Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 144 No. 5152 (2014)

Subclinical hypothyroidism: summary of evidence in 2014

  • Christine Baumgartner
  • Manuel Raphael Blum
  • Nicolas Rodondi
DOI
https://doi.org/10.4414/smw.2014.14058
Cite this as:
Swiss Med Wkly. 2014;144:w14058
Published
15.12.2014

Abstract

Subclinical hypothyroidism, which is defined as elevated thyroid-stimulating hormone (TSH) levels with free thyroxine concentrations within the reference range, is a common disorder that increases with age and affects up to 18% of the elderly, with a higher prevalence in women compared to men. Prospective data have shown an increased risk of coronary heart disease events, heart failure, and cardiovascular mortality among affected adults. Conflicting results have been found on the association between subclinical hypothyroidism and cognitive impairment, depression and the risk of fractures. Management strategies including screening and treatment of subclinical hypothyroidism are still controversial, while the ongoing European randomised controlled trial “TRUST” targets to solve these uncertainties. This narrative review aims to assess current evidence on the clinical aspects, as well as screening and treatment recommendations in adults with subclinical hypothyroidism.

References

  1. Helfand M. Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2004;140(2):128–41. Epub 2004/01/22. PubMed PMID: 14734337.
  2. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA: the journal of the American Medical Association. 2004;291(2):228–38. Epub 2004/01/15. doi: 10.1001/jama.291.2.228. PubMed PMID: 14722150.
  3. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526–34. Epub 2000/03/01. PubMed PMID: 10695693.
  4. Virgini V, Baumgartner C, Bischoff T, Haller DM, Frey P, Rosemann T, et al. Comment les médecins de famille prennent-ils en charge l’hypthyroïdie infraclinique? Revue medicale suisse. 2014;10(420):526–9. Epub 2014/04/08. PubMed PMID: 24701670.
  5. den Elzen WP, Lefèbre-van de Fliert AA, Virgini V, Frey P, Mooijaart SP, Kearney P, et al. International variation in GP treatment strategies for subclinical hypothyroidism in older adults. Br J Gen Pract. In press.
  6. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76–131. Epub 2007/11/10. doi: 10.1210/er.2006–0043. PubMed PMID: 17991805.
  7. Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. The Cochrane database of systematic reviews. 2007(3):CD003419. Epub 2007/07/20. doi: 10.1002/14651858.CD003419.pub2. PubMed PMID: 17636722.
  8. Rugge B, Balshem H, Sehgal R, Relevo R, Gorman P, Helfand M. Screening and treatment of subclinical hypothyroidism or hyperthyroidism. Comparative Effectiveness Reviews, No.24. Rockville (MD): Agency for Healthcare Research and Quality (US). 2011. http://effectivehealthcare.ahrq.gov/ehc/products/129/750/Hypo-Hyper-Thyroid_CER24_20111114.pdf http://effectivehealthcare.ahrq.gov/ehc/products/129/750/Hypo-Hyper-Thyroid_CER24_20111114.pd.
  9. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142–54.
  10. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA: the journal of the American Medical Association. 2010;304(12):1365–74. Epub 2010/09/23. doi: 10.1001/jama.2010.1361. PubMed PMID: 20858880; PubMed Central PMCID: PMC3923470.
  11. Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040–9. Epub 2012/07/24. doi: 10.1161/CIRCULATIONAHA.112.096024. PubMed PMID: 22821943; PubMed Central PMCID: PMC3884576.
  12. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clinical endocrinology. 1995;43(1):55–68. Epub 1995/07/01. PubMed PMID: 7641412.
  13. Somwaru LL, Rariy CM, Arnold AM, Cappola AR. The natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study. The Journal of clinical endocrinology and metabolism. 2012;97(6):1962–9. Epub 2012/03/23. doi: 10.1210/jc.2011–3047. PubMed PMID: 22438233; PubMed Central PMCID: PMC3387427.
  14. Surks MI, Goswami G, Daniels GH. The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metab. 2005;90(9):5489–96.
