515 results on '"Netea-Maier, R.T."'
Search Results
2. The association between treatment and systemic inflammation in acromegaly
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Wolters, T.L.C., van der Heijden, C.D.C.C., Pinzariu, O., Hijmans-Kersten, B.T.P., Jacobs, C., Kaffa, C., Hoischen, A., Netea, M.G., Smit, J.W.A., Thijssen, D.H.J., Georgescu, C.E., Riksen, N.P., and Netea-Maier, R.T.
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- 2021
- Full Text
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3. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
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Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., Medici, M., Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., and Medici, M.
- Abstract
Contains fulltext : 304858.pdf (Publisher’s version ) (Open Access), To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.
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- 2024
4. Cross-talk between the endocrine and the immune systems
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Netea-Maier, R.T., Netea, M.G., Jaeger, H.H.M., Peng, C., Netea-Maier, R.T., Netea, M.G., Jaeger, H.H.M., and Peng, C.
- Abstract
Contains fulltext : 306670.pdf (Publisher’s version ) (Open Access), Radboud University, 25 juni 2024, Promotores : Netea-Maier, R.T., Netea, M.G. Co-promotor : Jaeger, H.H.M., 186 p.
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- 2024
5. Schildkliercarcinoom
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Netea-Maier, R.T., Links, T.P., van der Hoeven, J., editor, and Lubbers, E., editor
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- 2015
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6. [18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules
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Koster, E.J. de, Geus-Oei, L.F. de, Brouwers, A.H., Dam, E.W.C.M. van, Dijkhorst-Oei, L.T., Engen-van Grunsven, A.C.H. van, Hout, W.B. van den, Klooker, T.K., Netea-Maier, R.T., Snel, M., Oyen, W.J.G., Vriens, D., EfFECTS Trial Study Grp, Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Internal medicine, and Endocrinology
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Indeterminate ,General Medicine ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,DIAGNOSIS ,CANCER ,Thyroid cytology ,Thyroid surgery ,FDG-PET/CT ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,COST-EFFECTIVENESS ,[F]FDG-PET/CT ,Thyroid carcinoma ,[F-18]FDG-PET/CT ,ASSOCIATION GUIDELINES ,MANAGEMENT ,Radiology, Nuclear Medicine and imaging ,HURTHLE CELL ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,Thyroid nodule ,TASK-FORCE ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Purpose To assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32–53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68–93%]) in the diagnostic surgery group (p 18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28–53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33–63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2–40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively. Conclusion An [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. Trial registration number This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.
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- 2022
7. Local and Systemic Immune Effects in Cancer: Myeloid Cells in the Spotlight
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Adema, G.J., Netea, M.G., Netea-Maier, R.T., Rabold, K., Adema, G.J., Netea, M.G., Netea-Maier, R.T., and Rabold, K.
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Radboud University, 11 april 2023, Promotores : Adema, G.J., Netea, M.G., Netea-Maier, R.T., Contains fulltext : 291358.pdf (Publisher’s version ) (Closed access)
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- 2023
8. Influence of Lenvatinib on the Functional Reprogramming of Peripheral Myeloid Cells in the Context of Non-Medullary Thyroid Carcinoma
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Chunying, P., Rabold, K., Netea, M.G., Jaeger, M., Netea-Maier, R.T., Chunying, P., Rabold, K., Netea, M.G., Jaeger, M., and Netea-Maier, R.T.
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Item does not contain fulltext
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- 2023
9. Differentiated thyroid carcinoma: An update.
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Houten, P. van, Netea-Maier, R.T., Smit, J.W.A., Houten, P. van, Netea-Maier, R.T., and Smit, J.W.A.
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01 januari 2023, Item does not contain fulltext, Differentiated thyroid carcinoma (DTC) is the most common endocrine cancer. Particularly the incidence of small clinically indolent tumors has been increasing significantly during the last decades because of increased diagnostic scrutiny, while the DTC-related mortality remained unchanged. In light of the increased awareness of the significant risk of detecting clinically indolent tumors and the potential harm and burden associated with overly diagnosis and the treatment, the approach towards management of DTC recently underwent a critical appraisal. The focus lays on reducing the unnecessary burden for patients with very low risk DTC and the correct identification of those who require treatment that is more intensive and/or follow-up. Management of DTC includes a range of different modalities, making multidisciplinary collaboration expedient. In this review, we elaborate on the recent developments in diagnosis, staging and management of DTC with specific focus on the more individualized risk assessment-based approach.
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- 2023
10. Current picture of anaplastic thyroid cancer patients' care and meetable needs: A survey of 94 Institutions from the EORTC Endocrine and Head and Neck Cancer Groups
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Locati, Laura D., Colombo, Elena, Dedecjus, M., Fouchardiere, C. de la, Sents, Ward, Bongiovanni, M., Netea-Maier, R.T., Locati, Laura D., Colombo, Elena, Dedecjus, M., Fouchardiere, C. de la, Sents, Ward, Bongiovanni, M., and Netea-Maier, R.T.
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Item does not contain fulltext
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- 2023
11. Clinical Characteristics, Diagnostic Approach and Outcome of Thyroid Incidental Findings vs. Clinically Overt Thyroid Nodules: An Observational Single-Centre Study.
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Jansen, T.J.P., Stikkelbroeck, N., Ven, A.C. van de, Engen-van Grunsven, I.A. van, Janssen, M.J.R., Bonenkamp, H., Gotthardt, M., Netea-Maier, R.T., Jansen, T.J.P., Stikkelbroeck, N., Ven, A.C. van de, Engen-van Grunsven, I.A. van, Janssen, M.J.R., Bonenkamp, H., Gotthardt, M., and Netea-Maier, R.T.
- Abstract
Item does not contain fulltext, Context: Thyroid nodules are common and can present as clinically overt nodules (visible, palpable or symptomatic nodules) and so-called incidentalomas (coincidental findings on imaging techniques). The majority are benign but recognizing clinically relevant nodules remains a challenge. Current Dutch guidelines recommend to refrain from additional diagnostic testing in incidentalomas other than FDG-PET-incidentalomas, unless there are suspicious clinical and/or sonographic features. However, there is no consensus on the further approach and no "real-life" data on the outcome of such an approach. Objective: To compare clinical characteristics, diagnostic approaches and clinical outcome between patients referred with thyroid incidentalomas and non-incidentalomas at one academic referral thyroid clinic. Methods: Clinical and demographical characteristics, diagnostic and therapeutic approaches and outcome were retrospectively obtained from the files of all patients newly referred because of thyroid incidentalomas or non-incidentalomas to our institution (between March 2011 and January 2017). Subsequently, the data were compared between both groups. Results: In total, 351 patients (64.3%) were referred because of non-incidentalomas and 195 (35.7%) because of incidentalomas. Incidentalomas were smaller (48.7% <2 cm) than non-incidentalomas (23.4% <2 cm). Furthermore, incidentalomas were less often symptomatic (15.9 vs. 42.7% p < 0.001). Fine-needle aspiration was performed in a similar percentage of the patients in the two groups (62.6% of incidentalomas vs. 69.8% in non-incidentaloma, p = 0.08). Significantly less malignancies were found among incidentalomas compared to non-incidentalomas (5.1% vs. 11.1%, p = 0.019). Moreover, significantly more malignancies occurred in PET-incidentalomas than non-PET-incidentalomas (11.8% vs. 2.8%, p = 0.023). In fact, the proportion of malignancies in PET-incidentalomas and non-incidentalomas was similar (11.8% vs. 11.1%, p = 0.895). S
