To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence?
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Is This a Patient With Hypothyroidism?
3.2. Effect of Initiating Treatment in Subclinical Hypothyroidism
3.3. Still Decreased Well-Being After Initiating Treatment in Patient With Subclinical Hypothyroidism
3.4. Could There Be Genetic Causes?
3.5. Subclinical Hypothyroidism in the Elderly
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Jonklaas, J.; Bianco, A.C.; Bauer, A.J.; Burman, K.D.; Cappola, A.R.; Celi, F.S.; Cooper, D.S.; Kim, B.W.; Peeters, R.P.; Rosenthal, M.S.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garber, J.R.; Cobin, R.H.; Gharib, H.; Hennessey, J.V.; Klein, I.; Mechanick, J.I.; Pessah-Pollack, R.; Singer, P.A.; Woeber, K.A.; American Association of Clinical Endocrinologists; et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the american association of clinical endocrinologists and the american thyroid association. Endocr. Pract. 2012, 18, 988–1028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pearce, S.H.; Brabant, G.; Duntas, L.H.; Monzani, F.; Peeters, R.P.; Razvi, S.; Wemeau, J.L. 2013 eta guideline: Management of subclinical hypothyroidism. Eur. Thyroid J. 2013, 2, 215–228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Almandoz, J.P.; Gharib, H. Hypothyroidism: Etiology, diagnosis, and management. Med. Clin. N. Am. 2012, 96, 203–221. [Google Scholar] [CrossRef]
- Baumgartner, C.; Blum, M.R.; Rodondi, N. Subclinical hypothyroidism: Summary of evidence in 2014. Swiss Med. Wkly. 2014, 144, w14058. [Google Scholar] [CrossRef] [Green Version]
- Vanderpump, M.P.; Tunbridge, W.M.; French, J.M.; Appleton, D.; Bates, D.; Clark, F.; Grimley Evans, J.; Hasan, D.M.; Rodgers, H.; Tunbridge, F.; et al. The incidence of thyroid disorders in the community: A twenty-year follow-up of the whickham survey. Clin. Endocrinol. 1995, 43, 55–68. [Google Scholar] [CrossRef]
- Surks, M.I.; Ortiz, E.; Daniels, G.H.; Sawin, C.T.; Col, N.F.; Cobin, R.H.; Franklyn, J.A.; Hershman, J.M.; Burman, K.D.; Denke, M.A.; et al. Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA 2004, 291, 228–238. [Google Scholar] [CrossRef]
- Gharib, H.; Tuttle, R.M.; Baskin, H.J.; Fish, L.H.; Singer, P.A.; McDermott, M.T.; American Association of Clinical Endocrinologists; American Thyroid Association; Endocrine Society. Consensus statement #1: Subclinical thyroid dysfunction: A joint statement on management from the american association of clinical endocrinologists, the american thyroid association, and the endocrine society. Thyroid 2005, 15, 24–28. [Google Scholar]
- Jonklaas, J.; Razvi, S. Reference intervals in the diagnosis of thyroid dysfunction: Treating patients not numbers. Lancet Diabetes Endocrinol. 2019, 7, 473–483. [Google Scholar] [CrossRef]
- Razvi, S.; Korevaar, T.I.M.; Taylor, P. Trends, determinants, and associations of treated hypothyroidism in the united kingdom, 2005–2014. Thyroid 2019, 29, 174–182. [Google Scholar] [CrossRef]
- Hollowell, J.G.; Staehling, N.W.; Flanders, W.D.; Hannon, W.H.; Gunter, E.W.; Spencer, C.A.; Braverman, L.E. 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. [Google Scholar] [CrossRef] [PubMed]
