A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

Abstract

Objective To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH).

Methods All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH.

Results Out of 206 members of the DGE’s thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p<0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p<0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p<0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p<0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another.

Conclusion For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.

Key words

Thyroid hormones - levothyroxine - liothyronine - combination therapy - bioavailability - hypothyroidism - questionnaire

Publikationsverlauf

Eingereicht: 08. Februar 2022
Eingereicht: 12. März 2022

Angenommen: 04. April 2022

Artikel online veröffentlicht:
31. Mai 2022

• References

• 1 Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F. et al. The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis. J Clin Endocrinol Metab 2014; 99: 923-931
• 2 Nagy EV, Perros P, Papini E. et al. New formulations of levothyroxine in the treatment of hypothyroidism: Trick or treat?. Thyroid 2021; 31: 193-201
• 3 Fallahi P, Ferrari SM, Ruffilli I. et al. Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: An update. Expert Opin Drug Deliv 2017; 14: 647-655
• 4 Thvilum M, Brandt F, Almind D. et al. Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: A nationwide register study. Thyroid 2014; 24: 802-808
• 5 Thvilum M, Brandt F, Almind D. et al. Type and extent of somatic morbidity before and after the diagnosis of hypothyroidism. A nationwide register study. PLoS One 2013; 8: e75789
• 6 Thvilum M, Brandt F, Almind D. et al. Excess mortality in patients diagnosed with hypothyroidism: A nationwide cohort study of singletons and twins. J Clin Endocrinol Metab 2013; 98: 1069-1075
• 7 Heiberg Brix T, Ferlov-Schwensen C, Thvilum M. et al. Death by unnatural causes, mainly suicide, is increased in patients with Hashimoto’s thyroiditis. A nationwide Danish register study. Endocrine 2019; 65: 616-622
• 8 Thvilum M, Brandt F, Brix TH. et al. Hypothyroidism is a predictor of disability pension and loss of labor market income: A Danish register-based study. J Clin Endocrinol Metab 2014; 99: 3129-3135
• 9 Winther KH, Cramon P, Watt T. et al. Disease-specific as well as generic quality of life is widely impacted in autoimmune hypothyroidism and improves during the first six months of levothyroxine therapy. PLoS One 2016; 11: e0156925
• 10 Hegedus L, Bianco AC, Jonklaas J. et al. Primary hypothyroidism and quality of life. Nat Rev Endocrinol 2022;
• 11 Negro R, Attanasio R, Nagy EV. et al. Use of thyroid hormones in hypothyroid and euthyroid patients; the 2019 Italian Survey. Eur Thyroid J 2020; 9: 25-31
• 12 Kraut E, Farahani P. A systematic review of Clinical Practice Guidelines’ Recommendations on levothyroxine therapy alone versus combination therapy (LT4 plus LT3) for hypothyroidism. Clin Invest Med 2015; 38: E305-E313
• 13 Wiersinga WM, Duntas L, Fadeyev V. et al. 2012 ETA Guidelines: The use of L-T4+L-T3 in the treatment of hypothyroidism. Eur Thyroid J 2012; 1: 55-71
• 14 Jonklaas J, Bianco AC, Cappola AR. et al. Evidence-based use of levothyroxine/liothyronine combinations in treating hypothyroidism: A consensus document. Eur Thyroid J 2021; 10: 10-38
• 15 Cerqueira C, Knudsen N, Ovesen L. et al. Doubling in the use of thyroid hormone replacement therapy in Denmark: Association to iodization of salt?. Eur J Epidemiol 2011; 26: 629-635
• 16 Taylor PN, Iqbal A, Minassian C. et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: Evidence from a large community-based study. JAMA Intern Med 2014; 174: 32-39
• 17 Michaelsson LF, Medici BB, la Cour JL. et al. Treating Hypothyroidism with thyroxine/triiodothyronine combination therapy in Denmark: Following guidelines or following trends?. Eur Thyroid J 2015; 4: 174-180
• 18 Pedersen IB, Laurberg P, Knudsen N. et al. An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: A prospective population study. J Clin Endocrinol Metab 2007; 92: 3122-3127
• 19 Medici BB, Nygaard B, la Cour JL. et al. Changes in prescription routines for treating hypothyroidism between 2001 and 2015: An observational study of 929,684 primary care patients in Copenhagen. Thyroid 2019; 29: 910-919
