Levothyroxine Deprescribing Framework Needed for Thyroid Replacement Hormone Tapering

Hormone replacement therapy of thyroid or hypothyroidism
Hormone replacement therapy of thyroid or hypothyroidism concept photo. Model of thyroid gland is close to drugs in blisters on which arrows are drawn to organ, symbolizing hormone replacement
Researchers set out to summarize clinical outcomes experienced by patients who discontinue thyroid hormone replacement therapy.

The development of a deprescribing framework focused on patient selection may guide clinicians and patients when discussing potential levothyroxine (LT4) discontinuation in people with subclinical or overt hypothyroidism. This is according to research results published in Thyroid.

Researchers set out to summarize clinical outcomes experienced by patients who discontinue thyroid hormone replacement therapy, as well as to identify the predictors of successful therapy discontinuation and evaluate the frameworks that clinicians use to deprescribe thyroid hormone replacement.

A systematic review and meta-analysis of both randomized controlled trials and observational studies (n=2673) was conducted, of which 17 observational studies were eligible for inclusion. These studies included 1105 patients (87% women).

Sixteen studies categorically evaluated thyroid hormone status, 8 evaluated thyroid hormone status numerically, and 4 evaluated clinical symptoms. Most of these studies were focused on adults.

In 14 studies, thyroid hormone replacement therapy included LT4. One study focused on LT4 and liothyronine, 1 studied variable regimens (combination LT4/liothyronine, LT4, and thyroid extract), and 1 did not specify the type of replacement studied. Three of the included studies discontinued therapies using a tapering regimen, which varied among studies.

Sixteen studies evaluated the proportion of patients who remained euthyroid after discontinuation of LT4. In total, 1092 patients were included, with an outcome assessment time ranging from 10 days to a median follow-up of 5 years. When all studies were evaluated as a whole, the pooled euthyroidism estimate at follow-up was 34.1%. The pooled estimate was lower for people with overt hypothyroidism and for adults (11.8% and 32.2%, respectively).

Nine studies evaluated the percentage of patients who restarted LT4 therapy during follow-up. This included 843 patients with an outcome assessment time of 3 weeks to a median of 5 years. In most studies, treatment reinitiation was based on laboratory evidence of subclinical hypothyroidism. When all studies were included, the pooled estimate for restarting LT4 was 62.5%; the pooled estimate for patients with overt hypothyroidism was higher (87.2%).

Four studies had available data for mean thyroid-stimulating hormone (TSH) values before and after LT4 withdrawal; 2 included people with subclinical hypothyroidism and 2 included people with overt hypothyroidism. Data regarding predictors for hypothyroidism development after LT4 withdrawal were not sufficient for meta-analysis, according to the researchers.

Four studies evaluated symptom development after LT4 withdrawal. In 2 of these studies, no symptoms developed. Two studies reported the development of symptoms of hypothyroidism after LT4 withdrawal, including fatigue. All 4 of these studies relied on self-reporting.

Finally, 3 studies evaluated adverse events following LT4 withdrawal. One reported no adverse events overall; 1 reported no adverse events in terms of growth, lipid profile, glucose homeostasis, or goiter; and 1 reported intolerable fatigue in 1 participant, who dropped out of the study.

Limitations include incomplete searching and arbitrary study selection, a high risk of reporting bias, and insufficient data that rendered it impossible for the researchers to evaluate certain characteristics or perform subgroup analyses.

“Low quality evidence suggests that up to a third of patients remained euthyroid after LT4 discontinuation, with a higher proportion of patients with an initial diagnosis of [subclinical hypothyroidism] remaining euthyroid than patients with an initial diagnosis of [overt hypothyroidism],” the researchers concluded.

“Patients and physicians can use this information when discussing if discontinuation of LT4 is a reasonable consideration.”


Burgos N, Toloza FJK, Singh Ospina NMS, et al. Clinical outcomes after discontinuation of thyroid hormone replacement: a systematic review and meta-analysis. Published online December 29, 2020. Thyroid. doi:10.1089/thy.2020.0679