- Biondi, B.; Cappola, A.R.; Cooper, D.S. Subclinical hypothyroidism: A review. JAMA 2019, 322, 153–160. [Google Scholar] [CrossRef] [PubMed]
- Bekkering, G.E.; Agoritsas, T.; Lytvyn, L.; Heen, A.F.; Feller, M.; Moutzouri, E.; Abdulazeem, H.; Aertgeerts, B.; Beecher, D.; Brito, J.P.; et al. Thyroid hormones treatment for subclinical hypothyroidism: A clinical practice guideline. BMJ 2019, 365, l2006. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodriguez-Gutierrez, R.; Maraka, S.; Ospina, N.S.; Montori, V.M.; Brito, J.P. Levothyroxine overuse: Time for an about face? Lancet Diabetes Endocrinol. 2017, 5, 246–248. [Google Scholar] [CrossRef]
- Villar, H.C.; Saconato, H.; Valente, O.; Atallah, A.N. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst. Rev. 2007, 3, CD003419. [Google Scholar] [CrossRef]
- Taylor, P.N.; Iqbal, A.; Minassian, C.; Sayers, A.; Draman, M.S.; Greenwood, R.; Hamilton, W.; Okosieme, O.; Panicker, V.; Thomas, S.L.; 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. [Google Scholar] [CrossRef] [Green Version]
- Bayram, C.; Valenti, L.; Britt, H. Orders for thyroid function tests—Changes over 10 years. Aust. Fam. Physician 2012, 41, 555. [Google Scholar]
- Okosieme, O.; Gilbert, J.; Abraham, P.; Boelaert, K.; Dayan, C.; Gurnell, M.; Leese, G.; McCabe, C.; Perros, P.; Smith, V.; et al. Management of primary hypothyroidism: Statement by the british thyroid association executive committee. Clin. Endocrinol. 2016, 84, 799–808. [Google Scholar] [CrossRef]
- Sgarbi, J.A.; Teixeira, P.F.; Maciel, L.M.; Mazeto, G.M.; Vaisman, M.; Montenegro Junior, R.M.; Ward, L.S.; Brazilian Society of Endocrinology and Metabolism. The brazilian consensus for the clinical approach and treatment of subclinical hypothyroidism in adults: Recommendations of the thyroid department of the brazilian society of endocrinology and metabolism. Arq. Bras. Endocrinol. Metabol. 2013, 57, 166–183. [Google Scholar] [CrossRef] [Green Version]
- Guglielmi, R.; Frasoldati, A.; Zini, M.; Grimaldi, F.; Gharib, H.; Garber, J.R.; Papini, E. Italian association of clinical endocrinologists statement-replacement therapy for primary hypothyroidism: A brief guide for clinical practice. Endocr. Pract. 2016, 22, 1319–1326. [Google Scholar] [CrossRef]
- Stott, D.J.; Rodondi, N.; Kearney, P.M.; Ford, I.; Westendorp, R.G.J.; Mooijaart, S.P.; Sattar, N.; Aubert, C.E.; Aujesky, D.; Bauer, D.C.; et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N. Engl. J. Med. 2017, 376, 2534–2544. [Google Scholar] [CrossRef] [PubMed]
- Koulouri, O.; Moran, C.; Halsall, D.; Chatterjee, K.; Gurnell, M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract. Res. Clin. Endocrinol. Metab. 2013, 27, 745–762. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meyerovitch, J.; Rotman-Pikielny, P.; Sherf, M.; Battat, E.; Levy, Y.; Surks, M.I. Serum thyrotropin measurements in the community: Five-year follow-up in a large network of primary care physicians. Arch. Intern. Med. 2007, 167, 1533–1538. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, E.T.; Bradley, S.G.; Schultz, A.L. Elevations of thyroid-stimulating hormone during acute nonthyroidal illness. Arch. Intern. Med. 1981, 141, 873–875. [Google Scholar] [CrossRef] [PubMed]
