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2. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

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.

Published
2024

3. Parma consensus statement on metabolic disruptors

Author

Heindel, JJ, Vom Saal, FS, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, BA, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Rizzir, L, Machtinger, R, Mantovani, A, Mendez, MA, Montanini, L, Molteni, L, Nagel, SC, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, TT, Street, ME, Suvorov, A, Volpi, R, Zoeller, RT, and Palanza, P

Subjects
Public Health and Health Services, Toxicology
Abstract

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Published
2015

5. The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis

Author

Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., Chaker, L., Xu, Y.F., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L.A., Riksen, N.P., Dullaart, R.P.F., Trompet, S., Dörr, M., Brown, S.J., Schmidt, Börge, Führer-Sakel, D., Vanderpump, M.P.J., Muendlein, A., Drexel, H., Fink, H.A., Ikram, M.K., Kavousi, M., Rhee, C.M., Bensenor, I.M., Azizi, F., Hankey, G.J., Iacoviello, M., Imaizumi, M., Ceresini, G., Ferrucci, L., Sgarbi, J.A., Bauer, D.C., Wareham, N., Boelaert, K., Bakker, S.J.L., Jukema, J.W., Vaes, B., Iervasi, G., Yeap, B.B., Westendorp, R.G.J., Korevaar, T.I.M., Völzke, H., Razvi, S., Gussekloo, J., Walsh, J.P., Cappola, A.R., Rodondi, N., Peeters, R.P., and Chaker, L.

Abstract

Contains fulltext : 297328.pdf (Publisher’s version ) (Closed access), BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT(4) based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT(4), and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT(4), thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 co

Published
2023

6. Incorporating Baseline Outcome Data in Individual Participant Data Meta-Analysis of Non-randomized Studies

Author

Syrogiannouli, L., Wildisen, L., Meuwese, C., Bauer, D.C., Cappola, A.R., Gussekloo, J., Elzen, W.P.J. den, Trompet, S., Westendorp, R.G.J., Jukema, J.W., Ferrucci, L., Ceresini, G., Asvold, B.O., Chaker, L., Peeters, R.P., Imaizumi, M., Ohishi, W., Vaes, B., Volzke, H., Sgarbi, J.A., Walsh, J.P., Dullaart, R.P.F., Bakker, S.J.L., Iacoviello, M., Rodondi, N., Giovane, C. del, Thyroid Studies Collaboration, Epidemiology, Internal Medicine, Laboratory for Endocrinology, APH - Personalized Medicine, APH - Aging & Later Life, Groningen Institute for Organ Transplantation (GIOT), and Groningen Kidney Center (GKC)

Subjects
baseline imbalance, cohorts, continuous outcome, individual participant data, non-randomized studies, Prevention, Clinical Sciences, 360 Soziale Probleme, Sozialdienste, 610 Medicine & health, Psychiatry and Mental health, SDG 3 - Good Health and Well-being, 360 Social problems & social services, Public Health and Health Services, Psychology, 610 Medizin und Gesundheit
Abstract

BackgroundIn non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC).MethodsFor the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA.ResultsTen of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score.ConclusionANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly.

Published
2022

7. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies

Author

Alwan, H., Villoz, F., Feller, M., Dullaart, R.P.F., Bakker, S.J.L., Peeters, R.P., Kavousi, M., Bauer, D.C., Cappola, A.R., Yeap, B.B., Walsh, J.P., Brown, S.J., Ceresini, G., Ferrucci, L., Gussekloo, J., Trompet, S., Iacoviello, M., Moon, J.H., Razvi, S., Bensenor, I.M., Azizi, F., Amouzegar, A., Valdes, S., Colomo, N., Wareham, N.J., Jukema, J.W., Westendorp, R.G.J., Kim, K.W., Rodondi, N., Giovane, C. del, Thyroid Studies Collaboration, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Internal Medicine, Epidemiology, Alwan, Heba [0000-0001-5516-6022], Bakker, Stephan JL [0000-0003-3356-6791], Peeters, Robin P [0000-0001-7732-9371], Yeap, Bu B [0000-0002-7612-5892], Razvi, Salman [0000-0002-9047-1556], Amouzegar, Atieh [0000-0001-9433-9408], and Apollo - University of Cambridge Repository

Subjects
Adult, Data Analysis, Male, Endocrinology, Diabetes and Metabolism, Clinical Sciences, Thyrotropin, 610 Medicine & health, Hyperthyroidism, Paediatrics and Reproductive Medicine, Cohort Studies, Endocrinology & Metabolism, Endocrinology, SDG 3 - Good Health and Well-being, Hypothyroidism, 360 Social problems & social services, Clinical Research, Diabetes Mellitus, Humans, Prospective Studies, Metabolic and endocrine, screening and diagnosis, Prevention, Diabetes, General Medicine, Middle Aged, Thyroid Diseases, Detection, Female, 4.2 Evaluation of markers and technologies
Abstract

ObjectiveFew prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes.MethodsWe performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up.ResultsAmong 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88–1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82–1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87–1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88–1.29). The results were robust in all sub-group and sensitivity analyses.ConclusionsThis is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes.Significance statementEvidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future. Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes. Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses. Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Published
2022
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8. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies

Author

Alwan H, Villoz F, Feller M, Dullaart RPF, Bakker SJL, Peeters RP, Kavousi M, Bauer DC, Cappola AR, Yeap BB, Walsh JP, Brown SJ, Ceresini G, Ferrucci L, Gussekloo J, Trompet S, Iacoviello M, Moon JH, Razvi S, Bensenor IM, Azizi F, Amouzegar A, Valdés S, Colomo N, Wareham NJ, Jukema JW, Westendorp RGJ, Kim KW, Rodondi N, Giovane CD

Published
2022
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13. An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms

