- Original research article
- Open Access
Validation of a novel method for localization of parathyroid adenomas using SPECT/CT
© The Author(s). 2018
- Received: 2 July 2018
- Accepted: 7 September 2018
- Published: 26 October 2018
Accurate localization of parathyroid adenomas is of critical importance in surgical planning for minimally invasive parathyroidectomy. SPECT/CT is considered the investigation of choice but has limitations regarding localization of superior versus inferior adenomas. We proposed a novel method for localization using SPECT/CT by determining the anterior-posterior relationship of the adenoma to a horizontal line in the coronal plane through the tracheoesophageal groove. Our objective was to determine the accuracy, validity, and inter-rater reliability of this method.
This was a retrospective review of patients who underwent parathyroidectomy for a single adenoma between 2010-2017. SPECT/CT images were reviewed by two staff Otolaryngologists, a Radiologist, an Otolaryngology fellow and Otolaryngology resident. Results were compared using intra-operative report as the gold standard.
Overall accuracy in determining superior/inferior and right/left adenomas was calculated, as well as Cohen's Kappa to determine agreement with operative report and inter-rater reliability. The performance was compared to that of the original radiology report.
One hundred thirty patients met criteria and were included. Our method correctly identified the location of the adenoma in terms of both side and superior/inferior position in 80.4% [76 - 84%] of patients, which considerably outperformed the original radiology report at 48.5% [4-78%] accuracy. The agreement level between our method and operative report was high (Kappa=0.717 [0.691-0.743]), as was the inter-rater reliability (Kappa=0.706 [0.674-0.738]).
We report a novel method for localization of parathyroid adenomas using SPECT/CT which outperforms standard radiology reporting. This tool can be used by surgeons and radiologists to better inform and plan for minimally invasive parathyroidectomy.
Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and elevated levels of parathyroid hormone (PTH) and is most commonly caused by a single glandular enlargement, or adenoma. Parathyroid adenoma may occur in any of the four glands but tends to involve the inferior glands more commonly than superior glands . The definitive management of primary hyperparathyroidism is surgical.
Although the number and position of parathyroid glands can vary, the most common arrangement involves four glands, two superior and two inferior glands . The superior glands originate embryologically from the fourth pharyngeal pouch, whereas the inferior glands originate from the third pharyngeal pouch. As a result of their embryological migration patterns, the glands tend to have a predictable position with relation to the thyroid, thymus, and recurrent laryngeal nerve. Superior glands tend to be more intimately related to the recurrent laryngeal nerve and lie deep to the plane of the nerve. Inferior glands in contrast tend to lie in a more superficial plane than the nerve and more inferiorly, between the thyroid and thymus [3–6].
Accurate pre-operative localization of parathyroid adenomas is critical for operative planning and the facilitation of minimally invasive surgery. In recent years, there has been development of more effective imaging methods to localize parathyroid adenomas, rather than the previous gold standard of surgical four-gland exploration. Non-invasive preoperative methods for localization of parathyroid adenomas include: ultrasonography, radioiodine or technetium scintigraphy, technetium 99 m sestamibi scintigraphy, computed tomography scan, and magnetic resonance imaging [1, 2, 7, 8]. Recently published studies have shown high utility in the use of single-photon emission CT (SPECT) using sestamibi radionucleotide imaging in combination with CT scanning (SPECT/CT). SPECT/CT has been found to have improved anatomic detail when compared with traditional sestamibi imaging .
