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Diagnostic performance of ultrasonography, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism

Abstract

Background

Secondary hyperparathyroidism (SHPT) usually requires parathyroidectomy when drug regimens fail. However, obtaining an exact preoperative map of the locations of the parathyroid glands is a challenge. The purpose of this study was to compare the diagnostic performance of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in patients with SHPT.

Methods

Sixty patients with SHPT who were undergoing dialysis were evaluated preoperatively by US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT. Postoperative pathology served as the gold standard. The sensitivity, specificity, and accuracy were determined for each method. Spearman correlation analysis was used to analyse the correlation of hyperplastic parathyroid calcification with serum alkaline phosphatase (ALP) and parathyroid hormone (PTH).

Results

A total of 229 lesions in 60 patients were pathologically confirmed to be parathyroid hyperplasia, with 209 lesions in typical sites, 15 lesions in the upper mediastinum and 5 lesions in the thyroid. A total of 88.33% (53/60) of patients had four lesions. US, early and delayed 99mTc-MIBI SPECT/CT had significantly higher sensitivity and accuracy than dual-phase 99mTc-MIBI scintigraphy (P < 0.001). Furthermore, early 99mTc-MIBI SPECT/CT had significantly higher sensitivity (P < 0.001) and accuracy (P = 0.001 and P < 0.001) than US and delayed 99mTc-MIBI SPECT/CT. In patients with ectopic hyperplastic parathyroid glands, the sensitivity of early 99mTc-MIBI SPECT/CT (90%) was significantly higher than that of US (55%) and dual-phase 99mTc-MIBI scintigraphy (50%) (P < 0.05). The Spearman correlation results showed a significant albeit weak association between calcification and both serum PTH and ALP (P = 0.002).

Conclusion

The ability of early 99mTc-MIBI SPECT/CT to detect hyperplastic parathyroid glands in patients with SHPT is superior to that of US, dual-phase 99mTc-MIBI scintigraphy and delayed 99mTc-MIBI SPECT/CT; furthermore, dual-phase 99mTc-MIBI SPECT/CT is not essential.

Peer Review reports

Background

Secondary hyperparathyroidism (SHPT) is a complex disease due to increased parathyroid hormone (PTH) production, which affects the metabolism of calcium and phosphorus and causes further abnormal PTH secretion, usually leading to 4-gland hyperplasia [1]. Severe SHPT mainly occurs in chronic kidney disease (CKD), which has been reported as a key causal factor of bone disease, muscle weakness, neurologic dysfunction, and soft tissue and vascular calcification, which increase cardiovascular morbidity and mortality [2, 3]. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) suggested parathyroidectomy to treat severe SHPT when drug regimens fail [4], and total parathyroidectomy has shown a minimum risk of postoperative relapse (0–4%) [5]. However, parathyroidectomy for SHPT is less satisfactory, and the occurrence of persistent SHPT after parathyroidectomy has been reported to be 0.4–25% [6]. Surgical failure is mainly due to the difficulty of resecting all parathyroid glands, especially because of the existence of supernumerary (more than 4) and ectopic parathyroid glands. The incidence of ectopic and supernumerary glands in patients with end-stage renal disease has been reported to be 17.5–39.3% and 6.3–37%, respectively [7,8,9]. Therefore, preoperative imaging and accurate localization are critical to a successful operation.

Parathyroid glands can be detected with multiple modalities, such as ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), but the performance of these anatomical examinations is not satisfactory [10]. In contrast to the above anatomical imaging modalities, technetium-99 m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy is a functional exploration and is regarded as the main preoperative localization method for patients with primary hyperparathyroidism (PHPT) or SHPT [11]. When combined with single-photon emission computed tomography/computed tomography (SPECT/CT), functional and anatomical, the sensitivity of scintigraphy is increased. Multiple studies have reported that dual-phase 99mTc-MIBI scintigraphy is superior to US, especially when combined with SPECT/CT, in patients with HPT [12,13,14], but these studies did not distinguish SHPT from PHPT for statistical analysis. For PHPT, several investigations have reported that 99mTc-MIBI SPECT/CT is superior to dual-phase 99mTc-MIBI scintigraphy [11, 15, 16].

PHPT is mostly caused by parathyroid adenoma, which can usually be identified; however, SHPT usually involves more than one lesion, and it is difficult to identify all of the abnormal parathyroid glands because parathyroid hyperplasia is an asynchronous and asymmetrical process [17,18,19]. For SHPT, Jae Bok et al. [17] reported that US (91.5%) had a higher sensitivity than dual-phase 99mTc-MIBI scintigraphy (56.1%), while Vulpio et al. [20] reported a slightly higher sensitivity for dual-phase 99mTc-MIBI scintigraphy (62%) than US (55%). When combined with SPECT/CT, 99mTc-MIBI SPECT/CT had a higher sensitivity than US [21, 22] and dual-phase 99mTc-MIBI scintigraphy [6]. However, in all of these studies, only a single set of SPECT/CT images was acquired, either early or delayed. One prior investigation directly compared early and delayed 99mTc-MIBI SPECT/CT and indicated that both early and delayed imaging should be performed [23]. The above studies reveal the value of SPECT/CT in patients with SHPT, but which phase of SPECT/CT is better in SHPT remains to be elucidated.