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- 2023
12. Cushing's syndrome in the elderly: data from the European Registry on Cushing's syndrome.
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Amodru, V., Ferriere, A., Tabarin, A., Castinetti, F., Tsagarakis, S., Toth, M., Feelders, R.A., Webb, S.M., Reincke, M., Netea-Maier, R.T., Kastelan, D., Elenkova, A., Maiter, D., Ragnarsson, O., Santos, A., Valassi, E., Amodru, V., Ferriere, A., Tabarin, A., Castinetti, F., Tsagarakis, S., Toth, M., Feelders, R.A., Webb, S.M., Reincke, M., Netea-Maier, R.T., Kastelan, D., Elenkova, A., Maiter, D., Ragnarsson, O., Santos, A., and Valassi, E.
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Item does not contain fulltext, OBJECTIVE: To evaluate whether age-related differences exist in clinical characteristics, diagnostic approach, and management strategies in patients with Cushing's syndrome (CS) included in the European Registry on Cushing's Syndrome (ERCUSYN). DESIGN: Cohort study. METHODS: We analyzed 1791 patients with CS, of whom 1234 (69%) had pituitary-dependent CS (PIT-CS), 450 (25%) adrenal-dependent CS (ADR-CS), and 107 (6%) had an ectopic source (ECT-CS). According to the WHO criteria, 1616 patients (90.2%) were classified as younger (<65 years old) and 175 (9.8%) as older (≥65 years old). RESULTS: Older patients were more frequently males and had a lower Body Mass Index (BMI) and waist circumference when compared with the younger. Older patients also had a lower prevalence of skin alterations, depression, hair loss, hirsutism, and reduced libido, but a higher prevalence of muscle weakness, diabetes, hypertension, cardiovascular disease, venous thromboembolism, and bone fractures than younger patients, regardless of sex (P < .01 for all comparisons). Measurement of urinary free cortisol supported the diagnosis of CS less frequently in older patients when compared with the younger (P < .05). An extrasellar macroadenoma (macrocorticotropinoma with extrasellar extension) was more common in older PIT-CS patients than in the younger (P < .01). Older PIT-CS patients more frequently received cortisol-lowering medications and radiotherapy as a first-line treatment, whereas surgery was the preferred approach in the younger (P < .01 for all comparisons). When transsphenoidal surgery was performed, the remission rate was lower in the elderly when compared with their younger counterpart (P < .05). CONCLUSIONS: Older CS patients lack several typical symptoms of hypercortisolism, present with more comorbidities regardless of sex, and are more often conservatively treated.
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- 2023
13. Patient decision aids for patients with differentiated thyroid carcinoma: development process and alpha and beta testing.
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Koot, A.W.A., Hermens, R.P., Ottevanger, P.B., Netea-Maier, R.T., Stalmeier, P.F., Koot, A.W.A., Hermens, R.P., Ottevanger, P.B., Netea-Maier, R.T., and Stalmeier, P.F.
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Contains fulltext : 293790.pdf (Publisher’s version ) (Open Access), BACKGROUND: Patient decision aids (PtDAs) are structured clinical tools that facilitate shared decision-making. Two important treatment decisions for patients with differentiated thyroid cancer (DTC), which could benefit from PtDAs, are as follows (1): the extent of surgery decision in patients with low-risk DTC and (2) the decision to start or delay starting the treatment with tyrosine kinase inhibitors (TKIs) in patients with advanced tumors. MATERIAL AND METHODS: PtDAs for these two decisions were developed using the International Patient Decision Aids Standards (IPDAS) quality criteria in an iterative process of prototype development via alpha and beta testing by patients and physicians. The information content of the PtDAs was based on the available literature, current guidelines, and patient's needs, preferences, and values. RESULTS: The web-based PtDAs underwent two rounds of alpha testing, revisions, and beta testing. The PtDAs have the same structure, consisting of six steps: a general introduction, information about the treatment options, comparing the treatment options, knowledge questions, a values clarification exercise, and saving the information. The alpha testing (n = 8 patients, n = 10 physicians) showed that the PtDAs were highly acceptable and usable for decision-making. Results of the beta testing in 20 patients showed that two patients did not use the PtDA; the other 18 patients found that the PtDAs were readable (n = 17) and helpful (n = 14) for decision-making. All patients recommend using the PtDAs. CONCLUSIONS: Evidence-based PtDAs were created for patients with DTC for two different treatment decisions. Our final version was judged to be clear, balanced, and helpful in decision-making.
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- 2023
14. European experience with the Afirma Gene Expression Classifier for indeterminate thyroid nodules: A clinical utility study in the Netherlands.
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Lončar, I., Velsen, E.F.S. van, Massolt, E.T., Kemenade, F.J. van, Engen-van Grunsven, A.C.H. van, Hemel, B.M. van, Nederveen, F.H. Van, Netea-Maier, R.T., Links, T.P., Peeters, R.P., Ginhoven, T.M. van, Lončar, I., Velsen, E.F.S. van, Massolt, E.T., Kemenade, F.J. van, Engen-van Grunsven, A.C.H. van, Hemel, B.M. van, Nederveen, F.H. Van, Netea-Maier, R.T., Links, T.P., Peeters, R.P., and Ginhoven, T.M. van
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01 september 2023, Contains fulltext : 296005.pdf (Publisher’s version ) (Open Access), BACKGROUND: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup. METHODS: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules. Diagnostic surgical rates for Bethesda III and IV nodules were compared to a historical cohort of 171 indeterminate nodules. Samples were post hoc tested with the GSC. RESULTS: The GEC classified 26% as benign. Surgical rates between the prospective and historical cohort did not differ (72.1% vs. 76.6%). The GSC classified 59% as benign, but misclassified six malignant lesions as benign. CONCLUSION: Implementation of GEC in management of indeterminate nodules in a European country with restrictive diagnostic workup is currently not supported, especially in oncocytic nodules. Prospective studies with the GSC in European countries are needed to determine the clinical utility.
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- 2023
15. Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice.
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Capdevila, J., Deandreis, D., Durante, C., Leboulleux, S., Luster, M., Netea-Maier, R.T., Newbold, K., Singer, S., Sykiotis, G.P., Bartes, B., Farnell, K., Locati, L.D., Capdevila, J., Deandreis, D., Durante, C., Leboulleux, S., Luster, M., Netea-Maier, R.T., Newbold, K., Singer, S., Sykiotis, G.P., Bartes, B., Farnell, K., and Locati, L.D.
