Elsevier

Surgery

Volume 165, Issue 2, February 2019, Pages 431-437
Surgery

Heterogeneous and low-intensity parathyroid autofluorescence: Patterns suggesting hyperfunction at parathyroid exploration

https://doi.org/10.1016/j.surg.2018.08.006Get rights and content

Abstract

Background

Although parathyroid glands have been found to exhibit autofluorescence with near-infrared fluorescence imaging, it is unknown if autofluorescence characteristics vary between hyperfunctioning and normofunctioning glands. The hypothesis was that pattern of autofluorescence exhibited by hyperfunctioning versus normofunctioning parathyroid glands would be different.

Methods

This is an Institutional Review Board–approved, prospective clinical study. Patients underwent bilateral neck exploration for primary hyperparathyroidism, during which autofluorescence from each gland was assessed with near-infrared fluorescence imaging. Pattern and intensity of autofluorescence between hyperfunctioning and normofunctioning parathyroid glands were compared.

Results

Overall, 199 parathyroid glands were identified in 50 patients (single gland disease, n = 31; multigland disease, n = 19). Autofluorescence was detected from 96% (n = 192) of parathyroid glands, all of which exhibited a higher intensity autofluorescence than the background tissues. Parathyroid gland location was revealed by near-infrared fluorescence imaging before dissection in 26% (n = 52). A total of 77 glands that were large or firm were excised and 122 were preserved because of normal appearance. Hyperfunctioning parathyroid glands had a lower mean normalized autofluorescence intensity than normofunctioning parathyroid glands (1.8, and 2.6, respectively, P < .001). Moreover, hyperfunctioning parathyroid glands more often exhibited a heterogeneous pattern of autofluorescence (75% and 5%, respectively, P < .001). On multivariate analysis, only parathyroid gland hyperfunction correlated with normalized autofluorescence intensity. On receiver operative characteristic curve, optimal cutoff of normalized autofluorescence intensity to differentiate hyperfunctioning from normofunctioning parathyroid glands was 2.0.

Conclusion

Our results indicate that hyperfunctioning and normofunctioning parathyroid glands exhibit different patterns of autofluorescence in hyperparathyroidism. Given these findings, autofluorescence pattern could be implemented as another adjunctive parameter for gland assessment during parathyroid exploration.

Introduction

Primary hyperparathyroidism (hyperparathyroidism) has a prevalence of 15.7 per 100,000 in the US population1 and if untreated can cause serious complications, including nephrolithiasis, chronic kidney disease, and osteoporosis.2 In eligible patients, surgery is the standard of care.3 Nevertheless, intraoperative identification and assessment of the parathyroid glands (PGs) can be challenging even for experienced surgeons. Neck ultrasound and sestamibi scans are the 2 most commonly used localizing studies, accuracies of which range between 59% and 89% and 54% and 88%, respectively.4 Despite the advances in these imaging modalities, the success of parathyroid surgery significantly depends on surgeon experience and has been reported to range from 91% to 100%.5, 6 The challenges with parathyroid localization and the importance of surgeon experience for a successful parathyroid surgery led to the famous quote by the interventional radiologist John L. Doppman: “In my opinion, the only localizing study indicated in a patient with untreated hyperparathyroidism is to localize an experienced parathyroid surgeon.”7

Over the years, several imaging modalities have been proposed to localize PGs intraoperatively, including the use of aminolevulinic acid,8 methylene blue,9 a handheld gamma probe,10 and most recently indocyanine green fluorescence.11 However, these modalities could not consistently identify PGs and were associated with adverse effects, such as injection-related complications, allergy, radiation exposure, and photosensitivity.12 Furthermore, none of them predicted parathyroid function.13

Recently a novel method of identification that relies on the detection of autofluorescence from PGs using near-infrared fluorescence imaging (NIFI) has become available.14 Initial reports have found up to 98% detection rates of PGs using this technique.15 More recently it has also been suggested that rates of postoperative hypocalcemia after total thyroidectomy may be decreased with the use of this technology.16 Despite many authors reporting the ability to detect autofluorescence from PGs intraoperatively,15, 17 whether this technology could be used to differentiate between hyperfunctioning and normofunctioning PGs has never been studied. Naturally a modality that could differentiate between hyperfunctioning and normofunctioning PGs would be very useful during parathyroid exploration. Therefore it is crucial to investigate this technology for a potential use in this regard. Our hypothesis was that the pattern of autofluorescence exhibited by hyperfunctioning versus normofunctioning PGs could be different. The aim of this study was to define these differences in autofluorescence patterns during parathyroid exploration for hyperparathyroidism.

Section snippets

Study design

This was a prospective clinical study approved by the Institutional Review Board at the Cleveland Clinic. All study patients underwent bilateral neck exploration for hyperparathyroidism using autofluorescence imaging by a single surgeon (E.B.) between July 2016 and February 2018. Patients undergoing reoperative surgery were excluded.

The autofluorescence patterns between hyperfunctioning and normofunctioning PGs have never been compared before. Therefore an arbitrary number of 50 patients was

Results

A total of 50 patients underwent bilateral neck exploration for hyperparathyroidism. A PG was localized successfully by preoperative ultrasound in 29 of 50 (58%), by sestamibi in 28 of 48 (58%), and by concordance of both studies in 21 patients. In 20 patients the sestamibi, in 21 patients the ultrasound, and in 13 patients both sestamibi and ultrasound were negative. Based on intraoperative findings, 31 patients were found to have a single adenoma, 11 patients double adenomas, and 8 patients

Discussion

To our knowledge this is the first study in the literature suggesting that different patterns of autofluorescence are exhibited by hyperfunctioning versus normofunctioning PGs in hyperparathyroidism. Despite the previous studies reporting the use of parathyroid autofluorescence imaging to identify PGs during thyroidectomy and parathyroidectomy,15, 17 its use to predict parathyroid function has not been reported before. We have found that hyperfunctioning glands have heterogeneous and

References (23)

  • JW Kunstman et al.

    Clinical review: parathyroid localization and implications for clinical management

    J Clin Endocrinol Metab

    (2013)
  • Cited by (64)

    • Future Directions in the Treatment of Thyroid and Parathyroid Disease

      2024, Otolaryngologic Clinics of North America
    • Smaller parathyroids have higher near-infrared autofluorescence intensity in hyperparathyroidism

      2022, Surgery (United States)
      Citation Excerpt :

      One study of 96 patients undergoing parathyroidectomy for both primary and secondary hyperparathyroidism found a correlation of intensity with preoperative calcium and preoperative serum parathyroid hormone (PTH) levels based on the surgeon’s subjective rank of fluorescence based on a scale of low-medium-high.18 Another study compared the fluorescence from normal and excised parathyroid glands in 50 patients having surgery for hyperparathyroidism capturing images from both in situ and excised glands.19 They found a higher intensity with normofunctioning glands compared with hyperfunctioning glands.

    View all citing articles on Scopus
    View full text