The purpose of this investigation was to directly compare the diagnostic performance of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT to obtain an exact preoperative map for the localization of abnormal parathyroid glands in SHPT and to determine whether dual-phase SPECT/CT is essential.

Methods

Clinical materials

From May 2017 to November 2019, a total of 60 CKD patients who were undergoing dialysis and parathyroidectomy for SHPT at the Sixth Affiliated Hospital of Sun Yat-sen University were included in this study. All patients underwent US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT, and SHPT was confirmed by pathology. Patient demographics (sex, age, dialysis vintage), imaging data, laboratory values, and operative and pathological results were collected. Laboratory values included serum calcium, phosphorus, creatinine, alkaline phosphatase (ALP), and PTH after the last dialysis before surgery and postoperative PTH within the first week.

Imaging methods

All patients with SHPT received an intravenous injection of 555 MBq 99mTc-MIBI. Dual-phase 99mTc-MIBI scintigraphy was obtained at 15 min and 120 min after injection. SPECT/CT integrated imaging was performed immediately after early and delayed 99mTc-MIBI scintigraphy. Images were acquired using a Symbia Intevo 6 system (Siemens Healthcare) at an energy peak of 140 keV, window width of 20%, matrix of 128 × 128, magnification of 1-fold, and 600 k counts per frame with low-energy, high-resolution collimation. The CT scanning parameters were set at a field of view (FOV) of 40 cm, tube current of 200 mA, tube voltage of 130 kV, slice thickness of 2.5 mm, reconstruction matrix of 128 × 128, and reconstruction thickness of 2.5 mm. Imaging data were reconstructed using flash 3D. US was performed using a LOGIQ E9 system (GE Healthcare, USA) equipped with a 9 L linear probe (8.4–9 MHz) and ML6–15 probe (10–15 MHz). The images were analysed by professional doctor who were blinded to the laboratory, surgical, and pathological results.

Image analysis

Dual-phase 99mTc-MIBI scintigraphy

The image was considered positive on visual analysis when it met one of the following criteria: (1) abnormal 99mTc-MIBI uptake was observed on both early and delayed imaging; (2) abnormal 99mTc-MIBI uptake was observed on either early or delayed imaging. The image was considered negative when abnormal 99mTc-MIBI uptake was observed on neither early nor delayed imaging [13].

Early and delayed 99mTc-MIBI SPECT/CT

SHPT was positively diagnosed on early or delayed 99mTc-MIBI SPECT/CT if CT indicated a parenchymal space-occupying lesion in the parathyroid region, while SPECT showed abnormal 99mTc-MIBI accumulation compared to neck muscles and blood vessels. The result was considered negative if abnormal 99mTc-MIBI uptake was observed on neither early nor delayed SPECT when CT indicated a parenchymal space-occupying lesion in the parathyroid region and if abnormal 99mTc-MIBI uptake was observed on both early and delayed imaging but no parenchymal space-occupying lesion in the parathyroid region was observed on CT [21].

Us

A typical US image demonstrated an oval or asymmetrical hypoechoic mass at the upper and lower pole of the posterior thyroid with variable dimensions and separated by the thyroid gland. The lesion may rarely present with cystic degeneration. Colour Doppler examination showed a parathyroid vascular pedicle and a vascular arch located at the periphery of the gland [24].

Definition of ectopic parathyroid glands

Parathyroid glands were considered eutopic when the lower glands were related to the lower pole of the thyroid gland and when the upper glands were found near the upper pole of the thyroid. Hyperplastic parathyroid glands located inside the superior mediastinum region and the thyroid gland were regarded as ectopic parathyroid glands [6, 25].

Parathyroidectomy and final diagnosis

Parathyroidectomy was performed in severe SHPT patients who failed to respond to medical therapy. Our operative indications included persistent serum PTH > 800 pg/mL nonresponsive to medical therapy and at least one enlarged parathyroid gland confirmed on imaging [26]. In our study, serum PTH levels less than 300 pg/mL detected in the first postoperative week served as indicators of successful parathyroidectomy [27]. All patients underwent surgery by the same surgical team. Subtotal or total parathyroidectomy with autotransplantation was performed. In subtotal parathyroidectomy, 3 glands and half of the fourth gland were removed, while half of the normal gland was left in situ. Parathyroid glands resected during surgery were examined by pathology for the final diagnosis. The US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT findings for each gland were defined as true positive, false positive, true negative, or false negative on the basis of the pathology results. Comparisons of the sensitivity (number of true-positives divided by number of true-positives plus false-negatives), specificity (number of true-negatives divided by number of true-negatives plus false-positives) and accuracy (number of true-positives plus true-negatives divided by number of total lesions resected) between groups were made according to the parathyroid pathology results.