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Contains fulltext : 296064.pdf (Publisher’s version ) (Open Access), BACKGROUND: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. METHODS: With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. CONCLUSIONS: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.
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- 2023
16. Detection and yield of thyroid cancer surveillance in adults with PTEN hamartoma tumour syndrome.
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Drissen, M.M.C.M., Vos, J.R., Netea-Maier, R.T., Gotthardt, M., Hoogerbrugge, N., Drissen, M.M.C.M., Vos, J.R., Netea-Maier, R.T., Gotthardt, M., and Hoogerbrugge, N.
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Item does not contain fulltext, Thyroid cancer surveillance (TCS) with ultrasound (US) is advised for PTEN hamartoma tumour syndrome (PHTS) patients due to increased thyroid cancer (TC) risk. However, data supporting TCS guidelines are scarce. We aimed to assess the detection and yield of annual TCS with US in adult PHTS patients without a TC history and to evaluate the impact of a reduced US interval on the TCS yield. A retrospective cohort study was conducted, including adult PHTS patients and medical record data between 2005 and 2021. The yield from annual TCS was compared with hypothetical biennial and triennial TCS after two initial US with annual interval by counting delayed detection of nodular growth, thyroid adenoma, and TC. During 279 follow-up years, 84 patients (median age 40 years) underwent 349 US. Thyroidectomy was performed in 6/84 (7%) patients, revealing a minimally invasive follicular TC in one patient aged 22 and a thyroid adenoma in two patients aged 21 and 53. Multiple thyroid nodules were diagnosed in 73/84 (87%) patients (median age 36 years). Nodular growth was detected in 9/56 (16%) patients, and its detection would have been delayed in 4-7% US rounds with biennial TCS, and in 2-6% US rounds with triennial TCS. US-based thyroiditis and indeterminate non-malignant lymph nodes were found in 8/74 (11%) and 7/72 (10%) patients, respectively. Following our findings combined with the literature, we propose starting TCS before age 18 and reducing the follow-up frequency after the initial two US from annual to biennial if no suspicious findings are detected.
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- 2023
17. Determinants and mediating mechanisms of quality of life and disease-specific symptoms among thyroid cancer patients: the design of the WaTCh study.
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Mols, F., Schoormans, D., Netea-Maier, R.T., Husson, O., Beijer, S., Deun, K. Van, Zandee, W., Kars, M., Wouters van Poppel, P.C.M., Simsek, S., Battum, P. van, Kisters, J.M.H., Boer, J.P. de, Massolt, E., Leeuwaarde, R. van, Oranje, W., Roerink, S., Vermeulen, Mechteld, Poll-Franse, L. van de, Mols, F., Schoormans, D., Netea-Maier, R.T., Husson, O., Beijer, S., Deun, K. Van, Zandee, W., Kars, M., Wouters van Poppel, P.C.M., Simsek, S., Battum, P. van, Kisters, J.M.H., Boer, J.P. de, Massolt, E., Leeuwaarde, R. van, Oranje, W., Roerink, S., Vermeulen, Mechteld, and Poll-Franse, L. van de
- Abstract
Contains fulltext : 294555.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thyroid cancer (TC) patients are understudied but appear to be at risk for poor physical and psychosocial outcomes. Knowledge of the course and determinants of these deteriorated outcomes is lacking. Furthermore, little is known about mediating biological mechanisms. OBJECTIVES: The WaTCh-study aims to; 1. Examine the course of physical and psychosocial outcomes. 2. Examine the association of demographic, environmental, clinical, physiological, and personality characteristics to those outcomes. In other words, who is at risk? 3. Reveal the association of mediating biological mechanisms (inflammation, kynurenine pathway) with poor physical and psychological outcomes. In other words, why is a person at risk? DESIGN AND METHODS: Newly diagnosed TC patients from 13 Dutch hospitals will be invited. Data collection will take place before treatment, and at 6, 12 and 24 months after diagnosis. Sociodemographic and clinical information is available from the Netherlands Cancer Registry. Patients fill-out validated questionnaires at each time-point to assess quality of life, TC-specific symptoms, physical activity, anxiety, depression, health care use, and employment. Patients are asked to donate blood three times to assess inflammation and kynurenine pathway. Optionally, at each occasion, patients can use a weighing scale with bioelectrical impedance analysis (BIA) system to assess body composition; can register food intake using an online food diary; and can wear an activity tracker to assess physical activity and sleep duration/quality. Representative Dutch normative data on the studied physical and psychosocial outcomes is already available. IMPACT: WaTCh will reveal the course of physical and psychosocial outcomes among TC patients over time and answers the question who is at risk for poor outcomes, and why. This knowledge can be used to provide personalized information, to improve screening, to develop and provide tailored treatment strategies and supportive
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- 2023
18. Concomitant systemic inflammation and cellular immunosuppression in patients with Cushing's syndrome.
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Houten, P. van, Peng, Chunying, Jaeger, M., Herwaarden, A.E. van, Netea, M.G., Ven, A.C. van de, Netea-Maier, R.T., Houten, P. van, Peng, Chunying, Jaeger, M., Herwaarden, A.E. van, Netea, M.G., Ven, A.C. van de, and Netea-Maier, R.T.
- Abstract
01 juli 2023, Contains fulltext : 294745.pdf (Publisher’s version ) (Open Access)
- Published
- 2023
19. Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social–emotional functioning in young adults with Turner syndrome
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Freriks, K., Verhaak, C.M., Sas, T.C.J., Menke, L.A., Wit, J.M., Otten, B.J., de Muinck Keizer-Schrama, S.M.P.F., Smeets, D.F.C.M., Netea-Maier, R.T., Hermus, A.R.M.M., Kessels, R.P.C., and Timmers, H.J.L.M.
