Indocyanine green (ICG) guided thyroidectomy versus conventional thyroidectomy and the impact on parathyroid function preservation: an updated GRADE-assessed systematic review and meta-analysis

Abstract

Abstract Background Thyroidectomy carries a significant risk of parathyroid gland injury, with transient hypoparathyroidism occurring in 15–50% of cases and permanent hypoparathyroidism in up to 5%, resulting in lifelong morbidity. Near-infrared (NIR) autofluorescence imaging combined with indocyanine green (ICG) fluorescence angiography has emerged as an intraoperative adjunct for parathyroid identification and perfusion assessment, but its comparative efficacy over conventional white-light surgery remains to be comprehensively quantified. Methods A systematic search across five databases through January 2026 identified randomized controlled trials and observational studies comparing NIR autofluorescence with ICG imaging versus conventional thyroidectomy without fluorescence guidance. Outcomes included inadvertent parathyroid removal, permanent and transient hypoparathyroidism, permanent and transient hypocalcemia, postoperative parathyroid hormone (PTH) levels, postoperative serum calcium levels, and operative time. Meta-analysis utilized a random-effects model to calculate pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Certainty of evidence was assessed using the GRADE approach. Results Eleven studies encompassing 2,203 patients (ICG: n = 897; Control: n = 1,306) were included. ICG-guided NIR imaging significantly reduced inadvertent parathyroid removal (RR 0.43, 95% CI 0.30–0.61, p = 0.002; I²=0%) and permanent hypocalcemia (RR 0.25, 95% CI 0.17–0.37, p = 0.004; I²=0%). A non-significant trend toward reduced permanent hypoparathyroidism was observed under our pre-specified random-effects model (RR 0.45, 95% CI 0.20–1.02, p = 0.054). A post-hoc sensitivity analysis using a fixed-effect model yielded a statistically significant result (RR 0.50, 95% CI 0.36–0.71, p < 0.001); however, this finding should be interpreted with caution, as it did not correspond to our primary pre-specified analytical approach. ICG guidance was associated with significantly higher postoperative PTH levels (MD 5.45 pg/mol, 95% CI 0.26–10.64, p = 0.042) and serum calcium levels (MD 0.06 mmol/L, 95% CI 0.01–0.11, p = 0.033). No significant differences were noted in transient hypoparathyroidism (RR 0.56, 95% CI 0.21–1.53, p = 0.185) or transient hypocalcemia (RR 0.67, 95% CI 0.33–1.34, p = 0.182), both characterized by substantial heterogeneity (I²=78.4% and 75.4%, respectively). Operative time was comparable between groups (MD 0.08 min, 95% CI − 18.25 to 18.42, p = 0.989). Conclusions NIR autofluorescence with ICG imaging is associated with a reduction in inadvertent parathyroid removal and permanent hypocalcemia, supported by high and moderate certainty evidence respectively, along with improvements in postoperative PTH and calcium levels (moderate certainty). Evidence for benefit in permanent hypoparathyroidism was directionally favorable but of low certainty, and findings for transient hypoparathyroidism and transient hypocalcemia were inconclusive, rated low to very low certainty due to substantial heterogeneity. These findings support ICG-guided NIR imaging as a promising intraoperative adjunct, with the strongest evidence for reducing inadvertent gland removal and permanent hypocalcemia specifically, rather than uniform benefit across all parathyroid-related outcomes. Future large-scale randomized trials with standardized imaging protocols, blinded outcome assessment, and extended follow-up are needed to resolve heterogeneity in transient outcomes and confirm long-term benefits in high-risk surgical populations.