkelen] (2023). TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours. Pituitary. ISSN 1386-341X. 26, s. 227–236. doi: 10.1007/s11102-023-01310-x. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data. Methods 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSHβ and LHβ was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells. Results TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LHβ (median 2 [IQR 0–3] in TGFBR3L negative and median 6 [IQR 3–9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSHβ (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9–9.6] and median 3.0 [IQR 1.8–5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9–3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L. Conclusion TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LHβ staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.

• Sørensen, Nina N.; Andreasen, Christina M.; Jensen, Pia R.; Hauge, Ellen M.; Bollerslev, Jens & Delaissé, Jean-Marie [Vis alle 10 forfattere av denne artikkelen] (2023). Disturbed bone marrow adiposity in patients with Cushing’s syndrome and glucocorticoid- and postmenopausal- induced osteoporosis. Frontiers in Endocrinology. 14. doi: 10.3389/fendo.2023.1232574. Fulltekst i vitenarkiv Vis sammendrag

  Background Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Methods Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Results Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (&amp;lt;100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (&amp;gt;100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar&amp;gt;100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Conclusion Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.

• Falch, Camilla Maria; Arlien-Søborg, Mai Christiansen; Dal, Jakob; Sundaram, Arvind; Michelsen, Annika Elisabet & Ueland, Thor [Vis alle 11 forfattere av denne artikkelen] (2023). Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 188(3), s. 310–321. doi: 10.1093/ejendo/lvad031. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Context Active acromegaly is characterized by lipolysis-induced insulin resistance, which suggests adipose tissue (AT) as a primary driver of metabolic aberrations. Objective To study the gene expression landscape in AT in patients with acromegaly before and after disease control in order to understand the changes and to identify disease-specific biomarkers. Methods RNA sequencing was performed on paired subcutaneous adipose tissue (SAT) biopsies from six patients with acromegaly at time of diagnosis and after curative surgery. Clustering and pathway analyses were performed in order to identify disease activity-dependent genes. In a larger patient cohort (n = 23), the corresponding proteins were measured in serum by immunoassay. Correlations between growth hormone (GH), insulin-like growth factor I (IGF-I), visceral AT (VAT), SAT, total AT, and serum proteins were analyzed. Results 743 genes were significantly differentially expressed (P-adjusted &amp;lt; .05) in SAT before and after disease control. The patients clustered according to disease activity. Pathways related to inflammation, cell adhesion and extracellular matrix, GH and insulin signaling, and fatty acid oxidation were differentially expressed. Serum levels of HTRA1, METRNL, S100A8/A9, and PDGFD significantly increased after disease control (P &amp;lt; .05). VAT correlated with HTRA1 (R = 0.73) and S100A8/A9 (R = 0.55) (P &amp;lt; .05 for both). Conclusion AT in active acromegaly is associated with a gene expression profile of fibrosis and inflammation, which may corroborate the hyper-metabolic state and provide a means for identifying novel biomarkers.

• Falch, Camilla Maria; Olarescu, Nicoleta Cristina; Bollerslev, Jens; Dekkers, Olaf M. & Heck, Ansgar (2022). Trends in incidence and mortality risk for acromegaly in Norway: a cohort study. Endocrine. ISSN 1355-008X. s. 1–8. doi: 10.1007/s12020-022-03275-6. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was to obtain updated epidemiological data from Norway in a clinically well-defined cohort with complete register-based follow-up. Methods Patients diagnosed with acromegaly from South-Eastern Norway between 1999–2019 (n = 262) and age and sex matched population controls (1:100) were included (n = 26,200). Mortality and cancer data were obtained from the Norwegian Cause of Death and Cancer Registry. Mortality and cancer incidence were compared by Kaplan–Meier analyses and Cox regression; we report hazard ratios (HRs) with 95% confidence intervals (95% CI). Results Median age at diagnosis was 48.0 years (interquartile range (IQR): 37.6–58.0). Mean annual acromegaly incidence rate was 4.7 (95% CI 4.2–5.3) cases/106 person-years, and the point prevalence (2019) was 83 (95% CI 72.6–93.5) cases/106 persons. Overall mortality was not increased in acromegaly, HR 0.8 (95% CI 0.5–1.4), cancer-specific and cardiovascular-specific mortality was also not increased (HR: 0.7 (95% CI 0.3–1.8) and 0.8 (95% CI: 0.3–2.5) respectively). The HR for all cancers was 1.45 (1.0–2.1; p = 0.052). Conclusion In this large cohort study, covering the period 1999–2019, patients were treated with individualized multimodal management. Mortality was not increased compared to the general population and comparable with recent registry studies from the Nordic countries and Europe. Overall cancer risk was slightly, but not significantly increased in the patients.

• Øystese, Kristin Astrid Berland; Casar-Borota, Olivera; Berg-Johnsen, Jon; Berg, Jens Petter & Bollerslev, Jens (2022). Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours. Endocrine. ISSN 1355-008X. 77(1), s. 151–159. doi: 10.1007/s12020-022-03051-6. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose Clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterise the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the course of the tumours. Methods The distribution of E- and N-cadherin was investigated by immunohistochemistry in a retrospective cohort of 30 tumours of the less common NF-PitNETs (corticotroph ( N  = 18), PIT1 ( N  = 8) and null-cell PitNETs ( N  = 4)). Immunoreactive scores (IRS) were compared to previously presented cohorts of gonadotroph NF-PitNETs ( N  = 105) and corticotroph functioning PitNETs ( N  = 17). Results We found a low IRS for the extra-cellular domain of E-cadherin (median 0 (IQR 0–0, N  = 135)), a medium to high IRS for the intra-cellular domain of E-cadherin (median 6 (IQR 4–9)) and a high IRS for N-cadherin (median 12 (IQR 10.5–12)) throughout the cohort of NF-PitNETs. The corticotroph NF-PitNETs presented a higher IRS for both the extra- and intra-cellular domain of E-cadherin (median 0 (IQR 0–1) and median 9 (IQR 6–12), respectively) than the gonadotroph NF-PitNETs ( p  &lt; 0.001 for both comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intra-cellular domain of E-cadherin (median 4 (IQR 0.5–6) and median 9 (IQR 9–12), for tumours with and without nuclear E-cadherin, respectively), and with a lower rate of re-intervention ( p  = 0.03). Conclusions Considering our results and the benign course of NF-PitNETs, we suggest that a high N-cadherin and downregulation of membranous E-cadherin are not associated with a more aggressive tumour behaviour in these subgroups of NF-PitNETs.

