Endocrinol Metab.  2021 Jun;36(3):500-513. 10.3803/EnM.2021.1066.

Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea

Abstract

Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Keyword

Subclinical hypothyroidism; Diagnosis; Prevalence; Treatment

Reference

1. Braverman LE, Cooper DS, Kopp PA. Werner & Ingbar’s the thyroid. 11th ed. Philadelphia: Wolters Kluwer;2021. Chapter 50:Subclinical hypothyroidism. p. 635–40.
2. Cooper DS. Clinical practice. Subclinical hypothyroidism. N Engl J Med. 2001; 345:260–5.
3. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008; 29:76–131.
Article
4. Hansen PS, Brix TH, Sorensen TI, Kyvik KO, Hegedus L. Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab. 2004; 89:1181–7.
Article
5. Kim WG, Kim WB, Woo G, Kim H, Cho Y, Kim TY, et al. Thyroid stimulating hormone reference range and prevalence of thyroid dysfunction in the Korean population: Korea National Health and Nutrition Examination Survey 2013 to 2015. Endocrinol Metab (Seoul). 2017; 32:106–14.
Article
6. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. 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; 87:489–99.
7. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379:1142–54.
Article
8. Mendes D, Alves C, Silverio N, Batel Marques F. Prevalence of undiagnosed hypothyroidism in Europe: a systematic review and meta-analysis. Eur Thyroid J. 2019; 8:130–43.
Article
9. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977; 7:481–93.
Article
10. Nystrom E, Bengtsson C, Lindquist O, Noppa H, Lindstedt G, Lundberg PA. Thyroid disease and high concentration of serum thyrotrophin in a population sample of women. A 4-year follow-up. Acta Med Scand. 1981; 210:39–46.
11. Drinka PJ, Nolten WE. Prevalence of previously undiagnosed hypothyroidism in residents of a midwestern nursing home. South Med J. 1990; 83:1259–61. 1265
Article
12. Konno N, Yuri K, Taguchi H, Miura K, Taguchi S, Hagiwara K, et al. Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations. Clin Endocrinol (Oxf). 1993; 38:273–81.
Article
13. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000; 160:526–34.
Article
14. Hoogendoorn EH, Hermus AR, de Vegt F, Ross HA, Verbeek AL, Kiemeney LA, et al. Thyroid function and prevalence of anti-thyroperoxidase antibodies in a population with borderline sufficient iodine intake: influences of age and sex. Clin Chem. 2006; 52:104–11.
Article
15. Perez-Campos Mayoral L, Hernandez-Huerta MT, Mayoral-Andrade G, Perez-Campo Mayoral E, Zenteno E, Martinez-Cruz R, et al. TSH levels in subclinical hypothyroidism in the 97.5th percentile of the population. Int J Endocrinol. 2020; 2020:2698627.
16. Chung JH. Evaluation of thyroid hormone levels and urinary iodine concentrations in Koreans based on the data from Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Endocrinol Metab (Seoul). 2018; 33:160–3.
Article
17. Biondi B. The normal TSH reference range: what has changed in the last decade? J Clin Endocrinol Metab. 2013; 98:3584–7.
Article
18. 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.
Article
19. Chung JH. Update on thyroid hormone levels and thyroid dysfunction in the Korean population based on data from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Endocrinol Metab (Seoul). 2020; 35:7–13.
Article
20. Park SY, Kim HI, Oh HK, Kim TH, Jang HW, Chung JH, et al. Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: data from Korean National Health and Nutrition Examination Survey IV (2013–2015). PLoS One. 2018; 13:e0190738.
Article
21. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017; 27:315–89.
Article
22. Li C, Shan Z, Mao J, Wang W, Xie X, Zhou W, et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women? J Clin Endocrinol Metab. 2014; 99:73–9.
Article
23. Moon HW, Chung HJ, Park CM, Hur M, Yun YM. Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women. Ann Lab Med. 2015; 35:198–204.
Article
24. Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017; 376:2556–65.
Article
25. Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: a review. JAMA. 2019; 322:153–60.
26. 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.
27. Kim YA, Park YJ. Prevalence and risk factors of subclinical thyroid disease. Endocrinol Metab (Seoul). 2014; 29:20–9.
Article
28. Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O’Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010; 95:1095–104.
Article
29. Moore DC. Natural course of ‘subclinical’ hypothyroidism in childhood and adolescence. Arch Pediatr Adolesc Med. 1996; 150:293–7.
Article
30. Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Levy Y, Surks MI. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med. 2007; 167:1533–8.
