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Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Hellenic Endocrine Society.

Abstract

Purpose

To investigate current practices of specialists in the use of thyroid hormone preparations in Greece as part of an ongoing international survey, namely THESIS—Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

Methods

An electronic link leading to an anonymized questionnaire was sent to all (n = 837) members of the Hellenic Endocrine Society.

Results

In total, 501 respondents participated in the survey, though only part of the questionnaire was filled in by some participants. A total of 88.2% were endocrinologists and 57.9% worked in private practice. Levothyroxine (LT4) was the first-line choice (98.6%) for the treatment of hypothyroid patients. In total, 70.2% preferred LT4 soft-gel capsules for patients reporting intolerance to various foods. Soft-gel capsules were the preferred LT4 formulation for patients on generic LT4 and with unexplained poor biochemical control of hypothyroidism (66.3%) or inability to take LT4 fasted and separate from food/drink (68.3%). It was found that 48.4% would never use combined LT4 + LT3. However, 25% would use combination therapy for a short period in patients recovering from protracted hypothyroidism or in patients with normal serum TSH but persistent symptoms. Concerning euthyroid individuals, 31.9% considered treatment with thyroid hormones in infertile females with positive thyroid antibodies and 24.4% in patients with growing goiter. Selenium or iodine supplementation was used occasionally, mostly in patients with coexisting autoimmune thyroiditis.

Conclusions

LT4 tablets are the treatment of choice for hypothyroidism in Greece. Several conditions may lead to various other practices, some of which deviate from current evidence-based guidelines and need more scrutiny.

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References

  1. 1.

    Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, Okosieme OE (2018) Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 14(5):301–316

    Article  Google Scholar 

  2. 2.

    GarmendiaMadariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC (2014) The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab 99(3):923–931

    Article  Google Scholar 

  3. 3.

    Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA, American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 18(6):988–1028

    Article  Google Scholar 

  4. 4.

    Taylor PN, Iqbal A, Minassian C, Sayers A, Draman MS, Greenwood R, Hamilton W, Okosieme O, Panicker V, Thomas SL, Dayan C (2014) Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern Med 174(1):32–39

    CAS  Article  Google Scholar 

  5. 5.

    Peeters RP (2017) Subclinical hypothyroidism. N Engl J Med 376(26):2556–2565

    Article  Google Scholar 

  6. 6.

    Peterson SJ, Cappola AR, Castro MR, Dayan CM, Farwell AP, Hennessey JV, Kopp PA, Ross DS, Samuels MH, Sawka AM, Taylor PN, Jonklaas J, Bianco AC (2018) An online survey of hypothyroid patients demonstrates prominent dissatisfaction. Thyroid 28(6):707–721

    CAS  Article  Google Scholar 

  7. 7.

    Mitchell AL, Hegedüs L, Žarković M, Hickey JL, Perros P (2021) Patient satisfaction and quality of life in hypothyroidism: an online survey by the British thyroid foundation. Clin Endocrinol (Oxf) 94(3):513–520

    CAS  Article  Google Scholar 

  8. 8.

    Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L (2018) Over- and under-treatment of hypothyroidism is associated with excess mortality: a register-based cohort study. Thyroid 28(5):566–574

    CAS  Article  Google Scholar 

  9. 9.

    Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L (2019) Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk. Eur J Endocrinol 180(6):407–416

    CAS  Article  Google Scholar 

  10. 10.

    Abrahamsen B, Jørgensen HL, Laulund AS, Nybo M, Bauer DC, Brix TH, Hegedüs L (2015) 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(5):898–905

    CAS  Article  Google Scholar 

  11. 11.

    Papaleontiou M, Levine DA, Reyes-Gastelum D, Hawley ST, Banerjee M, Haymart MR (2021) Thyroid hormone therapy and incident stroke. J Clin Endocrinol Metab 106(10):e3890–e3900

    Article  Google Scholar 

  12. 12.

    Fallahi P, Ferrari SM, Ruffilli I, Ragusa F, Biricotti M, Materazzi G, Miccoli P, Antonelli A (2017) Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update. Expert Opin Drug Deliv 14(5):647–655

    CAS  Article  Google Scholar 

  13. 13.

    Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M (2019) Gastrointestinal malabsorption of thyroxine. Endocr Rev 40(1):118–136

    Article  Google Scholar 

  14. 14.