• Pretorius, Mikkel; Lundstam, Karolina; Heck, Ansgar; Fagerland, Morten; Godang, Kristin & Mollerup, Charlotte [Vis alle 15 forfattere av denne artikkelen] (2022). Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation. Annals of Internal Medicine. ISSN 0003-4819. 175(6), s. 812–819. doi: 10.7326/M21-4416. Fulltekst i vitenarkiv
• Marstein, Henriette; Witczak, Birgit Nomeland; Godang, Kristin; Schwartz, Thomas; Flatø, Berit & Bollerslev, Jens [Vis alle 8 forfattere av denne artikkelen] (2022). Adipose tissue distribution is associated with cardio-metabolic alterations in adult patients with juvenile-onset dermatomyositis. Rheumatology. ISSN 1462-0324. 62(2), s. 1–9. doi: 10.1093/rheumatology/keac293. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objectives Primary aims were to compare adipose tissue distribution in adult patients with juvenile-onset DM (JDM), with matched controls. Secondary aims were to explore how adipose tissue distribution is associated with cardio-metabolic status (cardiac dysfunction and metabolic syndrome) in patients. Methods Thirty-nine JDM patients (all aged ≥18 y, mean age 31.7 y and 51% female) were examined mean 22.7 y (s.d. 8.9 y) after disease onset and compared with 39 age/sex-matched controls. In patients, disease activity and lipodystrophy were assessed by validated tools and use of prednisolone noted. In all participants, dual-energy X-ray absorptiometry (DXA) and echocardiography were used to measure visceral adipose tissue (VAT)(g) and cardiac function, respectively. Risk factors for metabolic syndrome were measured and associations with adipose tissue distribution explored. For primary and secondary aims, respectively, P-values ≤0.05 and ≤0.01 were considered significant. Results Patients exhibited a 2.4-fold increase in VAT, and reduced HDL-cholesterol values compared with controls (P-values ≤ 0.05). Metabolic syndrome was found in 25.7% of the patients and none of the controls. Cardiac dysfunction (systolic and/or diastolic) was found in 23.7% of patients and 8.1% of controls (P = 0.07). In patients, VAT levels were correlated with age, disease duration and occurrence of metabolic syndrome and cardiac dysfunction. Occurrence of lipodystrophy (P = 0.02) and male sex (P = 0.04) tended to be independently associated with cardiac dysfunction. Conclusion Adults with JDM showed more central adiposity and cardio-metabolic alterations than controls. Further, VAT was found increased with disease duration, which was associated with development of cardio-metabolic syndrome.

• Kvammen, Janne Anita; Stensvold, Einar; Godang, Kristin; Bollerslev, Jens; Myklebust, Tor Åge & Brandal, Petter [Vis alle 8 forfattere av denne artikkelen] (2022). Bone mineral density and nutrition in long-term survivors of childhood brain tumors. Clinical Nutrition ESPEN. ISSN 2405-4577. 50, s. 162–169. doi: 10.1016/j.clnesp.2022.05.025. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. Methods All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz −1 to −1.99 and very low BMDz ≤−2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. Results Fifty survivors with a median age of 25.5 years (5.5–51.9) and a median follow-up time of 19.5 years (3.2–40.5) were included. Mean BMDz lumbar spine was −0.8 (SD 1.1, 95% CI: −1.1 to −0.4), and BMDz total body was −0.6 (SD 1.1, 95% CI: −0.9 to −0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D < 50 nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. Conclusions Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D ≤ 50 nmol/L were detected.

• Bollerslev, Jens; Rejnmark, Lars; Zahn, Alexandra; Heck, Ansgar; Appelman-Dijkstra, Natasha M & Cardoso, Luis [Vis alle 35 forfattere av denne artikkelen] (2022). European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE Educational Program of Parathyroid Disorders (PARAT 2021). European Journal of Endocrinology (EJE). ISSN 0804-4643. 186(2), s. R33–R63. doi: 10.1530/EJE-21-1044. Fulltekst i vitenarkiv Vis sammendrag

  This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training.

• Henjum, Kristi; Watne, Leiv; Godang, Kristin; Halaas, Nathalie Bodd; Eldholm, Rannveig Sakshaug & Blennow, Kaj [Vis alle 10 forfattere av denne artikkelen] (2022). Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease. Translational Psychiatry. 12. doi: 10.1038/s41398-022-01901-5. Fulltekst i vitenarkiv Vis sammendrag

  Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A−T− cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A−T− cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.

• Lekva, Tove; Roland, Marie Cecilie; Estensen, M.E.; Norwitz, Errol R.; Tilburgs, Tamara & Henriksen, Tore [Vis alle 12 forfattere av denne artikkelen] (2021). Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence. Scientific Reports. 11(1). doi: 10.1038/s41598-021-99140-z. Fulltekst i vitenarkiv Vis sammendrag

  Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (PBMC) and circulating telomere associated senescence markers would be dysregulated in women with PE. We measured long non-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5′–3′ Exoribonuclease 1 (XRN1) in extracellular vesicles at 22–24 weeks, 36–38 weeks and, 5-year follow-up in controls and PE. We also measured telomere length at 22–24 weeks and 5-year follow-up. The circulating senescence markers cathelicidin antimicrobial peptide (CAMP), β-galactosidase, stathmin 1 (STMN1) and chitotriosidase/CHIT1 were measured at 14–16, 22–24, 36–38 weeks and at 5-year follow-up in the STORK study and before delivery and 6 months post-partum in the ACUTE PE study. We found decreased expression of TERC in PBMC early in pregnant women who subsequently developed PE. XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up. Further, we found that the senescence markers CAMP and β-galactosidase were increased in PE pregnancies, and CAMP remained higher at 5-year follow-up. β-galactosidase was associated with atherogenic lipid ratios during pregnancy and at 5-year follow-up, in PE particularly. This study suggests a potential involvement of dysfunctional telomerase biology in the pathophysiology of PE, which is not restricted to the placenta.

• Marstein, Henriette; Godang, Kristin; Flatø, Berit; Sjaastad, Ivar; Bollerslev, Jens & Sanner, Helga (2021). Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study. Pediatric Rheumatology. 19(1), s. 1–11. doi: 10.1186/s12969-021-00543-z. Fulltekst i vitenarkiv Vis sammendrag

  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.

