British Journal of Radiology (2004) 77, 100-103
© 2004 British Institute of Radiology
doi: 10.1259/bjr/44399050
Technetium-99m sestamibi scintigraphy and helical CT together in patients with primary hyperparathyroidism: a prospective clinical study
F Lumachi, MD
1
A Tregnaghi, MD
2
P Zucchetta, MD
3
M C Marzola, MD
3
D Cecchin, MD
3
P Marchesi, MD
2
F Fallo, MD
4 and
F Bui, MD, PhD
4
1 Endocrine Surgery Unit, Department of Surgical and Gastoenterological Sciences, 2 Radiology Section and 3 Nuclear Medicine Service, Department of Diagnostic Medical Sciences and 4 Department of Medical and Surgical Sciences, University of Padua, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy
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Abstract
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44 consecutive patients with confirmed primary hyperparathyroidism (HPT) undergoing surgery were prospectively enrolled in the study. There were 13 (29.5%) men and 31 (70.5%) women with an overall median age of 59 years (range 23–78 years). Prior to successful parathyroidectomy both 99Tcm-sestamibi/99Tcm-pertechnetate subtraction scintigraphy (SS) and helical CT were performed, and the results of imaging studies were compared against intraoperative findings. Final histopathology showed 40 (90.9%) solitary parathyroid (PT) adenomata (median size 18 mm, range 8–40 mm), that were in an ectopic location in 13 (32.5%) patients. Moreover, 3 (6.8%) patients had multiglandular disease (one patient with two PT adenomata, two patients with PT hyperplasia), while one (2.3%) patient had a PT carcinoma. The sensitivity and positive predictive value were 86.0% and 97.4% for SS, 88.1% and 94.9% for CT, and 100% and 97.4% for the combination of SS and CT, respectively. Calcium and parathyroid hormone (PTH) serum levels, and the mean size of the removed PT glands of patients with false negative results were lower than that of those with true positive results, but the difference was not significant. Among patients with solitary PT tumours (N=41) the sensitivity was 88.1% and 90.3% for SS and CT-scan, respectively. In conclusion, our study confirms the usefulness of SS, which should be the initial test for patients undergoing parathyroidectomy. However, the strategy of performing two tests in each patient with primary HPT could be of limited utility when the initial SS is positive.
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Introduction
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Primary hyperparathyroidism (HPT) is the most common cause of hypercalcaemia in outpatients. In the USA one in every 500 women and one in every 1000 men over 40 years may have primary HPT [1]. Since 1996, minimally-invasive parathyroidectomy has become extensively performed with the aim of reducing operative time, discharging patients earlier after surgery, and having better cosmetic results [2–8]. Consequently, improved sensitivity of localizing studies has become desirable.
Non-invasive imaging techniques used to evaluate patients with primary HPT include ultrasound (US), CT scanning, MRI, and parathyroid (PT) scintigraphy. Several studies consider the usefulness of a combination of two or more techniques, but it is unclear which procedures should be routinely chosen in unexplored patients. The aim of this prospective blinded study was to analyse the results obtained using 99Tcm-sestamibi/99Tcm-pertechnetate subtraction scintigraphy (SS) and helical CT together in patients initially diagnosed with primary HPT.
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Materials and methods
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Study population
44 consecutive patients with confirmed primary HPT undergoing surgery were prospectively enrolled in the study. There were 13 (29.5%) men and 31 (70.5%) women with an overall median age of 59 years (range 23–78 years). No patients with persistent or recurrent primary HPT were observed. The main pre-operative biochemical data of the study population are reported in Table 1
. Once the patients had given their informed consent, both SS and helical CT were performed within 1 week prior to successful parathyroidectomy. The results of imaging studies were interpreted independently, without knowledge of the other studies, and compared against the intraoperative and final histological findings. The removed PT glands were measured by the pathologist who recorded their greatest diameter (size).
As previously described, both SS and CT were considered true positives (TP) when one or more enlarged PT glands were correctly localized, false positives (FP) when no diseased PT glands were found at operation in the site suggested by each procedure, and false-negatives (FN) when the techniques did not detect any abnormal PT gland [9]. In patients with multiglandular disease the results were considered TP only when at least two diseased PT glands had been correctly localized. The ectopic sites in which the superior PT glands may be found included a retroesophageal, posterior mediastinal, and intrathyroidal location, while ectopic sites of the inferior PT glands included superior mediastinum, thymus, and carotid sheath [10, 11].