31. Volzke H, Alte D, Kohlmann T, Ludemann J, Nauck M, John U, et al. Reference intervals of serum thyroid function tests in a previously iodine-deficient area. Thyroid. 2005; 15:279–85.
Article
32. Caron PJ, Nieman LK, Rose SR, Nisula BC. Deficient nocturnal surge of thyrotropin in central hypothyroidism. J Clin Endocrinol Metab. 1986; 62:960–4.
Article
33. Kim TH, Kim KW, Ahn HY, Choi HS, Won H, Choi Y, et al. Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status. J Clin Endocrinol Metab. 2013; 98:3420–9.
Article
34. Hennessey JV, Espaillat R. Subclinical hypothyroidism: a historical view and shifting prevalence. Int J Clin Pract. 2015; 69:771–82.
Article
35. Lee MW, Shin DY, Kim KJ, Hwang S, Lee EJ. The biochemical prognostic factors of subclinical hypothyroidism. Endocrinol Metab (Seoul). 2014; 29:154–62.
Article
36. Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab. 2002; 87:3221–6.
Article
37. 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.
Article
38. Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab. 1994; 78:393–7.
Article
39. Cho NH, Choi HS, Kim KW, Kim HL, Lee SY, Choi SH, et al. Interaction between cigarette smoking and iodine intake and their impact on thyroid function. Clin Endocrinol (Oxf). 2010; 73:264–70.
40. Willms A, Bieler D, Wieler H, Willms D, Kaiser KP, Schwab R. Correlation between sonography and antibody activity in patients with Hashimoto thyroiditis. J Ultrasound Med. 2013; 32:1979–86.
Article
41. Mariotti S, Franceschi C, Cossarizza A, Pinchera A. The aging thyroid. Endocr Rev. 1995; 16:686–715.
Article
42. Boucai L, Hollowell JG, Surks MI. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid. 2011; 21:5–11.
Article
43. 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. 2004; 292:2591–9.
Article
44. Hyland KA, Arnold AM, Lee JS, Cappola AR. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study. J Clin Endocrinol Metab. 2013; 98:533–40.
Article
45. Pasqualetti G, Pagano G, Rengo G, Ferrara N, Monzani F. Subclinical hypothyroidism and cognitive impairment: systematic review and meta-analysis. J Clin Endocrinol Metab. 2015; 100:4240–8.
Article
46. Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017; 376:2534–44.
47. 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; 3:76–94.
Article
48. Kang MJ, Hwang IT, Chung HR. Excessive iodine intake and subclinical hypothyroidism in children and adolescents aged 6–19 years: results of the sixth Korean National Health and Nutrition Examination Survey, 2013–2015. Thyroid. 2018; 28:773–9.
Article
49. Cerbone M, Bravaccio C, Capalbo D, Polizzi M, Wasniewska M, Cioffi D, et al. Linear growth and intellectual outcome in children with long-term idiopathic subclinical hypothyroidism. Eur J Endocrinol. 2011; 164:591–7.
Article
50. Wasniewska M, Aversa T, Salerno M, Corrias A, Messina MF, Mussa A, et al. Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology. Eur J Endocrinol. 2015; 173:801–8.
Article
51. Aversa T, Valenzise M, Corrias A, Salerno M, De Luca F, Mussa A, et al. Underlying Hashimoto’s thyroiditis negatively affects the evolution of subclinical hypothyroidism in children irrespective of other concomitant risk factors. Thyroid. 2015; 25:183–7.
Article
52. Lee YJ, Jung SY, Jung HW, Kim SY, Lee YA, Lee SY, et al. Unfavorable course of subclinical hypothyroidism in children with Hashimoto’s thyroiditis compared to those with isolated non-autoimmune hyperthyrotropinemia. J Korean Med Sci. 2017; 32:124–9.
Article
53. Crisafulli G, Aversa T, Zirilli G, Pajno GB, Corica D, De Luca F, et al. Subclinical hypothyroidism in children: when a replacement hormonal treatment might be advisable. Front Endocrinol (Lausanne). 2019; 10:109.
Article
54. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001; 344:1743–9.
Article
55. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997; 18:404–33.
Article
56. Stricker R, Echenard M, Eberhart R, Chevailler MC, Perez V, Quinn FA, et al. Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals. Eur J Endocrinol. 2007; 157:509–14.
Article
57. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21:1081–125.