Author

Wildisen, L., Giovane, C. del, Moutzouri, E., Beglinger, S., Syrogiannouli, L., Collet, T.H., Cappola, A.R., Asvold, B.O., Bakker, S.J.L., Yeap, B.B., Almeida, O.P., Ceresini, G., Dullaart, R.P.F., Ferrucci, L., Grabe, H., Jukema, J.W., Nauck, M., Trompet, S., Volzke, H., Westendorp, R., Gussekloo, J., Kloppel, S., Aujesky, D., Bauer, D., Peeters, R., Feller, M., Rodondi, N., Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), and Internal Medicine

Subjects
Male, Quality of life, endocrine system, endocrine system diseases, Thyroid Gland, lcsh:Medicine, 610 Medicine & health, Thyroid Function Tests, Severity of Illness Index, Article, DISEASE, Endocrinology, Medical research, DESIGN, STAGE, Clinical Research, OSTEOPOROTIC FRACTURES, 360 Social problems & social services, Behavioral and Social Science, BASE-LINE CHARACTERISTICS, Humans, Psychology, lcsh:Science, METAANALYSIS, Public health, Depression, lcsh:R, MEN, Thyroid Diseases, Brain Disorders, Mental Health, HYPOTHYROIDISM, RISK-FACTORS, lcsh:Q, Female, HEALTH, Hormonal therapies
Abstract

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I 2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I 2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Published
2020

17. Correction to: Parma consensus statement on metabolic disruptors (Environmental Health: A Global Access Science Source (2015) 14:1 (54) DOI: 10.1186/s12940-015-0042-7)

Author

Heindel J. J., Heindel, J, Vom Saal, F, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, B, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Rizzi, L, Machtinger, R, Mantovani, A, Mendez, M, Montanini, L, Molteni, L, Nagel, S, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, T, Street, M, Suvorov, A, Volpi, R, Zoeller, R, Palanza, P, Heindel J. J., Vom Saal F. S., Blumberg B., Bovolin P., Calamandrei G., Ceresini G., Cohn B. A., Fabbri E., Gioiosa L., Kassotis C., Legler J., La Merrill M., Rizzi L., Machtinger R., Mantovani A., Mendez M. A., Montanini L., Molteni L., Nagel S. C., Parmigiani S., Panzica G., Paterlini S., Pomatto V., Ruzzin J., Sartor G., Schug T. T., Street M. E., Suvorov A., Volpi R., Zoeller R. T., Palanza P., Heindel J. J., Heindel, J, Vom Saal, F, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, B, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Rizzi, L, Machtinger, R, Mantovani, A, Mendez, M, Montanini, L, Molteni, L, Nagel, S, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, T, Street, M, Suvorov, A, Volpi, R, Zoeller, R, Palanza, P, Heindel J. J., Vom Saal F. S., Blumberg B., Bovolin P., Calamandrei G., Ceresini G., Cohn B. A., Fabbri E., Gioiosa L., Kassotis C., Legler J., La Merrill M., Rizzi L., Machtinger R., Mantovani A., Mendez M. A., Montanini L., Molteni L., Nagel S. C., Parmigiani S., Panzica G., Paterlini S., Pomatto V., Ruzzin J., Sartor G., Schug T. T., Street M. E., Suvorov A., Volpi R., Zoeller R. T., and Palanza P.

Abstract

After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

Published
2017

18. Acromegaly (ACROM) in Emilia Romagna (ER): results from the ACROMER, a multicentric survey over 45 years

Author

Rochira, V., Pagotto, U., Zatelli, M. C., Ambrosio, M. R., Balestrieri, A., Bondi, F., Bonadonna, R., Bondanelli, M., Cataldo, S., Ceresini, G., De Giovanni, R., Frasoldati, A., Guaraldi, F., Lopreiato, V., Maestri, E., Marina, M., Mazzatenta, D., Magnani, E., Monzani, M. L., Moretti, V., Nasi, M. T., Nizzoli, M., Pancotti, D., Riganti, F., Ribichini, D., Santini, C., Soriani, A., Tartaglia, A., Vezzani, S., Zini, M., and Faustini Fustini, M.

Subjects
Emilia Romagna, acromegaly, acromegaly, registry, Emilia Romagna, GH secreting adenoma, pituitary, multicentrico study, registry, GH secreting adenoma, pituitary, multicentrico study
Published
2019

19. Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

Author

Wildisen, L. (Lea), Moutzouri, E. (Elisavet), Beglinger, S. (Shanthi), Syrogiannouli, L. (Lamprini), Cappola, A.R. (Anne), Asvold, B.O. (Bjorn O.), Bakker, S.J.L. (Stephan), Ceresini, G. (Graziano), Dullaart, R.P.F. (Robin P.F.), Ferrucci, L. (Luigi), Grabe, H.J. (Hans Jörgen), Jukema, J.W. (Jan Wouter), Nauck, M. (Matthias), Trompet, S. (Stella), Völzke, H. (Henry), Westendorp, R.G.J. (Rudi), Gussekloo, J. (Jacobijn), Peeters, R.P. (Robin), Klöppel, S. (Stefan), Aujesky, D. (Drahomir), Bauer, D.C. (Douglas), Rodondi, N. (Nicolas), Del Giovane, C. (Cinzia), Feller, M. (Martin), Wildisen, L. (Lea), Moutzouri, E. (Elisavet), Beglinger, S. (Shanthi), Syrogiannouli, L. (Lamprini), Cappola, A.R. (Anne), Asvold, B.O. (Bjorn O.), Bakker, S.J.L. (Stephan), Ceresini, G. (Graziano), Dullaart, R.P.F. (Robin P.F.), Ferrucci, L. (Luigi), Grabe, H.J. (Hans Jörgen), Jukema, J.W. (Jan Wouter), Nauck, M. (Matthias), Trompet, S. (Stella), Völzke, H. (Henry), Westendorp, R.G.J. (Rudi), Gussekloo, J. (Jacobijn), Peeters, R.P. (Robin), Klöppel, S. (Stefan), Aujesky, D. (Drahomir), Bauer, D.C. (Douglas), Rodondi, N. (Nicolas), Del Giovane, C. (Cinzia), and Feller, M. (Martin)

