BACKGROUND: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

3rd Department of Medicine 1st Faculty of Medicine Charles University General University Hospital Prague Czech Republic

5 P Komisarenko Institute of Endocrinology and Metabolism of Academy of Medical Sciences of Ukraine Kyiv Ukraine

5th Medical Department Division of Endocrinology and Diabetes Medical Faculty Mannheim Heidelberg University Mannheim Germany

Belarusian State Medical University Department of Endocrinology Minsk Republic of Belarus

Cabinet Médical 2 rue Bellefontaine Lausanne Switzerland

Clinic of Endocrinology and Metabolism University Hospital Alexandrovska ; Department of Internal Medicine Medical University Sofia Sofia Bulgaria

Clinic of Endocrinology and Metabolism University Hospital Sofiamed Medical Faculty Sofia University Saint Kliment Ohridski Sofia Bulgaria

Department of Endocrinology and Diabetes Centre Hellenic Red Cross Hospital Athens Greece

Department of Endocrinology and Metabolism Regina Apostolorum Hospital Albano Laziale Rome Italy

Department of Endocrinology Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Endocrinology Clínica Universidad de Navarra Pamplona Spain

Department of Endocrinology Diabetes and Metabolic Diseases Mladen Sekso University Hospital Center Sisters of Mercy Zagreb Croatia

Department of Endocrinology Diabetes and Metabolism University Hospital Essen University of Duisburg Essen Essen Germany

Department of Endocrinology Diabetes and Metabolism; Medical Faculty University of Coimbra Coimbra Portugal

Department of Endocrinology Diabetology and Nutrition Cliniques Universitaires St Luc Université Catholique de Louvain Brussels Belgium

Department of Endocrinology Hospital Universitario Puerta de Hierro Majadahonda Majadahonda Madrid Spain

Department of Endocrinology Metabolism and Internal Medicine Poznan University of Medical Sciences Poznań Poland

Department of Endocrinology No 1 N 5 Sklifosovsky Institute of Clinical Medicine 1 M Sechenov 1st Moscow State Medical University Moscow Russian Federation

Department of Endocrinology Odense University Hospital Odense Denmark

Department of Endocrinology Skåne University Hospital Malmö Sweden

Department of Endocrinology Tampere University Hospital Tampere Finland

Department of Internal Medicine and Endocrinology Medical University of Warsaw Warsaw Poland

Department of Internal Medicine Division of Endocrinology Faculty of Medicine Gaziantep University Gaziantep Turkey

Department of Internal Medicine Endocrine Unit UZ Brussel Vrije Universiteit Brussel Brussels Belgium

Department of Medicine 1 Klinikum Vest GmbH Knappschaftskrankenhaus Recklinghausen Academic Teaching Hospital Ruhr University Bochum Recklinghausen Germany

Department of Medicine Universidad Autónoma de Madrid Madrid Spain

Department of Reproductive Endocrinology Institute of Endocrinology and Metabolism named after 5 P Komissarenko National Academy of Medical Science of Ukraine Kyiv Ukraine

Department of Surgery Tampere University Hospital Tampere Finland

Diabetes and Endocrinology Section Beacon Hospital Dublin Ireland

Division of Endocrinology Department of Medicine Faculty of Medicine University of Debrecen Debrecen Hungary

Division of Endocrinology Diabetes and Metabolism University of Lausanne Lausanne Switzerland

Division of Endocrinology Ospedale Fazzi Lecce Italy

East Surrey Hospital Surrey and Sussex Healthcare NHS Trust Redhill Surrey United Kingdom

Endocrine Unit and Diabetes Centre Department of Clinical Therapeutics Alexandra Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

Endocrinology Diabetes and Metabolism Service Centro Hospitalar Universitário de Santo António Porto Portugal

Faculty of Medicine University of Belgrade Belgrade Serbia

Institute of Translational and Clinical Research Newcastle University Newcastle upon Tyne United Kingdom

Instituto de Investigación Sanitaria de Navarra Pamplona Spain

Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana Majadahonda Madrid Spain

Internal Medicine 3 Division of Endocrinology and Metabolism Medical University of Vienna Vienna Austria

Koru Ankara Hospital Department of Endocrinology and Metabolism Çankaya Ankara Turkey

P J Šafárik University Košice 1st Department of Internal Medicine of the Medical Faculty Košice Slovakia

Rabin Medical Center Tel Aviv University Tel Aviv Israel

Robert Graves Institute Tallaght University Hospital Dublin Ireland

Rotterdam Thyroid Center Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands

School of Medicine University College Dublin Ireland

Scientific Committee Associazione Medici Endocrinologi Milan Italy

Section of Clinical Medicine Faculty of Health and Medical Sciences University of Surrey Guildford Surrey United Kingdom