Determining whether a parathyroid adenoma represents an inferior or superior adenoma can be difficult on imaging. This is preoperative localization is, however, paramount to successful excision, as superior and inferior glands are approached differently during surgery. Inaccurate localization seen in some traditional methods can result in more extensive or revision surgery. We have developed a novel method, known as the Harris method, of localizing parathyroid adenoma as inferior or superior based on SPECT/CT imaging. This method is based on the embryological origin and migration pathway of the parathyroid glands, as opposed to the traditional radiological method of their relation to the thyroid gland only. The technique consists of drawing a horizontal (coronal) line on axial cuts of SPECT/CT, bisecting the tracheoesophageal groove at the level of the cricoid cartilage. Adenomas that are anterior to this line on axial cuts are deemed inferior, while adenomas that are posterior to this line are superior. The aim of our study is to determine the validity and accuracy of this novel method for localization of parathyroid adenomas when compared to traditional radiological reporting, against the gold standard of intra-operative localization.
Institutional review board approval was obtained from the Human Research Ethics Board at the University of Alberta (Pro00077058). This was a retrospective diagnostic validation study evaluating the use of a novel method of determining the location of a parathyroid adenoma using axial cuts of SPECT/CT.
Participants who underwent parathyroidectomy for a single parathyroid adenoma between November 1, 2010 until November 30, 2017 within the Division of Otolaryngology - Head and Neck Surgery in Edmonton, Alberta were recruited. Eligible patients were those aged > 18 years with a clinical diagnosis of primary hyperparathyroidism. Patients were excluded if they had previous head and neck surgery, greater than one identified parathyroid adenoma, or if radiology reports, SPECT/CT images and/or operative reports were unavailable. Patients were also excluded if there was a failure to identify whether the adenoma was superior or inferior intraoperatively.
Using SPECT/CT images, two staff Otolaryngologist – Head and Neck Surgeons, a Nuclear Medicine Radiologist, an Otolaryngology – Head and Neck Surgery fellow and resident performed the novel method, blinded to the operative findings, on eligible patients that met the inclusion and exclusion criteria. This novel method consisted of finding the level of the cricoid cartilage on an axial cut of the SPECT/CT and drawing a horizontal line bisecting the tracheoesophageal groove. The participants were then to identify whether the adenoma is anterior or posterior to that line. Data was recorded and participants were given immediate feedback as to their diagnostic accuracy. Participants were given 30 scans in one session to prevent fatigue.
The primary outcome was the accuracy of the novel technique of parathyroid adenoma localization based on SPECT/CT using intra-operative identification as the gold standard. The accuracy was compared to that of the original radiology report using cohen’s kappa. Our secondary outcomes were inter-rater reliability of using this novel technique. A clinical diagnosis of PHPT included hypercalcemia and high PTH levels. Operative reports were used to identify the correct location of the adenoma causing hyperparathyroidism. Calcium, PTH, intraoperative identification of the adenoma location, radiology report identification, and the result of the performed task by participants were all recorded.
Statistical analysis was carried out using SPSS software (Statistical Package for the Social Sciences, Version 22.214.171.1240). The percentages were calculated by adding the correct answers when compared to the operative report as gold standard. Percentage of each adenoma was recorded and the overall accuracy was the mean of all rater accuracies. Cohen’s kappa was used to determine the inter-rater reliability between the original radiology report and the operative report. Fleiss kappa was used to calculate inter-rater reliability between the raters and the operative report and the raters themselves.
N = 130
Preoperative PTH (Average)
20.2 pmol/L (6.1–81.5 pmol/L)
Postoperative PTH (Average)
3.06 pmol/L (.60–12.40 pmol/L)
Preoperative Calcium (Average)
2.77 mmol/L (2.37–2.77 mmol/L)
Cohen’s Kappa comparing Operative Report and Original Radiology Report
Asymptotic Standard Error
Lower 95% Asymptotic CI Bound
Upper 95% Asymptotic CI Bound
Overall Fleiss Kappa for Inter-rater Reliability
Asymptotic Sandard Error
Lower 95% Asymptotic CI Bound
Upper 95% Asymptotic CI Bound
Fleiss Kappa for Overall Inter-rater Reliability and between Raters and Operative Report
Asymptotic Standard Error
Lower 95% Asymptotic CI Bound
Upper 95% Asymptotic CI Bound
Overall Between Raters and Operative Report
The gold standard of treatment for PHPTH caused by a parathyroid adenoma is surgical resection . When compared to four gland exploration, a minimally invasive approach has been associated with reduced complications such as including injury to the recurrent laryngeal nerve, hypocalcemia and bleeding risks, as well as shorter hospital stay [11–13].