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- 2015
- Full Text
- View/download PDF
20. Health-related quality of life following FDG-PET/CT for cytological indeterminate thyroid nodules
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Koster, E.J. de, Husson, O., Dam, E.W.C.M. van, Mijnhout, G.S., Netea-Maier, R.T., Oyen, W.J.G., Snel, M., Geus-Oei, L.F. de, Vriens, D., and EfFECTS Trial Study Grp
- Subjects
health-related quality of life ,Bethesda ,thyroid nodule ,indeterminate cytology ,diagnostic thyroid surgery ,FDG-PET/CT - Abstract
Objective: This study assessed the health-related quality of life (HRQoL) in patients undergoing 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT for an indeterminate (Bethesda III/IV) thyroid nodule. FDG-PET/CT accurately rules out malignancy and prevents 40% of futile diagnostic surgeries in these nodules. Design: Secondary analyses of HRQoL data from a randomised controlled multicentre trial (NCT02208544) in 126 patients from 15 hospitals in the Netherlands were done. Methods: Longitudinal HRQoL assessment was performed using the EuroQol 5-dimension 5-level (EQ-5D-5L), the RAND 36-item Health Survey v2.0 (RAND-36), and the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire on baseline, 3, 6, and 12 months, relative to the date of the FOG-PET/CT scan. Results: Patients who were randomised to active surveillance following an FDG-negative nodule instead of diagnostic surgery reported stable HRQoL scores throughout the year. Univariate analysis indicated better HRQoL for patients undergoing surveillance than surgical patients with benign histopathology on multiple physical and psychosocial domains. Univariate within-group analysis suggested both temporary and continued HRQoL deteriorations in patients with benign histopathology over time. Multivariate within-group analysis demonstrated no significant longitudinal HRQoL changes in patients undergoing active surveillance. In contrast, in patients with benign histopathology, worse HRQoL was observed with regard to ThyPRO cognitive impairment (P = 0.01) and cosmetic complaints (P = 0.02), whereas goitre symptoms (P < 0.001) and anxiety (P = 0.04) improved over time. In patients with malignant histopathology, anxiety also decreased (P = 0.05). Conclusions: The reassurance of a negative FDG-PET/CT resulted in sustained HRQoL throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology.
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- 2022
21. Reprogramming of myeloid cells and their progenitors in patients with non-medullary thyroid carcinoma
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Rabold, K., Zoodsma, Martijn, Grondman, I., Kuijpers, Yunus, Bremmers, M.E.J., Jaeger, M., Hobo, W.A., Bonenkamp, H., Wilt, J.H.W. de, Janssen, M.J.R., Cornelissen, L.A.M., Engen-van Grunsven, I.C.H. van, Mulder, W.J.M., Smit, J.W.A., Adema, G.J., Netea, M.G., Li, Y., Xu, C., Netea-Maier, R.T., Rabold, K., Zoodsma, Martijn, Grondman, I., Kuijpers, Yunus, Bremmers, M.E.J., Jaeger, M., Hobo, W.A., Bonenkamp, H., Wilt, J.H.W. de, Janssen, M.J.R., Cornelissen, L.A.M., Engen-van Grunsven, I.C.H. van, Mulder, W.J.M., Smit, J.W.A., Adema, G.J., Netea, M.G., Li, Y., Xu, C., and Netea-Maier, R.T.
- Abstract
Contains fulltext : 283851.pdf (Publisher’s version ) (Open Access)
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- 2022
22. The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations
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Sterenborg, R.B.T.M., Galesloot, T.E., Teumer, A., Netea-Maier, R.T., Speed, D., Meima, M.E., Visser, Wesley J., Smit, J.W.A., Peeters, R.P., Medici, M., Sterenborg, R.B.T.M., Galesloot, T.E., Teumer, A., Netea-Maier, R.T., Speed, D., Meima, M.E., Visser, Wesley J., Smit, J.W.A., Peeters, R.P., and Medici, M.
- Abstract
Contains fulltext : 251756.pdf (Publisher’s version ) (Open Access), OBJECTIVE: While most of the variation in thyroid function is determined by genetic factors, single nucleotide polymorphisms (SNPs) identified via genome-wide association analyses have only explained ~5% to 9% of this variance so far. Most SNPs were in or nearby genes with no known role in thyroid hormone (TH) regulation. Therefore, we performed a large-scale candidate gene study investigating the effect of common genetic variation in established TH regulating genes on serum thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine (FT4) concentrations. METHODS: SNPs in or within 10 kb of 96 TH regulating genes were included (30 031 TSH SNPs, and 29 962 FT4 SNPs). Associations were studied in 54 288 individuals from the ThyroidOmics Consortium. Linkage disequilibrium-based clumping was used to identify independently associated SNPs. SNP-based explained variances were calculated using SumHer software. RESULTS: We identified 23 novel TSH-associated SNPs in predominantly hypothalamic-pituitary-thyroid axis genes and 25 novel FT4-associated SNPs in mainly peripheral metabolism and transport genes. Genome-wide SNP variation explained ~21% (SD 1.7) of the total variation in both TSH and FT4 concentrations, whereas SNPs in the 96 TH regulating genes explained 1.9% to 2.6% (SD 0.4). CONCLUSION: Here we report the largest candidate gene analysis on thyroid function, resulting in a substantial increase in the number of genetic variants determining TSH and FT4 concentrations. Interestingly, these candidate gene SNPs explain only a minor part of the variation in TSH and FT4 concentrations, which substantiates the need for large genetic studies including common and rare variants to unravel novel, yet unknown, pathways in TH regulation.
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- 2022
23. Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN
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Valassi, E., Castinetti, F., Ferriere, A., Tsagarakis, S., Feelders, R.A., Netea-Maier, R.T., Droste, M., Strasburger, C.J., Maiter, D., Kastelan, D., Chanson, P., Webb, S.M., Demtröder, F., Pirags, V., Chabre, O., Franz, H., Santos, A., Reincke, M., Valassi, E., Castinetti, F., Ferriere, A., Tsagarakis, S., Feelders, R.A., Netea-Maier, R.T., Droste, M., Strasburger, C.J., Maiter, D., Kastelan, D., Chanson, P., Webb, S.M., Demtröder, F., Pirags, V., Chabre, O., Franz, H., Santos, A., and Reincke, M.
- Abstract
Item does not contain fulltext, Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.
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- 2022
24. [(18)F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial
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Koster, E.J. de, Geus-Oei, L.F. de, Brouwers, A.H., Dam, E. van, Dijkhorst-Oei, L.T., Engen-van Grunsven, A.C.H. van, Hout, W.B. Van den, Klooker, T.K., Netea-Maier, R.T., Snel, M., Oyen, W.J.G., Vriens, D., Koster, E.J. de, Geus-Oei, L.F. de, Brouwers, A.H., Dam, E. van, Dijkhorst-Oei, L.T., Engen-van Grunsven, A.C.H. van, Hout, W.B. Van den, Klooker, T.K., Netea-Maier, R.T., Snel, M., Oyen, W.J.G., and Vriens, D.
- Abstract
Contains fulltext : 251928.pdf (Publisher’s version ) (Open Access), PURPOSE: To assess the impact of an [(18)F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. METHODS: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [(18)F]FDG-PET/CT and were randomised to an [(18)F]FDG-PET/CT-driven or diagnostic surgery group. In the [(18)F]FDG-PET/CT-driven group, management was based on the [(18)F]FDG-PET/CT result: when the index nodule was visually [(18)F]FDG-positive, diagnostic surgery was advised; when [(18)F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. RESULTS: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [(18)F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [(18)F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2-40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [(18)F]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%)
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- 2022
25. Tackling Thyroid Cancer in Europe-The Challenges and Opportunities
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Horgan, D., Führer-Sakel, D., Soares, P., Alvarez, C.V., Fugazzola, L., Netea-Maier, R.T., Jarzab, B., Kozaric, M., Bartes, B., Schuster-Bruce, J., Maso, L. Dal, Schlumberger, M., Pacini, F., Horgan, D., Führer-Sakel, D., Soares, P., Alvarez, C.V., Fugazzola, L., Netea-Maier, R.T., Jarzab, B., Kozaric, M., Bartes, B., Schuster-Bruce, J., Maso, L. Dal, Schlumberger, M., and Pacini, F.