Article
58. Maraka S, Ospina NM, O’Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid. 2016; 26:580–90.
Article
59. Consortium on Thyroid and Pregnancy-Study Group on Preterm Birth. Korevaar TIM, Derakhshan A, Taylor PN, Meima M, Chen L, et al. Association of thyroid function test abnormalities and thyroid autoimmunity with preterm birth: a systematic review and meta-analysis. JAMA. 2019; 322:632–41.
Article
60. Correia N, Mullally S, Cooke G, Tun TK, Phelan N, Feeney J, et al. Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism. J Clin Endocrinol Metab. 2009; 94:3789–97.
Article
61. Zhu DF, Wang ZX, Zhang DR, Pan ZL, He S, Hu XP, et al. fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism. Brain. 2006; 129(Pt 11):2923–30.
Article
62. Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, Jenssen TG. Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab. 2006; 91:145–53.
Article
63. Loh HH, Lim LL, Yee A, Loh HS. Association between subclinical hypothyroidism and depression: an updated systematic review and meta-analysis. BMC Psychiatry. 2019; 19:12.
Article
64. Zhao T, Chen BM, Zhao XM, Shan ZY. Subclinical hypothyroidism and depression: a meta-analysis. Transl Psychiatry. 2018; 8:239.
Article
65. Demartini B, Ranieri R, Masu A, Selle V, Scarone S, Gambini O. Depressive symptoms and major depressive disorder in patients affected by subclinical hypothyroidism: a cross-sectional study. J Nerv Ment Dis. 2014; 202:603–7.
66. Park YJ, Lee EJ, Lee YJ, Choi SH, Park JH, Lee SB, et al. Subclinical hypothyroidism (SCH) is not associated with metabolic derangement, cognitive impairment, depression or poor quality of life (QoL) in elderly subjects. Arch Gerontol Geriatr. 2010; 50:e68–73.
Article
67. Kim JS, Zhang Y, Chang Y, Ryu S, Guallar E, Shin YC, et al. Subclinical hypothyroidism and incident depression in young and middle-age adults. J Clin Endocrinol Metab. 2018; 103:1827–33.
Article
68. Panicker V, Evans J, Bjoro 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.
Article
69. Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, 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; 320:1349–59.
Article
70. Mooijaart SP, Du Puy RS, Stott DJ, Kearney PM, Rodondi N, Westendorp RGJ, et al. Association between levothyroxine treatment and thyroid-related symptoms among adults aged 80 years and older with subclinical hypothyroidism. JAMA. 2019; 322:1977–86.
Article
71. Oiwa A, Minemura K, Nishio SI, Yamazaki M, Komatsu M. Implications of thyroid autoimmunity in infertile women with subclinical hypothyroidism in the absence of both goiter and anti-thyroid antibodies: lessons from three cases. Endocr J. 2019; 66:193–8.
Article
72. Chen X, Zhang N, Cai Y, Shi J. Evaluation of left ventricular diastolic function using tissue Doppler echocardiography and conventional doppler echocardiography in patients with subclinical hypothyroidism aged <60 years: a meta-analysis. J Cardiol. 2013; 61:8–15.
Article
73. Owen PJ, Sabit R, Lazarus JH. Thyroid disease and vascular function. Thyroid. 2007; 17:519–24.
Article
74. Gao N, Zhang W, Zhang YZ, Yang Q, Chen SH. Carotid intima-media thickness in patients with subclinical hypothyroidism: a meta-analysis. Atherosclerosis. 2013; 227:18–25.
Article
75. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med. 2000; 132:270–8.
Article
76. Singh S, Duggal J, Molnar J, Maldonado F, Barsano CP, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all- cause mortality: a meta-analysis. Int J Cardiol. 2008; 125:41–8.
77. Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Thyroid. 2018; 28:1101–10.
Article
78. Kim H, Kong SH, Moon JH, Kim SY, Park KH, Kim JS, et al. Subclinical hypothyroidism affects the long-term outcomes of patients who undergo coronary artery bypass grafting surgery but not heart valve surgery. Endocrinol Metab (Seoul). 2020; 35:308–18.
Article
79. Baumgartner C, da Costa BR, Collet TH, Feller M, Floriani C, Bauer DC, et al. Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation. Circulation. 2017; 136:2100–16.
Article
80. 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; 126:1040–9.
Article
81. Chaker L, Baumgartner C, den Elzen WP, Ikram MA, Blum MR, Collet TH, et al. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: an individual participant data analysis. J Clin Endocrinol Metab. 2015; 100:2181–91.
Article
82. 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.
Article
83. 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.