Abstract

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of

Published
2019
Full Text
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20. Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

Author

Wildisen, L, Moutzouri, E, Beglinger, S, Syrogiannouli, L, Cappola, AR, Asvold, BO, Bakker, SJ, Ceresini, G, Dullaart, R, Ferrucci, L, Grabe, H, Jukema, JW, Nauck, M, Trompet, S, Volzke, H, Westendorp, RG, Gussekloo, J, Peeters, Robin, Kloppel, S, Aujesky, D, Bauer, DC, Rodondi, N, Del Giovane, C, Feller, M, Wildisen, L, Moutzouri, E, Beglinger, S, Syrogiannouli, L, Cappola, AR, Asvold, BO, Bakker, SJ, Ceresini, G, Dullaart, R, Ferrucci, L, Grabe, H, Jukema, JW, Nauck, M, Trompet, S, Volzke, H, Westendorp, RG, Gussekloo, J, Peeters, Robin, Kloppel, S, Aujesky, D, Bauer, DC, Rodondi, N, Del Giovane, C, and Feller, M

Published
2019

24. Parma consensus statement on metabolic disruptors (vol 14, 54, 2015)

Author

Heindel, JJ, vom Saal, FS, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, BA, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Rizzi, L, Machtinger, R, Mantovani, A, Mendez, MA, Montanini, L, Molteni, L, Nagel, SC, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, TT, Street, ME, Suvorov, A, Volpi, R, Zoeller, RT, and Palanza, P

