Near-infrared autofluorescence parathyroid imaging during total thyroidectomy to reduce the rate of postoperative hypoparathyroidism: A prospective two-center randomized clinical trial with a comprehensive long-term follow-up

BACKGROUND: Postoperative hypoparathyroidism remains the most common complication after total thyroidectomy. Near-infrared autofluorescence leverages the intrinsic fluorescence of parathyroid glands, enabling intraoperative visualization and potentially improving gland preservation, thereby reducing postoperative hypoparathyroidism. METHODS: A randomized clinical trial conducted at two Danish centers assigned total thyroidectomy patients to either the near-infrared autofluorescence or control group. Blood samples and data on hypoparathyroidism treatment were collected preoperatively, postoperative day 1, and at 1-, 3-, 9-, and 12-months follow-up. Hypoparathyroidism was defined by (1) the European Society of Endocrinology guideline definition, (2) ionized calcium <1.15, and (3) parathyroid hormone below the lower reference limit. Primary end points were hypoparathyroidism rates at 3 and 12 months; secondary end points included parathyroid gland identification rate, surgical duration, signal-to-background ratio, and parathyroid hormone/ionized calcium ratio. RESULTS: A total of 189 patients were randomized (near-infrared autofluorescence: 93; control: 96). No significant difference in hypoparathyroidism rates was observed at 3 and 12 months (European Society of Endocrinology definition at 3 mo: near-infrared autofluorescence: 15.6%; control: 16.9%; P = .97). Subanalysis indicated greater near-infrared autofluorescence benefit during total thyroidectomy with central lymph node dissection. The parathyroid gland identification was significantly higher in the near-infrared autofluorescence group (3.1 vs 2.8; P = .045). The best-imaged parathyroid glands had a mean signal-to-background ratio_maximum of 2.3 and signal-to-background ratio_mean of 1.9. Near-infrared autofluorescence did not extend surgical duration or affect parathyroid hormone/ionized calcium ratios. A higher fraction of controls received calcium and vitamin D at 3 months (71.8% vs 59.0%; P = .16). CONCLUSIONS: Despite improved parathyroid gland identification with near-infrared autofluorescence, there was no significant difference in rates of postoperative hypoparathyroidism at any follow-up. Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.