Article
84. Redford C, Vaidya B. Subclinical hypothyroidism: should we treat? Post Reprod Health. 2017; 23:55–62.
Article
85. Jabbar A, Ingoe L, Junejo S, Carey P, Addison C, Thomas H, et al. Effect of levothyroxine on left ventricular ejection fraction in patients with subclinical hypothyroidism and acute myocardial infarction: a randomized clinical trial. JAMA. 2020; 324:249–58.
Article
86. 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; 71:201–7.
Article
87. Rieben C, Segna D, da Costa BR, Collet TH, Chaker L, Aubert CE, et al. Subclinical thyroid dysfunction and the risk of cognitive decline: a meta-analysis of prospective cohort studies. J Clin Endocrinol Metab. 2016; 101:4945–54.
Article
88. Akintola AA, Jansen SW, van Bodegom D, van der Grond J, Westendorp RG, de Craen AJ, et al. Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis. Front Aging Neurosci. 2015; 7:150.
Article
89. Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA. 2015; 313:2055–65.
90. Segna D, Bauer DC, Feller M, Schneider C, Fink HA, Aubert CE, et al. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med. 2018; 283:56–72.
Article
91. Siru R, Alfonso H, Chubb SAP, Golledge J, Flicker L, Yeap BB. Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men. Clin Endocrinol (Oxf). 2018; 89:93–9.
Article
92. Virgini VS, Rodondi N, Cawthon PM, Harrison SL, Hoffman AR, Orwoll ES, et al. Subclinical thyroid dysfunction and frailty among older men. J Clin Endocrinol Metab. 2015; 100:4524–32.
Article
93. Virgini VS, Wijsman LW, Rodondi N, Bauer DC, Kearney PM, Gussekloo J, et al. Subclinical thyroid dysfunction and functional capacity among elderly. Thyroid. 2014; 24:208–14.
Article
94. Da Costa AB, Pellizzari C, Carvalho GA, Sant’Anna BC, Montenegro RL, Zammar Filho RG, et al. High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis. Hemodial Int. 2016; 20:31–7.
Article
95. Shin DH, Lee MJ, Lee HS, Oh HJ, Ko KI, Kim CH, et al. Thyroid hormone replacement therapy attenuates the decline of renal function in chronic kidney disease patients with subclinical hypothyroidism. Thyroid. 2013; 23:654–61.
Article
96. Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, et al. Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab. 2015; 100:1386–95.
Article
97. Meuwese CL, van Diepen M, Cappola AR, Sarnak MJ, Shlipak MG, Bauer DC, et al. Low thyroid function is not associated with an accelerated deterioration in renal function. Nephrol Dial Transplant. 2019; 34:650–9.
Article
98. Posadas-Romero C, Jorge-Galarza E, Posadas-Sanchez R, Acuna-Valerio J, Juarez-Rojas JG, Kimura-Hayama E, et al. Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis. Eur J Endocrinol. 2014; 171:319–25.
Article
99. Liu L, Yu Y, Zhao M, Zheng D, Zhang X, Guan Q, et al. Benefits of levothyroxine replacement therapy on nonalcoholic fatty liver disease in subclinical hypothyroidism patients. Int J Endocrinol. 2017; 2017:5753039.
Article
100. 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. Endocr Pract. 2012; 18:988–1028.
Article
101. 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.
Article
102. Smith MW. The 10 most-prescribed and top-selling medications [Internet]. New York: WebMD;2015. [cited 2021 Jun 1]. Available from: https://www.webmd.com/drug-medication/news/20150508/most-prescribed-top-selling-drugs .
103. National Institute for Health and Care Excellence. Clinical Knowledge summaries Subclinical hypothyroidism (non-pregnant) [Internet]. London: NICE;2018. [cited 2021 Jun 1]. Available from: https://cks.nice.org.uk/hypothyroidism#!scenario:1 .
104. Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019; 365:l2006.
Article
105. Ruggeri RM, Trimarchi F, Biondi B. Management of endocrine disease: l-thyroxine replacement therapy in the frail elderly: a challenge in clinical practice. Eur J Endocrinol. 2017; 177:R199–217.
Article
106. Cooper DS. Thyroid disease in the oldest old: the exception to the rule. JAMA. 2004; 292:2651–4.
107. Calissendorff J, Falhammar H. To treat or not to treat subclinical hypothyroidism, what is the evidence? Medicina (Kaunas). 2020; 56:40.
Article
108. Taylor P, Bianco AC. Urgent need for further research in subclinical hypothyroidism. Nat Rev Endocrinol. 2019; 15:503–4.
Article
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