    Trimboli P, Scappaticcio L, De Bellis A, Maiorino MI, Knappe L, Esposito K, Bellastella G, Giovanella L (2020) Different formulations of levothyroxine for treating hypothyroidism: a real-life study. Int J Endocrinol 2020:4524759

    Article  Google Scholar 

  15. 15.

    Virili C, Trimboli P, Romanelli F, Centanni M (2016) Liquid and softgel levothyroxine use in clinical practice: state of the art. Endocrine 54(1):3–14

    CAS  Article  Google Scholar 

  16. 16.

    Jonklaas J, Bianco AC, Cappola AR, Celi FS, Fliers E, Heuer H, McAninch EA, Moeller LC, Nygaard B, Sawka AM, Watt T, Dayan CM (2021) Evidence-based use of levothyroxine/liothyronine combinations in treating hypothyroidism: a consensus document. Thyroid 31(2):156–182

    CAS  Article  Google Scholar 

  17. 17

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

    Article  Google Scholar 

  18. 18.

    Wiersinga WM, Duntas L, Fadeyev V, Nygaard B, Vanderpump MP (2012) 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism. Eur Thyroid J 1(2):55–71

    Article  Google Scholar 

  19. 19.

    Kraut E, Farahani P (2015) A systematic review of clinical practice guidelines’ recommendations on levothyroxine therapy alone versus combination therapy (LT4 plus LT3) for hypothyroidism. Clin Invest Med 38(6):E305–E313

    CAS  Article  Google Scholar 

  20. 20.

    Negro R, Attanasio R, Nagy EV, Papini E, Perros P, Hegedüs L (2020) Use of thyroid hormones in hypothyroid and euthyroid patients; the 2019 Italian survey. Eur Thyroid J 9(1):25–31

    CAS  Article  Google Scholar 

  21. 21.

    Riis KR, Frølich JS, Hegedüs L, Negro R, Attanasio R, Nagy EV, Papini E, Perros P, Bonnema SJ (2021) Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Danish Endocrine Society. J Endocrinol Invest 28:1–10. https://doi.org/10.1007/s40618-021-01555-y

    CAS  Article  Google Scholar 

  22. 22.

    Niculescu DA, Attanasio R, Hegedüs L, Nagy EV, Negro R, Papini E, Perros P, Poiana C (2020) 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) 16(4):462–469

    CAS  Article  Google Scholar 

  23. 23.

    Bednarczuk T, Attanasio R, Hegedüs L, Nagy EV, Negro R, Papini E, Perros P, Ruchała M (2021) 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. https://doi.org/10.5603/EP.a2021.0048

    Article  PubMed  Google Scholar 

  24. 24.

    Borissova AM, Boyanov M, Attanasio R, Hegedüs L, Nagy EV, Negro R, Papini E, Perros P. Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS questionnaire survey of Bulgarian physicians. https://endo-bg.com/en/prilozhenie-na-hormonite-na-shtitovidnata-zhleza-pri-hipotireoidni-i-eutireoidni-patsienti-anketno-prouchvane-thesis-sred-balgarski-lekari/. Accessed 24 Sept 2021

  25. 25.

    Galofré JC, Attanasio R, Hegedüs L, Nagy E, Negro R, Papini E, Perros P, Díez JJ (2021) Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: a THESIS* questionnaire survey. Endocrinol Diabetes Nutr :S2530–0164(21)00190–7. https://doi.org/10.1016/j.endinu.2021.07.003.

  26. 26.

    Nagy EV, Perros P, Papini E, Katko M, Hegedüs L (2021) New formulations of levothyroxine in the treatment of hypothyroidism: trick or treat? Thyroid 31(2):193–201

    CAS  Article  Google Scholar 

  27. 27.

    Ernst FR, Sandulli W, Elmor R, Welstead J, Sterman AB, Lavan M (2017) Retrospective study of patients switched from tablet formulations to a gel cap formulation of levothyroxine: results of the CONTROL Switch Study. Drugs R D 17(1):103–115

    CAS  Article  Google Scholar 

  28. 28.

    Wang X, Zhang Y, Tan H, Bai Y, Zhou L, Fang F, Faramand A, Chong W, Hai Y (2020) Effect of levothyroxine on pregnancy outcomes in women with thyroid autoimmunity: a systematic review with meta-analysis of randomized controlled trials. Fertil Steril 114(6):1306–1314

    CAS  Article  Google Scholar 

  29. 29.