Abstract

After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

Published
2017

26. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Author

Teumer, A. (Alexander), Chaker, L. (Layal), Groeneweg, S. (Stefan), Li, Y. (Yong), Di Munno, C. (Celia), Barbieri, C. (Caterina), Schultheiss, U.T. (Ulla T.), Traglia, M. (Michela), Ahluwalia, T.S. (Tarunveer Singh), Akiyama, M. (Masato), Appel, E.V.R. (Emil Vincent R.), Arking, D.E. (Dan), Arnold, A.M. (Alice), Astrup, A. (Arne), Beekman, M. (Marian), Beilby, J.P. (John), Bekaert, S. (Sofie), Boerwinkle, E. (Eric), Brown, S.J. (Stephen), Buyzere, M. (Marc) de, Campbell, P.J. (Purdey J.), Ceresini, G. (Graziano), Cerqueira, C. (Charlotte), Cucca, F. (Francesco), Deary, I.J. (Ian), Deelen, J. (Joris), Eckardt, K.-U. (Kai-Uwe), Ekici, A.B. (Arif B.), Hagen, K. (Knut), Ferrrucci, L. (Luigi), Fiers, T. (Tom), Fiorillo, E. (Edoardo), Ford, I. (Ian), Fox, C.S. (Caroline), Fuchsberger, C. (Christian), Galesloot, T.E. (Tessel), Gieger, C. (Christian), Gögele, M. (Martin), Grandi, A. (Alessandro) de, Grarup, N. (Niels), Greiser, K.H. (Karin Halina), Haljas, K. (Kadri), Hansen, T. (Torben), Harris, S.E. (Sarah), Heemst, D. (Diana) van, Heijer, M. (Martin) den, Hicks, A.A. (Andrew A.), Hollander, W. (Wouter) den, Homuth, G. (Georg), Hui, J. (Jennie), Ikram, M.A. (Arfan), Ittermann, T. (Till), Jensen, R.A. (Richard A.), Jing, J. (Jiaojiao), Jukema, J.W. (Jan Wouter), Kajantie, E. (Eero), Kamatani, Y. (Yoichiro), Kasbohm, E. (Elisa), Kaufman, J.-M. (Jean-Marc), Kiemeney, L.A. (Lambertus A.), Kloppenburg, M. (Margreet), Kronenberg, F. (Florian), Kubo, M. (Michiaki), Lahti, J. (Jari), Lapauw, B. (Bruno), Li, S. (Shuo), Liewald, D.C.M. (David C. M.), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (Marike), Franke, L. (Lude), van der Harst, P. (Pim), Navis, G. (Gerjan), Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M.A. (Morris A.), Wijmenga, C. (Cisca), Lim, E.M. (Ee Mun), Linneberg, A. (Allan), Marina, M. (Michela), Mascalzoni, D. (Deborah), Matsuda, K. (Koichi), Medenwald, D. (Daniel), Meisinger, C. (Christa), Meulenbelt, I. (Ingrid), Meyer, T. (Thorsten), Meyer zu Schwabedissen, H.E. (Henriette E.), Mikolajczyk, R. (Rafael), Moed, H. (Heleen), Netea-Maier, R.T. (Romana), Nolte, I.M. (Ilja), Okada, Y. (Yukinori), Pala, M. (Mauro), Penninx, B.W.J.H., Pedersen, O. (Oluf), Petersmann, A. (Astrid), Porcu, E. (Eleonora), Postmus, D. (Douwe), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Ramos, Y.F.M. (Yolande F. M.), Rawal, R. (Rajesh), Redmond, P. (Paul), Richards, J.B. (Brent), Rietzschel, E.R. (Ernst), Rivadeneira Ramirez, F. (Fernando), Roef, G.L. (Greet), Rotter, J.I. (Jerome I.), Sala, C. (Cinzia), Schlessinger, D. (David), Selvin, E. (Elizabeth), Slagboom, P.E. (Eline), Soranzo, N. (Nicole), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Starr, J.M. (John), Stott, D.J. (David. J.), Taes, Y.E. (Youri), Taliun, D. (Daniel), Tanaka, T. (Toshiko), Thuesen, L. (Leif), Tiller, D. (Daniel), Toniolo, D. (Daniela), Uitterlinden, A.G. (Andre G.), Visser, W.E. (Edward), Walsh, J.P. (John P.), Wilson, S.G. (Scott), Wolffenbuttel, B.H.R. (Bruce), Yang, Q. (Qiong Fang), Zheng, H.-F. (Hou-Feng), Cappola, A.R. (Anne), Peeters, R.P. (Robin), Naitza, S. (Silvia), Völzke, H. (Henry), Sanna, S. (Serena), Köttgen, A. (Anna), Visser, T.J. (Theo), Medici, M. (Marco), Teumer, A. (Alexander), Chaker, L. (Layal), Groeneweg, S. (Stefan), Li, Y. (Yong), Di Munno, C. (Celia), Barbieri, C. (Caterina), Schultheiss, U.T. (Ulla T.), Traglia, M. (Michela), Ahluwalia, T.S. (Tarunveer Singh), Akiyama, M. (Masato), Appel, E.V.R. (Emil Vincent R.), Arking, D.E. (Dan), Arnold, A.M. (Alice), Astrup, A. (Arne), Beekman, M. (Marian), Beilby, J.P. (John), Bekaert, S. (Sofie), Boerwinkle, E. (Eric), Brown, S.J. (Stephen), Buyzere, M. (Marc) de, Campbell, P.J. (Purdey J.), Ceresini, G. (Graziano), Cerqueira, C. (Charlotte), Cucca, F. (Francesco), Deary, I.J. (Ian), Deelen, J. (Joris), Eckardt, K.-U. (Kai-Uwe), Ekici, A.B. (Arif B.), Hagen, K. (Knut), Ferrrucci, L. (Luigi), Fiers, T. (Tom), Fiorillo, E. (Edoardo), Ford, I. (Ian), Fox, C.S. (Caroline), Fuchsberger, C. (Christian), Galesloot, T.E. (Tessel), Gieger, C. (Christian), Gögele, M. (Martin), Grandi, A. (Alessandro) de, Grarup, N. (Niels), Greiser, K.H. (Karin Halina), Haljas, K. (Kadri), Hansen, T. (Torben), Harris, S.E. (Sarah), Heemst, D. (Diana) van, Heijer, M. (Martin) den, Hicks, A.A. (Andrew A.), Hollander, W. (Wouter) den, Homuth, G. (Georg), Hui, J. (Jennie), Ikram, M.A. (Arfan), Ittermann, T. (Till), Jensen, R.A. (Richard A.), Jing, J. (Jiaojiao), Jukema, J.W. (Jan Wouter), Kajantie, E. (Eero), Kamatani, Y. (Yoichiro), Kasbohm, E. (Elisa), Kaufman, J.-M. (Jean-Marc), Kiemeney, L.A. (Lambertus A.), Kloppenburg, M. (Margreet), Kronenberg, F. (Florian), Kubo, M. (Michiaki), Lahti, J. (Jari), Lapauw, B. (Bruno), Li, S. (Shuo), Liewald, D.C.M. (David C. M.), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (Marike), Franke, L. (Lude), van der Harst, P. (Pim), Navis, G. (Gerjan), Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M.A. (Morris A.), Wijmenga, C. (Cisca), Lim, E.M. (Ee Mun), Linneberg, A. (Allan), Marina, M. (Michela), Mascalzoni, D. (Deborah), Matsuda, K. (Koichi), Medenwald, D. (Daniel), Meisinger, C. (Christa), Meulenbelt, I. (Ingrid), Meyer, T. (Thorsten), Meyer zu Schwabedissen, H.E. (Henriette E.), Mikolajczyk, R. (Rafael), Moed, H. (Heleen), Netea-Maier, R.T. (Romana), Nolte, I.M. (Ilja), Okada, Y. (Yukinori), Pala, M. (Mauro), Penninx, B.W.J.H., Pedersen, O. (Oluf), Petersmann, A. (Astrid), Porcu, E. (Eleonora), Postmus, D. (Douwe), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Ramos, Y.F.M. (Yolande F. M.), Rawal, R. (Rajesh), Redmond, P. (Paul), Richards, J.B. (Brent), Rietzschel, E.R. (Ernst), Rivadeneira Ramirez, F. (Fernando), Roef, G.L. (Greet), Rotter, J.I. (Jerome I.), Sala, C. (Cinzia), Schlessinger, D. (David), Selvin, E. (Elizabeth), Slagboom, P.E. (Eline), Soranzo, N. (Nicole), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Starr, J.M. (John), Stott, D.J. (David. J.), Taes, Y.E. (Youri), Taliun, D. (Daniel), Tanaka, T. (Toshiko), Thuesen, L. (Leif), Tiller, D. (Daniel), Toniolo, D. (Daniela), Uitterlinden, A.G. (Andre G.), Visser, W.E. (Edward), Walsh, J.P. (John P.), Wilson, S.G. (Scott), Wolffenbuttel, B.H.R. (Bruce), Yang, Q. (Qiong Fang), Zheng, H.-F. (Hou-Feng), Cappola, A.R. (Anne), Peeters, R.P. (Robin), Naitza, S. (Silvia), Völzke, H. (Henry), Sanna, S. (Serena), Köttgen, A. (Anna), Visser, T.J. (Theo), and Medici, M. (Marco)

Abstract

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.

Published
2018
Full Text
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27. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Author