- Abstract
Contains fulltext : 282378.pdf (Publisher’s version ) (Open Access), Thyroid cancer (TC) is the most common malignancy of the endocrine system that affects the thyroid gland. It is usually treatable and, in most cases, curable. The central issues are how to improve knowledge on TC, to accurately identify cases at an early stage that can benefit from effective intervention, optimise therapy, and reduce the risk of overdiagnosis and unnecessary treatment. Questions remain about management, about treating all patients in referral centres, and about which treatment should be proposed to any individual patient and how this can be optimised. The European Alliance for Personalised Medicine (EAPM) hosted an expert panel discussion to elucidate some of the challenges, and to identify possible steps towards effective responses at the EU and member state level, particularly in the context of the opportunities in the European Union's evolving initiatives-notably its Beating Cancer Plan, its Cancer Mission, and its research funding programmes. Recommendations emerging from the panel focus on improved infrastructure and funding, and on promoting multi-stakeholder collaboration between national and European initiatives to complement, support, and mutually reinforce efforts to improve patient care.
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- 2022
26. The impact of pre-existing thyroid diseases on susceptibility to respiratory infections or self-reported sickness during the SARS-CoV-2 pandemic
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Rops, M.A.J., Moorlag, S.J.C.F.M., Deuren, R.C. van, Jaeger, M., Joosten, L.A.B., Medici, M., Netea, M.G., Smit, J.W.A., Netea-Maier, R.T., Rops, M.A.J., Moorlag, S.J.C.F.M., Deuren, R.C. van, Jaeger, M., Joosten, L.A.B., Medici, M., Netea, M.G., Smit, J.W.A., and Netea-Maier, R.T.
- Abstract
Contains fulltext : 282326.pdf (Publisher’s version ) (Open Access), INTRODUCTION: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. SUBJECTS AND METHODS: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. RESULTS: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. CONCLUSION: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.
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- 2022
27. Overcoming resistance to radioactive iodide treatment in thyroid carcinoma: focus on autophagy
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Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., Tesselaar, M.H., Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., and Tesselaar, M.H.
- Abstract
Radboud University, 25 november 2022, Promotores : Smit, J.W.A., Netea-Maier, R.T. Co-promotor : Plantinga, T.S., Contains fulltext : 283485.pdf (Publisher’s version ) (Open Access)
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- 2022
28. Higher thyroid stimulating hormone leads to cardiovascular disease and an unfavorable lipid profile: EVidence from multi-cohort Mendelian randomization and metabolomic profiling
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Van Vliet, N.A., primary, Bos, M.M., additional, Thesing, C.S., additional, Chaker, L., additional, Pietzner, M., additional, Houtman, E., additional, Neville, M.J., additional, Li-Gao, R., additional, Trompet, S., additional, Mustafa, R., additional, Ahmadizar, F., additional, Beekman, M., additional, Bot, M., additional, Budde, K., additional, Christodoulides, C., additional, Dehghan, A., additional, Delles, C., additional, Elliott, P., additional, Evangelou, M., additional, Gao, H., additional, Ghanbari, M., additional, Van Herwaarden, A.E., additional, Ikram, M.A., additional, Jaeger, M., additional, Jukema, J.W., additional, Karaman, I., additional, Karpe, F., additional, Kloppenburg, M., additional, Meessen, J.M.T.A., additional, Meulenbelt, I., additional, Milaneschi, Y., additional, Mooijaart, S.P., additional, Mook-Kanamori, D.O., additional, Netea, M.G., additional, Netea-Maier, R.T., additional, Peeters, R.P., additional, Penninx, B.W.J.H., additional, Sattar, N., additional, Slagboom, P.E., additional, Suchiman, H.E.D., additional, Völzke, H., additional, Van Dijk, K. Willems, additional, and Noordam, R., additional
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- 2021
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- View/download PDF
29. Long-Term Effects of Radioiodine Treatment on Salivary Gland Function in Adult Survivors of Pediatric Differentiated Thyroid Carcinoma
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Selvakumar, T., Nies, M., Hesselink, M.S.K., Brouwers, A.H., Horst-Schrivers, A.N.A. van der, Hesselink, E.N.K., Tissing, W.J.E., Vissink, A., Links, T.P., Bocca, G., Burgerhof, J.G.M., Dam, E.W.C.M. van, Havekes, B., Heuvel-Eibrink, M.M. van den, Corssmit, E.P.M., Kremer, L.C.M., Netea-Maier, R.T., Pal, H.J.H. van der, Peeters, R.P., Smit, J.W.A., Plukker, J.T.M., Ronckers, C.M., Santen, H.M. van, Dutch Pediat Thyroid Canc Study Co, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Personalized Healthcare Technology (PHT), Translational Immunology Groningen (TRIGR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Internal medicine, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Internal Medicine, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, MUMC+: MA Endocrinologie (9), and Interne Geneeskunde
- Subjects
salivary gland dysfunction ,medicine.medical_specialty ,Saliva ,FLOW ,030209 endocrinology & metabolism ,XEROSTOMIA ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Gastroenterology ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Thyroid carcinoma ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,stomatognathic system ,QUALITY-OF-LIFE ,Internal medicine ,medicine ,FERTILITY ,Endocrine system ,Radiology, Nuclear Medicine and imaging ,I-131 THERAPY ,Thyroid cancer ,RISK ,radioiodine treatment ,Salivary gland ,business.industry ,Cancer ,pediatric differentiated thyroid carcinoma ,RADIOACTIVE IODINE THERAPY ,medicine.disease ,CANCER ,Sialadenitis ,INTERMEDIATE ,medicine.anatomical_structure ,SIALADENITIS ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,business ,Rare disease - Abstract
Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a total or near-total thyroidectomy and 131 I therapy. Previous studies on adults showed that 131 I treatment may reduce salivary gland function (SGF). Studies regarding SGF in children treated for DTC are sparse. Our aim was to assess the long-term effects of 131 I treatment on SGF in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, SGF in patients treated for pediatric DTC between 1970 and 2013 (.5 y after diagnosis, $18 y old at the time of evaluation) was studied. SGF was assessed by sialometry, sialochemistry, and a xerostomia inventory. Salivary gland dysfunction (SGD) was defined as an unstimulated whole saliva flow of no more than 0.2 mL/min or a stimulated whole saliva flow of no more than 0.7 mL/min. Results: Sixty-five patients underwent 131 I treatment (median age at evaluation, 33 y, with an interquartile range [IQR] of 25–40 y; 86.2% female; median follow-up period, 11 y, with an IQR of 6–22 y). Median cumulative 131 I activity was 5.88 GBq, with an IQR of 2.92–12.95 GBq, and 47.7% underwent multiple 131 I administrations. SGD was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and the severity of xerostomia complaints higher in patients treated with higher cumulative 131 I activity. Conclusion: In survivors of pediatric DTC, clinically significant SGD was found in 35.5% and was related to the cumulative 131 I activity of the treatment.