• NOMELAND, BIRGIT; Bollerslev, Jens; Godang, Kristin; Schwartz, Thomas; Flatø, Berit & Molberg, Øyvind [Vis alle 8 forfattere av denne artikkelen] (2021). Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures. Rheumatology. ISSN 1462-0324. 61(7), s. 2959–2968. doi: 10.1093/rheumatology/keab805. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objective To (i) compare body composition parameters in patients with longstanding juvenile dermatomyositis (JDM) and controls and (ii) explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQL) and cardiometabolic measures. Methods In a cross-sectional study, we included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls. Active/inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body dual-energy absorptiometry (DXA), inflammation by hs-CRP and cytokines, muscle strength by manual muscle test (MMT-8), HRQL by 36-item short form survey physical component score (SF-36 PCS) and cardiometabolic function by echocardiography (systolic and diastolic function) and serum-lipids. Results DXA analyses revealed lower appendicular lean mass index (ALMI) (reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and higher android: gynoid fat ratio (A: G ratio) (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 (MCP-1) and hs-CRP). Lower ALMI was associated with reduced muscle strength; higher BF% was associated with impaired HRQL. Central fat distribution (higher A: G ratio) was associated with impaired cardiac function and unfavorable serum-lipids. Conclusion : Despite normal BMI, patients with JDM, especially those with active disease, had unfavorable body composition, which was associated with impaired HRQL/muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.

• Ho, Ken; Fleseriu, Maria; Kaiser, Ursula; Salvatori, Roberto; Brue, Thierry & Lopes, M. Beatriz [Vis alle 48 forfattere av denne artikkelen] (2021). Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time? Journal of the Endocrine Society (JES). 5(3). doi: 10.1210/jendso/bvaa205. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The WHO Classification of Endocrine Tumours 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.

• Sjöstedt, Evelina; Kolnes, Anders Jensen; Olarescu, Nicoleta Cristina; Mitsios, Nicholas; Hikmet, Feria & Sivertsson, Åsa [Vis alle 11 forfattere av denne artikkelen] (2021). Tgfbr3l—an uncharacterised pituitary specific membrane protein detected in the gonadotroph cells in non-neoplastic and tumour tissue. Cancers. 13:114(1), s. 1–15. doi: 10.3390/CANCERS13010114. Fulltekst i vitenarkiv Vis sammendrag

  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 (R = 0.290) and LH (R = 0.390) immunostaining, and SSTR3 (R = 0.315). TGFBR3L correlated inversely to membranous E-cadherin staining (R = −0.351) and oestrogen receptor β mRNA (R = −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.

• Lundstam, Karolina; Godang, Kristin; Pretorius, Mikkel; Markwardt, Paul; Hellström, Mikael & Bollerslev, Jens [Vis alle 7 forfattere av denne artikkelen] (2021). The Influence of Dxa Hardware, Software, Reference Population and Software Analysis Settings on the Bone Mineral Density and T-Score Relationship. Journal of clinical densitometry. ISSN 1094-6950. 25(1), s. 24–33. doi: 10.1016/j.jocd.2021.07.002. Fulltekst i vitenarkiv Vis sammendrag

  Different dual-energy x-ray absorptiometry (DXA) hardware can affect bone mineral density (BMD) measurements and different reference populations can affect t-scores. Long-term analyses describing differences in the relationship between BMD and t-scores are lacking. BMD-values were plotted against t-scores for 241 Lunar DXA scans on females obtained over 18 years from several centers in Sweden and Norway. The result of the plot was compared to hardware/software versions, reference populations and different software analysis settings (Basic vs Enhanced analysis for total body and Single Photon Absorptiometry (SPA) vs Lunar calibration for forearm). For the forearm compartments, we found different BMD-t-score relationships depending on the use of SPA or Lunar calibration (p<0.001). With Lunar calibration, BMD-values were 24% higher, but there was no effect on t-scores. Total body measurements with iDXA scanners and Enhanced analysis for Prodigy scanners (software version 14.10) resulted in a different BMD-t-score relationship compared to the other hardware/software versions (p<0.001), with the largest discrepancy for lower BMD-values. Switching from Basic to Enhanced analysis generally decreased BMD-values and often changed t-scores (both increased and decreased). For the femoral neck, there were two different BMD-t-score relationships caused by different reference populations (p<0.001). In contrast to total body, the difference for femoral neck was more pronounced for higher values, with little impact in the clinical decision-making area. Hardware, software, reference populations and software analysis settings can affect the BMD-t-score relationship, but do so differently for different compartments. The BMD-t-score-plot is a simple and effective tool to discover systematic differences. Longitudinal analyses of DXA scans should be performed based on raw data analyzed in “one run” with the same software version and settings, in order to avoid systematic differences.

• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils; Braithwaite, Elizabeth; Bollerslev, Jens & Godang, Kristin [Vis alle 8 forfattere av denne artikkelen] (2021). Changes in maternal cortisol, cortisol binding globulin and cortisone levels following diagnosis of fetal anomaly. Psychoneuroendocrinology. ISSN 0306-4530. 135. doi: 10.1016/j.psyneuen.2021.105574. Fulltekst i vitenarkiv Vis sammendrag

  The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understanding of the relationship between psychological stress and cortisol in pregnancy is limited. This study examined: (1) differences in the ratio of serum cortisol to cortisol binding globulin (SC/CBG) and cortisone levels among women with and without a diagnosis of fetal anomaly, (2) the association between self-reported stress and cortisol from mid to late pregnancy, and (3) the agreement between two different techniques for analyzing cortisol: liquid chromatography-tandem mass spectrometry (LC-MS/MS) and radioimmunoassay (RIA). Thirty-six pregnant women with a diagnosis of fetal anomaly (study group) and 101 women with healthy pregnancies (comparison group) provided blood samples and completed self-report questionnaires at gestational weeks 18–24 (T1) and 30 (T2). In the comparison group, mean SC/CBG increased from 0.341 nmol/L at T1 to 0.415 at T2 (p < .001), whereas in the study group there was no change (0.342 nmol/L at T1, 0.343 at T2). There was no difference in cortisone levels between the groups at either timepoints. There was a negative association between both depression and traumatic stress at T1, and SC/CBG at T2 (p < .05). There was no association between general distress and SC/CBG. The two methods for analyzing cortisol gave similar results, but with LC-MS/MS showing a lower detection limit than RIA. Increased cortisol with advancing gestational age is expected, thus these findings indicate that under certain conditions of severe stress there may be a suppression of maternal cortisol increase from mid to late gestation. The discrepancy does not seem to be due to differences in the metabolization of cortisol, as indicated by the similar levels of cortisone. Further research is needed in order to understand the potential underlying mechanisms limiting the expression of cortisol in response to certain types of stress in pregnancy.