• 20 Peterson SJ, Cappola AR, Castro MR. et al. An online survey of hypothyroid patients demonstrates prominent dissatisfaction. Thyroid 2018; 28: 707-721
• 21 Mitchell AL, Hegedus L, Zarkovic M. et al. Patient satisfaction and quality of life in hypothyroidism: An online survey by the British Thyroid Foundation. Clin Endocrinol (Oxf) 2021; 94: 513-520
• 22 Abrahamsen B, Jorgensen HL, Laulund AS. 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
• 23 Lillevang-Johansen M, Abrahamsen B, Jorgensen HL. et al. Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk. Eur J Endocrinol 2019; 180: 407-416
• 24 Lillevang-Johansen M, Abrahamsen B, Jorgensen HL. et al. Over- and under-treatment of hypothyroidism is associated with excess mortality: A register-based cohort study. Thyroid 2018; 28: 566-574
• 25 Ittermann T, Albrecht D, Arohonka P. et al. Standardized map of iodine status in Europe. Thyroid 2020; 30: 1346-1354
• 26 Ellerth U, Kurth BM. Gesundheitsbezogene lebensqualität bei erwachsenen in Deutschland - Ergebnisse einer studie zur gesundheit erwachsener in Deutschland (DEGS1). Bundesgesundheitsblatt 2013; 56: 643-649
• 27 Schaffler A. Hormone replacement after thyroid and parathyroid surgery. Dtsch Arztebl Int 2010; 107: 827-834
• 28 Buffet C, Belin L, Attanasio R. et al. Real-life practice of thyroid hormone use in hypothyroid and euthyroid patients: A detailed view from the THESIS* questionnaire survey in France. Ann Endocrinol (Paris) 2021;
• 29 Borissova AM, Boyanov M, Attanasio R. et al. Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS* questionnaire survey of Bulgarian physicians *THESIS: Treatment of Hypthyroidism in Europe by Specialists: An international survey. Endocrinologia 2020; XXV: 299-309
• 30 Metso S, Hakkala T, Attanasio R. et al. Use of thyroid hormones in the treatment of hypothyroidism: Thesis questionnaire survey for Finnish specialists. Lääkärilehti 2021; 48: 2885-2889
• 31 Planck T, Lantz M, Perros P. et al. Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Swedish Endocrine Society. Front Endocrinol (Lausanne) 2021; 12: 795111
• 32 Bednarczuk T, Attanasio R, Hegedus L. 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
• 33 Niculescu DA, Attanasio R, Hegedus L. 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
• 34 Riis KR, Frolich JS, Hegedus L. 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; 44: 2435-2444
• 35 Jonklaas J, Bianco AC, Bauer AJ. et al. Guidelines for the treatment of hypothyroidism: Prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid 2014; 24: 1670-1751
• 36 Galofre JC, Attanasio R, Hegedus L. et al. Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: A THESIS* questionnaire survey. Endocrinol Diabetes Nutr (Engl Ed) 2021;
• 37 Buffet C, Golmard JL, Hoang C. et al. Scoring system for predicting recurrences in patients with papillary thyroid microcarcinoma. Eur J Endocrinol 2012; 167: 267-275
• 38 Wang X, Zhang Y, Tan H. et al. Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: A systematic review with meta-analysis of randomized controlled trials. Fertil Steril 2020; 114: 1306-1314
• 39 Dhillon-Smith RK, Middleton LJ, Sunner KK. et al. Levothyroxine in women with thyroid peroxidase antibodies before conception. N Engl J Med 2019; 380: 1316-1325
• 40 Poppe K, Bisschop P, Fugazzola L. et al. 2021 European Thyroid Association Guideline on thyroid disorders prior to and during assisted reproduction. Eur Thyroid J 2021; 9: 281-295
• 41 Gharib H, Papini E, Garber JR. et al. 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: 622-639
• 42 Esfandiari NH, Reyes-Gastelum D, Hawley ST. et al. Patient requests for tests and treatments impact physician management of hypothyroidism. Thyroid 2019; 29: 1536-1544
• 43 Hoang TD, Olsen CH, Mai VQ. et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: A randomized, double-blind, crossover study. J Clin Endocrinol Metab 2013; 98: 1982-1990
• 44 Winther KH, Rayman MP, Bonnema SJ. et al. Selenium in thyroid disorders – essential knowledge for clinicians. Nat Rev Endocrinol 2020; 16: 165-176
• 45 Wichman J, Winther KH, Bonnema SJ. et al. Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: A systematic review and meta-analysis. Thyroid 2016; 26: 1681-1692