Statistical analysis

Metric data are expressed as the median (25–75th percentile). Categorical variables were analysed using the χ2 or McNemar’s test. Spearman correlation was used for statistical analysis. A P value less than 0.05 was considered to indicate statistical significance. Statistical analysis was performed using IBM SPSS version 20.0 statistical software.

Results

In all 60 patients included in the study, the primary disease was stage 5 CKD. The clinical pathological characteristics of the patients with SHPT who underwent surgery are summarized in Table 1. There were 34 males and 26 females, with a median age of 48 years and a median dialysis vintage of 7 years. Fifty-one patients underwent regular hemodialysis, 5 underwent peritoneal dialysis, and 4 underwent both hemodialysis and peritoneal dialysis. All patients had significantly increased serum PTH preoperatively and decreased serum PTH postoperatively. A total of 23% (14/60), 95% (57/60) and 74% (40/54, 6 patients were not measured before surgery) of patients showed increased serum calcium, phosphorus and ALP levels, respectively. Moreover, 23 patients showed punctate and annular calcification in the hyperplastic parathyroid glands, and the correlations between calcification and laboratory parameters, such as serum PTH, calcium, phosphorus, ALP and creatinine, were analysed. Spearman correlation results showed a significant albeit weak association between calcification and both serum PTH (r = 0.398, P = 0.002) and serum ALP (r = 0.415, P = 0.002), while no significant correlation was observed between calcification and serum calcium, phosphorus, or creatinine. In addition, a significant albeit weak association was observed between serum PTH and ALP (r = 0.349, P = 0.011).

Table 1 Baseline patient characteristics

In all, 59 of the 60 patients underwent total parathyroidectomy with autotransplantation, and one patient underwent subtotal parathyroidectomy. Meanwhile, 8 patients underwent partial thyroidectomy, and 1 patient with papillary thyroid carcinoma underwent total thyroidectomy. As shown in Fig. 1, a total of 243 lesions were resected from the 60 patients; 229 lesions were pathologically confirmed to be parathyroid hyperplasia, 5 were normal parathyroid glands, 4 were lymph nodes, 4 were thyroid nodules and 1 was bone tissue. Of the 229 confirmed lesions, 209 were in typical sites, 15 were in the upper mediastinum, and 5 were in the thyroid gland. Among the 60 patients, four lesions were identified in 53 patients (88.33%), two lesions were identified in 4 patients (6.67%), and the other three patients had 1, 3, and 5 lesions, respectively. US showed 178 positive lesions in 60 patients, and 175 lesions were confirmed to be true positive. The three false-positive lesions were confirmed to be lymph nodes. Dual-phase planar imaging detected 116 positive lesions, and there were 2 false-positive lesions. One was confirmed to be thyroid nodule, and the other was due to the focal 99mTc-MIBI uptake of the manubrium sterni without destruction of bone observed on SPECT/CT. Early 99mTc-MIBI SPECT/CT showed 210 positive lesions, and 205 lesions were confirmed to be true-positive lesions. For the 5 false-positive lesions, three lesions were confirmed to be lymph nodes, and two lesions were thyroid nodules. Delayed 99mTc-MIBI SPECT/CT showed 171 positive lesions, including 168 true-positive and 3 false-positive lesions, of which two lesions were confirmed to be lymph nodes and the other was a thyroid nodule. Representative images are shown in Fig. 2.

Fig. 1
figure1

Flow chart of lesions analysed by US, dual-phase planar imaging, early SPECT/CT and delayed SPECT/CT. PH, parathyroid hyperplasia; PG, parathyroid gland; LN, lymph node; TN, thyroid nodule; BN, bone tissue

Fig. 2
figure2

Representative images of a middle-aged patient with SHPT. Dual-phase 99mTc-MIBI scintigraphy (A and B) showed 4 hyperplastic parathyroid glands. US (C) showed a typical enlarged parathyroid gland on the right. Early SPECT/CT (D) showed right inferior and left inferior hyperplastic parathyroid glands with 99mTc-MIBI uptake. Delayed SPECT/CT (E) showed right inferior hyperplastic parathyroid gland with 99mTc-MIBI uptake and left inferior hyperplastic parathyroid gland without 99mTc-MIBI uptake. Pathological examination (F) confirmed nodular parathyroid hyperplasia

Analysed by case number, the sensitivity of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT was 93.33% (56/60), 76.67% (46/60), 98.33% (59/60), and 98.33% (59/60), respectively. Analysed by lesion number, early 99mTc-MIBI SPECT/CT showed the highest sensitivity and accuracy (89.5 and 88.0%), while dual-phase 99mTc-MIBI scintigraphy showed the lowest (49.8 and 51.9%). US, early and delayed 99mTc-MIBI SPECT/CT showed significantly higher sensitivity and accuracy than dual-phase 99mTc-MIBI scintigraphy (P < 0.001). Furthermore, early 99mTc-MIBI SPECT/CT showed significantly higher sensitivity (P < 0.001) and accuracy (P = 0.001 and P < 0.001) than US and delayed 99mTc-MIBI SPECT/CT (Table 2). There was no significant difference in sensitivity or accuracy between US and delayed 99mTc-MIBI SPECT/CT. The specificity of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT was 78.6, 85.7, 64.3 and 78.6%, respectively.