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- 2018
30. The Association of TSH and Thyroid Hormones with Lymphopenia in Bacterial Sepsis and COVID-19
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Grondman, I. De Nooijer, A.H. Antonakos, N. Janssen, N.A.F. Mouktaroudi, M. Leventogiannis, K. Medici, M. Smit, J.W.A. Van Herwaarden, A.E. Joosten, L.A.B. Van De Veerdonk, F.L. Pickkers, P. Kox, M. Jaeger, M. Netea, M.G. Giamarellos-Bourboulis, E.J. Netea-Maier, R.T.
- Abstract
Context: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3′-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. Objective: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. Methods: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n=224) and COVID-19 patients (n=161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. Results: Only T3 significantly correlated (ρ=0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n=56 per group). Severe lymphopenic COVID-19 patients (n=17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n=18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. Conclusion: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
- Published
- 2021
31. The Association of TSH and Thyroid Hormones With Lymphopenia in Bacterial Sepsis and COVID-19
- Author
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Grondman, I., Nooijer, A.H. de, Antonakos, N., Janssen, N.A.F., Mouktaroudi, M., Leventogiannis, K., Medici, M., Smit, J.W.A., Herwaarden, A.E. van, Joosten, L.A.B., Veerdonk, F.L. van de, Pickkers, P., Kox, M., Jaeger, M., Netea, M.G., Giamarellos-Bourboulis, E.J., Netea-Maier, R.T., Grondman, I., Nooijer, A.H. de, Antonakos, N., Janssen, N.A.F., Mouktaroudi, M., Leventogiannis, K., Medici, M., Smit, J.W.A., Herwaarden, A.E. van, Joosten, L.A.B., Veerdonk, F.L. van de, Pickkers, P., Kox, M., Jaeger, M., Netea, M.G., Giamarellos-Bourboulis, E.J., and Netea-Maier, R.T.
- Abstract
Item does not contain fulltext, CONTEXT: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.
- Published
- 2021
32. Kinase Inhibitors' Effects on Innate Immunity in Solid Cancers
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Peng, C., Rabold, K., Mulder, W.J.M., Jaeger, M., Netea-Maier, R.T., Peng, C., Rabold, K., Mulder, W.J.M., Jaeger, M., and Netea-Maier, R.T.
- Abstract
Contains fulltext : 245695.pdf (Publisher’s version ) (Open Access), Innate immune cells constitute a plastic and heterogeneous cell population of the tumor microenvironment. Because of their high tumor infiltration and close interaction with resident tumor cells, they are compelling targets for anti-cancer therapy through either ablation or functionally reprogramming. Kinase inhibitors (KIs) that target aberrant signaling pathways in tumor proliferation and angiogenesis have been shown to have additional immunological effects on myeloid cells that may contribute to a protective antitumor immune response. However, in patients with malignancies, these effects are poorly described, warranting meticulous research to identify KIs' optimal immunomodulatory effect to support developing targeted and more effective immunotherapy. As many of these KIs are currently in clinical trials awaiting approval for the treatment of several types of solid cancer, we evaluate here the information on this drug class's immunological effects and how such mechanisms can be harnessed to improve combined treatment regimens in cancer.
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- 2021
33. Seasonal and Nonseasonal Longitudinal Variation of Immune Function
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Horst, R. ter, Jaeger, M., Wijer, L. van de, Heijden, W.A. van der, Janssen, Anna M.W., Smeekens, S.P., Brouwer, M.A.E., Cranenbroek, B. van, Netea-Maier, R.T., Herwaarden, A.E. van, Lemmers, H.L.M., Dijkstra, H.I., Joosten, I., Koenen, H.J., Netea, M.G., Joosten, L.A.B., Horst, R. ter, Jaeger, M., Wijer, L. van de, Heijden, W.A. van der, Janssen, Anna M.W., Smeekens, S.P., Brouwer, M.A.E., Cranenbroek, B. van, Netea-Maier, R.T., Herwaarden, A.E. van, Lemmers, H.L.M., Dijkstra, H.I., Joosten, I., Koenen, H.J., Netea, M.G., and Joosten, L.A.B.
- Abstract
Item does not contain fulltext
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- 2021
34. Voice Characteristics in Patients with Acromegaly during Treatment
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Wolters, T.L.C., Roerink, S.H.P.P., Drenthen, L.C.A., Wagenmakers, M.A.E.M., Broek, G.B. van den, Rutten, K., Herruer, J.M., Hermus, A.R.M.M., Netea-Maier, R.T., Wolters, T.L.C., Roerink, S.H.P.P., Drenthen, L.C.A., Wagenmakers, M.A.E.M., Broek, G.B. van den, Rutten, K., Herruer, J.M., Hermus, A.R.M.M., and Netea-Maier, R.T.
- Abstract
Item does not contain fulltext
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- 2021
35. Long-term male fertility after treatment with radioactive iodine for differentiated thyroid carcinoma
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Nies, M., Arts, E., Velsen, Evert F.S. van, Burgerhof, J.G.M., Muller Kobold, Anneke C., Corssmit, Eleonora P.M., Netea-Maier, R.T., Cantineau, A.E.P., Links, T.P., Nies, M., Arts, E., Velsen, Evert F.S. van, Burgerhof, J.G.M., Muller Kobold, Anneke C., Corssmit, Eleonora P.M., Netea-Maier, R.T., Cantineau, A.E.P., and Links, T.P.
- Abstract
Contains fulltext : 239799.pdf (Publisher’s version ) (Closed access)
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- 2021
36. Spontaneous bone infarction of the distal femur in a patient with Cushing's disease: a case report
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Houten, P. van, Rooy, J.W.J. de, Geest, I.C. van der, Netea-Maier, R.T., Ven, A.C. van de, Houten, P. van, Rooy, J.W.J. de, Geest, I.C. van der, Netea-Maier, R.T., and Ven, A.C. van de
- Abstract
Contains fulltext : 232516.pdf (Publisher’s version ) (Open Access), Avascular necrosis of the femoral head is a well-known complication of treatment with high dosage glucocorticoids and has been described in a few patients with Cushing's syndrome. In this case report, we describe the, to our knowledge, first case of a patient with endogenous Cushing's syndrome with a bone infarction located in the distal femur. In patients with Cushing's syndrome and bone pain, the diagnosis of bone infarction should be considered as it can occur as a rare complication of hypercortisolism.