Parathyroid scintigraphy
In all patients undergoing SS the recent use of iodine-containing preparations (contrast media, L-thyroxin) was excluded. Patients were examined in a supine position. Three planar images (300 s each, anterior view) of the neck in a 256 x 256 pixel matrix were obtained, 5 min after intravenous 370 MBq 99Tcm-methoxyisobutylisonitrile (sestamibi) administration. Scintigrams were acquired by using a single-head gamma camera fitted with a high-resolution parallel-hole collimator, with the window width at 10% centred on 140 keV. Keeping the patient immobile, 3 more images of the neck and chest were obtained after 150 MBq 99Tcm-pertechnetate administration (window width at 10% centred on 140 keV). The overall estimated effective dose was 5 mSv for each patient.
After inspection and correction of patient motion, if necessary, sestamibi and pertechnetate images were independently normalized and evaluated after computer subtraction. The mean operative time for acquiring images was 15 min. Abnormal PT tissue was defined as an area of relatively increased tracer uptake persisting after images subtraction, or a persistent mediastinal uptake, as previously described [9]. Delayed images were not performed. In selected patients with multiglandular PT disease, two or more foci of sestamibi uptake were obtained (Figure 1).
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Figure 1. 99Tcm-sestamibi/99Tcm-pertechnetate subtraction scintigraphy in a 56-year-old woman (planar anterior view) revealing two focal areas of increased tracer uptake (circle) corresponding to two parathyroid adenomata.
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Helical CT imaging
Patients undergoing helical CT had the neck in slight extension. Volumetric scanning of the neck and upper mediastinum using axial thin sections at a speed of 1 slice/0.8 s was performed. A frontal scout view identified the upper limit of the heart, which was the lower region of interest and the first scan at CT examination. The feet-to-head acquisition direction offered a better immobility with prolonged breath hold examination time. Slice collimation ranged from 3 mm to 5 mm, with pitch value of 1.5, and gantry rotation time of 0.8 s. A 80–100 ml bolus of non-ionic contrast medium was given by intravenous administration at a rate of 2–3 ml s-1, with a delay time of 40–50 s from the beginning of the injection.
The rich vascularity of the PT glands allowed the identification of the abnormal PT tissue even if the surrounding structures, such as thyroid gland or small tortuous arteries, showed high enhancement values mimicking PT lesions. In selected patients, multiplanar reconstruction was useful to identify the relationship between PT adenomata and contiguous structures. The CT diagnosis of abnormal PT glands requires identification of a bean shaped enhancing lesion, non-adherent to the surrounding tissues, with an average size of 15-20 mm, usually sited posteriorly to the thyroid gland [11, 12]. The typical CT appearance of a PT adenoma is shown in Figure 2.
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Figure 2. (a) Typical CT appearance of a parathyroid adenoma in a 67-year-old man. Contrast-enhanced axial helical CT-scanning (window width 440 H, level 40 H, collimation 5 mm) revealing a significantly enhanced nodule, 21 x 11 mm in size, posterior to the inferior aspect of the right thyroid lobe (arrow). (b) Helical CT image (window width 370 H, level 40 H, collimation 5 mm) from a 42-year-old woman showing a retrotracheal parathyroid adenoma (arrow) of the right inferior parathyroid gland, 17 x 18 mm in size.
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Statistical analysis
The reported data are expressed as mean±standard deviation (SD). Differences between means, i.e. age, biochemical parameters, were tested by ANOVA and unpaired Student's t-test or, in case of non-normal distribution, i.e. ectopic vs eutopic location of the removed PT glands, the Mann-Whitney U-test. The chi-square test with Yates correction, and the Fisher's exact test were used for fractions, i.e. sensitivity of imaging tests. The Pearson's correlation coefficient (R) calculation were also used, to evaluate the linear relationship between pairs of variables. Sensitivity was defined as TP/(TP+FN), and the positive predictive value (PPV) was defined as TP/(TP+FP). A p-value<0.05 was considered statistically significant.
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Results
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Women were older than men (57.8±13.1 vs 51.6±17.8 years; p=0.20). Final histopathology showed 40 (90.9%) solitary PT adenomata (median size 18 mm, range 8–40 mm), that were in an ectopic location in 13 (32.5%) patients: 4 in the retroesophageal space, 4 in the middle or lower mediastinum, 3 in the thymus, 2 in the carotid sheath. Three (6.8%) patients had a multiglandular disease (one patient with two PT adenomata, two patients with PT hyperplasia), while one (2.3%) patient had a PT carcinoma. Overall, 43 PT tumours were excised. Both mean size of the removed PT glands (19.1±8.6 vs 18.7±6.1 mm; p=0.86) and the main biochemical parameters, enclosed calcium (2.96±0.29 vs 2.84±0.28 mmol l-1; p=0.21) and PTH (250.1±231.4 vs 179.5±110.1 ng l-1; p=0.17) serum levels, did not differ (p=not significant [NS]) between men and women. Overall, there was no relationship (p=NS) between age of the patients, calcium (R=0.25, p=0.09) and PTH (R=0.18, p=0.25) serum levels, and between size of the PT gland, age (R=0.05, p=0.73), and calcium serum levels (R=0.24, p=0.10). A significant correlation (p<0.05) between serum PTH, serum calcium and size of the removed PT glands was found.