Table 2 Preoperative imaging and postoperative parathyroid pathology results

Then, the sensitivity of preoperative eutopic and ectopic parathyroid imaging was compared (Table 3). Twenty ectopic parathyroid glands (20/229, 8.73%) were detected in 16 patients (16/60, 26.67%). The sensitivity of parathyroid imaging for eutopic lesions (US, 78.5%; dual-phase 99mTc-MIBI scintigraphy, 49.8%; early 99mTc-MIBI SPECT/CT, 89.5%; and delayed 99mTc-MIBI SPECT/CT, 73.2%) was similar to the sensitivity of imaging for all lesions (US, 76.4%; dual-phase 99mTc-MIBI scintigraphy, 49.8%; early 99mTc-MIBI SPECT/CT, 89.5%; and delayed 99mTc-MIBI SPECT/CT, 73.4%). However, for ectopic parathyroid lesions, the sensitivity of early 99mTc-MIBI SPECT/CT was significantly higher than that of US and dual-phase 99mTc-MIBI scintigraphy (P < 0.05). Delayed 99mTc-MIBI SPECT/CT was not significantly superior to US or dual-phase 99mTc-MIBI scintigraphy in terms of sensitivity.

Table 3 Comparison of eutopic and ectopic parathyroid glands among the four techniques

Discussion

SHPT is a common complication of CKD and is followed by disorders of calcium and phosphorus metabolism, abnormal PTH secretion, and parathyroid hyperplasia. Serum PTH plays a critical role in the maintenance of calcium and phosphate levels. Unlike PHPT, which is independent of PTH secretion by the parathyroid tissue, in SHPT, compensatory PTH secretion occurs due to hypocalcaemia [22]. Therefore, in patients with SHPT, the serum calcium level can be increased or remain normal. In our study, all patients had increased serum PTH, but only 23.33% of patients showed increased serum calcium. We found that 23 patients showed punctate and annular calcification in the hyperplastic parathyroid glands, and annular calcification might be a special sign of SHPT [28,29,30]. Soft tissue and vascular calcification is commonly present in end-stage renal disease, secondary to disturbances in the calcium and phosphate balance and HPT, which may explain why the parathyroid glands were more prone to calcification in patients with SHPT [31, 32]. A previous study showed an association between serum ALP and vascular calcification via modulation of the pyrophosphate pathway [33, 34]. Serum PTH can increase bone metabolic conversion to elevate the serum ALP level [22]. Therefore, as we reported, calcification of the parathyroid glands might be correlated with serum PTH and ALP.

For severe SHPT, parathyroidectomy remains the best treatment option when drug treatment fails. However, surgical results among SHPT patients are less satisfactory compared with PHPT due to the incomplete intraoperative identification of all parathyroid glands [23]. Therefore, preoperative imaging and localization are critical to a successful operation. US is the most commonly used imaging modality due to its advantages of low cost and simple manipulation, but it is limited in the detection of ectopic parathyroid glands and is dependent on the examiner’s experience [24]. CT may be necessary to locate parathyroid glands precisely, especially for the ectopic glands in the mediastinum [7]. MRI has the advantage of no radiation and a slightly greater sensitivity than CT, and it is especially useful in detecting mediastinal parathyroid glands [24]. Different from the above anatomical imaging modalities, 99mTc-MIBI imaging is a functional exploration with the advantage of detecting ectopic glands and is based on the different washout rates between the thyroid tissue and hyperplastic parathyroid tissue [35]. Dual-phase 99mTc-MIBI scintigraphy has high sensitivity and specificity but also has multiple limitations, such as the lack of a precise anatomical location of the lesion [36], which increased the difficulty of distinguishing hyperplastic parathyroid lesions from thyroid lesions. 99mTc-MIBI SPECT/CT is significantly superior to planar imaging in the detection of parathyroid abnormalities because it provides more precise anatomical localization, particularly for ectopic lesions, as well as the identification of supernumerary glands and parathyroid glands with the lowest 99mTc-MIBI uptake [11, 37].