Teumer, A, Chaker, Layal, Groeneweg, Stefan, Li, Yi, Di Munno, Celia, Barbieri, C, Schultheiss, UT, Traglia, M, Ahluwalia, TS, Akiyama, M, Appel, EVR, Arking, DE, Arnold, A, Astrup, A, Beekman, M, Beilby, JP, Bekaert, S, Boerwinkle, E, Brown, SJ, de Buyzere, M, Campbell, PJ, Ceresini, G, Cerqueira, C, Cucca, F, Deary, IJ, Deelen, J, Eckardt, KU, Ekici, AB, Eriksson, JG, Ferrrucci, L, Fiers, T, Fiorillo, E, Ford, I, Fox, CS, Fuchsberger, C, Galesloot, TE, Gieger, C, Gogele, M, De Grandi, A, Grarup, N, Greiser, KH, Haljas, K, Hansen, T, Harris, SE, van Heemst, D, Heijer, M, Hicks, AA, den Hollander, W, Homuth, G, Hui, JN, Ikram, Arfan, Ittermann, T, Jensen, RA, Jing, J, Jukema, JW, Kajalltie, E, Kamatani, Y, Kasbohm, E, Kaufman, JM, Kiemeney, LA, Kloppenburg, M, Kronenberg, F, Kubo, M, Lahti, J, Lapauw, B, Li, S, Liewald, DCM, Lim, EM, Linneberg, A, Marina, M, Mascalzoni, D, Matsuda, K, Medenwald, D, Meisinger, C, Meulenbelt, I, Meyer, T, zu Schwabedissen, HEM, Mikolajczyk, R, Moed, M, Netea-Maier, RT, Nolte, IM, Okadah, Y, Pala, M, Pattaro, C, Pedersen, O, Petersmann, A, Porcu, E, Postmus, I, Pramstaller, PP, Psaty, BM, Ramos, YFM, Rawal, R, Redmond, P, Richards, JB, Rietzschel, ER, Rivadeneira, Fernando, Roef, G, Rotter, JI, Sala, CF, Schlessinger, D, Selvin, E, Slagboom, PE (Eline), Soranzo, N, Sorensen, TIA, Spector, TD, Starr, JM, Stott, DJ, Taes, Y, Taliun, D, Tanaka, T, Thuesen, B, Tiller, D, Toniolo, D, Uitterlinden, André, Visser, Edward, Walsh, JP, Wilson, SG, Wolffenbuttel, BHR, Yang, Q, Zheng, HF, Cappola, A, Peeters, Robin, Naitza, S, Volzke, H, Sanna, S, Kottgen, A, Visser, Theo, Medici, Marco, Teumer, A, Chaker, Layal, Groeneweg, Stefan, Li, Yi, Di Munno, Celia, Barbieri, C, Schultheiss, UT, Traglia, M, Ahluwalia, TS, Akiyama, M, Appel, EVR, Arking, DE, Arnold, A, Astrup, A, Beekman, M, Beilby, JP, Bekaert, S, Boerwinkle, E, Brown, SJ, de Buyzere, M, Campbell, PJ, Ceresini, G, Cerqueira, C, Cucca, F, Deary, IJ, Deelen, J, Eckardt, KU, Ekici, AB, Eriksson, JG, Ferrrucci, L, Fiers, T, Fiorillo, E, Ford, I, Fox, CS, Fuchsberger, C, Galesloot, TE, Gieger, C, Gogele, M, De Grandi, A, Grarup, N, Greiser, KH, Haljas, K, Hansen, T, Harris, SE, van Heemst, D, Heijer, M, Hicks, AA, den Hollander, W, Homuth, G, Hui, JN, Ikram, Arfan, Ittermann, T, Jensen, RA, Jing, J, Jukema, JW, Kajalltie, E, Kamatani, Y, Kasbohm, E, Kaufman, JM, Kiemeney, LA, Kloppenburg, M, Kronenberg, F, Kubo, M, Lahti, J, Lapauw, B, Li, S, Liewald, DCM, Lim, EM, Linneberg, A, Marina, M, Mascalzoni, D, Matsuda, K, Medenwald, D, Meisinger, C, Meulenbelt, I, Meyer, T, zu Schwabedissen, HEM, Mikolajczyk, R, Moed, M, Netea-Maier, RT, Nolte, IM, Okadah, Y, Pala, M, Pattaro, C, Pedersen, O, Petersmann, A, Porcu, E, Postmus, I, Pramstaller, PP, Psaty, BM, Ramos, YFM, Rawal, R, Redmond, P, Richards, JB, Rietzschel, ER, Rivadeneira, Fernando, Roef, G, Rotter, JI, Sala, CF, Schlessinger, D, Selvin, E, Slagboom, PE (Eline), Soranzo, N, Sorensen, TIA, Spector, TD, Starr, JM, Stott, DJ, Taes, Y, Taliun, D, Tanaka, T, Thuesen, B, Tiller, D, Toniolo, D, Uitterlinden, André, Visser, Edward, Walsh, JP, Wilson, SG, Wolffenbuttel, BHR, Yang, Q, Zheng, HF, Cappola, A, Peeters, Robin, Naitza, S, Volzke, H, Sanna, S, Kottgen, A, Visser, Theo, and Medici, Marco

Published
2018

28. Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

Author

Wildisen, L., Moutzouri, E., Beglinger, S., Syrogiannouli, L., Cappola, A.R., Asvold, B.O., Bakker, S.J.L., Ceresini, G., Dullaart, R., Ferrucci, L., Grabe, H., Jukema, J.W., Nauck, M., Trompet, S., Volzke, H., Westendorp, R.G.J., Gussekloo, J., Peeters, R.P., Kloppel, S., Aujesky, D., Bauer, D.C., Rodondi, N., Giovane, C. del, Feller, M., Thyroid Studies Collaboration, Erasmus MC other, and Internal Medicine

Subjects
Epidemiology, Thyrotropin, Thyroid Function Tests, 030204 cardiovascular system & hematology, Logistic regression, Cohort Studies, depressive symptoms, 0302 clinical medicine, systematic review, Protocol, Medicine, 030212 general & internal medicine, 610 Medicine & health, Prospective cohort study, Depression (differential diagnoses), Subclinical infection, RISK, Depression, General Medicine, individual participant data (IPD) meta-analysis, subclinical hypothyroidism, Mental Health, Research Design, Meta-analysis, Cohort, Public Health and Health Services, subclinical hyperthyroidism, 360 Social problems & social services, Clinical psychology, Thyroid Hormones, Clinical Sciences, CINAHL, 03 medical and health sciences, Meta-Analysis as Topic, Behavioral and Social Science, Humans, Psychiatric Status Rating Scales, Other Medical and Health Sciences, subclinical thyroid dysfunction, business.industry, Prevention, Thyroid Studies Collaboration, Beck Depression Inventory, Thyroid Diseases, HYPOTHYROIDISM, business, Systematic Reviews as Topic
Abstract

IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysis: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/