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- 2021
37. Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study
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Coopmans, Eva C., Postma, M.R., Wolters, T.L.C., Meyel, Sebastiaan W.F. van, Netea-Maier, R.T., Beek, Andre P. van, Neggers, Sebastian J. C. M. M., Coopmans, Eva C., Postma, M.R., Wolters, T.L.C., Meyel, Sebastiaan W.F. van, Netea-Maier, R.T., Beek, Andre P. van, and Neggers, Sebastian J. C. M. M.
- Abstract
Contains fulltext : 234210.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
38. Translational Studies on Radioactive Iodide Resistance in Non-medullary Thyroid Carcinoma.
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Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., Crezee, T., Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., and Crezee, T.
- Abstract
Radboud University, 05 november 2021, Promotores : Smit, J.W.A., Netea-Maier, R.T. Co-promotor : Plantinga, T.S., Contains fulltext : 238970.pdf (Publisher’s version ) (Open Access)
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- 2021
39. European Thyroid Association and Cardiovascular and Interventional Radiological Society of Europe 2021 Clinical Practice Guideline for the Use of Minimally Invasive Treatments in Malignant Thyroid Lesions
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Mauri, Giovanni, Hegedus, Laszlo, Bandula, Steven, Cazzato, Roberto Luigi, Czarniecka, Agnieszka, Dudeck, Oliver, Netea-Maier, R.T., Wallin, Goran, Papini, Enrico, Mauri, Giovanni, Hegedus, Laszlo, Bandula, Steven, Cazzato, Roberto Luigi, Czarniecka, Agnieszka, Dudeck, Oliver, Netea-Maier, R.T., Wallin, Goran, and Papini, Enrico
- Abstract
Item does not contain fulltext
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- 2021
40. Persistent improvement of bone mineral density up to 20 years after treatment of Cushing's syndrome
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Houten, P. van, Netea-Maier, R.T., Wagenmakers, M.A.E.M., Roerink, S.H.P.P., Hermus, A.R.M.M., Ven, A.C. van de, Houten, P. van, Netea-Maier, R.T., Wagenmakers, M.A.E.M., Roerink, S.H.P.P., Hermus, A.R.M.M., and Ven, A.C. van de
- Abstract
Item does not contain fulltext, OBJECTIVE: Cushing's syndrome (CS) is associated with osteoporosis and high fracture risk. Besides male sex, it is unknown which variables influence bone mineral density (BMD) at diagnosis and it is unclear to what extent BMD normalizes during long-term follow-up after treatment of CS. The aim of this study was to determine factors associated with BMD at diagnosis of CS and to determine the long-term course of BMD and fracture rate after successful treatment of CS. DESIGN: Retrospective cross-sectional and longitudinal cohort study. METHODS: Data were collected from 231 patients with CS who were treated at the Radboud University Medical Centre between 1968 and 2020. RESULTS: At diagnosis, male sex was associated with lower Z-scores at the lumbar spine (LS) compared with female sex: -0.97s.d. (-1.45 to -0.49) after correction for possible confounders. Shorter duration of symptoms and younger age were also associated with lower Z-scores at diagnosis, while etiology of CS, urinary cortisol excretion and gonadal status were not associated with Z-scores at diagnosis. Z-scores improved up to 20 years after treatment. Fifteen years after treatment, men showed larger improvements of Z-scores than women; +2.56 (1.82-3.30) increase in LS Z-score vs +1.48 (0.96-2.00) respectively. Fracture incidence was highest during the 2 years before diagnosis and decreased after treatment. CONCLUSION: Male sex, younger age and shorter duration of symptoms are associated with lower BMD at diagnosis of CS. BMD continues to improve up to 20 years after treatment of CS. Fracture rate decreases after treatment of CS.
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- 2021
41. Digoxin treatment reactivates in vivo radioactive iodide uptake and correlates with favorable clinical outcome in non-medullary thyroid cancer
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Crezee, T., Tesselaar, M.H., Nagarajah, J., Corver, W.E., Morreau, J., Pritchard, C., Kimura, S., Kuiper, J.G.J., Engen-van Grunsven, I.A. van, Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., Crezee, T., Tesselaar, M.H., Nagarajah, J., Corver, W.E., Morreau, J., Pritchard, C., Kimura, S., Kuiper, J.G.J., Engen-van Grunsven, I.A. van, Smit, J.W.A., Netea-Maier, R.T., and Plantinga, T.S.
- Abstract
Contains fulltext : 235280.pdf (Publisher’s version ) (Open Access), PURPOSE: Non-medullary thyroid cancer (NMTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). However, in a subset of NMTC patients tumor dedifferentiation occurs, leading to RAI resistance. Digoxin has been demonstrated to restore iodide uptake capacity in vitro in poorly differentiated and anaplastic NMTC cells, termed redifferentiation. The aim of the present study was to investigate the in vivo effects of digoxin in TPO-Cre/LSL-Braf(V600E) mice and digoxin-treated NMTC patients. METHODS: Mice with thyroid cancer were subjected to 3D ultrasound for monitoring tumor growth and (124)I PET/CT for measurement of intratumoral iodide uptake. Post-mortem analyses on tumor tissues comprised gene expression profiling and measurement of intratumoral autophagy activity. Through PALGA (Dutch Pathology Registry), archived tumor material was obtained from 11 non-anaplastic NMTC patients who were using digoxin. Clinical characteristics and tumor material of these patients were compared to 11 matched control NMTC patients never treated with digoxin. RESULTS: We found that in mice, tumor growth was inhibited and (124)I accumulation was sustainably increased after short-course digoxin treatment. Post-mortem analyses revealed that digoxin treatment increased autophagy activity and enhanced expression of thyroid-specific genes in mouse tumors compared to vehicle-treated mice. Digoxin-treated NMTC patients exhibited significantly higher autophagy activity and a higher differentiation status as compared to matched control NMTC patients, and were associated with favourable clinical outcome. CONCLUSIONS: These in vivo data support the hypothesis that digoxin may represent a repositioned adjunctive treatment modality that suppresses tumor growth and improves RAI sensitivity in patients with RAI-refractory NMTC.
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- 2021
42. IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer
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Crezee, T., Tesselaar, M.H., Jaeger, M., Rabold, K., Corver, Willem, Morreau, H., Engen-van Grunsven, A.C.H. van, Smit, J.W.A., Netea-Maier, R.T., Plantinga, T.S., Crezee, T., Tesselaar, M.H., Jaeger, M., Rabold, K., Corver, Willem, Morreau, H., Engen-van Grunsven, A.C.H. van, Smit, J.W.A., Netea-Maier, R.T., and Plantinga, T.S.