In our study, we directly compared US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in SHPT patients. The overall sensitivity and accuracy of early SPECT/CT were higher than those of the other techniques and slightly higher than those in previous studies [23, 24]. For detecting ectopic parathyroid glands, the sensitivity of early 99mTc-MIBI SPECT/CT was significantly higher than that of US and dual-phase 99mTc-MIBI scintigraphy, and the percentage was similar to that reported in a previous study (90.5%) [6]. Our results show that early 99mTc-MIBI SPECT/CT was superior to the other modalities in detecting parathyroid lesions in SHPT patients. Hybrid SPECT/CT can provide not only functional information acquired through SPECT but also an accurate anatomical depiction of the parathyroid gland location and size and adjacent structures through CT, especially in cases of ectopic and supernumerary parathyroid glands. With delayed 99mTc-MIBI SPECT/CT, two investigational groups reported a high sensitivity of 59.3% [22] and 85% [21], and in our study, the sensitivity was 73.4%. In our investigation, we found that the 99mTc-MIBI uptake of some hyperplastic parathyroid glands on early 99mTc-MIBI SPECT/CT was slightly higher than the background uptake but lower than the thyroid uptake and that further clearance in delayed SPECT/CT caused false-negative results on delayed SPECT/CT. Schachter et al. reported that delayed 99mTc-MIBI SPECT/CT may be nondiagnostic when similar washout rates are found in thyroid and parathyroid tissue [38]. Therefore, dual-phase 99mTc-MIBI scintigraphy in combination with early 99mTc-MIBI SPECT/CT may be considered as a valuable preoperative evaluation method. Meanwhile, dual-phase 99mTc-MIBI scintigraphy cannot be replaced by early 99mTc-MIBI SPECT/CT because the former can roughly show the location of parathyroid hyperplasia especially ectopic parathyroid hyperplasia, and help to determine the SPECT/CT scan range.

Most patients in our study had four proven lesions, which reminds us to identify as many as four parathyroid lesions as possible when diagnosing SHPT. As we found that all of the calcified parathyroid glands (45 lesions) were confirmed to be parathyroid hyperplasia by pathology, if calcified nodules are observed in the parathyroid region, parathyroid hyperplasia should be suspected. However, large-sample, multicentre studies are still needed to confirm these findings.

The main reason for the low sensitivity of US is believed to be the frequent misdiagnosis of inferior parathyroid lesions, especially mediastinal ectopic parathyroid glands. The examiner’s experience in the accurate determination of lesions is also a critical factor that cannot be ignored. It was reported that the sensitivity of US for diagnosing SHPT ranged from 46.24 to 91.5% [17, 21, 22], which is similar to our result (75.65%).

Our observations show that the sensitivity of dual-phase 99mTc-MIBI scintigraphy was the lowest of the four modalities. The reasons are as follows. First, although dual-phase 99mTc-MIBI scintigraphy can effectively detect ectopic parathyroid glands, only a general increase in radioactivity can be observed, and the number of lesions cannot be clearly distinguished when multiple parathyroid gland lesions are adjacent to each other. Second, some hyperplastic parathyroid glands were positive for p-glycoprotein, and 99mTc-MIBI was quickly eliminated from the parathyroid glands, leading to negative uptake images on scintigraphy [39]. Third, the findings on dual-phase 99mTc-MIBI scintigraphy are related to the size and weight of the parathyroid glands, and smaller parathyroid gland lesions can be easily missed [24, 40]. Fourth, lesions located behind the thyroid gland and with similar 99mTc-MIBI uptake are difficult to detect on scintigraphy but can be identified on SPECT/CT. In a meta-analysis, the pooled sensitivity of dual-phase 99mTc-MIBI scintigraphy in SHPT was 58% [41], which is slightly higher than our result.

David Taieb et al. [40] reported that the most common causes of false-positive results on parathyroid scintigraphy were the presence of thyroid nodules, thymoma, metastatic and inflammatory lymph nodes, while skeletal brown tumours may also be a rare cause of false-positive lesions. However, in our study, multiple false-positive lesions found on US, early and delayed 99mTc-MIBI SPECT/CT were mostly confirmed to be lymph nodes, followed by thyroid nodules. The most likely explanation for this difference is that we identified fewer false-positive lesions, and all our patients were SHPT patients and not PHPT patients. One false-positive lesion found on dual-phase 99mTc-MIBI scintigraphy was attributed to the focal 99mTc-MIBI uptake of the manubrium sterni. A previous study suggested that the 99mTc-MIBI uptake of bone might reflect the presence of active metabolic bone disease but did not reflect changes that occurred in the microstructure of bone [42]. However, this remains to be evaluated further. In addition, the specificity of early 99mTc-MIBI SPECT/CT in our study is lower than that in a previous study (75%) [6], probably due to the small number of true-negative cases.

Our study is limited by its retrospective design and relatively small cohort of patients. Therefore, future prospective randomized studies of preoperative imaging modalities are needed for more accurate and objective investigations.

