BACKGROUND: Inconsistencies in the management of hypothyroidism have been reported among endocrinologists in different European countries. Aim of this study was to explore Czech endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: We used a web-based survey containing 32 questions regarding the use of thyroid hormones. Four-hundred thirty-two members of the Czech Society of Endocrinology received an e-mail invitation to participate in the survey. RESULTS: We received and analysed 157 responses (112 females and 45 males) from the 432 members (36.3%). According to 99.4% of the respondents, levothyroxine (LT4) is the primary drug of choice for the treatment of hypothyroidism. Liothyronine (LT3) was used in clinical practice by 29.9% of responders. According to 90.5% of respondents, thyroid hormones may be indicated in biochemically euthyroid patients. Female physicians prescribe thyroid hormones in euthyroid infertile women with high antibody levels more frequently than male physicians (P = 0.003). Most Czech endocrinologists (76.4%) consider combined therapy with LT4 and LT3 in various clinical scenarios, but only 1 of 29 hypothyroid physicians (3.5%) would recommend it to their patients, and only 4 out of 128 respondents (3.1%) would consider LT3 or desiccated thyroid for themselves, if diagnosed with hypothyroidism. CONCLUSION: LT4 is the primary thyroid hormone used in the Czech Republic for treatment of hypothyroidism. At variance with thyroid guideline recommendations, Czech endocrinologists are quite liberal when prescribing thyroid hormones to euthyroid patients and in the use of LT4/LT3 combination treatment for hypothyroid patients with persisting symptoms.

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

Department of Endocrinology and Metabolism Regina Apostolorum Hospital Rome Italy

Department of Endocrinology Odense University Hospital Odense Denmark

Department of Endocrinology Royal Victoria Infirmary Newcastle upon Tyne UK

Division of Endocrinology 5 Fazzi Hospital Lecce Italy

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

Scientific Committee of Associazione Medici Endocrinologi Milan Italy

See more in PubMed

Asvold BO, Vatten LJ, Bjøro T. Changes in the prevalence of hypothyroidism: the HUNT Study in Norway. Eur J Endocrinol. 2013;169:613–620. doi: 10.1530/EJE-13-0459. PubMed DOI

Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) J Clin Endocrinol Metab. 2002;87:489–499. doi: 10.1210/jcem.87.2.8182. PubMed DOI

Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24:1670–751. doi: 10.1089/thy.2014.0028. PubMed DOI PMC

Benvenga S, Carlé A. Levothyroxine Formulations: Pharmacological and Clinical Implications of Generic Substitution. Adv Ther. 2019;36:59–71. doi: 10.1007/s12325-019-01079-1. PubMed DOI PMC

Nagy EV, Perros P, Papini E, Katko M, Hegedüs L. New Formulations of Levothyroxine in the Treatment of Hypothyroidism: Trick or Treat? Thyroid. 2021;31:193–201. doi: 10.1089/thy.2020.0515. PubMed DOI

Jonklaas J, Bianco AC, Cappola AR, Celi FS, Fliers E, Heuer H, et al. Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Thyroid. 2021;31:156–182. doi: 10.1089/thy.2020.0720. PubMed DOI PMC

Hegedüs L, Bianco AC, Jonklaas J, Pearce SH, Weetman AP, Perros P. Primary hypothyroidism and quality of life. Nat Rev Endocrinol. 2022. 10.1038/s41574-021-00625-8. Epub ahead of print. PubMed PMC

Límanová Z, Jiskra J, Moravčíková D, Karen I. Diagnostika a léčba tyreopatií. Doporučené diagnostické a terapeutické postupy pro všeobecné praktické lékaře. Společnost všeobecného lékařství 2015, pp. 33, ISBN 978–80–86998–77–0, DP Štítná žláza.indd (svl.cz)

Negro R, Attanasio R, Nagy EV, Papini E, Perros P, Hegedüs L. Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients; the 2019 Italian Survey. Eur Thyroid J. 2020;9:25–31. doi: 10.1159/000502057. PubMed DOI PMC

Jonklaas J, DeSale S. Levothyroxine prescriptions trends may indicate a downtrend in prescribing. Ther Adv Endocrinol Metab. 2020;11:2042018820920551. PubMed PMC

Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2:215–228. doi: 10.1159/000356507. PubMed DOI PMC

Shakir MKM, Brooks DI, McAninch EA, Fonseca TL, Mai VQ, Bianco AC, et al. Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism. J Clin Endocrinol Metab. 2021;106(11):e4400–e4413. doi: 10.1210/clinem/dgab478. PubMed DOI PMC

Jonklaas J, Tefera E, Shara N. Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics. Thyroid. 2019;29:44–52. doi: 10.1089/thy.2018.0369. PubMed DOI PMC

Riis KR, Frølich JS, Hegedüs L, Negro R, Attanasio R, Nagy EV, et al. Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society. J Endocrinol Invest. 2021;28:1–10. PubMed PMC

Niculescu DA, Attanasio R, Hegedüs L, Nagy EV, Negro R, Papini E, et al. Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey. Acta Endocrinol (Buchar) 2020;16:462–469. doi: 10.4183/aeb.2020.462. PubMed DOI PMC

Borissova AMI, Boyanov MA, Attanasio R, Hegedüs L, Nagy E, Negro R, et al. Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: a THESIS* Questionnaire Survey of Bulgarian Physicians. Endocrinologia. 2020;4:299–309.

