An ageing population is a global phenomenon; it has been estimated that, by 2050, one in six people in the world will be over the age of 65 (16%), compared with one in 11 in 2019 (9%).1 This has important implications for the management of thyroid dysfunction, since the thyroid undergoes a range of morphological and physiological changes during the ageing process, and can fail to respond to other metabolic changes.2 The symptoms of thyroid dysfunction in the elderly are non-specific and variable. Presentations of thyroid disease may be atypical, and may be confounded by comorbidities, therefore diagnosis is often based on biochemical testing of thyroid function, in particular, serum levels of the pituitary hormone thyroid-stimulating hormone (TSH).3
<2> Overt hypothyroidism
Overt hypothyroidism is defined by increase in serum TSH values, together with reduced circulating levels of the thyroid hormones thyroxine (T4) and tri-iodothyronine (T3). Overt hypothyroidism is common in elderly populations, but is not associated with the classic symptoms of hypothyroidism, and onset can be insidious, so it tends to be underdiagnosed.4 Elderly patients with overt hypothyroidism are more likely to present with myxoedema coma, a life-threatening presentation of hypothyroidism.5 Overt hypothyroidism is associated with the impairment of attention, concentration, memory, perceptual functions, language, and executive functions, which can be reversed if treated appropriately.6
<2> Subclinical hypothyroidism
Subclinical hypothyroidism, defined by above normal serum TSH with normal FT4, is far more common than overt hypothyroidism. While the need to treat overt hypothyroidism is clear , the treatment of subclinical hypothyroidism is still controversial. Subclinical hypothyroidism is not associated with increased mortality in elderly populations,7 but is of concern as it can be associated with decreased bone mineral density and a higher incidence of fractures.8 (this is true for hyper- not hypo-) While subclinical hypothyroidism is known to be associated with an increased risk of ischaemic heart disease and stroke, several studies suggest that these risks are greater in younger individuals, and the risks in elderly populations have not been fully elucidated.4
In recent years, data from observational studies have suggested that serum TSH levels increase in older people, regardless of the presence of thyroid disease, and that this is not associated with worse outcomes.9 In fact, a number of studies have found increased levels of TSH in extreme old age, suggesting that increased TSH might be beneficial for longevity.10 In addition, serum TSH levels are affected by a number of factors, some transient, including genetic and environmental factors.11 Therefore, an elevation of TSH in an individual might not indicate a diagnosis of subclinical hypothyroidism, but may be a natural consequence of ageing. However, elderly patients are often treated using a standard serum TSH reference range (usually 0.4–4.5 mU/L), which does not account for age-related changes.3 The resulting overdiagnosis of hypothyroidism may lead to overtreatment, with important clinical consequences.
<2> Treatment of hypothyroidism
Treatment of both overt and subclinical hypothyroidism involves levothyroxine replacement therapy, although this does not have any beneficial effect on cognitive function in the elderly.12 Elderly patients are more susceptible to adverse effects of excess thyroid hormone, including increased fracture risk and atrial fibrillation (AF).4 It is therefore important to tailor therapy to the individual, particularly in patients with other cardiovascular risk factors. It is also important to assess potential frailty and comorbidities, and to regularly monitor thyroid hormone levels and adjust the levothyroxine dose at regular intervals to avoid iatrogenic hyperthyroidism.10 A recent study investigated levothyroxine treatment of patients aged 65 or over with subclinical hyperthyroidism and concluded that there was no benefit of treatment on quality of life or symptoms.13 The use of age-specific TSH reference ranges could minimise or avoid the unnecessary diagnosis of thyroid disease in elderly patients.2
Hyperthyroidism, which is characterised by serum TSH levels below the lower limit of the reference range and normal serum T4 levels, is less common in the elderly, but is observed in about 8% of individuals aged 65 years and older.14 Its diagnosis is challenging in elderly people due to the presence of nodules and atrophy of thyroid gland with advancing age. In addition, the classical signs and symptoms of hyperthyroidism such as tremor, weight loss, palpitations, diarrhoea and heat intolerance, may not occur in the elderly.15
Hyperthyroidism may be associated with mild, nonspecific symptoms and go undiagnosed for some time, hence the term “apathetic hyperthyroisim” for the condition in the elderly. Hyperthyroidism has been associated with cognitive impairment, as well as an increased risk of all-cause mortality, coronary heart disease related mortality and AF in elderly people.16 The safety of thyroid surgery in elderly patients remains controversial, and radioiodine or thionamide are the preferred treatment options.16 Treatment decisions must be individualised, and should account for life expectancy, comorbidities, and side effects of therapy.