Sorbonne Universitè GRC n 16 GRC Thyroid Tumors Thyroid Disease and Endocrine Tumor Department APHP Hôpital Pitié Salpêtriére Paris France

Thyroid and Osteoporosis Praxis Kumberg Austria

Thyroid Cancer Service Endocrinology and Metabolism Institute Beilinson Hospital and Davidoff Cancer Center Rabin Medical Center Sackler Faculty of Medicine Tel Aviv University Petah Tikva Israel

Thyroid Practice for Radiofrequency Ablation Vienna Austria

Zobrazit více v PubMed

W.G.M. Tunbridge, D.C. Evered, R. Hall et al. The spectrum of thyroid disease in a community: The Whickham survey. Clin. Endocrinol. 7, 481–493 (1977). https://doi.org/10.1111/j.1365-2265.1977.tb01340.x DOI

L. Hegedüs, S.J. Bonnema, F.N. Bennedbaek, Management of simple nodular goiter: current status and future perspectives. Endocr. Rev. 24, 102–132 (2003). https://doi.org/10.1210/er.2002-0016 PubMed DOI

O.P. Kimball, The prevention of simple goiter. Am. J. Publ. Health 13, 81–87 (1923). DOI

P. Xiang, S. Ahmadi, A. Coleman et al. Identifying and predicting diverse patterns of benign nodule growth. J. Clin. Endocrinol. Metab. 108(7), e458–e463 (2023). https://doi.org/10.1210/clinem/dgad007 PubMed DOI

C. Durante, L. Hegedüs, A. Czarniecka et al. 2023 European Thyroid Association clinical practice guidelines for thyroid nodule management. Eur. Thyroid J. 12, e230067 (2023). https://doi.org/10.1530/ETJ-23-0067 PubMed DOI PMC

E. Papini, V. Bacci, C. Panunzi et al. A prospective randomized trial of levothyroxine suppressive therapy for solitary thyroid nodules. Clin. Endocrinol. 38, 507–513 (1993). https://doi.org/10.1111/j.1365-2265.1993.tb00347.x DOI

M.R. Castro, P.J. Caraballo, J.C. Morris, Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis. J. Clin. Endocrinol. Metab. 87, 4154–4159 (2002). https://doi.org/10.1210/jc.2001-011762 PubMed DOI

F. Brandt, D. Almid, K. Christensen, A. Green, T.H. Brix, L. Hegedüs, Excess mortality in hyperthyroidism: the influence of pre-existing comorbidity and genetic confounding: a Danish nationwide register-based cohort study of twins and singletons. J. Clin. Endocrinol. Metab. 97, 4123–4129 (2012). https://doi.org/10.1210/jc.2012-2268 PubMed DOI PMC

M. Lillevang-Johansen, B. Abrahamsen, H.L. Jørgensen, T.H. Brix, L. Hegedüs, Over- and under-treatment of hypothyroidism is associated with excess mortality: a register-based cohort study. Thyroid 28, 566–574 (2018). https://doi.org/10.1089/thy.2017.0517 PubMed DOI

R. Thayakaran, N.J. Adderley, C. Sainsbury et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ 366, l4892 (2019). https://doi.org/10.1136/bmj.l4892 PubMed DOI PMC

J.M. Evron, S.L. Hummel, D. Reyes-Gastelum, M.R. Haymart, M. Banerjee, M. Papaleontiou, Association of thyroid hormone treatment intensity with cardiovascular mortality among US veterans. JAMA Netw. Open 5, e2211863 (2022). https://doi.org/10.1001/jamanetworkopen.2022.11863 PubMed DOI PMC

J. Jonklaas, A.C. Bianco, A.J. Bauer et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid 24, 1670–1751 (2014). https://doi.org/10.1089/thy.2014.0028 PubMed DOI PMC

R. Guglielmi, A. Frasoldati, M. Zini et al. Replacement therapy for primary hypothyroidism. Italian Association of Clinical Endocrinologists statement: a brief guide for clinical practice. Endocr. Pract. 11, 1319–1326 (2016). https://doi.org/10.4158/EP161308.OR DOI

NICE. Thyroid disease: assessment and management. 1.9 Diagnosing, managing and monitoring thyroid enlargement with normal thyroid function. In NICE guideline (National Institute for Care and Clinical Excellence, London, UK, 2019), p. 145

M. Žarković, R. Attanasio, E.V. Nagy et al. Characteristics of specialists treating hypothyroid patients: The “THESIS” Collaboration*. Front. Endocrinol. 14, 1225202 (2023). https://doi.org/10.3389/fendo.2023.1225202 DOI

R. Attanasio, M. Zarkovic, E. Papini, et al., Influence of patients’ persistent symptoms, clinician demographics and geoeconomic factors on choice of therapy for hypothyroidism by European thyroid specialists: the “THESIS”* collaboration. Thyroid 34, 429–441 (2024). https://doi.org/10.1089/thy.2023.0580 PubMed DOI