In 2009, Perrier et al. have developed a nomenclature that provides a precise means of communicating the most frequently encountered parathyroid adenoma locations. Using the Perrier method, a uniform and reliable description of exact locations of parathyroid adenomas can aid in proper localization preoperatively . The system essentially uses the letters A – G to describe exact gland locations. Keidar et al. found that using the Perrier method, 80% of cases accurately localized parathyroid adenomas preoperatively using SPECT/CT . This method however is not widely used in radiology reports due to its complexity.
It is important to take into account that the superior glands may never be separated from the thyroid gland during embryological migration . If a superior gland is adenomatous, the potential course could result in the gland in the inferior and posterior position. Dasgupta et al. reported that when radiology reports are duel reported by a surgeon and a nuclear medicine physician, there was a statistically significant improvement in localization [2, 3]. This finding may be attributed to the fact that surgeons may have a better understanding of the anatomy and embryology of the parathyroid glands than the nuclear medicine physician [3, 19]. The use of multiple imaging modalities, our newly described method, and dual reporting with nuclear medicine physicians and surgeons may improve the accuracy of preoperative localization.
The importance of preoperative localization by the operating surgeon cannot be underestimated. Increasing the localization accuracy allows an endocrine surgeon to further minimize the amount of dissection required during surgery which directly reduces the risk profile associated with minimally invasive parathyroid surgery.
There are a few limitations that can be identified in this present study. Using SPECT/CT in itself has limitations including patient motion during the study for accurate registration in SPECT/CT, attenuation and scatter correction, spatial registration, and radiation exposure considerations . Another limitation is the size of the thyroid gland. Theoretically, if the thyroid gland size is larger, it would potentially push the parathyroid glands either more posterior or anterior with respect to the tracheoesophageal groove and could therefore alter our findings or explain some of the incorrect localization results. A larger prospective study may help to address these limitations in the future.
Another limitation is that when the radiology reports were originally dictated, the radiologist did not have the benefit of knowing whether or not there indeed was an adenoma present before reading the study, as opposed to the subjects used for this research study. Thus, localization may have been more challenging for the original radiologist. We attempted to correct for this by eliminating patients that were originally described as non-localizing, regardless of the final operative findings.
We also did not perform intra-rater reliability testing, nor were we able to track a learning curve for our novel method. We plan to collect and analyze these metrics in a follow-up study.
The Harris method correctly identified the location of the parathyroid adenoma in terms of both side and superior/inferior position in 80.4% of patients, which considerably outperformed the original radiology reports accuracy of 48.5%. There was substantial agreement between our method and the operative report (Kappa = 0.717 [0.691–0.743]), as well as the inter-rater reliability (Kappa = 0.706 [0.674–0.738]). The Harris method is easily performed by the surgeon and radiologist and is less complex and time consuming than the previously reported Perrier method, with very similar localization success. By using this method, preoperative localization of parathyroid adenomas can be improved allowing the surgeon to plan for efficient, effective, and safe minimally invasive parathyroidectomy.
RL carried out the study design, collected and recorded the data, performed the data analysis, and drafted the manuscript. AI performed the novel method and participated in creating the study design, helped with statistical analysis, as well as edited the manuscript. JA, VB, MH all performed the novel method and helped edit the manuscript. DC helped with statistical analysis and manuscript review. DOC participated in study design, data aquisition and manuscript review. HS participated in the study design and helped revise the manuscript. JH participated in study design, performed the novel method, and manuscript revision. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Prior to commencement of this study, ethics approval was obtained from the University of Alberta Health Research Ethics Board.
Consent for publication
The authors declare that they have no competing interests.
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