    Fast S, Bonnema SJ, Hegedüs L (2008) The majority of Danish nontoxic goitre patients are ineligible for levothyroxine suppressive therapy. Clin Endocrinol (Oxf) 69(4):653–658

    Article  Google Scholar 

  30. 30.

    Hegedüs L, Bonnema SJ, Bennedbaek FN (2003) Management of simple nodular goiter: current status and future perspectives. Endocr Rev 24(1):102–132

    Article  Google Scholar 

  31. 31

    Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, Paschke R, Valcavi R, Vitti P, AACE/ACE/AME Task Force on Thyroid Nodules (2016) 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 22(5):622–39

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Livadas S, Bothou C, Androulakis I, Boniakos A, Angelopoulos N, Duntas L (2018) Levothyroxine replacement therapy and overuse: a timely diagnostic approach. Thyroid. https://doi.org/10.1089/thy.2018.0014

    Article  PubMed  Google Scholar 

  33. 33.

    Hoang TD, Olsen CH, Mai VQ, Clyde PW, Shakir MK (2013) Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab 98(5):1982–1990

    CAS  Article  Google Scholar 

  34. 34.

    Panicker V, Saravanan P, Vaidya B, Evans J, Hattersley AT, Frayling TM, Dayan CM (2009) Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab 94(5):1623–1629

    CAS  Article  Google Scholar 

  35. 35

    Thvilum M, Brandt F, Almind D, Christensen K, Brix TH, Hegedüs L (2013) Type and extent of somatic morbidity before and after the diagnosis of hypothyroidism. a nationwide register study. PLoS One 8(9):e75789

    CAS  Article  Google Scholar 

  36. 36.

    Thvilum M, Brandt F, Almind D, Christensen K, Brix TH, Hegedüs L (2014) Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: a nationwide register study. Thyroid 24(5):802–808

    Article  Google Scholar 

  37. 37.

    Thvilum M, Brandt F, Brix TH, Hegedüs L (2014) Hypothyroidism is a predictor of disability pension and loss of labor market income: a Danish register-based study. J Clin Endocrinol Metab 99(9):3129–3135

    CAS  Article  Google Scholar 

  38. 38.

    Thvilum M, Brandt F, Lillevang-Johansen M, Folkestad L, Brix TH, Hegedüs L (2021) Increased risk of dementia in hypothyroidism: a Danish nationwide register-based study. Clin Endocrinol (Oxf) 94(6):1017–1024

    CAS  Article  Google Scholar 

  39. 39.

    Heiberg Brix T, Ferløv-Schwensen C, Thvilum M, Hegedüs L (2019) Death by unnatural causes, mainly suicide, is increased in patients with Hashimoto’s thyroiditis. A nationwide Danish register study. Endocrine 65(3):616–622

    CAS  Article  Google Scholar 

  40. 40.

    Carlé A, Karmisholt JS, Knudsen N, Perrild H, Thuesen BH, Ovesen L, Rasmussen LB, Pedersen IB (2021) Does subclinical hypothyroidism add any symptoms? Evidence from a Danish population-based study. Am J Med 134(9):1115–1126.e1

    Article  Google Scholar 

  41. 41.

    Winther KH, Papini E, Attanasio R, Negro R, Hegedüs L (2020) A 2018 European Thyroid Association survey on the use of selenium supplementation in Hashimoto’s thyroiditis. Eur Thyroid J 9(2):99–105

    CAS  Article  Google Scholar 

  42. 42.

    Winther KH, Rayman MP, Bonnema SJ, Hegedüs L (2020) Selenium in thyroid disorders - essential knowledge for clinicians. Nat Rev Endocrinol 16(3):165–176

    CAS  Article  Google Scholar 

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Correspondence to Andromachi Vryonidou.

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Ethical approval was not required.

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A signed informed consent was not required from participants in this anonymous and voluntary questionnaire survey.

Conflict of interest

THESIS is supported by IBSA Institut Biochimique SA. PP, LH, EVN, and EP are scientific board members of and have received consultancy fees from IBSA Biochimique. IBSA had no role in the design of the survey, data analysis, data presentation, data interpretation, or writing the manuscript.

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THESIS - Treatment of Hypothyroidism in Europe by Specialists: An International Survey

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Paschou, S.A., Alevizaki, M., Attanasio, R. et al. Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Hellenic Endocrine Society.. Hormones (2021). https://doi.org/10.1007/s42000-021-00335-w

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Keywords

  • Thyroid
  • Hypothyroidism
  • Thyroid hormones
  • Autoimmune thyroiditis
  • Survey