NIRAF and ICG: Equivalent Technologies — or a Dangerous Misconception in Parathyroid Preservation?

Carlos E Costa Almeida
19 de fev.
5 min de leitura

Preserving the parathyroid glands (PGs) remains a major challenge during thyroid surgery. Devascularization of the PGs or failure to identify them, leading to inadvertent removal, may result in permanent postoperative hypoparathyroidism and hypocalcemia. Transient postoperative hypocalcemia has been reported in 15–30% of cases in some series, whereas permanent hypocalcemia occurs in approximately 1–3% of patients (with recent studies suggesting higher rates). When central neck dissection is performed, the rates of transient and permanent hypoparathyroidism increase to 27.7–51.9% and 6.3–16.2%, respectively. Although many surgeons consider this complication manageable with simple calcium supplementation, it may lead to significant long-term consequences, including an increased mortality rate in subsequent years.

In recent years, two techniques have been introduced to help preserve the PGs: near-infrared autofluorescence (NIRAF) and indocyanine green (ICG) angiography. Although many clinicians refer to these techniques as if they were equivalent for parathyroid gland identification, they serve different purposes and are in fact complementary. Understanding this distinction is essential to reduce the incidence of postoperative hypocalcemia.

During thyroid surgery, surgeons must address the following questions:

Where is the parathyroid gland?
Is this parathyroid gland well perfused?
Should this parathyroid gland be autotransplanted?

For PG identification—particularly when their location is uncertain—the two techniques are not equivalent. NIRAF is based on the natural fluorescence emitted by the PGs when exposed to near-infrared light. This principle makes the technique especially useful when the glands are not visually apparent. It can also help differentiate parathyroid tissue from surrounding fatty tissue, lymph nodes, or fibrotic tissue. Importantly, NIRAF does not depend on blood perfusion, which allows identification of partially devascularized glands and even detection of a PG within a thyroidectomy specimen. Therefore, NIRAF is the technique that answers the question: Where is the parathyroid gland?

On the other hand, ICG is a fluorescent dye administered intravenously. Therefore, the ICG signal depends on both dye injection and adequate blood flow. This technique is useful for real-time assessment of PG perfusion after the glands have been anatomically identified. In other words, ICG is most valuable once the gland has already been located, as it helps determine whether it is well vascularized or at risk of ischemia. Surgeons should also be aware that ICG fluorescence is not specific to parathyroid tissue; it can also be detected in the thyroid gland, muscle, lymph nodes, and inflamed tissue, which may potentially confuse the interpretation. Additionally, after extensive dissection, partial devascularization of a PG may result in reduced or absent ICG uptake, potentially influencing intraoperative decision-making. ICG answers the second question: Is this parathyroid gland well perfused? The answer to this question forms the basis for addressing the third question.

In the setting of reoperation, these differences become even more relevant. During reoperative surgery, surgeons encounter dense fibrosis and distorted anatomy, while facing a higher risk of gland devascularization and permanent hypoparathyroidism. In this context, NIRAF becomes even more valuable for PG identification, for the reasons described above. ICG, in turn, maintains its crucial role in assessing PG vascularization.

NIRAF and ICG for parathyroid gland preservation during thyroid surgery

A study published in 2017 by Dr. Bora Kahramangil et al., from the Department of Endocrine Surgery at the Cleveland Clinic (USA), was already aligned with this concept. The authors evaluated the ability of each technique to identify parathyroid glands (PGs) compared with naked-eye (NE) identification during thyroid surgery. They reported similar overall detection rates for both techniques (98% for NIRAF vs 95% for ICG); however, the timing of identification differed substantially. In my view, the timing of identification is the most clinically relevant factor. NIRAF detected 52% of PGs before naked-eye identification, whereas ICG detected only 6% before NE (p < 0.001). This represents the key advantage of NIRAF for PG identification. Additionally, in the NIRAF group, 82% of patients had at least one PG detected before NE, compared with only 14% in the ICG group (p < 0.001). The median number of PGs detected before naked-eye identification was also significantly higher in the NIRAF group (p < 0.001).

Another study, published in 2024 in the British Journal of Surgery (BJS) by Dr. Sofia Di Lorenzo et al. from France and Italy, evaluated the impact of combining NIRAF and ICG on postoperative hypoparathyroidism after total thyroidectomy with central neck dissection (CND). Three groups were included: a control group, a NIRAF-alone group, and a NIRAF + ICG group. The rates of transient hypoparathyroidism were 48.9%, 37.8%, and 5.1%, respectively (p < 0.0001). The rates of permanent hypoparathyroidism were 8.5% in the control group, 2.2% in the NIRAF-alone group, and 0% in the NIRAF + ICG group. Inadvertent resection of PGs occurred in 15.4% of patients in the control group, 7.9% in the NIRAF-alone group, and 4.5% in the NIRAF + ICG group, demonstrating statistical significance. Overall, the rate of transient hypoparathyroidism was significantly lower in the NIRAF + ICG group compared with both the control and NIRAF-alone groups. Although no statistically significant difference was observed in permanent hypoparathyroidism, the rate decreased progressively from the control group to the NIRAF-alone group, reaching 0% in the NIRAF + ICG group. The rate of autotransplantation was higher in the NIRAF + ICG group (2/29 removed PGs in the control group; 2/15 in the NIRAF-alone group; 3/7 in the NIRAF + ICG group), further supporting the complementary role of both techniques. As the authors concluded, “while most clinical studies have reported that NIRAF alone can reduce the rate of transient postoperative hypoparathyroidism, the results from the present study show how a combination of NIRAF and ICG can provide even better results.”

The following table summarizes the key differences between NIRAF and ICG discussed above. Understanding these distinctions is crucial for clinical practice.

		🔬 NIRAF	💉 ICG
Mechanism		Intrinsic fluorescence of PGs	Fluorescence of intravenous dye
Contrast injection		No	Yes (IV)
Depends on vascular perfusion		No	Yes
Primary purpose		Anatomical identification	Perfusion assessment
Clinical question answered		Where is the PG?	Is this PG well perfused?
Ability to scan surgical field		Excellent	Not good
Specificity for parathyroid tissue		High	Other tissues fluoresce (e.g. thyroid, lymph nodes, muscle)
Identification of already devascularized glands		Yes	Very limited (false negative)
Utility in reoperations	Distorted anatomy	✅	⚠️ Limited
	Fibrosis	✅ May help find the PGs within the fibrosis ⚠️ Weak signal	⚠️ Limited
	Ectopic gland	✅ May help	❌
	Perfusion	❌	✅ Very good
Risk		No	Rare allergic reactions
Learning curve		Short	Subjective interpretation

In summary, NIRAF and ICG are complementary techniques. Autofluorescence enhances anatomical identification of the parathyroid glands (PGs), whereas ICG improves functional assessment of their vascular supply. The combined use of both techniques may reduce the incidence of postoperative hypoparathyroidism more effectively than either technique alone.

So, what should be done during a thyroidectomy?