- Abstract
Item does not contain fulltext
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- 2021
43. Thyrotrophin and thyroxine support immune homeostasis in humans
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Jaeger, M., Sloot, Y.J.E., Horst, R. ter, Chu, X., Koenen, H.J.P.M., Koeken, V.A.C.M., Moorlag, S.J.C.F.M., Bree, L.C.J. de, Mourits, V.P., Lemmers, H.L.M., Dijkstra, H.I., Medici, M., Herwaarden, A.E. van, Joosten, I., Joosten, L.A.B., Li, Y., Smit, J.W.A., Netea, M.G., Netea-Maier, R.T., Jaeger, M., Sloot, Y.J.E., Horst, R. ter, Chu, X., Koenen, H.J.P.M., Koeken, V.A.C.M., Moorlag, S.J.C.F.M., Bree, L.C.J. de, Mourits, V.P., Lemmers, H.L.M., Dijkstra, H.I., Medici, M., Herwaarden, A.E. van, Joosten, I., Joosten, L.A.B., Li, Y., Smit, J.W.A., Netea, M.G., and Netea-Maier, R.T.
- Abstract
Item does not contain fulltext, The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease.
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- 2021
44. Thyroid Microcarcinoma in Pediatric Population in Romania
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Stefan, Andreea-Ioana, Piciu, Andra, Cosnarovici, Maria Margareta, Dragomir, Monica, Netea-Maier, R.T., Piciu, D., Stefan, Andreea-Ioana, Piciu, Andra, Cosnarovici, Maria Margareta, Dragomir, Monica, Netea-Maier, R.T., and Piciu, D.
- Abstract
Contains fulltext : 233741.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
45. Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk
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Devalraju, Kamakshi Prudhula, Tripathi, D., Kumar Neela, Venkata Sanjeev, Paidipally, Padmaja, Radhakrishnan, Rajesh Kumar, Singh, K., Jaeger, M., Netea-Maier, R.T., Netea, M.G., Valluri, Vijaya Lakshmi, Vankayalapati, Ramakrishna, Devalraju, Kamakshi Prudhula, Tripathi, D., Kumar Neela, Venkata Sanjeev, Paidipally, Padmaja, Radhakrishnan, Rajesh Kumar, Singh, K., Jaeger, M., Netea-Maier, R.T., Netea, M.G., Valluri, Vijaya Lakshmi, and Vankayalapati, Ramakrishna
- Abstract
Contains fulltext : 235482.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
46. Needs, Preferences, and Values during Different Treatment Decisions of Patients with Differentiated Thyroid Cancer
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Koot, A.W.A., Netea-Maier, R.T., Ottevanger, P.B., Hermens, R.P., Stalmeier, P.F.M., Koot, A.W.A., Netea-Maier, R.T., Ottevanger, P.B., Hermens, R.P., and Stalmeier, P.F.M.
- Abstract
Contains fulltext : 236911.pdf (Publisher’s version ) (Open Access)
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- 2021
47. Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
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Chu, X., Jaeger, M., Beumer, J.H., Bakker, O.B., Aguirre-Gamboa, R., Oosting, M., Smeekens, S.P., Moorlag, S.J.C.F.M., Mourits, V.P., Koeken, V.A.C.M., Bree, L.C.J. de, Jansen, T.J., Joosten, I., Koenen, H.J.P.M., Netea-Maier, R.T., Joosten, L.A.B., Kumar, V., Netea, M.G., Li, Y., Chu, X., Jaeger, M., Beumer, J.H., Bakker, O.B., Aguirre-Gamboa, R., Oosting, M., Smeekens, S.P., Moorlag, S.J.C.F.M., Mourits, V.P., Koeken, V.A.C.M., Bree, L.C.J. de, Jansen, T.J., Joosten, I., Koenen, H.J.P.M., Netea-Maier, R.T., Joosten, L.A.B., Kumar, V., Netea, M.G., and Li, Y.
- Abstract
Contains fulltext : 235149.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
48. Long-Term Effects of Radioiodine Treatment on Female Fertility in Survivors of Childhood Differentiated Thyroid Carcinoma
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Nies, M., Cantineau, A.E.P., Arts, E., Berg, M.H. van den, Leeuwen, F.E. van, Kobold, A.C., Hesselink, M.S. Klein, Burgerhof, J.G., Brouwers, A.H., Dam, E. van, Havekes, B., Heuvel-Eibrink, M.M. van den, Corssmit, E.P.M., Kremer, L.C., Netea-Maier, R.T., Pal, H.J. van der, Peeters, R.P., Plukker, J.T., Ronckers, C.M., Santen, H.M. van, Horst-Schrivers, Anouk N. van de, Tissing, W.J., Bocca, G., Dulmen-den Broeder, E. van, Links, T.P., Nies, M., Cantineau, A.E.P., Arts, E., Berg, M.H. van den, Leeuwen, F.E. van, Kobold, A.C., Hesselink, M.S. Klein, Burgerhof, J.G., Brouwers, A.H., Dam, E. van, Havekes, B., Heuvel-Eibrink, M.M. van den, Corssmit, E.P.M., Kremer, L.C., Netea-Maier, R.T., Pal, H.J. van der, Peeters, R.P., Plukker, J.T., Ronckers, C.M., Santen, H.M. van, Horst-Schrivers, Anouk N. van de, Tissing, W.J., Bocca, G., Dulmen-den Broeder, E. van, and Links, T.P.
- Abstract
Item does not contain fulltext, Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1-39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3-24.7) years. The median cumulative dose of (131)I administered was 7.4 (IQR 3.7-13.0) GBq/200.0 (IQR 100.0-350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0-3.7) μg/L vs. 1.6 (IQR 0.6-3.1) μg/L, respectively, p = 0.244]. The cumulative dose of (131)I was not associated with AMH levels in DTC survivors (r(s) = 0.210, p
- Published
- 2020
49. GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
- Author
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Zhou, W., Brumpton, Ben, Kabil, Omer, Gudmundsson, J., Thorleifsson, G., Weinstock, Josh, Medici, M., Kiemeney, L.A.L.M., Netea-Maier, R.T., Plantinga, T.S., Willer, C.J., Asvold, Bjorn Olav, Zhou, W., Brumpton, Ben, Kabil, Omer, Gudmundsson, J., Thorleifsson, G., Weinstock, Josh, Medici, M., Kiemeney, L.A.L.M., Netea-Maier, R.T., Plantinga, T.S., Willer, C.J., and Asvold, Bjorn Olav
- Abstract
Contains fulltext : 222135.pdf (publisher's version ) (Open Access)
- Published
- 2020
50. Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics
- Author
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Rabold, K., Aschenbrenner, A., Thiele, C., Boahen, C.K., Schiltmans, A., Smit, J.W.A., Schultze, J.L., Netea, M.G., Adema, G.J., Netea-Maier, R.T., Rabold, K., Aschenbrenner, A., Thiele, C., Boahen, C.K., Schiltmans, A., Smit, J.W.A., Schultze, J.L., Netea, M.G., Adema, G.J., and Netea-Maier, R.T.
- Abstract
Contains fulltext : 225323.pdf (publisher's version ) (Open Access), BACKGROUND: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs. METHODS: In a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways. RESULTS: Based on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME. CONCLUSIONS: Taken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME.
- Published
- 2020
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