• Jørgensen, Hanne Skou; Eide, Ivar Anders; Jenssen, Trond; Åsberg, Anders; Bollerslev, Jens & Godang, Kristin [Vis alle 9 forfattere av denne artikkelen] (2021). Marine n-3 polyunsaturated fatty acids and bone mineral density in kidney transplant recipients: A randomized, placebo-controlled trial. Nutrients. 13(7). doi: 10.3390/nu13072361. Fulltekst i vitenarkiv Vis sammendrag

  Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student’s t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (−0.020 ± 0.08 vs. −0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. −0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.

• Ulvestad, Mariann; Godang, Kristin; Durheim, Michael; Kongerud, Johny S.; Lund, May-Brith & Bollerslev, Jens [Vis alle 7 forfattere av denne artikkelen] (2021). Effect of high-intensity training on bone health and body composition in lung transplant recipients: A secondary analysis of a randomized controlled trial. Clinical Transplantation. ISSN 0902-0063. s. 1–9. doi: 10.1111/ctr.14375. Fulltekst i vitenarkiv Vis sammendrag

  Background: Loss of bone mineral and skeletal muscle mass is common after lung transplantation (LTx), and physical activity (PA) may prevent further deterioration. We aimed to assess the effects of 20-week high-intensity training (HIT) on body composition, bone health, and PA in LTx recipients, 6–60 months after surgery. Methods: In a randomized controlled trial, 51 LTx recipients underwent Dual-energy X-ray absorptiometry (DXA), and PA level and sedentary time were objectively recorded by accelerometers for seven consecutive days. Of these, 39 participants completed the study, including 19 participants in the HIT group and 20 participants in the standard care group. Results: Following the intervention, ANCOVA models revealed a nonsignificant between-group difference for change in lean body mass (LBM) and bone mineral density (BMD) of the lumbar spine of 0.4% (95% CI = −3.2, 1.5) (p = .464) and 1.0% (95% CI=−1.3, 3.4) (p = .373), respectively. Trabecular bone score (TBS) of the lumbar spine (L1-L4), however, increased by 2.2 ± 5.0% in the exercise group and decreased by −1.6 ± 5.9% in the control group, giving a between-group difference of 3.8% (95% CI=0.1, 7.5) (p = .043). There were no between-group differences in PA or sedentary time. Conclusion: High-intensity training after LTx improved TBS significantly, but not PA, LBM or BMD.

• Henjum, Kristi; Godang, Kristin; Quist-Paulsen, Else; Idland, Ane-Victoria; Neerland, Bjørn Erik & Sandvig, Heidi Vihovde [Vis alle 13 forfattere av denne artikkelen] (2021). Cerebrospinal fluid catecholamines in delirium and dementia. Brain Communications. 3(3), s. 1–11. doi: 10.1093/braincomms/fcab121. Fulltekst i vitenarkiv Vis sammendrag

  Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly patients (n¼122); (ii) hip fracture patients with or without delirium and dementia (n¼118); and (iii) patients with delirium precipitated by another medical condition (medical delirium, n¼26). Delirium was assessed by the Confusion Assessment Method. The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P<0.001). Within the hip fracture cohort those with delirium (n¼65) had lower CSF adrenaline and dopamine levels than those without delirium (n¼52, P¼0.03, P¼0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively normal elderly (P<0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.

• Lauterlein, Jens-Jacob Lindegaard; Gossiel, Fatma; Weigl, Moritz; Eastell, Richard; Hackl, Matthias & Hermann, Pernille [Vis alle 8 forfattere av denne artikkelen] (2021). Development of the Bone Phenotype and microRNA Profile in Adults With Low-Density Lipoprotein Receptor-Related Protein 5–High Bone Mass (LRP5-HBM) Disease. JBMR Plus. 5(9), s. 1–11. doi: 10.1002/jbm4.10534. Fulltekst i vitenarkiv Vis sammendrag

  Pathogenic variants in the Wnt-pathway co-receptor low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) cause high bone mass (LRP5-HBM) due to insensitivity to the endogenous antagonist of Wnt-signaling. Although indicating incessant progression of BMD and biomarkers reflecting bone formation, this has not been confirmed in individuals with LRP5-HBM. We investigated how the LRP5-HBM bone phenotype changes with age in adults and is associated with quantitative changes of bone turnover markers and bone-related microRNAs (miRNAs) in the circulation. Whole body, lumbar spine, total hip, and femoral neck areal BMD (aBMD) and radial and tibial bone microarchitecture and geometry were assessed using DXA and HR-pQCT scans of 15 individuals with LRP5-HBMT253I (11 women; median age 51 years; range, 19 to 85 years) with a time interval between scans of 5.8 years (range, 4.9 to 7.6 years). Fasting P1NP and CTX were measured in 14 LRP5-HBMT253I individuals and age-, sex-, and body mass index (BMI)-matched controls, and 187 preselected miRNAs were quantified using qPCR in 12 individuals and age-, sex-, and BMI-matched controls. DXA and HR-pQCT scans were assessed in subjects who had reached peak bone mass (aged >25 years, n = 12). Femoral neck aBMD decreased by 0.8%/year (p = 0.01) and total hip by 0.3%/year, and radial volumetric BMD (vBMD) increased 0.3%/year (p = 0.03). Differences in bone turnover markers at follow-up were not observed. Compared to controls, 11 of the 178 detectable miRNAs were downregulated and none upregulated in LRP5-HBM individuals, and five of the downregulated miRNAs are reported to be involved in Wnt-signaling. Bone loss at the hip in LRP5-HBM individuals demonstrates that the bone phenotype does not uniformly progress with age. Differentially expressed miRNAs may reflect changes in the regulation of bone turnover and balance in LRP5-HBM individuals.

• Kolnes, Anders Jensen; Øystese, Kristin Astrid; Dahlberg, Daniel; Berg-Johnsen, Jon; Niehusmann, Pitt & Pahnke, Jens [Vis alle 8 forfattere av denne artikkelen] (2020). Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma. Acta Neurochirurgica. ISSN 0001-6268. 162(4), s. 845–852. doi: 10.1007/s00701-019-04068-z. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Ueland, Thor; Estensen, Mette-Elise; Grindheim, Guro; Bollerslev, Jens; Henriksen, Tore & Aukrust, Pål [Vis alle 9 forfattere av denne artikkelen] (2020). Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies. Journal of Hypertension. ISSN 0263-6352. 38(7), s. 1347–1354. doi: 10.1097/HJH.0000000000002362. Fulltekst i vitenarkiv Vis sammendrag

  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 Ca2+/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.

