Abstract
This review summarizes the current knowledge regarding subclinical hypothyroidism, with special focus on etiology and the challenges in establishing the diagnosis and selection of those patients who will benefit from treatment. The disease is stratified into mild, moderate, and severe, thus type of therapy should be decided taking into consideration the stage of the disease together with the patient’s gender, comorbidities, and age. While most younger patients will benefit from treatment, among the elderly treatment decisions need to be based on a personalized approach.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22:1200–35.
Duntas LH. Subclinical hypothyroidism: a misnomer in search of a new name. Thyroid. 2001;11:361–2.
Evered DC, Ormston BJ, Smith PA, Hall R, Bird T. Grades of hypothyroidism. Br Med J. 1973;17(5854):657–62.
Baumgartner C, Blum MR, Rodondi N. Subclinical hypothyroidism: summary of evidence in 2014. Swiss Med Wkly. 2014;144:w14058. https://doi.org/10.4414/smw.2014.14058.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Wickham survey. Clin Endocrinol (Oxf). 1997;7:481–93.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526–34.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a 20-year follow-up of the Wickham survey. Clin Endocrinol (Oxf). 1995;43:55–68.
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. 2004;291:228–38.
Diez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89:4890–7.
Somwaru LL, Rariy CM, Arnold AM, Cappola AR. The natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study. J Clin Endocrinol Metab. 2012;97:1962–9.
Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations. in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87:1068–72.
Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017;376:2556–65.
Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab. 2007;92:4575–82.
Sichieri R, Baima J, Marante T, de Vasconcellos MT, Moura AS, Vaisman M. Low prevalence of hypothyroidism among black and mulatto people in a population-based study of Brazilian women. Clin Endocrinol (Oxf). 2007;66:803–70.
Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, et al. Moderate alcohol consumption may protect against overt autoimmune hypothyroidism: a population-based case-control study. Eur J Endocrinol. 2012;167:483–90.
Starkenburg S, Munroe ME, Waltenbaugh C. Early alteration in leukocyte populations and Th1/Th2 function in ethanol consuming mice. Alcohol Clin Exp Res. 2001;25:1221–30. https://doi.org/10.1111/j.1530-0277.2001.tb02339.x.
Belin RM, Astor BC, Powe NR, Ladenson PW. Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a high prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2004;89:6077–86.
Laurberg P, Jørgensen T, Perrild H, Ovesen L, Knudsen N, Bulow Pedersen I, et al. The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur J Endocrinol. 2006;155:219–28.
Tognini S, Pasqualetti G, Calsolaro V, Polini A, Monzani F. Cognitive function and quality of life in mild thyroid hormone deficiency. Recent Pat Endocr Metab Immune Drug Discov. 2014;8:124–34.
Duntas LH, Maillis A. Hypothyroidism and depression: salient aspects of pathogenesis and management. Minerva Endocrinol. 2013;38:365–77.
Panicker V, Evans J, Bjøro T, Asvold BO, Dayan CM, Bjerkeset O. A paradoxical difference in relationship between anxiety, depression and thyroid function in subjects on and not on T4: findings from the HUNT study. Clin Endocrinol (Oxf). 2009;71:574–80.
Dayan CM, Panicker V. Hypothyroidism and depression. Eur Thyroid J. 2013;2:168–79.
Joffe RT, Pearce EN, Hennessey JV, Ryan JJ, Stern RA. Subclinical hypothyroidism, mood, and cognition in older adults: a review. Int J Geriatr Psychiatry. 2013;28:111–8. https://doi.org/10.1002/gps.3796.
Park YJ, Lee EJ, Lee YJ, Choi SH, Park JH, Lee SB. Subclinical hypothyroidism (SCH) is not associated with metabolic derangement, cognitive impairment, depression or poor quality of life in elderly subjects. Arch Gerontol Geriatr. 2010;50:e68–73.
Chueire VB, Romaldini JH, Ward LS. Subclinical hypothyroidism increases the risk of depression in the elderly. Arch Gerontol Geriatr. 2006;44:21–8.
Vanderpump MP, Tunbridge WM, French JM, Tunbridge F, Young ET. The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid. 1996;6:155–60.
Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham survey cohort. J Clin Endocrinol Metab. 2010;95:1734–40.
Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab. 2004;89:3365–70.
Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med. 2005;165:2467–72.
Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005;165:2460–6.
Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a meta-analysis. J Clin Endocrinol Metab. 2008;93:2998–3007. https://doi.org/10.1210/jc.2008-0167.
Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292:2591–9.
Collet TH, Bauer DC, Cappola AR, Asvold BO, Weiler S, Vittinghoff E, et al. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis. J Clin Endocrinol Metab. 2014;99:3353–62. https://doi.org/10.1210/jc.2014-1250.
Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29:76–131.
Dong J, Gao C, Liu J, Cao Y, Tian L. TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes. Oncotarget. 2016;28:39207–15. https://doi.org/10.18632/oncotarget.9393.
Duntas LH, Brenta G. The effect of thyroid disorders on lipid levels and metabolism. Med Clin North Am. 2012;96:269–81. https://doi.org/10.1016/j.mcna.2012.01.012.
Duntas LH, Wartofsky L. Cardiovascular risk and subclinical hypothyroidism: focus on lipids and new emerging risk factors. What is the evidence? Thyroid. 2007;17:1075–84.