- Bhakri, H.L.; Fisher, R.; Khadri, A.; MacMahon, D.G. Longitudinal study of thyroid function in acutely ill elderly patients using a sensitive tsh assay-defer testing until recovery. Gerontology 1990, 36, 140–144. [Google Scholar] [CrossRef]
- Bartalena, L.; Bogazzi, F.; Chiovato, L.; Hubalewska-Dydejczyk, A.; Links, T.P.; Vanderpump, M. 2018 european thyroid association (eta) guidelines for the management of amiodarone-associated thyroid dysfunction. Eur. Thyroid J. 2018, 7, 55–66. [Google Scholar] [CrossRef] [Green Version]
- Hattori, N.; Ishihara, T.; Shimatsu, A. Variability in the detection of macro tsh in different immunoassay systems. Eur. J. Endocrinol./Eur. Fed. Endocr. Soc. 2016, 174, 9–15. [Google Scholar] [CrossRef] [Green Version]
- Hattori, N.; Ishihara, T.; Yamagami, K.; Shimatsu, A. Macro tsh in patients with subclinical hypothyroidism. Clin. Endocrinol. 2015, 83, 923–930. [Google Scholar] [CrossRef]
- Brennan, M.D.; Klee, G.G.; Preissner, C.M.; Hay, I.D. Heterophilic serum antibodies: A cause for falsely elevated serum thyrotropin levels. Mayo Clin. Proc. 1987, 62, 894–898. [Google Scholar] [CrossRef]
- Ward, G.; McKinnon, L.; Badrick, T.; Hickman, P.E. Heterophilic antibodies remain a problem for the immunoassay laboratory. Am. J. Clin. Pathol. 1997, 108, 417–421. [Google Scholar] [CrossRef] [Green Version]
- Alexander, E.K.; Pearce, E.N.; Brent, G.A.; Brown, R.S.; Chen, H.; Dosiou, C.; Grobman, W.A.; Laurberg, P.; Lazarus, J.H.; Mandel, S.J.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jonklaas, J.; Tefera, E.; Shara, N. Prescribing therapy for hypothyroidism: Influence of physician characteristics. Thyroid 2019, 29, 44–52. [Google Scholar] [CrossRef] [PubMed]
- Samuels, M.H.; Schuff, K.G.; Carlson, N.E.; Carello, P.; Janowsky, J.S. Health status, psychological symptoms, mood, and cognition in l-thyroxine-treated hypothyroid subjects. Thyroid 2007, 17, 249–258. [Google Scholar] [CrossRef] [PubMed]
- Flynn, R.W.; Bonellie, S.R.; Jung, R.T.; MacDonald, T.M.; Morris, A.D.; Leese, G.P. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J. Clin. Endocrinol. Metab. 2010, 95, 186–193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klein Hesselink, E.N.; Klein Hesselink, M.S.; de Bock, G.H.; Gansevoort, R.T.; Bakker, S.J.; Vredeveld, E.J.; van der Horst-Schrivers, A.N.; van der Horst, I.C.; Kamphuisen, P.W.; Plukker, J.T.; et al. Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: An observational study. J. Clin. Oncol. 2013, 31, 4046–4053. [Google Scholar] [CrossRef] [Green Version]
- Weetman, A.P. Diseases associated with thyroid autoimmunity: Explanations for the expanding spectrum. Clin. Endocrinol. 2011, 74, 411–418. [Google Scholar] [CrossRef]
- Ismail, A.A.; Burr, W.A.; Walker, P.L. Acute changes in serum thyrotrophin in treated addison’s disease. Clin. Endocrinol. 1989, 30, 225–230. [Google Scholar] [CrossRef]
- Pawlikowska, T.; Chalder, T.; Hirsch, S.R.; Wallace, P.; Wright, D.J.; Wessely, S.C. Population based study of fatigue and psychological distress. BMJ 1994, 308, 763–766. [Google Scholar] [CrossRef] [Green Version]
- Lerdal, A.; Wahl, A.; Rustoen, T.; Hanestad, B.R.; Moum, T. Fatigue in the general population: A translation and test of the psychometric properties of the norwegian version of the fatigue severity scale. Scand. J. Public Health 2005, 33, 123–130. [Google Scholar] [CrossRef]