• Bollerslev, Jens; Sjöstedt, Evelina & Rejnmark, Lars (2020). Cardiovascular consequences of parathyroid disorders in adults. Annales d'Endocrinologie. ISSN 0003-4266. s. 1–7. doi: 10.1016/j.ando.2020.02.003. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Giustina, Andrea; Bouillon, Roger; Binkley, Neil; Sempos, Christopher T.; Adler, Robert A & Bollerslev, Jens [Vis alle 22 forfattere av denne artikkelen] (2020). Controversies in vitamin D: A statement From the third international conference. JBMR Plus. 4(12), s. 1–13. doi: 10.1002/jbm4.10417. Fulltekst i vitenarkiv Vis sammendrag

  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. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

• Eieland, Alexander K.; Normann, Kjersti R.; Sundaram, Arvind Y. M.; Nyman, Tuula A.; Øystese, Kristin A. B. & Lekva, Tove [Vis alle 9 forfattere av denne artikkelen] (2020). Distinct pattern of endoplasmic reticulum protein processing and extracellular matrix proteins in functioning and silent corticotroph pituitary adenomas. Cancers. 12(10), s. 1–20. doi: 10.3390/cancers12102980. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Gittoes, Neil J.; Criseno, Sherwin; Appelman-Dijkstra, Natasha M.; Bollerslev, Jens; Canalis, Ernesto & Rejnmark, Lars [Vis alle 7 forfattere av denne artikkelen] (2020). Management of calcium metabolic disorders and osteoporosis. European Journal of Endocrinology (EJE). ISSN 0804-4643. 183(2), s. G57–G65. doi: 10.1530/EJE-20-0385. Fulltekst i vitenarkiv
• Pretorius, Mikkel; Lundstam, Karolina; Hellström, Mikael; Fagerland, Morten; Godang, Kristin & Mollerup, Charlotte [Vis alle 15 forfattere av denne artikkelen] (2020). Effects of Parathyroidectomy on Quality of Life: 10 Years of Data From a Prospective Randomized Controlled Trial on Primary Hyperparathyroidism (the SIPH-Study). Journal of Bone and Mineral Research. ISSN 0884-0431. 36(1), s. 3–11. doi: 10.1002/jbmr.4199. Fulltekst i vitenarkiv
• Kolnes, Anders Jensen; Øystese, Kristin Astrid; Olarescu, Nicoleta Cristina; Ringstad, Geir Andre; Berg-Johnsen, Jon & Casar-Borota, Olivera [Vis alle 8 forfattere av denne artikkelen] (2020). FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 105(8), s. 1–8. doi: 10.1210/clinem/dgaa281. Fulltekst i vitenarkiv Vis sammendrag

  Abstract 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 &amp;lt; .0001) and increased staining for nuclear E-cadherin (P &amp;lt; .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.

• Giustina, Andrea; Barkhoudarian, Garni; Beckers, Albert; Ben-Shlomo, Anat; Biermasz, Nienke & Biller, Beverly [Vis alle 48 forfattere av denne artikkelen] (2020). Multidisciplinary management of acromegaly: A consensus. Reviews in endocrine and metabolic disorders (Print). ISSN 1389-9155. 21(4), s. 667–678. doi: 10.1007/s11154-020-09588-z. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Giustina, Andrea; Adler, Robert A.; Binkley, Neil; Bollerslev, Jens; Bouillon, Roger & Dawson-Hughes, Bess [Vis alle 14 forfattere av denne artikkelen] (2020). Consensus statement from 2nd International Conference on Controversies in Vitamin D. Reviews in endocrine and metabolic disorders (Print). ISSN 1389-9155. 21(1), s. 89–116. doi: 10.1007/s11154-019-09532-w. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The 2 nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) “Laboratory”: assays and threshold values to define vitamin D status; 2) “Clinical”: sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) “Therapeutics”: controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

• Kvammen, Janne Anita; Thomassen, Rut Anne; Kjeserud, Christina; Sæland, Camilla; Godang, Kristin & Bollerslev, Jens [Vis alle 10 forfattere av denne artikkelen] (2020). Bone mineral density and vitamin D in paediatric intestinal failure patients receiving home parenteral nutrition. Clinical Nutrition ESPEN. ISSN 2405-4577. 39, s. 234–241. doi: 10.1016/j.clnesp.2020.06.006. Fulltekst i vitenarkiv Vis sammendrag

  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)2D). 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)2D 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)2D 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.

• Seljelid, Berit; Varsi, Cecilie; Nes, Lise Solberg; Stenehjem, Aud-Eldrid; Bollerslev, Jens & Børøsund, Elin (2020). Content and system development of a digital patient-provider communication tool to support shared decision making in chronic health care: InvolveMe. BMC Medical Informatics and Decision Making. 20(1). doi: 10.1186/s12911-020-1065-8. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Roland, Marie Cecilie; Lekva, Tove; Godang, Kristin; Bollerslev, Jens & Henriksen, Tore (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. 15:e0232749(6), s. 1–12. doi: 10.1371/journal.pone.0232749. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Siggelkow, Heide; Clarke, Bart; Germak, John; Marelli, Claudio; Chen, Kristina & Dahl-Hansen, Helen [Vis alle 11 forfattere av denne artikkelen] (2020). Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey. Clinical Endocrinology. ISSN 0300-0664. 92(2), s. 159–168. doi: 10.1111/cen.14128. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Glad, Trygve Andreas Holm; Godang, Kristin; Bollerslev, Jens; Røkkum, Magne & Reigstad, Ole (2020). Assessing periprosthetic bone in total wrist arthroplasty: The validity of DXA. Journal of clinical densitometry. ISSN 1094-6950. s. 1–9. doi: 10.1016/j.jocd.2020.10.006. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Retterstøl, Kjetil; Henriksen, Tore & Bollerslev, Jens [Vis alle 10 forfattere av denne artikkelen] (2019). Serum Omega-6 Fatty Acids and Immunology-Related Gene Expression in Peripheral Blood Mononuclear Cells: A Cross-Sectional Analysis in Healthy Children. Molecular Nutrition & Food Research. ISSN 1613-4125. 63(7). doi: 10.1002/mnfr.201800990. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Ueland, Thor; Michelsen, Annika; Aukrust, Pål; Henriksen, Tore; Bollerslev, Jens & Lekva, Tove (2019). Adipokines and macrophage markers during pregnancy?Possible role for sCD163 in prediction and progression of gestational diabetes mellitus. Diabetes/Metabolism Research and Reviews. ISSN 1520-7552. :e3114, s. 1–9. doi: 10.1002/dmrr.3114. Fulltekst i vitenarkiv Vis sammendrag

  <i>Aims</i> - 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.<p> <p><i>Materials and methods</i> - Population‐based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5‐year follow‐up.<p> <p><i>Results</i> - sCD163 was higher (25% at 14‐16 weeks, <i>P</i> < 0.001) and adiponectin lower (−17% at 14‐16 weeks, <i>P</i> < 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.<p> <p><i>Conclusions</i> - 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.

