The World Health Organization. The top 10 causes of death.  Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Cited 2021 Nov 26.

National population projections - Office for National Statistics. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationprojections/bulletins/nationalpopulationprojections/2018based#changes-since-the-2016-based-projections. Cited 2021 Nov 26.

British Heart Foundation. Heart Statistics. Available from: https://www.bhf.org.uk/what-we-do/our-research/heart-statistics. Cited 2021 Nov 29.

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(21):2460–6.

Article  PubMed  Google Scholar 

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(2):533–40.

Article  CAS  PubMed  Google Scholar 

de Jongh RT, Lips P, van Schoor NM, Rijs KJ, Deeg DJH, Comijs HC, et al. Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals. Eur J Endocrinol. 2011;165(4):545–54.

Article  PubMed  Google Scholar 

Boekholdt SM, Titan SM, Wiersinga WM, Chatterjee K, Basart DCG, Luben R, et al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin Endocrinol (Oxf). 2010;72(3):404–10.

Article  CAS  PubMed  Google Scholar 

Waring AC, Harrison S, Samuels MH, Ensrud KE, LeBLanc ES, Hoffman AR, et al. Thyroid function and mortality in older men: a prospective study. J Clin Endocrinol Metab. 2012;97(3):862–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295(9):1033–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gammage MD, Parle JV, Holder RL, Roberts LM, Hobbs FDR, Wilson S, et al. Association between serum free thyroxine concentration and atrial fibrillation. Arch Intern Med. 2007;167(9):928–34.

Article  CAS  PubMed  Google Scholar 

Abrahamsen B, Jørgensen HL, Laulund AS, Nybo M, Bauer DC, Brix TH, et al. 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. 2015;30(5):898–905.

Article  CAS  PubMed  Google Scholar 

Gonzalez Rodriguez E, Stuber M, Del Giovane C, Feller M, Collet TH, Löwe AL, et al. Skeletal effects of levothyroxine for subclinical hypothyroidism in older adults: a TRUST randomized trial nested study. J Clin Endocrinol Metab. 2020;105(1):dgz058.

Article  PubMed  Google Scholar 

Meier C, Beat M, Guglielmetti M, Christ-Crain M, Staub J, Kraenzlin M. Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: a randomized controlled trial. Osteoporos Int. 2004;15(3):209–16.

Article  PubMed  Google Scholar 

Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142–54.

Article  PubMed  Google Scholar 

Okosieme O, Gilbert J, Abraham P, Boelaert K, Dayan C, Gurnell M, et al. Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. Clin Endocrinol (Oxf). 2016;84(6):799–808.

Article  PubMed  Google Scholar 

Mitchell AL, Hickey B, Hickey JL, Pearce SH. Trends in thyroid hormone prescribing and consumption in the UK. BMC Public Health. 2009;9(1):132.

Article  PubMed  PubMed Central  Google Scholar 

Razvi S, Korevaar TIM, Taylor P. Trends, determinants, and associations of treated hypothyroidism in the United Kingdom, 2005–2014. Thyroid. 2019;29(2):174–82.

Article  CAS  PubMed  Google Scholar 

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(2):489–99.

Article  CAS  PubMed  Google Scholar 

Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab. 2013;98(3):1147–53.

Article  CAS  PubMed  Google Scholar 

Overview | Thyroid disease: assessment and management | Guidance | NICE. NICE; 2019. Available from: https://www.nice.org.uk/guidance/ng145. Cited 2023 Oct 5.

Assessment | Diagnosis | Hypothyroidism | CKS | NICE. Available from: https://cks.nice.org.uk/topics/hypothyroidism/diagnosis/assessment/. Cited 2023 Oct 5.

Eligar V, Taylor P, Okosieme O, Leese G, Dayan C. Thyroxine replacement: a clinical endocrinologist’s viewpoint. Ann Clin Biochem. 2016;53(4):421–33.

Article  CAS  PubMed  Google Scholar 

Thyroid Disease in Aging - PMC.  Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462896/#. Cited 2023 Sep 25.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;29(372):n71.

Article  Google Scholar 

Sterne JAC, Egger M, Moher D, Boutron I (editors). Chapter 10: Addressing reporting biases. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.

Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;18(343):d5928.

Article  Google Scholar 

Ottawa Hospital Research Institute. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Cited 2023 Mar 23.

Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.

Article  PubMed  Google Scholar 

Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.

Article  PubMed  Google Scholar 

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

Article  PubMed  PubMed Central  Google Scholar 

World Health Organization Protocol EUCTR2012–004160–22-NL. IEMO 80-plus thyroid trial. 2013. Available from: https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2012-004160-22-NL.

Nygaard Andersen M, Schjerning-Olsen, Clausager Madsen J, Faber J, Torp-Pedersen C, Gislason G, et al. Major adverse cardiac events (MACE) and all-cause mortality in levothyroxine substituted individuals with subclinical hypothyroidism: a large cohort study. Eur Heart J. 2014;35:903.

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.

Article  CAS  PubMed  Google Scholar 

Razvi S, Weaver JU, Vanderpump MP, Pearce SHS. 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(4):1734–40.

Article  CAS  PubMed  Google Scholar 

Alotaibe HF, Alolaiwi LA, Almutairi A, Alsubaie N, Badri M, Balaha MF, et al. Association between levothyroxine replacement therapy and osteoporosis in Riyadh, Saudi Arabia: a matched case-control study. Pharmazie. 2022;77(10):295–8.

CAS  PubMed  Google Scholar 

Huang HK, Wang JH, Kao SL. Association of hypothyroidism with all-cause mortality: a cohort study in an older adult population. J Clin Endocrinol Metab. 2018;103(9):3310–8.

Article  PubMed  Google Scholar 

Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L. Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk. Eur J Endocrinol. 2019;180(6):407–16.

Article  CAS  PubMed  Google Scholar 

Vestergaard P, Rejnmark L, Mosekilde L. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int. 2005;77(3):139–44.

Article  CAS  PubMed  Google Scholar 

Viniol A, Hickstein L, Walker J, Donner-Banzhoff N, Baum E, Becker A. Influence of thyroid hormone therapy on the fracture rate - a claims data cohort study. Bone. 2016;86:86–90.

Article  CAS  PubMed  Google Scholar 

Lillevang-Johansen M, Abrahamsen B, Jørgensen HL, Brix TH, Hegedüs L. Over- and under-treatment of hypothyroidism is associated with excess mortality: a register-based cohort study. Thyroid. 2018;28(5):566–74.

Article  CAS  PubMed  Google Scholar 

Abbey EJ, McGready J, Ferrucci L, Simonsick EM, Mammen JSR. Thyroid hormone supplementation and all-cause mortality in community-dwelling older adults: results from the Baltimore Longitudinal Study of Aging. J Am Geriatr Soc. 2021;69(5):1283–90.

Article  PubMed  PubMed Central  Google Scholar 

Thayakaran R, Adderley NJ, Sainsbury C, Torlinska B, Boelaert K, Šumilo D, et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ. 2019;3(366):l4892.

Article  Google Scholar 

Waring AC, Harrison S, Fink HA, Samuels MH, Cawthon PM, Zmuda JM, et al. A prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J Bone Miner Res. 2013;28(3):472–9.

Article  CAS  PubMed  Google Scholar 

Inoue K, Ritz B, Brent GA, Ebrahimi R, Rhee CM, Leung AM. Association of subclinical hypothyroidism and cardiovascular disease with mortality. JAMA Netw Open. 2020;3(2):e1920745.