- Bay, E.; de-Leon, M.B. Chronic stress and fatigue-related quality of life after mild to moderate traumatic brain injury. J. Head Trauma Rehabil. 2011, 26, 355–363. [Google Scholar] [CrossRef] [Green Version]
- Kroenke, K.; Arrington, M.E.; Mangelsdorff, A.D. The prevalence of symptoms in medical outpatients and the adequacy of therapy. Arch. Intern. Med. 1990, 150, 1685–1689. [Google Scholar] [CrossRef] [PubMed]
- Canaris, G.J.; Manowitz, N.R.; Mayor, G.; Ridgway, E.C. The colorado thyroid disease prevalence study. Arch. Intern. Med. 2000, 160, 526–534. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jorde, R.; Waterloo, K.; Storhaug, H.; Nyrnes, A.; Sundsfjord, J.; Jenssen, T.G. Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J. Clin. Endocrinol. Metab. 2006, 91, 145–153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feller, M.; Snel, M.; Moutzouri, E.; Bauer, D.C.; de Montmollin, M.; Aujesky, D.; Ford, I.; Gussekloo, J.; Kearney, P.M.; Mooijaart, S.; et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: A systematic review and meta-analysis. JAMA 2018, 320, 1349–1359. [Google Scholar] [CrossRef] [PubMed]
- Livadas, S.; Bothou, C.; Androulakis, I.; Boniakos, A.; Angelopoulos, N.; Duntas, L. Levothyroxine replacement therapy and overuse: A timely diagnostic approach. Thyroid 2018, 28, 1580–1586. [Google Scholar] [CrossRef] [PubMed]
- Walsh, J.P.; Ward, L.C.; Burke, V.; Bhagat, C.I.; Shiels, L.; Henley, D.; Gillett, M.J.; Gilbert, R.; Tanner, M.; Stuckey, B.G. Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: Results of a double-blind, randomized clinical trial. J. Clin. Endocrinol. Metab. 2006, 91, 2624–2630. [Google Scholar] [CrossRef] [Green Version]
- Saravanan, P.; Chau, W.F.; Roberts, N.; Vedhara, K.; Greenwood, R.; Dayan, C.M. Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: Results of a large, controlled community-based questionnaire study. Clin. Endocrinol. 2002, 57, 577–585. [Google Scholar] [CrossRef]
- Wekking, E.M.; Appelhof, B.C.; Fliers, E.; Schene, A.H.; Huyser, J.; Tijssen, J.G.; Wiersinga, W.M. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur. J. Endocrinol. 2005, 153, 747–753. [Google Scholar] [CrossRef]
- Somwaru, L.L.; Arnold, A.M.; Joshi, N.; Fried, L.P.; Cappola, A.R. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J. Clin. Endocrinol. Metab. 2009, 94, 1342–1345. [Google Scholar] [CrossRef]
- Bakhteyar, H.; Cassone, C.; Kohan, H.G.; Sani, S.N. Kinetic analysis of drug release from compounded slow-release capsules of liothyronine sodium (t3). Int. J. Pharm. Compd. 2017, 21, 418–425. [Google Scholar]
- Wiersinga, W.M. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat. Rev. Endocrinol. 2014, 10, 164–174. [Google Scholar] [CrossRef]
- Baillet, J.; Paillard, J.; Behar, A.; Sainte-Laudy, B.; Albagli, B.; Dureuil, J. Effectiveness of various hormonal preparations in adults with hypothyroidism (author’s transl). Nouv. Presse Med. 1981, 10, 235–237. [Google Scholar]
- Jackson, I.M.; Cobb, W.E. Why does anyone still use desiccated thyroid usp? Am. J. Med. 1978, 64, 284–288. [Google Scholar] [CrossRef]