• Bollerslev, Jens; Heck, Ansgar & Olarescu, Nicoleta Cristina (2019). Individualised management of acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 181(2), s. R57–R71. doi: 10.1530/EJE-19-0124. Fulltekst i vitenarkiv
• Stomby, Andreas; Salami, Alireza; Dahlqvist, Per; Evang, Johan Arild; Ryberg, Mats & Bollerslev, Jens [Vis alle 9 forfattere av denne artikkelen] (2019). Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing's syndrome in remission. European Journal of Endocrinology (EJE). ISSN 0804-4643. 180(5), s. 329–338. doi: 10.1530/EJE-19-0028. Fulltekst i vitenarkiv
• Halden, Thea Anine Strøm; Kvitne, Kine Eide; Midtvedt, Karsten; Rajakumar, Laavanyaah; Robertsen, Ida & Brox, Jan [Vis alle 10 forfattere av denne artikkelen] (2019). Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. ISSN 0149-5992. 42(6), s. 1067–1074. doi: 10.2337/dc19-0093. Fulltekst i vitenarkiv Vis sammendrag

  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 m2), 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 (HbA1c) 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]) (P = 0.025). The magnitude of glucose reduction was dependent on GFR and baseline HbA1c. 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 (P = 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.

• Lewis, Joshua R.; Eggermont, Celeste J.; Schousboe, John T.; Lim, Wai H.; Wong, Germaine & Khoo, Ben [Vis alle 15 forfattere av denne artikkelen] (2019). Association between abdominal aortic calcification, bone mineral density, and fracture in older women. Journal of Bone and Mineral Research. ISSN 0884-0431. 34(11), s. 2052–2060. doi: 10.1002/jbmr.3830. Fulltekst i vitenarkiv
• Øystese, Kristin Astrid Berland; Hisanawi, Sheren; Zucknick, Manuela; Bollerslev, Jens & Ringstad, Geir (2019). Are volume measurements of non-functioning pituitary adenomas reliable? Endocrine. ISSN 1355-008X. 63(1), s. 171–176. doi: 10.1007/s12020-018-1752-8. Fulltekst i vitenarkiv
• Ueland, Thor; Roland, Marie Cecilie; Michelsen, Annika; Godang, Kristin; Aukrust, Pål & Henriksen, Tore [Vis alle 8 forfattere av denne artikkelen] (2019). Elevated cholesteryl ester transfer protein activity early in pregnancy predicts prediabetes 5 years later. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. doi: 10.1210/clinem/dgz119. Fulltekst i vitenarkiv Vis sammendrag

  <i>Context</i> - 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.<p> <p><i>Objective</i> - 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.<p> <p><i>Design</i> - A population-based longitudinal cohort study was conducted from 2001 to 2013.<p> <p><i>Setting</i> - The study setting was Oslo University Hospital.<p> <p><i>Patients or Other Participants</i> - A total of 300 women during pregnancy and at 5 years postpartum participated in this study.<p> <p><i>Main Outcome Measures</i> - 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.<p> <p><i>Results</i> - 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.<p> <p><i>Conclusions</i> - CETP activity during pregnancy identifies women at risk for later diabetes development.

• Manojlović, Emilija Gačić; Bollerslev, Jens & Casar-Borota, Olivera (2019). Invited review: Pathology of pituitary neuroendocrine tumours: present status, modern diagnostic approach, controversies and future perspectives from a neuropathological and clinical standpoint. Neuropathology and Applied Neurobiology. ISSN 0305-1846. s. 1–22. doi: 10.1111/nan.12568. Fulltekst i vitenarkiv Vis sammendrag

  Neuroendocrine tumours of the adenohypophysis have traditionally been designated as pituitary adenomas to underline their usually indolent growth and lack of metastatic potential. However, they may demonstrate a huge spectrum of growth patterns and endocrine disturbances, some of them significantly affecting health and quality of life. To predict tumour growth, risk of postoperative recurrence and response to medical therapy in patients with pituitary neuroendocrine tumours is challenging. A thorough histopathological and immunohistochemical diagnostic work‐up is an obligatory part of a multidisciplinary effort to precisely define the tumour type and assess prognostic and predictive factors on an individual basis. In this review, we have summarized the current status in the pathology in pituitary neuroendocrine tumours based on the selection of references from the PubMed database. We have presented possible diagnostic approaches according to the current pituitary cell lineage‐based classification. The importance of recognizing histological subtypes with potentially aggressive behaviour and identification of prognostic and predictive tissue biomarkers have been highlighted. Controversies related to particular subtypes of pituitary tumours and a still limited prognostic impact of the current classification indicate the need for further refinement. Multidisciplinary approach including clinical, pathological and molecular genetic characterization will be essential for improved personalized therapy and the search for novel therapeutic targets in patients with pituitary neuroendocrine tumours.

• Bollerslev, Jens; Schalin-Jäntti, Camilla; Rejnmark, Lars; Siggelkow, Heide; Morreau, Hans & Thakker, Rajesh V. [Vis alle 9 forfattere av denne artikkelen] (2019). Unmet therapeutic, educational and scientific needs in parathyroid disorders. European Journal of Endocrinology (EJE). ISSN 0804-4643. 181(3), s. P1–P19. doi: 10.1530/EJE-19-0316. Fulltekst i vitenarkiv Vis sammendrag

  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, 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 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.

• Ueland, Thor; Stilgren, Lis & Bollerslev, Jens (2019). Bone matrix levels of Dickkopf and sclerostin are positively correlated with bone mass and strength in postmenopausal osteoporosis. International Journal of Molecular Sciences. ISSN 1661-6596. 20:2896(12), s. 1–11. doi: 10.3390/ijms20122896. Fulltekst i vitenarkiv Vis sammendrag

  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 (<i>r</i> between 0.28 and 0.45, <i>p</i> < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) (<i>r</i> = 0.32, <i>p</i> < 0.05) and femoral neck BMD (<i>r</i> = 0.41, <i>p</i> < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength (<i>r</i> between 0.34 and 0.51, <i>p</i> < 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.