Conclusion

Our study demonstrates that the ability of early 99mTc-MIBI SPECT/CT to detect parathyroid lesions in SHPT patients is superior to that of US, dual-phase 99mTc-MIBI scintigraphy and delayed 99mTc-MIBI SPECT/CT. In cases of ectopic hyperplastic parathyroid glands, the sensitivity of early 99mTc-MIBI SPECT/CT (90%) was significantly higher than that of US (55%) and dual-phase 99mTc-MIBI scintigraphy (50%). These findings suggest that dual phase 99mTc-MIBI scintigraphy, with early 99mTc-MIBI SPECT/CT may be considered as part of the preoperative evaluation of patients with SHPT. The results of our small-sample study suggest that parathyroid gland calcification may be related to the levels of PTH and ALP and could help provide evidence for the identification of SHPT.

Availability of data and materials

Data and materials during the current study are available from the corresponding author upon reasonable request.

Abbreviations

99mTc-MIBI:

Technetium-99 m methoxyisobutylisonitrile

SHPT:

Secondary hyperparathyroidism

PHPT:

Primary hyperparathyroidism

ALP:

Alkaline phosphatase

PTH:

Parathyroid hormone

US:

Ultrasonography

CT:

Computed tomography

MRI:

Magnetic resonance imaging

SPECT/CT:

Single-photon emission computed tomography/computed tomography 

CKD:

Chronic kidney disease

References

  1. 1.

    Tominaga Y, Tanaka Y, Sato K, Nagasaka T, Takagi H. Histopathology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism. Semin Surg Oncol. 1997;13(2):78–86.

    CAS  PubMed  Google Scholar 

  2. 2.

    Trainor D, Borthwick E, Ferguson A. Perioperative management of the hemodialysis patient. Semin Dial. 2011;24(3):314–26.

    PubMed  Google Scholar 

  3. 3.

    Evans M, Methven S, Gasparini A, Barany P, Birnie K, MacNeill S, May MT, Caskey FJ, Carrero JJ. Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism. Sci Rep. 2018;8(1):2103.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Kidney Disease: Improving Global Outcomes CKDMBDWG. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.

    Google Scholar 

  5. 5.

    Madorin C, Owen RP, Fraser WD, Pellitteri PK, Radbill B, Rinaldo A, Seethala RR, Shaha AR, Silver CE, Suh MY, et al. The surgical management of renal hyperparathyroidism. Eur Arch Otorhinolaryngol. 2012;269(6):1565–76.

    PubMed  Google Scholar 

  6. 6.

    Zeng M, Liu W, Zha X, Tang S, Liu J, Yang G, Mao H, Yu X, Sun B, Zhang B, et al. (99m)Tc-MIBI SPECT/CT imaging had high sensitivity in accurate localization of parathyroids before parathyroidectomy for patients with secondary hyperparathyroidism. Ren Fail. 2019;41(1):885–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Hiramitsu T, Tomosugi T, Okada M, Futamura K, Tsujita M, Goto N, Narumi S, Watarai Y, Tominaga Y, Ichimori T. Pre-operative localisation of the parathyroid glands in secondary hyperparathyroidism: a retrospective cohort study. Sci Rep. 2019;9(1):14634.

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Schneider R, Waldmann J, Ramaswamy A, Fernandez ED, Bartsch DK, Schlosser K. Frequency of ectopic and supernumerary intrathymic parathyroid glands in patients with renal hyperparathyroidism: analysis of 461 patients undergoing initial parathyroidectomy with bilateral cervical thymectomy. World J Surg. 2011;35(6):1260–5.

    PubMed  Google Scholar 

  9. 9.

    Taterra D, Wong LM, Vikse J, Sanna B, Pekala P, Walocha J, Cirocchi R, Tomaszewski K, Henry BM. The prevalence and anatomy of parathyroid glands: a meta-analysis with implications for parathyroid surgery. Langenbeck's Arch Surg. 2019;404(1):63–70.

    Google Scholar 

  10. 10.

    Kettle AG, O'Doherty MJ. Parathyroid imaging: how good is it and how should it be done? Semin Nucl Med. 2006;36(3):206–11.

    PubMed  Google Scholar 

  11. 11.

    Lavely WC, Goetze S, Friedman KP, Leal JP, Zhang Z, Garret-Mayer E, Dackiw AP, Tufano RP, Zeiger MA, Ziessman HA. Comparison of SPECT/CT, SPECT, and planar imaging with single- and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy. J Nucl Med. 2007;48(7):1084–9.

    PubMed  Google Scholar 

  12. 12.

    Kobylecka M, Plazinska MT, Chudzinski W, Fronczewska-Wieniawska K, Maczewska J, Bajera A, Karlinska M, Krolicki L. Comparison of scintigraphy and ultrasound imaging in patients with primary, secondary and tertiary hyperparathyroidism - own experience. J Ultrason. 2017;17(68):17–22.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Zhou J, Lu DY, Xia L, Cheng XJ. Diagnosis performance of (99m)Tc-MIBI and multimodality imaging for hyperparathyroidism. J Huazhong Univ Sci Technol Med Sci. 2017;37(4):582–6.

    PubMed  Google Scholar 

  14. 14.