- Krenning, E.P.; Docter, R.; Visser, T.J.; Hennemann, G. Replacement therapy with l-thyroxine: Serum thyroid hormone and thyrotropin levels in hypothyroid patients changing from desiccated thyroid to pure thyroxine substitution therapy. Neth. J. Med. 1981, 24, 1–5. [Google Scholar] [PubMed]
- Penny, R.; Frasier, S.D. Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving usp thyroid. Am. J. Dis. Child. 1980, 134, 16–18. [Google Scholar] [CrossRef] [PubMed]
- Bindels, A.J.; Meinders, A.E. The serum concentrations of t3, t4 and tsh in evaluating replacement therapy in primary hypothyroidism. Neth. J. Med. 1988, 32, 59–71. [Google Scholar] [PubMed]
- Hoang, T.D.; Olsen, C.H.; Mai, V.Q.; Clyde, P.W.; Shakir, M.K. 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. [Google Scholar] [CrossRef] [Green Version]
- Peterson, S.J.; Cappola, A.R.; Castro, M.R.; Dayan, C.M.; Farwell, A.P.; Hennessey, J.V.; Kopp, P.A.; Ross, D.S.; Samuels, M.H.; Sawka, A.M.; et al. An online survey of hypothyroid patients demonstrates prominent dissatisfaction. Thyroid 2018, 28, 707–721. [Google Scholar] [CrossRef] [Green Version]
- Gullo, D.; Latina, A.; Frasca, F.; Le Moli, R.; Pellegriti, G.; Vigneri, R. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS ONE 2011, 6, e22552. [Google Scholar] [CrossRef] [Green Version]
- Grozinsky-Glasberg, S.; Fraser, A.; Nahshoni, E.; Weizman, A.; Leibovici, L. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: Meta-analysis of randomized controlled trials. J. Clin. Endocrinol. Metab. 2006, 91, 2592–2599. [Google Scholar] [CrossRef] [Green Version]
- Nygaard, B.; Jensen, E.W.; Kvetny, J.; Jarlov, A.; Faber, J. Effect of combination therapy with thyroxine (t4) and 3,5,3′-triiodothyronine versus t4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Eur. J. Endocrinol. 2009, 161, 895–902. [Google Scholar] [CrossRef] [PubMed]
- Surks, M.I.; Schadlow, A.R.; Oppenheimer, J.H. A new radioimmunoassay for plasma l-triiodothyronine: Measurements in thyroid disease and in patients maintained on hormonal replacement. J. Clin. Investig. 1972, 51, 3104–3113. [Google Scholar] [CrossRef] [PubMed]
- Wiersinga, W.M.; Duntas, L.; Fadeyev, V.; Nygaard, B.; Vanderpump, M.P. 2012 eta guidelines: The use of l-t4 + l-t3 in the treatment of hypothyroidism. Eur. Thyroid J. 2012, 1, 55–71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Samuels, M.H.; Kolobova, I.; Niederhausen, M.; Janowsky, J.S.; Schuff, K.G. 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Asvold, B.O.; Vatten, L.J.; Nilsen, T.I.; Bjoro, T. The association between tsh within the reference range and serum lipid concentrations in a population-based study. The hunt study. Eur. J. Endocrinol. 2007, 156, 181–186. [Google Scholar] [CrossRef]
- Ning, Y.; Cheng, Y.J.; Liu, L.J.; Sara, J.D.; Cao, Z.Y.; Zheng, W.P.; Zhang, T.S.; Han, H.J.; Yang, Z.Y.; Zhang, Y.; et al. What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants. BMC Med. 2017, 15, 21. [Google Scholar] [CrossRef] [Green Version]
- Chaker, L.; Baumgartner, C.; den Elzen, W.P.; Ikram, M.A.; Blum, M.R.; Collet, T.H.; Bakker, S.J.; Dehghan, A.; Drechsler, C.; Luben, R.N.; et al. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis. J. Clin. Endocrinol. Metab. 2015, 100, 2181–2191. [Google Scholar] [CrossRef] [Green Version]