  15. Waring AC, Arnold AM, Newman AB, Buzkova P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97(11):3944–50.
  16. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA: the journal of the American Medical Association. 2004;292(21):2591–9. Epub 2004/12/02. doi: 10.1001/jama.292.21.2591. PubMed PMID: 15572717.
  17. Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001;86(3):1110–5.
  18. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92(5):1715–23.
  19. Monzani F, Caraccio N, Kozakowa M, Dardano A, Vittone F, Virdis A, et al. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J Clin Endocrinol Metab. 2004;89(5):2099–106. Epub 2004/05/06. doi: 10.1210/jc.2003–031669. PubMed PMID: 15126526.
  20. Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab. 2000;85(9):2993–3001.
  21. Liu D, Jiang F, Shan Z, Wang B, Wang J, Lai Y, et al. A cross-sectional survey of relationship between serum TSH level and blood pressure. J Hum Hypertens. 2010;24(2):134–8.
  22. Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, et al. Subclinical thyroid dysfunction and blood pressure: a community-based study. Clin Endocrinol. 2006;65(4):486–91. Epub 2006/09/21. doi: 10.1111/j.1365–2265.2006.02619.x. PubMed PMID: 16984241.
  23. Adrees M, Gibney J, El-Saeity N, Boran G. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clin Endocrinol. 2009;71(2):298–303.
  24. Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study. Clin Endocrinol. 2012;76(6):911–8. Epub 2011/12/23. doi: 10.1111/j.1365–2265.2011.04328.x. PubMed PMID: 22187968; PubMed Central PMCID: PMC3334430.
  25. Garin MC, Arnold AM, Lee JS, Tracy RP, Cappola AR. Subclinical hypothyroidism, weight change, and body composition in the elderly: the Cardiovascular Health Study. J Clin Endocrinol Metab. 2014;99(4):1220–6. Epub 2014/01/18. doi: 10.1210/jc.2013–3591. PubMed PMID: 24432998; PubMed Central PMCID: PMC3973778.
  26. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med. 2012;172(10):811–7.
  27. Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012;172(10):799–809.
  28. Selmer C, Olesen JB, Hansen ML, Lindhardsen J, Olsen AM, Madsen JC, et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012;345:e7895. Epub 2012/11/29. doi: 10.1136/bmj.e7895. PubMed PMID: 23186910; PubMed Central PMCID: PMC3508199.
  29. Reuters VS, Teixeira Pde F, Vigario PS, Almeida CP, Buescu A, Ferreira MM, et al. Functional capacity and muscular abnormalities in subclinical hypothyroidism. Am J Med Sci. 2009;338(4):259–63.
  30. Brennan MD, Powell C, Kaufman KR, Sun PC, Bahn RS, Nair KS. The impact of overt and subclinical hyperthyroidism on skeletal muscle. Thyroid. 2006;16(4):375–80.
  31. Mainenti MR, Vigario PS, Teixeira PF, Maia MD, Oliveira FP, Vaisman M. Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism. J Endocrinol Invest. 2009;32(5):470–3.
  32. Ravanbod M, Asadipooya K, Kalantarhormozi M, Nabipour I, Omrani GR. Treatment of iron-deficiency anemia in patients with subclinical hypothyroidism. Am J Med. 2013;126(5):420–4.
  33. Simonsick EM, Newman AB, Ferrucci L, Satterfield S, Harris TB, Rodondi N, et al. Subclinical hypothyroidism and functional mobility in older adults. Arch Intern Med. 2009;169(21):2011–7. Epub 2009/11/26. doi: 10.1001/archinternmed.2009.392. PubMed PMID: 19933964; PubMed Central PMCID: PMC2879334.
  34. Virgini VS, Wijsman LW, Rodondi N, Bauer DC, Kearney PM, Gussekloo J, et al. Subclinical thyroid dysfunction and functional capacity among elderly. Thyroid. 2014;24(2):208–14.
  35. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003;115(2):151–62.
  36. Lee JS, Buzkova P, Fink HA, Vu J, Carbone L, Chen Z, et al. Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med. 2010;170(21):1876–83. Epub 2010/11/26. doi: 10.1001/archinternmed.2010.424. PubMed PMID: 21098345.
  37. Svare A, Nilsen TI, Asvold BO, Forsmo S, Schei B, Bjoro T, et al. Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway. European journal of endocrinology / European Federation of Endocrine Societies. 2013;169(6):845–52. Epub 2013/09/14. doi: 10.1530/EJE-13–0546. PubMed PMID: 24031093.
