Levothyroxine Dosing in Older Individuals

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PROJECT SUMMARY Approximately 10% of US adults aged 65 years or older take levothyroxine to treat hypothyroidism. Guidance for its management has vast and important implications for the health and health care expenditures of millions of older people. Levothyroxine has a narrow therapeutic index that requires monitoring of dosing through thyroid stimulating hormone (TSH) testing. The current TSH reference range is based on the population distribution of younger people, despite evidence for a shift to higher levels with increasing age. Furthermore, observational data do not demonstrate adverse clinical consequences if people with TSH levels just above the reference range are left untreated, and a large clinical trial of people aged 65 years or older showed no benefit to treating this group of patients with levothyroxine. The trial of treatment of subclinical hypothyroidism used low doses of levothyroxine because of underlying endogenous thyroid function. These data may not be generalizable to individuals who have no endogenous thyroid function and rely entirely on exogenous levothyroxine. Small trials in younger people taking levothyroxine suggest that there are no physiologic differences between higher doses of levothyroxine that maintain TSH levels in the lower end of the reference range compared with lower doses of levothyroxine that maintain a TSH level just above the upper limit of the reference range. Our overall goal is to determine the clinical consequences that allowing greater flexibility in levothyroxine dosing would have in older individuals who take levothyroxine. We propose to perform a randomized, double-blind clinical trial of two 6-month dosing strategies of levothyroxine in patients aged 65 years and older who are already taking a stable dose of levothyroxine therapy, one to maintain a target TSH of 0.5-2.0 mU/L and another of a lower levothyroxine dose to achieve a target TSH of 5.5-7.0 mU/L. We will assess the effects of levothyroxine therapy at two different TSH targets on symptoms of hypothyroidism, mood, sleep, measures of memory and executive function, weight, lipids, and a marker of bone turnover. This clinical trial will provide essential data to inform the clinical value of increased flexibility in LT4 dosing for older LT4 users. Implications include widening the LT4 therapeutic window, decreasing the frequency of LT4 titration and TSH testing, and reducing the risk of LT4 overtreatment. In sum, this study could transform treatment of hypothyroidism into an easier, safer, and less costly clinical practice for millions of older adults.