- Rodondi, N.; den Elzen, W.P.; Bauer, D.C.; Cappola, A.R.; Razvi, S.; Walsh, J.P.; Asvold, B.O.; Iervasi, G.; Imaizumi, M.; Collet, T.H.; et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010, 304, 1365–1374. [Google Scholar] [CrossRef]
- Razvi, S.; Weaver, J.U.; Butler, T.J.; Pearce, S.H. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch. Intern. Med. 2012, 172, 811–817. [Google Scholar] [CrossRef] [Green Version]
- Gulseren, S.; Gulseren, L.; Hekimsoy, Z.; Cetinay, P.; Ozen, C.; Tokatlioglu, B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch. Med. Res. 2006, 37, 133–139. [Google Scholar] [CrossRef]
- Kim, J.S.; Zhang, Y.; Chang, Y.; Ryu, S.; Guallar, E.; Shin, Y.C.; Shin, H.; Lim, S.W.; Cho, J. Subclinical hypothyroidism and incident depression in young and middle-age adults. J. Clin. Endocrinol. Metab. 2018, 103, 1827–1833. [Google Scholar] [CrossRef] [PubMed]
- Panicker, V.; Saravanan, P.; Vaidya, B.; Evans, J.; Hattersley, A.T.; Frayling, T.M.; Dayan, C.M. 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. 2009, 94, 1623–1629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Appelhof, B.C.; Peeters, R.P.; Wiersinga, W.M.; Visser, T.J.; Wekking, E.M.; Huyser, J.; Schene, A.H.; Tijssen, J.G.; Hoogendijk, W.J.; Fliers, E. Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3′-triiodothyronine therapy. J. Clin. Endocrinol. Metab. 2005, 90, 6296–6299. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peeters, R.P.; van den Beld, A.W.; Attalki, H.; Toor, H.; de Rijke, Y.B.; Kuiper, G.G.; Lamberts, S.W.; Janssen, J.A.; Uitterlinden, A.G.; Visser, T.J. A new polymorphism in the type ii deiodinase gene is associated with circulating thyroid hormone parameters. Am. J. Physiol. Endocrinol. Metab. 2005, 289, E75–E81. [Google Scholar] [CrossRef] [PubMed]
- Heemstra, K.A.; Hoftijzer, H.C.; van der Deure, W.M.; Peeters, R.P.; Fliers, E.; Appelhof, B.C.; Wiersinga, W.M.; Corssmit, E.P.; Visser, T.J.; Smit, J.W. Thr92ala polymorphism in the type 2 deiodinase is not associated with t4 dose in athyroid patients or patients with hashimoto thyroiditis. Clin. Endocrinol. 2009, 71, 279–283. [Google Scholar] [CrossRef] [PubMed]
- Carle, A.; Faber, J.; Steffensen, R.; Laurberg, P.; Nygaard, B. Hypothyroid patients encoding combined mct10 and dio2 gene polymorphisms may prefer l-t3 + l-t4 combination treatment—Data using a blind, randomized, clinical study. Eur. Thyroid J. 2017, 6, 143–151. [Google Scholar] [CrossRef] [Green Version]
- Teumer, A.; Chaker, L.; Groeneweg, S.; Li, Y.; Di Munno, C.; Barbieri, C.; Schultheiss, U.T.; Traglia, M.; Ahluwalia, T.S.; Akiyama, M.; et al. Genome-wide analyses identify a role for slc17a4 and aadat in thyroid hormone regulation. Nat. Commun. 2018, 9, 4455. [Google Scholar] [CrossRef] [Green Version]
- Biondi, B. The normal tsh reference range: What has changed in the last decade? J. Clin. Endocrinol. Metab. 2013, 98, 3584–3587. [Google Scholar] [CrossRef] [Green Version]
- Hyland, K.A.; Arnold, A.M.; Lee, J.S.; Cappola, A.R. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: The cardiovascular health study. J. Clin. Endocrinol. Metab. 2013, 98, 533–540. [Google Scholar] [CrossRef] [Green Version]