Published
2019

31. Thyroid function tests in the reference range and fracture: Individual participant analysis of prospective cohorts

Author

Aubert, C.E. (Carole E.), Floriani, C. (Carmen), Bauer, D.C. (Douglas), B.R. da Costa (Bruno), Segna, D. (Daniel), Blum, M.R. (Manuel), Collet, T.-H. (Tinh-Hai), Fink, H.A. (Howard A.), Cappola, A.R. (Anne), Syrogiannouli, L. (Lamprini), Peeters, R.P. (Robin), Asvold, B.O. (Bjorn O.), Elzen, W.P.J. (Wendy) den, Luben, R.N. (Robert), Bremner, A. (Alexandra), Gogakos, A. (Apostolos), Eastell, R. (Richard), Kearney, P.M. (Patricia M.), Hoff, M. (Mari), Le Blanc, E. (Erin), Ceresini, G. (Graziano), Rivadeneira, F. (Fernando), Uitterlinden, A.G. (André), Khaw, K.T., Langhammer, A. (Arnulf), Stott, D.J. (David. J.), Westendorp, R.G.J. (Rudi), Ferrucci, L. (Luigi), Williams, G. (Graham), Gussekloo, J. (Jacobijn), Walsh, J.P. (John), Aujesky, D. (Drahomir), Rodondi, N. (Nicolas), Aubert, C.E. (Carole E.), Floriani, C. (Carmen), Bauer, D.C. (Douglas), B.R. da Costa (Bruno), Segna, D. (Daniel), Blum, M.R. (Manuel), Collet, T.-H. (Tinh-Hai), Fink, H.A. (Howard A.), Cappola, A.R. (Anne), Syrogiannouli, L. (Lamprini), Peeters, R.P. (Robin), Asvold, B.O. (Bjorn O.), Elzen, W.P.J. (Wendy) den, Luben, R.N. (Robert), Bremner, A. (Alexandra), Gogakos, A. (Apostolos), Eastell, R. (Richard), Kearney, P.M. (Patricia M.), Hoff, M. (Mari), Le Blanc, E. (Erin), Ceresini, G. (Graziano), Rivadeneira, F. (Fernando), Uitterlinden, A.G. (André), Khaw, K.T., Langhammer, A. (Arnulf), Stott, D.J. (David. J.), Westendorp, R.G.J. (Rudi), Ferrucci, L. (Luigi), Williams, G. (Graham), Gussekloo, J. (Jacobijn), Walsh, J.P. (John), Aujesky, D. (Drahomir), and Rodondi, N. (Nicolas)

Abstract

Context: Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective: To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design: Individual participant data analysis. Setting: Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants: Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures: Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results: During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions: Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.

Published
2017
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33. ASSOCIAZIONE TRA LIVELLI DI MAGNESIO ED ORMONI ANABOLICI NEL SOGGETTO ANZIANO DI SESSO MASCHILE

Author

Avantaggiato, E, Maggio, M, Lauretani, F, Cattabiani, C, Parrino, S, Catelli, P, Ceresini, G, Morganti, S, Ferrara, E, Centonza, AM, Ablondi, F, Bandinelli, S, Paolisso, G, Semba, RD, Ferrucci, L, Ceda, GP, DOMINGUEZ RODRIGUEZ, Ligia Juliana, BARBAGALLO, Mario, Avantaggiato, E, Maggio, M, Lauretani, F, Cattabiani, C, Parrino, S, Catelli, P, Ceresini, G, Morganti, S, Ferrara, E, Centonza, AM, Ablondi, F, Bandinelli, S, Dominguez Rodriguez, LJ, Barbagallo, M, Paolisso, G, Semba, RD, Ferrucci, L, and Ceda, GP

Subjects
Settore MED/09 - Medicina Interna, MAGNESIO, ORMONI ANABOLICI, INVECCHIAMENTO
Published
2010

34. SUBCLINICAL THYROID DYSFUNCTION AND FRACTURE RISK: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS OF PROSPECTIVE COHORTS

Author

Blum, M.R., Bauer, D., Costa, B.R. da, Wirth, C.D., Cappola, A.R., Peeters, R.P., Asvold, B.O., Fink, H.A., Elzen, W.P. den, Luben, R.N., Imaizumi, M., Langhammer, A., Bremner, A.P., Gogakos, A., Eastell, R., Strotmeyer, E.S., Wallace, E., Hoff, M., Khaw, K.T., Ceresini, G., Rivadeneira, F., Ferrucci, L., Uitterlinden, A., Williams, G.R., Westendorp, R.G., Walsh, J.P., Gussekloo, J., Aujesky, D., and Rodondi, N.

Published
2014

35. Subclinical thyroid dysfunction and fracture risk a meta-analysis

Author

Blum, M.R. (Manuel), Bauer, D.C. (Douglas C.), Collet, T.-H. (Tinh-Hai), Fink, H.A. (Howard A.), Cappola, A.R. (Anne), B.R. da Costa (Bruno), Wirth, C.D. (Christina), Peeters, R.P. (Robin), Asvold, B.O. (Bjorn O.), Elzen, W.P.J. (Wendy) den, Luben, R.N. (Robert), Imaizumi, M. (Misa), Bremner, A.P. (Alexandra P.), Gogakos, A. (Apostolos), Eastell, R. (Richard), Kearney, P.M. (Patricia M.), Strotmeyer, E.S. (Elsa S.), Wallace, E.R. (Erin R.), Hoff, M. (Mari), Ceresini, G. (Graziano), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Stott, D.J. (David. J.), Westendorp, R.G.J. (Rudi), Khaw, K.T., Langhammer, A. (Arnuf), Ferrucci, L. (Luigi), Gussekloo, J. (Jacobijn), Williams, G. (Graham), Walsh, J.P. (John), Jüni, P. (Peter), Aujesky, D. (Drahomir), Rodondi, N. (Nicolas), Blum, M.R. (Manuel), Bauer, D.C. (Douglas C.), Collet, T.-H. (Tinh-Hai), Fink, H.A. (Howard A.), Cappola, A.R. (Anne), B.R. da Costa (Bruno), Wirth, C.D. (Christina), Peeters, R.P. (Robin), Asvold, B.O. (Bjorn O.), Elzen, W.P.J. (Wendy) den, Luben, R.N. (Robert), Imaizumi, M. (Misa), Bremner, A.P. (Alexandra P.), Gogakos, A. (Apostolos), Eastell, R. (Richard), Kearney, P.M. (Patricia M.), Strotmeyer, E.S. (Elsa S.), Wallace, E.R. (Erin R.), Hoff, M. (Mari), Ceresini, G. (Graziano), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Stott, D.J. (David. J.), Westendorp, R.G.J. (Rudi), Khaw, K.T., Langhammer, A. (Arnuf), Ferrucci, L. (Luigi), Gussekloo, J. (Jacobijn), Williams, G. (Graham), Walsh, J.P. (John), Jüni, P. (Peter), Aujesky, D. (Drahomir), and Rodondi, N. (Nicolas)