R. Negro, M. Žarković, R. Attanasio, et al. Use of levothyroxine for euthyroid, antibody positive women with infertility: analyses of aggregate data from a survey of European thyroid specialists (THESIS*) (Treatment of Hypothyroidism in Europe by Specialists: an International Survey). Clin. Endocrinol. (2024), https://doi.org/10.1111/cen.15099

J.C. Galofré, J.J. Díez, R. Attanasio, et al.: Treatment of obesity with thyroid hormones in Europe. Data from the THESIS* collaboration. J. Endocrinol. Invest. (2024). https://link.springer.com/article/10.1007/s40618-024-02409-z

J.F. Cassemiro, V. Ilera, S. Batalles et al. Use of thyroid hormones in hypothyroid and euthyroid patients: a 2022 THESIS questionnaire survey of members of the Latin American Thyroid Society (LATS). Thyroid Res. 16, 40 (2023). https://doi.org/10.1186/s13044-023-00182-4 PubMed DOI PMC

N. Lafontaine, S.J. Brown, P. Perros et al. Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS questionnaire survey of members of the Endocrine Society of Australia. Clin. Endocrinol. 100, 477–485 (2024). https://doi.org/10.1111/cen.15049 DOI

R. Negro, R. Attanasio, E.V. Nagy, E. Papini, P. Perros, L. Hegedüs, Use of thyroid hormones in hypothyroid and euthyroid patients; the 2019 Italian survey. Eur. Thyroid J. 9, 25–31 (2020). https://doi.org/10.1159/000502057 PubMed DOI

D. Dunkler, M. Haller, R. Oberbauer, G. Heinze, To test or to estimate? P‐values versus effect sizes. Transpl. Int. 33, 50–55 (2020). https://doi.org/10.1111/tri.13535 PubMed DOI

G.M. Sullivan, R. Feinn, Using effect size—or why the P value is not enough. J. Grad. Med. Educ. 4, 279–282 (2012). 0.4300/JGME-D-12-00156.1 PubMed DOI PMC

Rea, L.M., Parker, R.A.: Designing and conducting survey research: a comprehensive guide. Fourth edition. Jossey-Bass, a Wiley brand, San Francisco, CA (2014): 332

C. Dutang, V. Goulet, M. Pigeon, Actuar: An R Package for Actuarial Science. J. Stat. Softw. 25, 38 (2008). https://doi.org/10.18637/jss.v025.i07 DOI

H. Studer, H. Gerber, J. Zbaeren, H.J. Peter, Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells. J. Clin. Endocrinol. Metab. 75, 1151–1158 (1992). https://doi.org/10.1210/jcem.75.4.1400886 PubMed DOI

O.H. Clark, TSH suppression in the management of thyroid nodules and thyroid cancer. World J. Surg. 5, 39–47 (1981). https://doi.org/10.1007/BF01657832 PubMed DOI

E. Papini, L. Petrucci, R. Guglielmi, C. Panunzi, R. Rinaldi, V. Bacci, Long-term changes in nodular goiter: a 5-year prospective randomized trial of levothyroxine suppressive therapy for benign cold thyroid nodules. J. Clin. Endocrinol. Metab. 83, 780–783 (1998). https://doi.org/10.1210/jcem.83.3.4615 PubMed DOI

B. Abrahamsen, H.L. Jørgensen, A.S. Laulund, M. Nybo, T.H. Brix, L. Hegedüs, Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J. Bone Miner. Res. 29, 2040–2050 (2014). https://doi.org/10.1002/jbmr.2244 PubMed DOI

B. Abrahamsen, H.L. Jørgensen, A.S. Laulund, M. Nybo, D.C. Bauer, T.H. Brix, L. Hegedüs, The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J. Bone Miner. Res. 30, 898–905 (2015). https://doi.org/10.1002/jbmr.2416 PubMed DOI

M. Lillevang-Johansen, B. Abrahamsen, H.L. Jørgensen, T.H. Brix, L. Hegedüs, Duration of hyperthyroidism and lack of sufficient treatment are associated with increased cardiovascular risk. Thyroid 29, 332–340 (2019). https://doi.org/10.1089/thy.2018.0320 PubMed DOI

M. Lillevang-Johansen, B. Abrahamsen, H.L. Jørgensen, T.H. Brix, L. Hegedüs, Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk. Eur. J. Endocrinol. 180, 407–416 (2019). https://doi.org/10.1530/EJE-19-0006 PubMed DOI

M. Lillevang-Johansen, B. Abrahamsen, H.L. Jørgensen, T.H. Brix, L. Hegedüs, Excess mortality in treated and untreated hyperthyroidism is related to cumulative periods of low serum TSH. J. Clin. Endocrinol. Metab. 102, 2301–2309 (2017). https://doi.org/10.1210/jc.2017-00166 PubMed DOI

