Treatment of subclinical hypothyroidism ineffective in older adults

1. There were no significant differences at one year regarding hypothyroid-related symptoms or cardiovascular outcomes between patients with subclinical hypothyroidism who were treated with levothyroxine or placebo.

2. There was a high rate of spontaneous reversion to a euthyroid state for patients deemed to have subclinical hypothyroidism prior to treatment with levothyroxine.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Prior randomized studies investigating the role of thyroid hormone replacement in subclinical hypothyroidism, defined as an elevated serum thyrotropin (TSH) level and a serum free thyroxine level within the reference age, have been small and have yielded only limited evidence regarding its efficacy. Given the multiple effects of thyroid homeostasis on diverse organ systems, there may be a benefit to the treatment of subclinical hypothyroidism, particularly in older adults in which this set of lab abnormalities is more prevalent. In this randomized, placebo-controlled trial, a large group of older adults were randomized to receive thyroid repletion or placebo and followed for a year. There were no differences between groups at the one-year mark in terms of thyroid-related symptoms. There were no differences in a number of other secondary outcomes, such as cardiovascular events of interest or grip strength. There was a small difference in tiredness index between groups during extended follow-up, though this was considered likely a chance result. This trial draws strength from its randomized and pragmatic design to answer an important clinical question affecting a large number of patients who have been tagged as having subclinical hypothyroidism based on laboratory abnormalities. Three out of five individuals originally screened into the trial went on to have self-resolving subclinical hypothyroidism without intervention, emphasizing the natural history of this condition. Drawbacks of the study are that it was not powered to investigate cardiovascular outcomes or mortality, or to look for differences between subgroups including those with symptoms and those with relatively higher TSH levels at time of study entry.

Click to read the study, published in NEJM

Relevant Reading: Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism

In-Depth [randomized controlled trial]: This study screened 2647 adults for eligibility and randomized 737 into the study, largely due to 1645 individuals having reversion of TSH level to normal without intervention. Characteristics of randomized individuals were similar between treatment and placebo arms; there was an average age of 74 years, approximately 53% female, largely white, and with an entry TSH level in the range of 6.3-6.4. Patients with current thyroid hormone medications, medications affecting the thyroid axis (e.g. lithium), recent thyroid surgeries, recent hospitalization, or dementia were excluded. Patients in the treatment arm were started on levothyroxine at doses of 50 micrograms daily, or 25 micrograms in those with body weight <50 kg, which could be titrated based on a goal TSH of 0.40 to 4.59 mIU per liter. There was a statistically significant difference in TSH between groups at both 6 to 8 weeks and one to two years after randomization (p < 0.001 for between group differences). At 12 months, the mean Hypothyroid Symptoms score was 16.7±17.5 in the placebo group and 16.6±16.9 in the treatment group (p = 0.99). Similarly, there were no differences at the one-year mark between groups in terms of the mean Tiredness score (both scales range from 0 to 100, with higher scores indicating more hypothyroidism-related symptoms and tiredness, respectively). There were no significant differences between groups in terms of cardiovascular outcomes or adverse outcomes of particular interest including hyperthyroid-related symptoms of atrial fibrillation, heart failure, fracture, or new diagnosis of osteoporosis.

Image: PD

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