The Effect of Thyroid Hormone Therapy on Muscle Mass and Function in Older Adults With Subclinical Hypothyroidism

Background

Subclinical hypothyroidism (SCH) is common among the elderly population, with an estimated prevalence of 6-15%. It has been associated with multiple adverse outcomes such as cardiovascular diseases and neuropsychological disturbance. Muscular function impairment has also been associated with SCH. However, the association between subclinical hypothyroidism and physical performance in older adults remains unclear and randomized controlled trials are lacking.

Physical performance is an important prognostic indicator for older adults. Prospective studies showed that it is related to hospitalization, institutionalization, cardiovascular disease, disability and mortality. Gait speed is one of the most widely used measures of physical performance in clinical and research settings, with a solid prognostic value.

Aside from overall physical performance, two other dimensions of muscular function can be assessed: muscle function, usually assessed by handgrip strength (predictive validity for decline in cognition, mobility, functional status and mortality for older people), and muscle mass, usually assessed by dual-energy X-absorptiometry). Those three dimension together form the definition of sarcopenia, a relatively new concept which has been gaining visibility in the last years because of its high prevalence and clinical relevance.

Both subclinical hypothyroidism and muscle function impairment are highly prevalent among the older population, and the latter bears a heavy personal, social and economic burden. Therefore, evaluating the potential benefit of levothyroxine therapy on muscle function in this population holds the potential to prevent adverse health-related outcomes and maintain the patients' autonomy and quality of life.

Objectives

To investigate whether levothyroxine therapy in older adults with subclinical hypothyroidism affects sarcopenia measures (mass, strength and physical performance) in a substudy of the TRUST and IEMO trial.

Methods

The existing trial infrastructure (TRUST and IEMO trials, clinicaltrials.gov ID: NCT 01660126) will be utilized to collect information on muscle mass and function from 322 participants with persistent subclinical hypothyroidism randomized to either thyroxine or placebo. Utilized outcomes are specified in the corresponding section.

Inclusion criteria

(TRUST):

• Community-dwelling elderly patients aged ≥65 years with subclinical hypothyroidism (SCH).

[SCH is defined as elevated TSH levels (4.6 to 19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.]

Inclusion criteria

(IEMO)

• Community-dwelling elderly patients aged ≥80 years with SCH, as above defined

Exclusion criteria

(TRUST and IEMO):

• Currently on Levothyroxine or antithyroid drugs, amiodarone or lithium.
• Recent thyroid surgery or radio-iodine (within 12 months).
• Grade IV NYHA heart failure.
• Prior clinical diagnosis of dementia.
• Recent hospitalisation for major illness or elective surgery (within 4 weeks).
• Recent acute coronary syndrome, including myocardial infarction or unstable angina (within 4 weeks).
• Terminal illness.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Individuals participating in ongoing RCTs of therapeutic interventions (including CTIMPs)
• Individuals planning to move out of the region in which the trial is being conducted within the next 2 years (proposed minimum follow-up period).