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Thyroid Disease in The Elderly; an Update

Authors: Hossein Gharib, Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MI, USA

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

<1> Hypothyroidism

<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

<1> Hyperthyroidism

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

<1> Summary

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.


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