Levothyroxine

Levothyroxine is indicated for hypothyroidism [177]. In frail, older people or those with severe ischemic heart disease, levothyroxine treatment for hypothyroidism, if clinically indicated, should be initiated with smaller doses and under specialist advice, due to the increased risk of cardiovascular adverse effects [177]. Thyroid dysfunction is associated with metabolic syndrome, contributing to an increased risk of cardiovascular disease, type 2 diabetes, and all-cause mortality [455]. The prevalence of hypothyroidism increases with age [456]. In older people, a higher serum TSH target is generally acceptable for several reasons: thyroid hormone requirements naturally decline with age, normal TSH levels increase (especially after age 80), and older people are more vulnerable to the adverse effects of overtreatment of hypothyroidism, including an increased risk of unrecognised cardiac ischemia [457]. For this reason, Therapeutic Guidelines recommend a target TSH range of 1-5 mU/L for those aged 60 and older and 4-6 mU/L for individuals over 80 [457].

Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).

Many older people who initiate thyroid hormone therapy often continue it for life without dose adjustments for prolonged periods [458]. However, thyroid function changes with age and so does thyroid hormone requirement [456]. In some cases, dose reduction or discontinuation may be appropriate, particularly in asymptomatic individuals with subclinical hypothyroidism, where thyroid hormone levels remain within the normal reference range but serum TSH is mildly elevated [459]. Subclinical hypothyroidism affects between 8-18% of older people, with a higher prevalence in women than men [460]. The management of subclinical hypothyroidism in older people remains a topic of debate. The AMH Aged Care Companion suggests that in asymptomatic older adults with negative antithyroid antibodies, treatment is generally not required, though periodic TSH monitoring is recommended, with a follow-up test in three months. However, individuals with positive antithyroid antibodies and rising TSH levels have a greater risk of progressing to overt hypothyroidism, making antibody testing a useful tool in clinical decision-making [177].

In older people, global fatigue is a common reason for thyroid hormone testing in primary care which often leads to levothyroxine prescription [461, 462]. However, current evidence suggests that thyroid hormone therapy in older people with subclinical hypothyroidism does not significantly improve physical or mental fatigue [463, 464]. Even in individuals with cardiovascular risk factors, a large cohort study found no significant association between levothyroxine use for subclinical hypothyroidism and reduced mortality, major adverse cardiac events, or hospitalisation [465]. A fine balance is required, as both undertreatment and overtreatment of hypothyroidism can increase the risk of cardiovascular events and mortality [466].

It is important to rule out any medicine-related causes to prevent an inappropriate prescribing cascade as medicines such as lithium and amiodarone can cause thyroid dysfunction [467].

Most people with hypothyroidism caused by permanent underlying conditions (e.g. autoimmune conditions including Hashimoto thyroiditis, post-ablative therapy including radioiodine therapy and thyroidectomy) often require lifelong maintenance therapy after the initial treatment [468].

We identified one before-and-after study related to levothyroxine deprescribing from the systematic review and meta-analysis [469]. The current evidence for deprescribing levothyroxine is based on a single-arm study. Although one in two participants was able to successfully discontinue their thyroid hormone therapy in the study, the certainty of the evidence is very low certainty due to a very small sample size, lack of a comparison group, and other methodological limitations. The evidence at this stage is insufficient to inform evidence-based recommendations.

If levothyroxine is considered appropriate to deprescribe, closely monitoring for any hypothyroidism symptoms including fatigue, weight gain, cold intolerance, poor mental concentration, and mood changes may be appropriate. It may be helpful to provide examples of common symptoms when encouraging individuals to self-monitor and report symptoms. As some symptoms are non-specific and could be attributed to age-related changes or other health conditions, many individuals may not recognise that they could be indicative of hypothyroidism.

A deprescribing protocol was used in which thyroxine treatment was approximately halved if TSH concentrations were ≤ 7mU/L at baseline, then discontinued after a month if TSH remained ≤ 7mU/L. For instance:

• 125 mcg daily dose reduced to 75mcg daily
• 75 mcg daily dose reduced to 50 mcg daily