• Diab, Simone; Godang, Kristin; Müller, Lil-Sofie Ording; Almaas, Runar; Lange, Charlotte de & Brunvand, Leif [Vis alle 12 forfattere av denne artikkelen] (2019). Progressive loss of bone mass in children with Fontan circulation. Congenital Heart Disease. ISSN 1747-079X. s. 1–9. doi: 10.1111/chd.12848. Fulltekst i vitenarkiv
• Godang, Kristin; Lekva, Tove; Normann, Kjersti Ringvoll; Olarescu, Nicoleta Cristina; Øystese, Kristin Astrid & Kolnes, Anders Jensen [Vis alle 9 forfattere av denne artikkelen] (2019). Hip Structure Analyses in Acromegaly: Decrease of Cortical Bone Thickness After Treatment: A Longitudinal Cohort Study. JBMR Plus. 3(12), s. e10240–e10240. doi: 10.1002/jbm4.10240. Fulltekst i vitenarkiv Vis sammendrag

  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 (n = 56) and NFPA (n = 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] (p = 0.006), CBTcalcar 4.8 [4.2, 5.7] versus 4.0 [3.2, 4.5] (p < 0.001), CBTshaft 6.2 [5.1, 7.2] versus 5.2 [4.6, 6.0], (p = 0.003). In acromegaly, GH was correlated with CBTneck (r = 0.31, p = 0.020), whereas IGF‐1 was correlated with CBTcalcar (r = 0.39, p = 0.003) at baseline. In acromegaly, CBTneck decreased by 11.2%, p = 0.002 during follow‐up. Finally, the decrease in CBTneck and CBTcalcar in acromegaly was significant compared with NFPA (p = 0.023 and p = 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.

• Annexstad, Ellen Johanne; Bollerslev, Jens; Westvik, Jostein; Myhre, A. G.; Godang, Kristin & Holm, Inger [Vis alle 7 forfattere av denne artikkelen] (2019). The role of delayed bone age in the evaluation of stature and bone health in glucocorticoid treated patients With Duchenne muscular dystrophy. International Journal of Pediatric Endocrinology. ISSN 1687-9848. 4. doi: 10.1186/s13633-019-0070-0. Fulltekst i vitenarkiv Vis sammendrag

  Background Low bone mineral density and an increased risk of appendicular and vertebral fractures are well-established consequences of Duchenne muscular dystrophy (DMD) and the risk of fractures is exacerbated by long-term glucocorticoid treatment. Monitoring of endocrine and skeletal health and timely intervention in at-risk patients is important in the management of children with DMD. Methods As part of the Norwegian Duchenne muscular dystrophy cohort study, we examined the skeletal maturation of 62 boys less than 18 years old, both currently glucocorticoid treated (n = 44), previously treated (n = 6) and naïve (n = 12). The relationship between bone age, height and bone mineral density (BMD) Z-scores was explored. Results The participants in the glucocorticoid treated group were short in stature and puberty was delayed. Bone age was significantly delayed, and the delay increased with age and duration of treatment. The difference in height between glucocorticoid treated and naïve boys was no longer significant when height was corrected for delayed skeletal maturation. Mean BMD Z-scores fell below − 2 before 12 years of age in the glucocorticoid treated group, with scores significantly correlated with age, duration of treatment and pubertal development. When BMD Z-scores were corrected for by retarded bone age, the increase in BMD Z-scores was significant for all age groups. Conclusion Our results suggest that skeletal maturation should be assessed in the evaluation of short stature and bone health in GC treated boys with DMD, as failing to consider delayed bone age leads to underestimation of BMD Z-scores and potentially overestimation of fracture risk.

• Bollerslev, Jens; Pretorius, Mikkel & Heck, Ansgar (2018). Parathyroid hormone independent hypercalcemia in adults. Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. ISSN 1521-690X. In Press, Corrected Proof, s. 1–18. doi: 10.1016/j.beem.2018.06.005. Fulltekst i vitenarkiv
• Astor, Marianne; Zhu, Wendy; Björnsdóttir, Sigrídur; Bollerslev, Jens; Kämpe, Olle & Husebye, Eystein Sverre (2018). Is there a need for an emergency card in hypoparathyroidism? Journal of Internal Medicine. ISSN 0954-6820. s. 1–7. doi: 10.1111/joim.12865. Fulltekst i vitenarkiv
• Khan, Aliya Aziz; Koch, Christian; Uum, Stanislaus Hendrikus Maria Van; Baillargeon, Jean Patrice; Bollerslev, Jens & Brandi, Maria Luisa [Vis alle 13 forfattere av denne artikkelen] (2018). Standards of care for hypoparathyroidism in adults: A Canadian and international consensus. European Journal of Endocrinology (EJE). ISSN 0804-4643. 180(3), s. P1–P22. doi: 10.1530/EJE-18-0609. Fulltekst i vitenarkiv
• Risum, Kristine; Edvardsen, Elisabeth; Godang, Kristin; Selvaag, Anne Marit G; Hansen, Bjørge Hermann & Molberg, Øyvind [Vis alle 10 forfattere av denne artikkelen] (2018). Physical Fitness in Patients With Oligoarticular and Polyarticular Juvenile Idiopathic arthritis diagnosed in the era of biologics: A controlled cross-sectional study. Arthritis care & research. ISSN 2151-464X. 71(12), s. 1611–1620. doi: 10.1002/acr.23818. Fulltekst i vitenarkiv
• Düring, Marit Elizabeth Von; Jenssen, Trond Geir; Bollerslev, Jens; Godang, Kristin; Hartmann, Anders & Åsberg, Anders (2018). Arterial stiffness is associated with visceral fat mass in kidney transplanted patients—A nationwide cohort study. Clinical Transplantation. ISSN 0902-0063. 32(8). doi: 10.1111/ctr.13341. Fulltekst i vitenarkiv
• Godang, Kristin; Lundstam, Karolina; Mollerup, Charlotte; Fougner, Stine Lyngvi; Pernow, Ylva & Nordenström, Jörgen [Vis alle 11 forfattere av denne artikkelen] (2018). The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism. Endocrine Connections. 7(8), s. 941–948. doi: 10.1530/EC-18-0259. Fulltekst i vitenarkiv Vis sammendrag

  Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results: In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

• Sempos, Christopher T.; Heijboer, Annemieke C.; Bikle, Daniel D.; Bollerslev, Jens; Bouillon, Roger & Brannon, Patsy M. [Vis alle 12 forfattere av denne artikkelen] (2018). Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D. British Journal of Clinical Pharmacology. ISSN 0306-5251. 84(10), s. 2194–2207. doi: 10.1111/bcp.13652. Fulltekst i vitenarkiv
• Lekva, Tove; Godang, Kristin; Michelsen, Annika; Qvigstad, Elisabeth; Normann, Kjersti Ringvoll & Norwitz, Errol R. [Vis alle 11 forfattere av denne artikkelen] (2018). Prediction of gestational diabetes mellitus and pre-diabetes 5 years postpartum using 75 g oral glucose tolerance test at 14-16 Weeks' gestation. Scientific Reports. 8:13392, s. 1–9. doi: 10.1038/s41598-018-31614-z. Fulltekst i vitenarkiv Vis sammendrag