  38. Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, et al. Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment. Clin Investig. 1993;71(5):367–71.
  39. Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006;145(8):573–81. Epub 2006/10/18. PubMed PMID: 17043339.
  40. Pae CU, Mandelli L, Han C, Ham BJ, Masand PS, Patkar AA, et al. Thyroid hormones affect recovery from depression during antidepressant treatment. Psychiatry Clin Neurosci. 2009;63(3):305–13.
  41. Ceresini G, Lauretani F, Maggio M, Ceda GP, Morganti S, Usberti E, et al. Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J Am Geriatr Soc. 2009;57(1):89–93. Epub 2008/12/05. doi: 10.1111/j.1532–5415.2008.02080.x. PubMed PMID: 19054181; PubMed Central PMCID: PMC2631617.
  42. Parsaik AK, Singh B, Roberts RO, Pankratz S, Edwards KK, Geda YE, et al. Hypothyroidism and risk of mild cognitive impairment in elderly persons: a population-based study. JAMA Neurol. 2014;71(2):201–7.
  43. Parle J, Roberts L, Wilson S, Pattison H, Roalfe A, Haque MS, et al. A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study. J Clin Endocrinol Metab. 2010;95(8):3623–32. Epub 2010/05/27. doi: 10.1210/jc.2009–2571. PubMed PMID: 20501682.
  44. Canpolat AG, Kav T, Sivri B, Yildiz BO. Effects of L-thyroxine on gastric motility and ghrelin in subclinical hypothyroidism: a prospective study. J Clin Endocrinol Metab. 2013;98(11):2013–1488.
  45. Chung GE, Kim D, Kim W, Yim JY, Park MJ, Kim YJ, et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol. 2012;57(1):150–6.
  46. Bremner AP, Feddema P, Joske DJ, Leedman PJ, O’Leary PC, Olynyk JK, et al. Significant association between thyroid hormones and erythrocyte indices in euthyroid subjects. Clin Endocrinol. 2012;76(2):304–11.
  47. Cinemre H, Bilir C, Gokosmanoglu F, Bahcebasi T. Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study. J Clin Endocrinol Metab. 2009;94(1):151–6.
  48. Christ-Crain M, Meier C, Huber P, Zulewski H, Staub JJ, Muller B. Effect of restoration of euthyroidism on peripheral blood cells and erythropoietin in women with subclinical hypothyroidism. Hormones (Athens). 2003;2(4):237–42.
  49. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239–45.
  50. Benhadi N, Wiersinga WM, Reitsma JB, Vrijkotte TG, Bonsel GJ. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. European journal of endocrinology / European Federation of Endocrine Societies. 2009;160(6):985–91.
  51. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012;119(2 Pt 1):315–20.
  52. Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493–501.
  53. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):76–94.
  54. Kong WM, Sheikh MH, Lumb PJ, Naoumova RP, Freedman DB, Crook M, et al. A 6–month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med. 2002;112(5):348–54. Epub 2002/03/21. PubMed PMID: 11904108.
  55. Müller B. “Subklinische” Hypo- und Hyperthyreose. Schweizerische Gesellschaft für Endokrinologie und Diabetologie. http://www.sgedssed.ch/fileadmin/files/dokumente/EDM_Key_Slides_2010–2011/SGED_Subklinische_Hypo_Hyperthyresose.pdf http://effectivehealthcare.ahrq.gov/ehc/products/129/750/Hypo-Hyper-Thyroid_CER24_20111114.pdf 2010–2011.
  56. Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, et al. 2013 ETA Guideline: Management of subclinical hypothyroidism. Eur Thyroid J. 2013;2(4):215–28.
  57. Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP. 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(1):186–93.
  58. Rodondi N, Bauer DC. Subclinical hypothyroidism and cardiovascular risk: how to end the controversy. J Clin Endocrinol Metab. 2013;98(6):2267–9. Epub 2013/05/02. doi: 10.1210/jc.2013–1875. PubMed PMID: 23633199; PubMed Central PMCID: PMC3667255.
  59. Blum MR, Collet TH, Krebs D, Stettler C, Christ E, Virgini V, et al. Subklinische Hypothyreose. Schweiz Med Forum. 2013;13(39):772–5.

Most read articles by the same author(s)