Another consequence of ageing is an increased risk of thyroid nodules and thyroid neoplasms. Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy in older individuals, and is associated with a worse prognosis and greater likelihood of distant metastases than in younger people.17,18 The incidence of follicular and medullary thyroid cancers, as well as the highly aggressive anaplastic thyroid cancer is also increased in elderly individuals.18 Therapeutic decisions between surgery or radioiodine in an elderly patient require individual evaluation of comorbidities and life expectancy. Sorafenib and lenvatinib are recently approved for the treatment of symptomatic, progressive , radio-resistant metastatic differentiated thyroid cancer.18
In summary, hypothyroidism, hyperthyroidism and thyroid neoplasms require special attention in elderly individuals. While the treatment of overt hypothyroidism is always warranted, it is reasonable to raise the target serum TSH in elderly individuals, particularly if they are at risk of cardiac arrhythmias or osteoporotic fractures. A reassessment of the TSH reference range in older patients is clearly needed. There is also a need for further research to fully understand whether reduced thyroid function is normal, and perhaps even desirable, in elderly individuals.
- United Nations, Department of Economic and Social Affairs. World Population Prospects, 2019. Available at: https://population.un.org/wpp/Publications/Files/WPP2019_Highlights.pdf (Accessed 21 August 2019).
- Jasim S, Gharib H. Thyroid and aging. Endocr Pract. 2018;24:369–74.
- Garber JR, Cobin RH, Gharib H, 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.
- Leng O, Razvi S. Hypothyroidism in the older population. Thyroid Res. 2019;12:2.
- Ono Y, Ono S, Yasunaga H, et al. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan. J Epidemiol. 2017;27:117–22.
- Kramer CK, von Muhlen D, Kritz-Silverstein D, et al. Treated hypothyroidism, cognitive function, and depressed mood in old age: the Rancho Bernardo Study. Eur J Endocrinol. 2009;161:917–21.
- de Jongh RT, Lips P, van Schoor NM, et al. Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals. Eur J Endocrinol. 2011;165:545–54.
- Blum MR, Bauer DC, Collet TH, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA. 2015;313:2055–65.
- Pearce SH, Razvi S, Yadegarfar ME, et al., Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study, J Clin Endocrinol Metab, 2016;101:4385–94.
- Calsolaro V, Niccolai F, Pasqualetti G, et al. Hypothyroidism in the elderly: who should be treated and how? J Endocr Soc. 2019;3:146–58.
- Jonklaas J, Razvi S. Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers. Lancet Diabetes Endocrinol. 2019;7:473–83.
- Parle J, Roberts L, Wilson S, 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;95:3623–32.
- Stott DJ, Rodondi N, Kearney PM, et al., Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376:2534–44.
- Ceresini G, Lauretani F, Maggio M, et al. Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J Am Geriatr Soc. 2009;57:89–93.
- Trivalle C, Doucet J, Chassagne P, et al. Differences in the signs and symptoms of hyperthyroidism in older and younger patients. J Am Geriatr Soc. 1996;44:50–3.
- Samuels MH. Hyperthyroidism in aging. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A and Wilson DP (eds.), Endotext. South Dartmouth, Massachusetts, United States: MDText.com, Inc., 2000.
- Toniato A, Bernardi C, Piotto A, et al. Features of papillary thyroid carcinoma in patients older than 75 years. Updates Surg. 2011;63:115–8.
- Lechner MG, Hershman JM. Thyroid nodules and cancer in the elderly. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A and Wilson DP (eds.), Endotext. South Dartmouth, Massachusetts, United States: MDText.com, Inc., 2000.