Discontinuation of levothyroxine therapy in patients with subclinical hypothyroidism: a pilot randomized clinical trial.

The pilot RCT demonstrated feasibility of study procedures for levothyroxine discontinuation in patients with subclinical hypothyroidism.

• 50 participants were randomized with a 32% enrollment rate
• Five participants were excluded post-randomization due to unconfirmed subclinical hypothyroidism, yielding 45 participants (21 levothyroxine, 24 placebo)
• One patient in the placebo group withdrew for personal reasons, resulting in a 98% completion rate
• The study was conducted at a Veterans Affairs Medical Center with a 6-month follow-up period

At 6 months, there was no statistically significant difference between placebo and levothyroxine groups in hypothyroid symptom scores.

• ThyPRO-Hypothyroid Symptoms scores were 28.3 (SD 22.8) in the placebo group vs. 22.9 (SD 19.5) in the levothyroxine group
• Tiredness scores were 27.6 (SD 22.8) in the placebo group vs. 32.8 (SD 22.1) in the levothyroxine group
• EQ-5D quality of life scores were 0.750 (SD 0.232) in the placebo group vs. 0.741 (SD 0.180) in the levothyroxine group
• No statistically significant differences were found for any of these outcomes

The occurrence of adverse events in the levothyroxine discontinuation group was low.

• The only notable adverse event was rib fractures in one placebo group participant, who had a TSH of 3.04 mIU/L at 6 months
• Two participants in the placebo group restarted levothyroxine: one due to TSH >10 mIU/L and one due to fatigue
• No other notable adverse events were reported in either group

The study population consisted predominantly of older male White veterans on low-dose levothyroxine.

• Participants' mean age was 68.2 years (SD 9.7)
• 80% of participants were male
• 86.7% of participants were White
• Eligible adults were those with subclinical hypothyroidism on levothyroxine ≤75 mcg daily

Prior randomized clinical trials have shown no benefit of levothyroxine for subclinical hypothyroidism in improving well-being, cardiovascular outcomes, or mortality.

• This prior evidence motivated the current trial examining whether levothyroxine could be safely discontinued in patients with subclinical hypothyroidism
• The pilot trial was designed as a double-blind, placebo-controlled RCT
• Findings from this pilot support conducting a larger multi-site RCT to comprehensively assess the effects of levothyroxine discontinuation