Abstract

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant datawere obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid functionwere defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcomewas hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70 298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age-and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidismwas 1.36 for hip fracture (95%CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HRwas 1.28 (95%CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HRwas 1.16 (95%CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HRwas 1.51 (95%CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSHwas associated with higher fracture rates: for TSH of less than0.10 mIU/L, HRwas

Published
2015
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36. Thyroid function within the normal range and risk of coronary heart disease an individual participant data analysis of 14 cohorts

Author

Asvold, B.O. (Bjorn O.), Vatten, L. (Lars), Bjøro, T. (Trine), Bauer, D.C. (Douglas), Bremner, A.P. (Alexandra P.), Cappola, A.R. (Anne), Ceresini, G. (Graziano), Elzen, W.P.J. (Wendy) den, Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franklyn, J.A. (Jayne), Gussekloo, J. (Jacobijn), Iervasi, G. (Giorgio), Imaizumi, M. (Misa), Kearney, P.M. (Patricia M.), Khaw, K.T., Maciel, R.M.B. (Rui M. B.), Newman, A.B. (Anne B.), Peeters, R.P. (Robin), Psaty, B.M. (Bruce), Razvi, S. (Salman), Sgarbi, J.A. (José A.), Stott, D.J. (David. J.), Trompet, S. (Stella), Vanderpump, M.P.J. (Mark P. J.), Völzke, H. (Henry), Walsh, J.P. (John), Westendorp, R.G.J. (Rudi), Rodondi, N. (Nicolas), Asvold, B.O. (Bjorn O.), Vatten, L. (Lars), Bjøro, T. (Trine), Bauer, D.C. (Douglas), Bremner, A.P. (Alexandra P.), Cappola, A.R. (Anne), Ceresini, G. (Graziano), Elzen, W.P.J. (Wendy) den, Ferrucci, L. (Luigi), Franco, O.H. (Oscar), Franklyn, J.A. (Jayne), Gussekloo, J. (Jacobijn), Iervasi, G. (Giorgio), Imaizumi, M. (Misa), Kearney, P.M. (Patricia M.), Khaw, K.T., Maciel, R.M.B. (Rui M. B.), Newman, A.B. (Anne B.), Peeters, R.P. (Robin), Psaty, B.M. (Bruce), Razvi, S. (Salman), Sgarbi, J.A. (José A.), Stott, D.J. (David. J.), Trompet, S. (Stella), Vanderpump, M.P.J. (Mark P. J.), Völzke, H. (Henry), Walsh, J.P. (John), Westendorp, R.G.J. (Rudi), and Rodondi, N. (Nicolas)

Abstract

IMPORTANCE Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN, SETTING, AND P

Published
2015
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37. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis

Author

Chaker, L. (Layal), Baumgartner, C. (Christine), Elzen, W.P.J. (Wendy) den, Ikram, M.A. (Arfan), Blum, M.R. (Manuel), Collet, T.-H. (Tinh-Hai), Bakker, S.J.L. (Stephan), Dehghan, A. (Abbas), Drechsler, C. (Christiane), Luben, R.N. (Robert), Hofman, A. (Albert), Portegies, M.L.P. (Marileen), Medici, M. (Marco), Iervasi, G. (Giorgio), Stott, D.J. (David. J.), Ford, I. (Ian), Bremner, A.P. (Alexandra P.), Wanner, C. (Christoph), Ferrucci, L. (Luigi), Newman, A.B. (Anne B.), Dullaart, R.P.F. (Robin), Sgarbi, J.A. (José A.), Ceresini, G. (Graziano), Maciel, R.M.B. (Rui M. B.), Westendorp, R.G.J. (Rudi), Jukema, J.W. (Jan Wouter), Imaizumi, M. (Misa), Franklyn, J.A. (Jayne), Bauer, D.C. (Douglas C.), Walsh, J.P. (John), Razvi, S. (Salman), Khaw, K.T., Cappola, A.R. (Anne), Völzke, H. (Henry), Franco, O.H. (Oscar), Gussekloo, J. (Jacobijn), Rodondi, N. (Nicolas), Peeters, R.P. (Robin), Chaker, L. (Layal), Baumgartner, C. (Christine), Elzen, W.P.J. (Wendy) den, Ikram, M.A. (Arfan), Blum, M.R. (Manuel), Collet, T.-H. (Tinh-Hai), Bakker, S.J.L. (Stephan), Dehghan, A. (Abbas), Drechsler, C. (Christiane), Luben, R.N. (Robert), Hofman, A. (Albert), Portegies, M.L.P. (Marileen), Medici, M. (Marco), Iervasi, G. (Giorgio), Stott, D.J. (David. J.), Ford, I. (Ian), Bremner, A.P. (Alexandra P.), Wanner, C. (Christoph), Ferrucci, L. (Luigi), Newman, A.B. (Anne B.), Dullaart, R.P.F. (Robin), Sgarbi, J.A. (José A.), Ceresini, G. (Graziano), Maciel, R.M.B. (Rui M. B.), Westendorp, R.G.J. (Rudi), Jukema, J.W. (Jan Wouter), Imaizumi, M. (Misa), Franklyn, J.A. (Jayne), Bauer, D.C. (Douglas C.), Walsh, J.P. (John), Razvi, S. (Salman), Khaw, K.T., Cappola, A.R. (Anne), Völzke, H. (Henry), Franco, O.H. (Oscar), Gussekloo, J. (Jacobijn), Rodondi, N. (Nicolas), and Peeters, R.P. (Robin)

