Parathyroid autofluorescence: can we find without searching?

Postoperative hypoparathyroidism remains one of the most significant and feared complications of neck endocrine surgery. Its importance goes far beyond acute postoperative symptoms, as it is responsible for an increase in long-term complications, including dystrophic calcifications, nephrocalcinosis, renal failure, impairment of quality of life, and even decreased length of life (1-3). At the same time, these complications and their management involve a significant increase in healthcare-related costs, especially following the advent of recombinant parathyroid hormone (PTH) formulations.

The evolution of surgical techniques, in terms of preventing hypoparathyroidism, has undergone few changes in the last 50 years. Although we know from almost a century ago that identifying the recurrent laryngeal nerve reduces the risk of vocal cord palsy (4), we still have not reached a consensus on whether systematic identification of the four parathyroid glands prevents or increases the risk of postoperative hypoparathyroidism (5,6).

Following the development of intraoperative neurostimulation systems, current technological advances in endocrine surgery are focused on improving the identification and management of the parathyroid glands. Two tools are available for this purpose: indocyanine green (ICG) arteriography and near-infrared autofluorescence (NIRAF). It is essential to understand that both technologies share a common basis, fluorescence, and through different mechanisms, they seek the same purpose: the prevention of hypoparathyroidism. Unfortunately, the combined use of both technologies is limited, as current systems do not allow differentiation between the autofluorescence signal and that emitted by ICG.

ICG arteriography allows us to evaluate parathyroid vascularization. Although it emerged as a predictive tool for hypoparathyroidism (7), its main use today is in the prevention of this condition through arteriography-guided thyroidectomy (8). Several studies have shown that identifying the vascular pattern of the parathyroid glands can facilitate their management during thyroidectomy, allowing for the preservation of well-vascularized glands after surgery and, therefore, a lower rate of hypoparathyroidism (9).

On the other hand, NIRAF aims to facilitate the identification of the parathyroid glands thanks to their intrinsic ability to emit fluorescence in the near-infrared spectrum when stimulated with laser light. This phenomenon, discovered in 2008 at Vanderbilt University, has been reinforced by the results of a multicenter randomized clinical trial coordinated by this center (10). In this study, a probe-based NIRAF system was used in 712 patients undergoing thyroidectomies or parathyroidectomies. This study obtained positive results in terms of its main objective, the identification of parathyroid glands, which increased during thyroidectomies (3.3 vs. 2.8; P<0.001) and during bilateral explorations (3.5 vs. 3.2; P<0.001). A higher degree of confidence was also achieved by the surgical team when identifying parathyroid tissue, and the use of intraoperative biopsies decreased. However, it was not possible to demonstrate a decrease in the rate of postsurgical hypoparathyroidism, which would probably have been essential to consolidate this technology. Unfortunately, the sample size was calculated to compare the number of glands identified, not the rate of hypoparathyroidism, for which the study is underpowered.

Other clinical trials based on NIRAF imaging systems, designed for this purpose, have succeeded in demonstrating a lower rate of postoperative hypoparathyroidism in the whole cohort (11) or in populations at particular risk of inadvertent parathyroidectomy (12). These findings would confirm that the higher rate of glands identified and preserved in situ with NIRAF facilitates this potential decrease in the rate of hypoparathyroidism (13).

However, this promising technology still has several weaknesses. The first is that we still do not know with certainty the physiological mechanism by which the parathyroid glands emit this signal, so we cannot design improvements that increase the specificity of these systems. It has been argued that the objective of this technology is to confirm the parathyroid nature of suspicious lesions. Unfortunately, the high false positive rate described in some studies makes this role really challenging (14). Its real usefulness is more likely based on the low false negative rate, which could let us rule out parathyroid origin in tissues without autofluorescence. On the other hand, as with all technologies in the early years after their launch on the market, cost remains an important determinant. A recent cost-effectiveness study has shown that these systems could be cost-effective in populations with a permanent hypoparathyroidism rate of more than 5%, which opens the door to at least selective use in high-risk populations (15).

Finally, given that the intermediate mechanism for reducing the rate of hypoparathyroidism would be a greater preservation of parathyroid glands remaining in situ, the potential benefit for low-risk patients (without central neck dissection) treated by surgeons with a low rate of inadvertent parathyroidectomies remains unclear. In these patients, hypoparathyroidism is probably more related to devascularization than to failure at identifying the glands. Each surgeon must know their Achilles heel: those with a high rate of inadvertent parathyroidectomies will probably find NIRAF devices useful, while those whose problem lies in parathyroid devascularization will find more help in ICG-guided surgery. Endocrine surgery should not pursue the indiscriminate adoption of technology, but rather a thoughtful and personalized application.

It is essential that more multicenter or real-life studies be developed to understand the true usefulness of this technology. The debate over whether or not we should systematically search for all parathyroid glands during thyroidectomy remains open, but perhaps the possibility of locating these glands without requiring additional dissection, without risk of damaging them during this search, can help us close it.

Acknowledgments

None.

Footnote

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

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-555/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-555/coif). J.L.M.d.N. has participated in a group of experts related to the development of fluorescence in endocrine surgery at the national level and in a presentation related to his experience. This has not influenced the manuscript in any way. No company has knowledge of this manuscript or its content. The author has no other conflicts of interest to declare.

Ethical Statement: The author is 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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