R. Adams, E.S. Oh, S. Yasar, C.G. Lyketsos, J.S. Mammen, Endogenous and exogenous thyrotoxicosis and risk of incident cognitive disorders in older adults. JAMA Intern Med 183, 1324–1331 (2023). https://doi.org/10.1001/jamainternmed.2023.5619 PubMed DOI PMC

S.J. Bonnema, F.N. Bennedbaek, W.M. Wiersinga, L. Hegedüs, Management of the nontoxic multinodular goitre: a European questionnaire study. Clin. Endocrinol. 53, 5–12 (2000). https://doi.org/10.1046/j.1365-2265.2000.01060.x DOI

S.J. Bonnema, F.N. Bennedbaek, P.W. Ladenson, L. Hegedüs, Management of the nontoxic multinodular goiter: a North American survey. J. Clin. Endocrinol. Metab. 87, 112–117 (2002). https://doi.org/10.1210/jcem.87.1.8169 PubMed DOI

L.A. Diehl, V. Garcia, S.J. Bonnema, L. Hegedüs, C.C. Albino, H. Graf, Latin American Thyroid Society: Management of the nontoxic multinodular goiter in Latin America: comparison with North America and Europe, an electronic survey. J. Clin. Endocrinol. Metab. 90(1), 117–123 (2005). https://doi.org/10.1210/jc.2004-1722 PubMed DOI

J.P. Walsh, S.A. Ryan, D. Lisewski et al. Differences between endocrinologists and endocrine surgeons in management of the solitary thyroid nodule. Clin. Endocrinol. (Oxf.) 66(6), 844–853 (2007). https://doi.org/10.1111/j.1365-2265.2007.02823.x PubMed DOI

M. Papaleontiou, M.R. Haymart, Inappropriate use of suppressive doses of thyroid hormone in thyroid nodule management: Results from a nationwide survey. Endocr. Pract. 22, 1358–1360 (2016). https://doi.org/10.4158/1934-2403-22.11.1358 PubMed DOI PMC

Iodine Global Network 2020 scorecard (2020) https://ign.org/scorecard/

G. Rönnefarth, E. Kauf, F. Deschner, M. Forberger, Therapy of iodine deficiency goiter in adolescents with iodine or a combination of iodine and levothyroxine with special reference to lipid parameters. Klin. Padiatr. 208(3), 123–128 (1996). https://doi.org/10.1055/s-2008-1046460 PubMed DOI

Q.M. Anstee, K. Hallsworth, N. Lynch et al. Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions. JHEP Rep. 4, 100411 (2022). https://doi.org/10.1016/j.jhepr.2021.100411 PubMed DOI

S. Razvi, B. Arnott, D. Teare, S. Hiu, N. O’Brien, S.H. Pearce, Multinational survey of treatment practices of clinicians managing subclinical hypothyroidism in older people in 2019. Eur. Thyroid J. 10(4), 330–338 (2021). https://doi.org/10.1159/000509228 PubMed DOI

J.B. McKinlay, C.L. Link, K.M. Freund, L.D. Marceau, A.B. O’Donnell, K.L. Lutfey, Sources of variation in physician adherence with clinical guidelines: results from a factorial experiment. J. Gen. Intern Med 22(3), 289–296 (2007). https://doi.org/10.1007/s11606-006-0075-2 PubMed DOI PMC

A. Francke, M. Smit, A. de Veer, P. Mistiaen, Factors influencing the implementation of clinical guidelines for health care professionals: a systematic meta-review. BMC Med Inf. Decis. Mak. 8(1), 38 (2008). https://doi.org/10.1186/1472-6947-8-38 DOI

P. Taba, M. Rosenthal, J. Habicht et al. Barriers and facilitators to the implementation of clinical practice guidelines: a cross-sectional survey among physicians in Estonia. BMC Health Serv. Res 12(1), 455 (2012). https://doi.org/10.1186/1472-6963-12-455 PubMed DOI PMC

S.J. Bonnema, L. Hegedüs, Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr. Rev. 33, 920–980 (2012). https://doi.org/10.1210/er.2012-1030 PubMed DOI

E. Papini, H. Monpeyssen, A. Frasoldati, L. Hegedüs, 2020 European Thyroid Association clinical practice guideline for the use of image-guided ablation in benign thyroid nodules. Eur. Thyroid J. 9, 172–185 (2020). https://doi.org/10.1159/000508484 PubMed DOI PMC

L. Hegedüs, A. Frasoldati, R. Negro, E. Papini, European Thyroid Association survey on use of minimally invasive techniques for thyroid nodules. Eur. Thyroid J. 9, 194–204 (2020). https://doi.org/10.1159/000506513 PubMed DOI PMC