The sensitivity and PPV were 86.0% and 97.4% for SS, 88.1% and 94.9% for CT, and 100% and 97.4% for the combination of SS and CT, respectively (p=NS). The sensitivity of both SS and CT did not differ significantly (p=NS) between men and women, and between patients with ectopic and eutopic PT glands. Two (4.5%) and one (2.3%) FP results were observed by using CT and SS, respectively, and thus the PT adenoma was not correctly localized. These patients had a uninodular or multinodular goiter with subclinical hyperthyroidism (normal FT4, raised thyroid stimulating hormone (TSH)), and this may suggest a reason for these FP results.
Calcium and PTH serum levels, and the mean size of the removed PT tumours of patients with FN results were lower than that of those with TP results, but the difference was not significant (Table 2). Among patients with solitary PT tumours (N=41) the sensitivity was 88.1% and 90.3% for SS and CT (p=NS), respectively.
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Table 2. Differences between parathyroid tumours correctly localized (true positives) and undetected (false negatives) at helical CT and sestamibi scintigraphy (ANOVA, chi squared and Fisher's exact test*)
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Discussion
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Several benefits may be obtained by performing imaging studies prior to parathyroidectomy, including pre-operative detection of other cervical masses, i.e. thyroid nodules, recognition of ectopic PT glands, unilateral surgical exploration, and reduction in surgical trauma and hospital stay [11]. Usually, a single cross-sectional study is used to localize hyperfunctioning PT glands before first cervical exploration, while for patients with recurrent or persistent HPT often a functional method such as PT scintigraphy and an anatomic method such as US, CT, or MRI are used [12].
The usefulness of 99Tcm-sestamibi scintigraphy for patients with primary HPT undergoing surgery is well established, although a variety of different imaging protocols are available. The reported sensitivity varies widely, ranging from 70% to 95% [13–17]. Recently, Haber et al [18], by using 99Tcm-sestamibi/123I subtraction scan and delayed views obtained 88% sensitivity, while Civelek et al [19], by using 99Tcm-sestamibi alone and the SPECT technique obtained an overall sensitivity of 87%. In a previous study, we found similar results by performing SS with planar image acquisition without delayed views [9], and in the present study the sensitivity of SS was 86%. Certainly, each technique was chosen by the authors depending on their local experiences, but in any case the usefulness of PT scintigraphy was confirmed. CT of the neck and mediastinum is usually considered a relatively invasive test that requires a longer operative time when compared with US, the use of intravenous contrast, and radiation exposure. Thereby, few studies reported the results of CT for localizing enlarged PT glands in unexplored patients, although its sensitivity ranged from 76% to 83% [13, 20–22]. Van Dalen et al [8] suggested performing helical CT in patients with negative neck US; overall, 69 PT adenomata were found by using US alone, and 3 additional ones with helical CT. In our study helical CT correctly depicted 36 out of 40 (90%) solitary PT adenomata, of which 13 (32.5%) were in an ectopic location, and all the diseased PT glands (N=5) undetected by SS, including two enlarged PT glands in a patient with PT hyperplasia. It enabled the diagnosis of multiglandular disease, suggesting the need for bilateral neck exploration. Our Department is a tertiary referral centre which may explain the high rate of ectopic PT glands in our series.
In conclusion, our preliminary study confirms the usefulness of SS, which should be the initial test for patients undergoing parathyroidectomy. According to Haber et al [18] the strategy of performing two tests in each patient with primary HPT could be of limited utility when the initial SS is positive, since only one FP result (2.3%) was obtained by using SS. However, CT may better describe anatomical detail, such as the relationship with surrounding tissues and detection of concomitant thyroid nodules, guiding the surgical exploration especially in patients with ectopic PT glands. Further studies are need to verify the potential advantages that such combinations may offer.
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Footnotes
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This paper was presented in part at the 1st Joint Meeting of the International Bone and Mineral Society (IBMS) and the European Calcified Tissue Society (ECTS), Madrid, Spain, 5–10 June, 2001. 
Received for publication March 26, 2003.
Revision received August 13, 2003.
Accepted for publication November 6, 2003.
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Abstract
Introduction