Cheserek MJ, Wu GR, Ntazinda A, Shi YH, Shen LY, Le GW. Association between thyroid hormones, lipids and oxidative stress markers in subclinical hypothyroidism. J Med Biochem. 2015;34:323–31. https://doi.org/10.2478/jomb-2014-0044.
Brenta G, Berg G, Arias P, Zago V, Schnitman M, Muzzio ML, et al. Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism: response to L-T(4) treatment. Thyroid. 2007;17:453–60.
Pearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab. 2012;97:326–33. https://doi.org/10.1210/jc.2011-2532.
Khazan M, Amouzegar A, Gharibzadeh S, Mehran L, Tohidi M, Azizi F. Prevalence of hypothyroidism in patients with dyslipidemia: Tehran thyroid study (TTS). Horm Metab Res. 2014;46:980–4. https://doi.org/10.1055/s-0034-1389997.
Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160:785–90. https://doi.org/10.1530/EJE-08-0797.
Rotondi M, Leporati P, Rizza MI, Clerici A, Groppelli G, Pallavicini C. Raised serum TSH in morbid-obese and non-obese patients: effect on the circulating lipid profile. Endocrine. 2014;45:92–7. https://doi.org/10.1007/s12020-013-9928-8.
Asvold BO, Bjoro T, Vatten LJ. Associations of TSH levels within the reference range with future blood pressure and lipid concentrations: 11-year follow-up of the HUNT study. Eur J Endocrinol. 2013;169:73–82.
Brenta G, Berg G, Miksztowicz V, Lopez G, Lucero D, Faingold C, et al. Atherogenic lipoproteins in subclinical hypothyroidism and their relationship with hepatic lipase activity: response to replacement treatment with levothyroxine. Thyroid. 2016;26:365–72. https://doi.org/10.1089/thy.2015.0140.
Staub JJ, Althaus BU, Engler H, Ryff AS, Trabucco P, Marquardt K, et al. Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med. 1992;92:631–42.
Efstathiadou Z, Bitsis S, Milionis HJ, Kukuvitis A, Bairaktari ET, Elisaf MS, et al. Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial? Eur J Endocrinol. 2001;145:705–10.
Franklyn JA, Daykin J, Betteridge J, Hughes EA, Holder R, Jones SR, Sheppard MC. Thyroxine replacement therapy and circulating lipid concentrations. Clin Endocrinol. 1993;38:453–9.
Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel thyroid study). J Clin Endocrinol Metab. 2001;86:4860–6.
Danese MD, Ladenson PW, Meinert CL, Powe NR. Effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab. 2000;85:2993–3001.
Monzani F, Caraccio N, Kozàkowà 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;89:2099–106.
Ito M, Arishima T, Kudo T, Nishihara E, Ohye H, Kubota S, et al. Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients. J Clin Endocrinol Metab. 2007;92:608–11.
Sniderman A, McQueen M, Contois J, Williams K, Furberg CD. Why is non-high-density lipoprotein cholesterol a better marker of the risk of vascular disease than low-density lipoprotein cholesterol? J Clin Lipidol. 2010;4:152–5. https://doi.org/10.1016/j.jacl.2010.03.005.
Michalopoulou G, Alevizaki M, Piperingos G, Mitsibounas D, Mantzos E, Adamopoulos P, et al. High serum cholesterol levels in persons with ‘high-normal’ TSH levels: should one extend the definition of subclinical hypothyroidism? Eur J Endocrinol. 1998;138:141–5.
Duntas LH, Biondi B. New insights into subclinical hypothyroidism and cardiovascular risk. Semin Thromb Hemost. 2011;37:27–34.
Wang G, Liu J, Yang N, Hu Y, Zhang H, Miao L, et al. Levothyroxine treatment restored the decreased circulating fibroblast growth factor 21 levels in patients with hypothyroidism. Eur J Intern Med. 2016;31:94–8. https://doi.org/10.1016/j.ejim.2016.03.028.
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;2:215–28. https://doi.org/10.1159/000356507.
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. https://doi.org/10.1089/thy.2014.0028.
Decandia F. Risk factors for cardiovascular disease in subclinical hypothyroidism. Ir J Med Sci. 2017;187(1):39–43. https://doi.org/10.1007/s11845-017-1617-9.
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 (IPD) analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040.
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. 2010;304:1365–74.
Biondi B. Cardiovascular effects of mild hypothyroidism. Thyroid. 2007;17:625–30.
Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379:1142–54. https://doi.org/10.1016/S0140-6736(11)60276-6.
Lioudaki E, Mavroeidi NG, Mikhailidis DP, Ganotakis ES. Subclinical hypothyroidism and vascular risk: Αn update. Hormones (Athens). 2013;12:495–506. https://doi.org/10.14310/horm.2002.1437.
Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, The TRUST Study Group, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376:2534–44. https://doi.org/10.1056/NEJMoa1603825.
Floriani C, Gencer B, Collet TH, Rodondi N. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Clin Endocrinol. 2017;86:830–6. https://doi.org/10.1111/cen.13340.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Biondi, B., Duntas, L.H. (2019). Subclinical Hypothyroidism. In: Luster, M., Duntas, L., Wartofsky, L. (eds) The Thyroid and Its Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-72102-6_18
Download citation
DOI: https://doi.org/10.1007/978-3-319-72102-6_18
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-72100-2
Online ISBN: 978-3-319-72102-6
eBook Packages: MedicineMedicine (R0)