    Kim YI, Jung YH, Hwang KT, Lee HY. Efficacy of (9)(9)mTc-sestamibi SPECT/CT for minimally invasive parathyroidectomy: comparative study with (9)(9)mTc-sestamibi scintigraphy, SPECT, US and CT. Ann Nucl Med. 2012;26(10):804–10.

    CAS  PubMed  Google Scholar 

  15. 15.

    Slater A, Gleeson FV. Increased sensitivity and confidence of SPECT over planar imaging in dual-phase sestamibi for parathyroid adenoma detection. Clin Nucl Med. 2005;30(1):1–3.

    PubMed  Google Scholar 

  16. 16.

    Moka D, Voth E, Dietlein M, Larena-Avellaneda A, Schicha H. Technetium 99m-MIBI-SPECT: a highly sensitive diagnostic tool for localization of parathyroid adenomas. Surgery. 2000;128(1):29–35.

    CAS  PubMed  Google Scholar 

  17. 17.

    Lee JB, Kim WY, Lee YM. The role of preoperative ultrasonography, computed tomography, and sestamibi scintigraphy localization in secondary hyperparathyroidism. Ann Surg Treat Res. 2015;89(6):300–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005;132(3):359–72.

    PubMed  Google Scholar 

  19. 19.

    Xue J, Liu Y, Ji T, Zhao A, Liang Y, Deng H, Wang Q, Zhang Y, Yang L, Yang A. Comparison between technetium-99m methoxyisobutylisonitrile scintigraphy and ultrasound in the diagnosis of parathyroid adenoma and parathyroid hyperplasia. Nucl Med Commun. 2018;39(12):1129–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Vulpio C, Bossola M, De Gaetano A, Maresca G, Bruno I, Fadda G, Morassi F, Magalini SC, Giordano A, Castagneto M. Usefulness of the combination of ultrasonography and 99mTc-sestamibi scintigraphy in the preoperative evaluation of uremic secondary hyperparathyroidism. Head Neck. 2010;32(9):1226–35.

    PubMed  Google Scholar 

  21. 21.

    Yuan LL, Kan Y, Ma DQ, Yang JG. Combined application of ultrasound and SPECT/CT has incremental value in detecting parathyroid tissue in SHPT patients. Diagn Interv Imaging. 2016;97(2):219–25.

    CAS  PubMed  Google Scholar 

  22. 22.

    Li P, Liu Q, Tang D, Zhu Y, Xu L, Sun X, Song S. Lesion based diagnostic performance of dual phase (99m)Tc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism. BMC Med Imaging. 2017;17(1):60.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Yang J, Hao R, Yuan L, Li C, Yan J, Zhen L. Value of dual-phase (99m)Tc-sestamibi scintigraphy with neck and thoracic SPECT/CT in secondary hyperparathyroidism. AJR Am J Roentgenol. 2014;202(1):180–4.

    PubMed  Google Scholar 

  24. 24.

    Strambu V, Bratucu M, Garofil D, Paic V, Zurzu M, Tigora A, Popa F, Radu P, Costin P. The value of imaging of the parathyroid glands in secondary hyperparathyroidism. Chirurgia. 2019;114(5):541–9.

    PubMed  Google Scholar 

  25. 25.

    Andrade JS, Mangussi-Gomes JP, Rocha LA, Ohe MN, Rosano M, das Neves MC, Santos Rde O. Localization of ectopic and supernumerary parathyroid glands in patients with secondary and tertiary hyperparathyroidism: surgical description and correlation with preoperative ultrasonography and Tc99m-Sestamibi scintigraphy. Br J Otorhinolaryngol. 2014;80(1):29–34.

    Google Scholar 

  26. 26.

    Lau WL, Obi Y, Kalantar-Zadeh K. Parathyroidectomy in the management of secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2018;13(6):952–61.

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Kara M, Tellioglu G, Bugan U, Krand O, Berber I, Seymen P, Eren PA, Ozel L, Titiz I. Evaluation of intraoperative parathormone measurement for predicting successful surgery in patients undergoing subtotal/total parathyroidectomy due to secondary hyperparathyroidism. Laryngoscope. 2010;120(8):1538–44.

    CAS  PubMed  Google Scholar 

  28. 28.

    Li X, Xie X, Wang R, Liu Y, Fu X, Han X. Comparative analysis of calcification features of primary and secondary hyperparathyroidism by 99Tcm-MIBI SPECT/CT imaging. J Third Mil Med Univ. 2014;36(15):1626–9.

    Google Scholar 

  29. 29.

    Peng S, Li P, Zhang A, Liu Q, Xu L, Sun X, Huang G, Song S. Importance of 99Tcm-MIBI SPECT/CT fusion imaging in primary and secondary hyperparathyroidism. Int J Radiat Med Nucl Med. 2018;42(3):195–200.

    Google Scholar 

  30. 30.

