Interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms: A systematic review

source extracted confidence: high 2026-04-09
#humans #hypothyroidism #thyroxine #hormone-replacement-therapy #female

Interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms: A systematic review

Hidalgo et al., 2024 | Endocrine | Systematic Review

Citation

Hidalgo Jessica, Lincango Eddy P, ... Brito Juan P. Interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms: A systematic review. Endocrine. 2024-Jun;84(3):864-873. doi:10.1007/s12020-024-03816-1

Abstract

BACKGROUND: Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however, 10-15% of patients have persistent hypothyroid symptoms despite normalizing thyroid hormone levels with LT4. This study aims to summarize the best available evidence on interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms. METHODS: A systematic search was conducted in March 2022 for randomized controlled trials and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement. RESULTS: A total of 277 articles were reviewed and seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 (±2.8) years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidism related symptoms and general health. The two clinical trials with the largest improvement in fatigue scores were the use of ginger and surgery. One observational study comparing thyroidectomy vs observation found no significant difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and quality of life. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group. CONCLUSIONS: There is no high-quality evidence supporting any intervention for persistent symptoms in hypothyroidism. Available evidence, limited by the risk of bias, inconsistency, and heterogeneity, suggests that some persistent symptoms, particularly fatigue, could improve with ginger and thyroidectomy.

Key Findings

A total of 277 articles were reviewed and seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 (±2.8) years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidis

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population hypothyroidism and persistent symptoms
Sample Size 455
Age Range mean age of 47.5
Condition See abstract

MeSH Terms

  • Humans
  • Hypothyroidism
  • Thyroxine
  • Hormone Replacement Therapy
  • Female
  • Adult
  • Male
  • Middle Aged
  • Zingiber officinale
  • Thyroidectomy

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article
  • Vertical: ginger

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09