Clinical Outcomes after Deprescribing Thyroid Hormone Therapy: An Updated Systematic Review and Meta-Analysis
In brief
About 4 in 10 with subclinical hypothyroidism stayed euthyroid off treatment
Across 23 studies, 41% of patients initially treated for subclinical hypothyroidism remained euthyroid after supervised thyroid hormone withdrawal, compared with 11% of those with overt hypothyroidism. Overall, 60% restarted therapy, while symptoms generally did not change and adverse events were uncommon. Most evidence was observational and highly variable, so deprescribing calls for close monitoring and clear restart criteria.
- Journal
- Thyroid : official journal of the American Thyroid Association (Q1)
- Published
- 2 November 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Freddy J K Toloza, Kimberley Ho, Nydia Burgos, Naykky M Singh Ospina, Spyridoula Maraka, Ramzi G Salloum, et al.
- PMID
- 42969098
- DOI
- 10.1177/10507256261502928
Why clinicians should know about it
- Picked for Biochemistry (medical) (paper of the day, 3 November 2026): Thyroid function outcomes inform biochemical monitoring after levothyroxine withdrawal
Abstract
BACKGROUND: Levothyroxine (LT4) is widely prescribed, often for subclinical hypothyroidism (SCH), despite limited evidence of clinical benefit in patients without overt hypothyroidism. This updated systematic review synthesizes current evidence on biochemical, symptom, and safety outcomes following thyroid hormone (TH) discontinuation. METHODS: In this systematic review, electronic databases were searched from inception to September 25, 2026, for randomized controlled trials (RCTs) and observational studies evaluating supervised TH discontinuation. Primary outcomes included postdiscontinuation thyroid function, symptom changes, adverse events, and need for therapy reinitiation. Random-effects meta-analyses estimated pooled proportions and mean differences. RESULTS: Twenty-three studies met inclusion criteria (22 observational studies, 1 RCT), most evaluating LT4 monotherapy discontinuation (n = 20). Twenty-one studies including 2020 participants reported categorical TH status outcomes; 37% of participants (CI, 26%-48%; I2 = 94.5%) remained euthyroid after discontinuation. Euthyroidism was less frequent among patients with initial overt hypothyroidism (11%, CI, 2%-38%) than among those with SCH (41%, CI, 21%-65%). Eleven studies (1104 participants) reported TH reinitiation, with 60% of patients restarting therapy (CI, 39%-78%; I2 = 97.1%) in the overall population, increasing to 87% (CI, 66%-96%) among those with overt hypothyroidism. Thyroid autoantibody positivity, heterogeneous thyroid ultrasound findings, and higher baseline TSH levels were associated with therapy reinitiation. Thyroid-related symptoms after discontinuation were generally unchanged, and adverse events were uncommon. CONCLUSIONS: Approximately 37% of patients remained euthyroid after TH discontinuation, with higher success rates among those initially treated for SCH. These findings support consideration of deprescribing in selected patients, particularly those without clear indications for treatment initiation, using a structured approach with close biochemical monitoring and predefined criteria for therapy reinitiation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.