    Liang XX, Li F, Gao F, Liu Y, Qiao XH, Zhang Z, Du LF. The value of the model and quantitative parameters of contrast-enhanced ultrasound in judging the severity of SHPT. Biomed Res Int. 2016;2016:6064526.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Yeh SM, Hwang SJ, Chen HC. Treatment of severe metastatic calcification in hemodialysis patients. Hemodial Int. 2009;13(2):163–7.

    PubMed  Google Scholar 

  32. 32.

    Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2006;69(11):1945–53.

    CAS  PubMed  Google Scholar 

  33. 33.

    Shantouf R, Kovesdy CP, Kim Y, Ahmadi N, Luna A, Luna C, Rambod M, Nissenson AR, Budoff MJ, Kalantar-Zadeh K. Association of serum alkaline phosphatase with coronary artery calcification in maintenance hemodialysis patients. Clin J Am Soc Nephrol. 2009;4(6):1106–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Lomashvili KA, Garg P, Narisawa S, Millan JL, O'Neill WC. Upregulation of alkaline phosphatase and pyrophosphate hydrolysis: potential mechanism for uremic vascular calcification. Kidney Int. 2008;73(9):1024–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Delbeke D, Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, Townsend DW, Berland LL, Parker JA, Zubal G, et al. Procedure guideline for SPECT/CT imaging 1.0. J Nucl Med. 2006;47(7):1227–34.

    PubMed  Google Scholar 

  36. 36.

    Greenspan BS, Dillehay G, Intenzo C, Lavely WC, O'Doherty M, Palestro CJ, Scheve W, Stabin MG, Sylvestros D, Tulchinsky M. SNM practice guideline for parathyroid scintigraphy 4.0. J Nucl Med Technol. 2012;40(2):111–8.

    PubMed  Google Scholar 

  37. 37.

    Thomas DL, Bartel T, Menda Y, Howe J, Graham MM, Juweid ME. Single photon emission computed tomography (SPECT) should be routinely performed for the detection of parathyroid abnormalities utilizing technetium-99m sestamibi parathyroid scintigraphy. Clin Nucl Med. 2009;34(10):651–5.

    PubMed  Google Scholar 

  38. 38.

    Schachter PP, Issa N, Shimonov M, Czerniak A, Lorberboym M. Early, postinjection MIBI-SPECT as the only preoperative localizing study for minimally invasive parathyroidectomy. Arch Surg. 2004;139(4):433–7.

    PubMed  Google Scholar 

  39. 39.

    Yamaguchi S, Yachiku S, Hashimoto H, Kaneko S, Nishihara M, Niibori D, Shuke N, Aburano T. Relation between technetium 99m-methoxyisobutylisonitrile accumulation and multidrug resistance protein in the parathyroid glands. World J Surg. 2002;26(1):29–34.

    PubMed  Google Scholar 

  40. 40.

    Taieb D, Hindie E, Grassetto G, Colletti PM, Rubello D. Parathyroid scintigraphy: when, how, and why? A concise systematic review. Clin Nucl Med. 2012;37(6):568–74.

    PubMed  Google Scholar 

  41. 41.

    Caldarella C, Treglia G, Pontecorvi A, Giordano A. Diagnostic performance of planar scintigraphy using (9)(9)mTc-MIBI in patients with secondary hyperparathyroidism: a meta-analysis. Ann Nucl Med. 2012;26(10):794–803.

    PubMed  Google Scholar 

  42. 42.

    Zhao Y, Wang Q. Bone uptake of Tc-99m MIBI in patients with hyperparathyroidism. Ann Nucl Med. 2014;28(4):349–55.

    CAS  PubMed  Google Scholar 

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Acknowledgements

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Funding

This work was financially supported by the National Natural Science Foundation of China (No. 81702404, No. 81901772), the Natural Science Foundation of Guangdong Province, China (No. 2017A030313536, No. 2019A1515011893), the Fundamental Research Funds for the Central Universities, China (No. 19ykpy06) and the Medical Science and Technology Research Fund Project of Guangdong Province, China (No. A2019110) for the collection and analysis of data.

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RZ, ZZ and PH2 participated in the study design. RZ, ZZ and PH1 carried out the data collection and statistical analysis and drafting of the manuscript. RZ, ZL, RH, JZ and WQ performed drafting and clinical review of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Ping Hu.

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The study was approved by the ethical committee of the Sixth Affiliated Hospital of Sun Yat-sen University. According to the ethical committee policy, this is a completely anonymous, retrospective study and is exempt from informed consent from patients.

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Zhang, R., Zhang, Z., Huang, P. et al. Diagnostic performance of ultrasonography, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism. BMC Med Imaging 20, 91 (2020). https://doi.org/10.1186/s12880-020-00490-3

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Keywords

  • Secondary hyperparathyroidism
  • Ultrasonography
  • Dual-phase 99mTc-MIBI scintigraphy
  • 99mTc-MIBI SPECT/CT