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Additional treatment strategies for hypothyroidism: a network meta-analysis.

  • 2026-03-13
  • Endocrine connections 15(4)
    • Xingang Lv
    • Wentao Qin
    • Jiarui Li
    • Likun Du

Study Design

Type
Systematic Review
Sample size
n = 508
Population
3,508 patients with hypothyroidism
Methods
Systematic search of PubMed, Embase, Cochrane Library, and Web of Science for RCTs; Bayesian NMA performed

Background

Hypothyroidism often impairs quality of life (QoL). This network meta-analysis (NMA) evaluated the efficacy and safety of additional interventions alongside levothyroxine (LT4).

Methods

This study adhered to the PRISMA guidelines and is registered on PROSPERO (CRD420251085765). PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched for randomized controlled trials (RCTs) on the treatment of hypothyroidism. A Bayesian NMA was performed, reporting standardized mean differences (SMDs) or risk ratios (RRs) with 95% credible intervals (CrIs). Evidence certainty was assessed using the CINeMA framework.

Results

Thirty-five RCTs involving 3,508 patients were included. Compared with placebo, levothyroxine (LT4) + aerobic training (AT) + resistance training (RT) significantly reduced thyroid-stimulating hormone (TSH) levels (SMD = -3.97, 95% CrI: -5.76, -2.18, CINeMA: high certainty); LT4 + zinc (Zn) + magnesium (Mg) + vitamin A (VA) raised free thyroxine (FT4) (SMD = 1.95, 95% CrI: 1.37, 2.53, CINeMA: high certainty); and LT4 + Zn increased free triiodothyronine (FT3) (SMD = 1.46, 95% CrI: 0.40, 2.51, CINeMA: low certainty). In addition, LT4 + AT + RT significantly improved QoL score (SMD = 1.62, 95% CrI: 0.78, 2.46) and mental health score (MHS) (SMD = 2.1, 95% CrI: 1.19, 3.01, CINeMA: low certainty) compared with LT4 alone. LT4 + RT significantly improved physical function score (SMD = 1.59, 95% CrI: 0.76, 2.43). Liothyronine (LT3) increased adverse events versus placebo (RR = 15.54, 95% CrI: 2.68, 501.14, CINeMA: very low certainty).

Conclusion

The combination of LT4, AT, and RT may be the preferred strategy for reducing TSH, enhancing QoL, and improving MHS. Clinical interventions should be tailored based on individual patient profiles.

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