Abstract

Copyright

Published
2015
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38. Parma consensus statement on metabolic disruptors

Author

Heindel, J, vom Saal, F, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, B, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Machtinger, R, Mantovani, A, Mendez, M, Montanini, L, Molteni, L, Nagel, S, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, T, Street, M, Suvorov, A, Volpi, R, Zoeller, R, Palanza, P, Rizzi, L, MOLTENI, LAURA, RIZZI, LAURA, Heindel, J, vom Saal, F, Blumberg, B, Bovolin, P, Calamandrei, G, Ceresini, G, Cohn, B, Fabbri, E, Gioiosa, L, Kassotis, C, Legler, J, La Merrill, M, Machtinger, R, Mantovani, A, Mendez, M, Montanini, L, Molteni, L, Nagel, S, Parmigiani, S, Panzica, G, Paterlini, S, Pomatto, V, Ruzzin, J, Sartor, G, Schug, T, Street, M, Suvorov, A, Volpi, R, Zoeller, R, Palanza, P, Rizzi, L, MOLTENI, LAURA, and RIZZI, LAURA

Abstract

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Published
2015

40. Thyroid disease in the elderly: sex-related differences in clinical expression

Author

Morganti S, Gian Paolo Ceda, Saccani M, Milli B, Ugolotti D, Prampolini R, Maggio M, Valenti G, and Ceresini G

Subjects
Aged, 80 and over, Male, Aging, Sex Characteristics, Cross-Sectional Studies, Risk Factors, Humans, Female, Middle Aged, Thyroid Diseases, Aged
Abstract

Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.

Published
2006

41. Consensus Document on substitution therapy with DHEA in the elderly

Author

VALENTI G, DENTI L, SACCÒ M, CERESINI G, BOSSONI S, A. GIUSTINA, MAUGERI D, VIGNA GB, PAOLISSO G, BARBAGALLO M, MAGGIO M, STROLLO F, BOLLANTI L, ROMANELLI F, LATINI M, G, Valenti, L, Denti, M, Saccò, G, Ceresini, S, Bossoni, Giustina, A., D, Maugeri, Gb, Vigna, G, Paolisso, M, Barbagallo, M, Maggio, F, Strollo, L, Bollanti, F, Romanelli, and M, Latini

Published
2006

44. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine

Author

Panicker, V. (Vijay), Cluett, C. (Christie), Shields, B.M. (Beverley), Murray, J.C. (Jeffrey), Parnell, K.S. (Kirstie), Perry, J.R.B. (John), Weedon, M.N. (Michael), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Evans, J. (Jonathan Mark), Durant, C. (Claire), Ferrucci, L. (Luigi), Melzer, D. (David), Saravanan, P. (Ponnusamy), Visser, T.J. (Theo), Ceresini, G. (Graziano), Hattersley, A.T. (Andrew), Vaidya, B. (Bijay), Dayan, C.M. (Colin), Frayling, T.M. (Timothy), Panicker, V. (Vijay), Cluett, C. (Christie), Shields, B.M. (Beverley), Murray, J.C. (Jeffrey), Parnell, K.S. (Kirstie), Perry, J.R.B. (John), Weedon, M.N. (Michael), Singleton, A. (Andrew), Hernandez, D.G. (Dena), Evans, J. (Jonathan Mark), Durant, C. (Claire), Ferrucci, L. (Luigi), Melzer, D. (David), Saravanan, P. (Ponnusamy), Visser, T.J. (Theo), Ceresini, G. (Graziano), Hattersley, A.T. (Andrew), Vaidya, B. (Bijay), Dayan, C.M. (Colin), and Frayling, T.M. (Timothy)

Abstract

Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. Methods: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T4replacement. Suggestive findingsweretakenforwardinto three additional studies in people not on T4(total n = 2513) and metaanalyzed for confirmation. Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T3to free T4ratio with genome-wide levels of significance (P = 3.6 × 10-13). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T3/T4ratio and free T3and decrease in free T4and rT3. There was no effect on serum TSH levels. None of the SNPs in the g

Published
2008
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45. Sex hormone binding globulin and endothelial function in older subjects: The PIVUS study

Author

Sutti, E., primary, Maggio, M., additional, Cattabiani, C., additional, Lauretani, F., additional, Mantovani, M., additional, Buttò, V., additional, De Vita, F., additional, Artoni, A., additional, Giallauria, F., additional, Zuliani, G., additional, Aloe, R., additional, Lippi, G., additional, Ceresini, G., additional, Cederholm, T., additional, Lind, L., additional, and Ceda, G.P., additional

Published
2013
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46. OP029 VITAMIN D AND INFLAMMATORY MARKERS IN OLDER SUBJECTS

Author

De Vita, F., primary, Lauretani, F., additional, Cattabiani, C., additional, Cherubini, A., additional, Bandinelli, S., additional, Ceresini, G., additional, Verzicco, I., additional, Franchi, F., additional, Ceda, G.P., additional, Ferrucci, L., additional, and Maggio, M., additional

Published
2013
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49. The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons

Author

Maggio, M., primary, Cattabiani, C., additional, Lauretani, F., additional, Artoni, A., additional, Bandinelli, S., additional, Schiavi, G., additional, Vignali, A., additional, Volpi, R., additional, Ceresini, G., additional, Lippi, G., additional, Aloe, R., additional, De Vita, F., additional, Giallauria, F., additional, McDermott, M.M., additional, Ferrucci, L., additional, and Ceda, G.P., additional

Published
2012
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