  Early detection and treatment of women at risk for gestational diabetes mellitus (GDM) could improve perinatal and long-term outcomes in GDM women and their offspring. We explored if a 75 g oral glucose tolerance test (OGTT) at 14-16 weeks of gestation could identify women who will (1) develop GDM or give birth to large-for-gestational-age (LGA) babies in 1031 pregnant women from the STORK study using different diagnostic criteria (WHO1999, IADPSG2010, WHO2013, NORWAY2017) and (2) develop pre-diabetes 5 years postpartum focusing on first trimester β-cell function in a separate study of 300 women from the STORK cohort. The sensitivity of the 14-16 week OGTT to identify women who would develop GDM or have LGA babies was low, and we could not identify alternative cut-offs to exclude women not at risk or identify women that could benefit from early intervention. First trimester β-cell function was a stronger determinant than third trimester β-cell function of predicting maternal pre-diabetes. In conclusion, in our normal low-risk population, the 75 g OGTT at 14-16 weeks is insufficient to identify candidates for early treatment of GDM or identify women not likely to develop GDM or have LGA babies. First trimester β-cell function may predict pre-diabetes 5 years postpartum.

• Øystese, Kristin Astrid Berland; Berg, Jens Petter; Normann, Kjersti Ringvoll; Zucknick, Manuela; Casar-Borota, Olivera & Bollerslev, Jens (2018). The role of E and N-cadherin in the postoperative course of gonadotroph pituitary tumours. Endocrine. ISSN 1355-008X. 62(2), s. 351–360. doi: 10.1007/s12020-018-1679-0. Fulltekst i vitenarkiv
• Walker, Marcella D. & Bollerslev, Jens (2018). Vitamin D and primary hyperparathyroidism. Frontiers of Hormone Research. ISSN 0301-3073. 50, s. 125–137. doi: 10.1159/000486076. Fulltekst i vitenarkiv

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• Åsberg, Anders; Midtvedt, Karsten; Lindahl, Jørn Petter Hanto; Pihlstrøm, Hege K.; Bollerslev, Jens & Godang, Kristin (2025). Impact of Potassium-Binders on the Interpretation of Bone Mineral Density Following Kidney Transplantation. Clinical Transplantation. ISSN 0902-0063. 39(10). doi: 10.1111/ctr.70352. Fulltekst i vitenarkiv
• Risum, Kristine; Godang, Kristin; Olarescu, Nicoleta Cristina; Marstein, Henriette; Bollerslev, Jens & Sanner, Helga (2023). Visceral adipose tissue is associated with cardiorespiratory fitness, but not with physical activity and disease variables in patients with juvenile idiopathic arthritis. Fulltekst i vitenarkiv
• Risum, Kristine; Olarescu, Nicoleta Cristina; Godang, Kristin; Marstein, Henriette; Bollerslev, Jens & Sanner, Helga (2023). Visceral adipose tissue and adipokines/cytokines in juvenile idiopathic arthritis. Fulltekst i vitenarkiv
• Giustina, Andrea; Filippo, Luigi di; Facciorusso, Antonio; Adler, Robert A.; Binkley, Neil & Bollerslev, Jens [Vis alle 29 forfattere av denne artikkelen] (2023). Correction: Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta‑analysis (Reviews in Endocrine and Metabolic Disorders, (2023), 10.1007/s11154-023-09837-x). Reviews in endocrine and metabolic disorders (Print). ISSN 1389-9155. doi: 10.1007/s11154-023-09837-x. Fulltekst i vitenarkiv
• Lekva, Tove; Roland, Marie Cecilie Paasche; Estensen, Mette E.; Norwitz, Errol R.; Tilburgs, Tamara & Henriksen, Tore [Vis alle 12 forfattere av denne artikkelen] (2021). Author Correction: Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence (Scientific Reports, (2021), 11, 1, (19735), 10.1038/s41598-021-99140-z). Scientific Reports. 11(1). doi: 10.1038/s41598-021-00917-z. Fulltekst i vitenarkiv
• Seljelid, Berit; Abelsen, Kari; Krabbe, Line Cecilie; Bollerslev, Jens; Varsi, Cecilie & Nes, Lise Solberg [Vis alle 7 forfattere av denne artikkelen] (2020). Development of a digital patient-provider communication tool to facilitate shared decision making for patients with non-functioning pituitary adenomas: InvolveMe. Fulltekst i vitenarkiv
• Seljelid, Berit; Varsi, Cecilie; Stenehjem, Aud Eldrid; Bollerslev, Jens; Nes, Lise Solberg & Børøsund, Elin (2019). Content development of an electronic shared decision making tool for patients with chronic illness; mapping symptoms and needs. Fulltekst i vitenarkiv
• Seljelid, Berit; Varsi, Cecilie; Nes, Lise Solberg; Stenehjem, Aud Eldrid; Bollerslev, Jens & Børøsund, Elin (2019). Symptomkartlegging + sikker meldingstjeneste = samvalg? Fulltekst i vitenarkiv
• Kvammen, Janne Anita; Thomassen, Rut Anne; Kjeserud, Christina; Sæland, Camilla; Godang, Kristin & Thorsby, Per Medbøe [Vis alle 10 forfattere av denne artikkelen] (2019). Bone health and vitamin D in paediatric intestinal failure patients receiving home parenteral nutrition. Fulltekst i vitenarkiv
• Risum, Kristine; Godang, Kristin; Selvaag, Anne Marit; Hansen, Bjørge Hermann; Molberg, Øyvind & Bollerslev, Jens [Vis alle 9 forfattere av denne artikkelen] (2018). Suboptimal muscle strength and bone health in patients with oligo- and polyarticular juvenile idiopathic arthritis diagnosed in the era of biologics. Fulltekst i vitenarkiv
• Casar-Borota, Olivera; Bollerslev, Jens & Pontén, Fredrik (2018). Immunohistochemistry for transcription factor T-Pit as a tool in diagnostics of corticotroph pituitary tumours. Pituitary. ISSN 1386-341X. 21(4), s. 443–443. doi: 10.1007/s11102-018-0879-1. Fulltekst i vitenarkiv
• Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Retterstøl, Kjetil; Henriksen, Tore & Bollerslev, Jens [Vis alle 10 forfattere av denne artikkelen] (2018). Association between omega 6 fatty acids and inflammation-related gene expression in PBMCs: a cross-sectional study in healthy children. Fulltekst i vitenarkiv

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