- Gussekloo, J.; van Exel, E.; de Craen, A.J.; Meinders, A.E.; Frolich, M.; Westendorp, R.G. Thyroid status, disability and cognitive function, and survival in old age. JAMA 2004, 292, 2591–2599. [Google Scholar] [CrossRef] [Green Version]
- Gencer, B.; Collet, T.H.; Virgini, V.; Bauer, D.C.; Gussekloo, J.; Cappola, A.R.; Nanchen, D.; den Elzen, W.P.; Balmer, P.; Luben, R.N.; et al. Subclinical thyroid dysfunction and the risk of heart failure events: An individual participant data analysis from 6 prospective cohorts. Circulation 2012, 126, 1040–1049. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baek, J.H.; Chung, P.W.; Kim, Y.B.; Moon, H.S.; Suh, B.C.; Jin, D.K.; Kim, B.M.; Rhee, E.J.; Lee, Y.T.; Park, K.Y. Favorable influence of subclinical hypothyroidism on the functional outcomes in stroke patients. Endocr. J. 2010, 57, 23–29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dhital, R.; Poudel, D.R.; Tachamo, N.; Gyawali, B.; Basnet, S.; Shrestha, P.; Karmacharya, P. Ischemic stroke and impact of thyroid profile at presentation: A systematic review and meta-analysis of observational studies. J. Stroke Cerebrovasc. Dis. 2017, 26, 2926–2934. [Google Scholar] [CrossRef] [PubMed]
- Moon, S.; Kim, M.J.; Yu, J.M.; Yoo, H.J.; Park, Y.J. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies. Thyroid 2018, 28, 1101–1110. [Google Scholar] [CrossRef] [PubMed]
- Calsolaro, V.; Niccolai, F.; Pasqualetti, G.; Calabrese, A.M.; Polini, A.; Okoye, C.; Magno, S.; Caraccio, N.; Monzani, F. Overt and subclinical hypothyroidism in the elderly: When to treat? Front. Endocrinol. (Lausanne) 2019, 10, 177. [Google Scholar] [CrossRef] [PubMed]
- Van Vliet, N.A.; Noordam, R.; van Klinken, J.B.; Westendorp, R.G.; Bassett, J.D.; Williams, G.R.; van Heemst, D. Thyroid stimulating hormone and bone mineral density: Evidence from a two-sample mendelian randomization study and a candidate gene association study. J. Bone Miner. Res. 2018, 33, 1318–1325. [Google Scholar] [CrossRef]
TSH Level (mIU/L) | Treatment, Goal TSH (mIU/L) | Addition with DTE | Addition with Liothyronine | First Author (ref. nr.) | |
---|---|---|---|---|---|
ATA | >10 | 0.5–3.5 | No | Not recommended, subgroups may benefit | Jonklass [1] |
AACE + ATA | >10 Individualize | No | Garber [2] | ||
BTA | Not specified | Okosieme [18] | |||
ETA | >10 A trial in <65 yo | 0.4–2.5 | No | Experimentally, dose ratio 13:1–20:1 | Pearce [3] |
BSEM | >10 | No recomm. | No recomm. | No recommendation | Sgarbi [19] |
AME | 1–3, upper normal in elderly | Divided doses, ratio 10:1–20:1 | A trial, dose ratio 10:1–20:1, not in elderly | Guglielmi [20] | |
Clinical Guidelines | TSH >20 | No recommendation | Bekkering [13] |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Calissendorff, J.; Falhammar, H. To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina 2020, 56, 40. https://doi.org/10.3390/medicina56010040
Calissendorff J, Falhammar H. To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina. 2020; 56(1):40. https://doi.org/10.3390/medicina56010040
Chicago/Turabian StyleCalissendorff, Jan, and Henrik Falhammar. 2020. "To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence?" Medicina 56, no. 1: 40. https://doi.org/10.3390/medicina56010040