Is it worth the effort?—examining the use of combined autofluorescence and indocyanine green angiography for parathyroid preservation during thyroid surgery

Postoperative hypocalcemia is the most common complication following thyroidectomy. Although the reasons for postoperative hypocalcemia may be multifactorial, the most common cause is due to iatrogenic parathyroid gland injury or devascularization during surgical dissection (1-4). Transient hypocalcemia—typically defined as low calcium levels or symptoms of hypocalcemia within the first 6 months following thyroidectomy—can often be managed with standardized calcium supplementation protocols to help avoid severe symptoms or hospital readmissions (5). However, permanent postoperative hypocalcemia is much more difficult to treat and often leads to lifelong calcium supplementation (6,7). Studies suggest that the rates of permanent postoperative hypocalcemia following thyroidectomy fall within 0–3% of cases (3,6,7).

Attempts to lower the incidence of iatrogenic hypocalcemia have been made, but a clear solution has not yet emerged. Parathyroid autotransplantation is often performed for devascularized or accidentally removed glands, but this has varying rates of success at preventing permanent hypocalcemia (8,9). Newer intraoperative tools, such as near-infrared autofluorescence (NIRAF) and indocyanine green angiography (ICGA) have recently been utilized by some surgeons in hopes of reducing parathyroid injury rate (10,11). A few randomized controlled trials have found that the use of NIRAF and ICGA is associated with increased intraoperative parathyroid identification and lower rates of postoperative hypocalcemia (12-14).

A recent study by Michaelsen et al. adds to the growing body of literature examining these new technologies (15). In their study, the authors combined the use of NIRAF and ICGA in a prospective intervention group consisting of patients who underwent total or completion thyroidectomy and then compared their outcomes to a retrospective cohort of similar patients at their institution from the previous decade. Permanent postoperative hypoparathyroidism was defined as the use of an active vitamin D agonist (AVDA) at 1 year postoperatively. They found a significant reduction of permanent postoperative hypoparathyroidism in the intervention group when compared to the retrospective control group, with an odds ratio of 0.16 after adjusting for confounders (15).

Michaelsen et al.’s study is important because it is one of the largest published cohorts of patients to have undergone a thyroidectomy with combined utilization of NIRAF and ICGA technology (15). Their finding of reduced postoperative hypoparathyroidism from 12.3% down to 6.5% is promising and aligns with previous literature that has demonstrated a clinical benefit to utilizing the technology (10-14). Additionally, their use of a retrospective control group demonstrates similar postoperative hypocalcemia rates to other Scandinavian countries that further corroborates their findings (16,17).

An important question regarding Michaelsen et al.’s study is the potentially fluctuating level of expertise of the surgeon performing the total or completion thyroidectomy. The authors mention that some of the surgeons in the cohort are low-volume, meaning that they perform less than ten of those operations each year (15). It would be interesting to know if these low-volume surgeons experienced a greater benefit from the NIRAF and ICGA technology compared to experienced surgeons. This would align with prior literature if so (18,19), but this was not specifically commented on in the study.

The authors note that the number of surgeons increased from eight to ten because of new additions, so it is assumed that the majority of the surgeons remained the same. Since the control group was from 2011 to 2020 and the intervention group was 2021 to 2023, presumably those same surgeons’ level of expertise increased over that decade which could account for some of the improvement in postoperative hypocalcemia that was observed between groups. Additionally, although extensive matching was undertaken, matching for the operative surgeon was only performed in 78% of cases and was significantly different between the control and intervention arms (15). The authors do address this and state that there is an overweight of newer (low-volume) surgeons in the intervention group compared to the control group, but it highlights the difficulty with combining a retrospective control group with a prospective intervention group. Ultimately, despite the imperfect matching, the findings still highlight an important result for low-volume thyroid surgeons.

Michaelsen et al.’s finding that four of the ten patients with permanent hypoparathyroidism had a well-vascularized pedicle identified on post-resection ICGA does raise concerns about the clinical utility of the technology (15). Additional studies would be needed to examine this phenomenon further. The surgeons themselves only used ICGA in 78% of cases, and then only rated the ICGA to be helpful in 61% of cases in which it was utilized. Comparatively, NIRAF had 73% perceived helpfulness by the surgeons that used it. Ultimately, it is unclear whether this difference reflects a pre-supposed bias against ICGA or a decrease in perceived utility. This distinction between the perceived clinical utility of NIRAF and ICGA may lead surgeons to choose to use NIRAF in isolation for parathyroid preservation instead of combining it with ICGA.

Another interesting question raised by this study is whether the improvement in the number of parathyroid glands identified with combined NIRAF + ICGA differs from the improvement seen in NIRAF alone. The authors do not directly address this question in their study, but it would be interesting to investigate given prior studies have demonstrated an increased quantitative parathyroid estimation with use of NIRAF technology (20,21). Interestingly, a prior randomized study did not demonstrate a significant difference in postoperative hypocalcemia rates despite increased parathyroid gland identification rates, which differs from Michaelsen et al.’s finding of reduced postoperative hypocalcemia with use of combine NIRAF + ICGA technology (15,21).

Although the authors found a statistical difference in hospital length of stay between groups, it does not appear to be a clinically relevant difference, as the median length of hospital nights was still 2.0 in both the control and intervention group (although the interquartile range decreased) (15). Additionally, with the advent of outpatient thyroid surgery that has been documented at many centers (22), it appears that this benefit of decreased length of stay can be achieved in other ways without requiring the use of NIRAF or ICGA technology.

A final point of discussion when considering the use of NIRAF and ICGA is the added cost and operative time. Adoption of a new technology hinges on the cost/benefit analysis of its implementation. In the case of NIRAF and ICGA, there does appear to be demonstrated benefit for improving parathyroid identification and preservation, but it is unclear what that benefit would be for experienced parathyroid surgeons who otherwise have low postoperative hypocalcemic rates. However, there does appear to be significant cost and resource utilization associated with adoption of the technology, as it would require new autofluorescent/near-infrared equipment and would require use of indocyanine green. In Michaelsen et al.’s study, even after 2 years of implementation, the overall operative time was still increased by nine minutes with combined use of NIRAF and ICGA (15). This increase in time may not be palatable for high-volume thyroid surgeons but may be worth it for low- to mid-volume thyroid surgeons, especially if they observe a decrease in their postoperative hypoarathyroidism rate.

In summary, Michaelsen et al.’s finding of reduced postoperative hypoparathyroidism with the use of NIRAF and ICGA is remarkable and the study is well-designed. Their findings are somewhat limited by the retrospective nature of their control group and their inability to fully account for surgeon experience. Ultimately, it does appear that these technologies could provide benefit particularly for low-volume thyroid surgeons. Studies comprising prospective control and intervention arms would be helpful to further elucidate the potential clinical relevance of NIRAF and ICGA technology in maximizing parathyroid preservation.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Thyroid. The article has undergone external peer review.

Peer Review File: Available at https://aot.amegroups.com/article/view/10.21037/aot-2026-1-0003/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aot.amegroups.com/article/view/10.21037/aot-2026-1-0003/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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