Bednarczuk T, Attanasio R, Hegedüs L, Nagy EV, Negro R, Papini E, et al. Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* questionnaire survey of Polish physicians *THESIS: Treatment of Hypothyroidism in Europe by Specialists: an International Survey. Endokrynol Pol. 2021;72:357–365. doi: 10.5603/EP.a2021.0048. PubMed DOI

Hendra R, Hill A. Rethinking Response Rates: New Evidence of Little Relationship Between Survey Response Rates and Nonresponse Bias. Eval Rev. 2019;43:307–330. doi: 10.1177/0193841X18807719. PubMed DOI

Rea LM, Parker RA. Designing and conducting survey research: a comprehensive guide. Fourth edition. San Francisco, CA: Jossey-Bass, a Wiley brand. 2014;332 p.

Halbesleben JRB, Whitman MV. Evaluating survey quality in health services research: a decision framework for assessing nonresponse bias. Health Serv Res. 2013;48:913–930. doi: 10.1111/1475-6773.12002. PubMed DOI PMC

Thvilum M, Brandt F, Almind D, Christensen K, Brix TH, Hegedüs L. Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: a nationwide register study. Thyroid. 2014;24:802–808. doi: 10.1089/thy.2013.0555. PubMed DOI

Samuels MH, Kolobova I, Niederhausen M, Janowsky JS, Schuff KG. Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects. J Clin Endocrinol Metab. 2018;103:1997–2008. doi: 10.1210/jc.2017-02668. PubMed DOI PMC

Park SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, et al. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol (Oxf) 2017;87:87–96. doi: 10.1111/cen.13345. PubMed DOI

Hegedüs L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003;24:102–132. doi: 10.1210/er.2002-0016. PubMed DOI

Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, et al. AACE/ACE/AME Task Force on Thyroid Nodules. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE. Endocr Pract. 2016;22:622–39. doi: 10.4158/EP161208.GL. PubMed DOI

Brenta G, Schnitman M, Fretes O, Facco E, Gurfinkel M, Damilano S, et al. Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid. J Clin Endocrinol Metab. 2003;88:5287–5292. doi: 10.1210/jc.2003-030095. PubMed DOI

Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab. 2006;91:4295–4301. doi: 10.1210/jc.2006-0527. PubMed DOI

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

Abrahamsen B, Jørgensen HL, Laulund AS, Nybo M, Bauer DC, Brix TH, et al. 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. 2015;30:898–905. doi: 10.1002/jbmr.2416. PubMed DOI

Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedüs L, et al. Hyperthyroidism and psychiatric morbidity: evidence from a Danish nationwide register study. Eur J Endocrinol. 2013;170:341–348. doi: 10.1530/EJE-13-0708. PubMed DOI

Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L. Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study. Thyroid. 2018;28:566–574. doi: 10.1089/thy.2017.0517. PubMed DOI

Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616. doi: 10.1136/bmj.d2616. PubMed DOI PMC

Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab. 2006;91:2587–2591. doi: 10.1210/jc.2005-1603. PubMed DOI

Negro R, Schwartz A, Stagnaro-Green A. Impact of Levothyroxine in Miscarriage and Preterm Delivery Rates in First Trimester Thyroid Antibody-Positive Women With TSH Less Than 2.5 mIU/L. J Clin Endocrinol Metab. 2016;101:3685–95. doi: 10.1210/jc.2016-1803. PubMed DOI

Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, et al. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019;380:1316–1325. doi: 10.1056/NEJMoa1812537. PubMed DOI

Winther KH, Rayman MP, Bonnema SJ, Hegedüs L. Selenium in thyroid disorders - essential knowledge for clinicians. Nat Rev Endocrinol. 2020;16:165–176. doi: 10.1038/s41574-019-0311-6. PubMed DOI

Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. Thyroid. 2016;26:1681–1692. doi: 10.1089/thy.2016.0256. PubMed DOI

Wiersinga WM, Duntas L, Fadeyev V, Nygaard B, Vanderpump MP. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. Eur Thyroid J. 2012;1:55–71. doi: 10.1159/000339444. PubMed DOI PMC

Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27:315–389. doi: 10.1089/thy.2016.0457. PubMed DOI

Mitchell AL, Hegedüs L, Žarković M, Hickey JL, Perros P. Patient satisfaction and quality of life in hypothyroidism: An online survey by the british thyroid foundation. Clin Endocrinol (Oxf) 2021;94:513–520. doi: 10.1111/cen.14340. PubMed DOI

Perros P, Van Der Feltz-Cornelis C, Papini E, Nagy EV, Weetman AP, Hegedüs L. The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review. Clin Endocrinol (Oxf). 2021. 10.1111/cen.14473. PubMed

Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative