Addressing the challenges of missed parathyroid glands in ultrasonography for secondary hyperparathyroidism.

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Shen-En Chou, Cheng-Hsi Yeh, Shun-Yu Chi, Fong-Fu Chou, Yi-Ju Wu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3970012/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Preoperative localization plays an important role in secondary hyperparathyroidism (SHPT) surgery. The advantages of neck ultrasound (US) include high availability and low cost. However, the reported sensitivity of US is 54–76%, and the reason for missed PG on US has been rarely addressed. Methods Fifty-four patients who were diagnosed with renal SHPT from September 2020 to March 2022 were included in this retrospective study. Preoperative localization included surgeon-oriented US and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT). Results A total of 212 parathyroid glands (PGs) were pathologically confirmed, resulting in success rate of 96.2% (52/54). Using echo, 193 (91.0%) PGs were accurately localized, while 19 (9.0%) glands were not identified, including those in ectopic positions (n = 12, at thymus or intra-thyroid or others), of a small size (< 1 cm, n = 6), or overlapping with an ipsilateral PG (n = 1). US accurately detected four PGs in 36 (66.7%) patients, while SPECT/CT localized four glands in 19 (35.2%) patients. Although the number of US-detectable PGs was not associated with success rate, it showed significant negative correlation with surgical time ( r s =-0.459, P = 0.002). Conclusion US detected four glands in 66% of SHPT patients with a sensitivity of 90% for localization. Ectopic position and small size were the most common reasons of failing to detect PG on US. Complete preoperative echo localization might shorten the operating time. ultrasonography renal hyperparathyroidism secondary hyperparathyroidism localization Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Chronic kidney disease (CKD) is a major burden on global health. Patients with CKD stage III or higher often develop secondary parathyroid hyperplasia, caused by hyperphosphatemia and hypocalcemia [ 1 ]. Secondary hyperparathyroidism (SHPT) results in abnormal calcium deposition, osteoporosis, bone deformity, or fracture [ 2 ]. Surgical resection is the treatment option for severe SHPT when drug regimens fail. Several studies have confirmed that parathyroidectomy provides better quality of life, fewer major cardiovascular events, and lower risk of postoperative recurrence [ 3 – 5 ]. Currently, the success of parathyroidectomy relies on localization with imaging and the experience of surgeon [ 6 , 7 ]. However, the incidence of surgical failure, defined as persistent and recurrent SHPT after operation, is estimated to be 10–30%, largely due to incomplete localization. Therefore, thorough localization by imaging might prevent surgical failure [ 6 , 8 , 9 ]. Ultrasound (US) localization for SHPT is commonly practiced in various centers due to its widespread availability, real-time imaging, lack of contrast requirement, absence of renal dysfunction risk, and cost-effectiveness [ 10 ]. Compared with normal PGs, four-gland hyperplasia in SHPT may be more easily detected because of enlarged size. However, the preoperative imaging modality did not have high sensitivity in the detection of all the glands. The sensitivity of US localization ranges from 54–76% [ 11 – 13 ]. The reported rate of ultrasound-detection of four parathyroid glands ranges from 7.8–47.5% [ 14 , 15 ]. Our objective aimed to assess the use of US and determine the reason for echo-detection failure. We may improve our technique accordingly to reduce surgical time and surgical failure rate. Methods Patients and methods We retrospectively reviewed all SHPT patients who underwent total parathyroidectomy ± auto-transplantation between September 2020 and March 2022 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. The indications for surgery were SHPT with any of the following: (1) age > 18 years old; (2) serum intact parathyroid hormone (iPTH) ≥ 800 pg/mL; (3) associated symptoms (pruritis, bone pain, fracture, calciphylaxis); (4) refractory hypercalcemia (≥ 10.2 mg/dL) and/or hyperphosphatemia (≥ 6.0 mg/dL) despite pharmacologic therapy [ 16 ]. Initially, 63 SHPT patients were enrolled. Patients who had recurrent SHPT (n = 5), a history of thyroidectomy (n = 2), no preoperative US (n = 1), or were lost to follow-up (n = 1) were excluded, thus leaving 54 patients for the final analysis (Fig. 1 ). This study was approved by the Change Gung Medical Foundation Institutional Review Board (number: 202300239B0). The need for informed consent from patients was waived because of the study’s retrospective design. The PGs were determined to be eutopic or ectopic during operation [ 9 ]. An intrathyroidal PG was defined as a gland that was completely surrounded by thyroid tissue [ 17 ]. The normal range for iPTH is 15–76 pg/ml. Early surgical success was defined as the iPTH ≤ normal range on the 5th postoperative day. Persistent SHPT was defined as the lowest iPTH exceeding the normal range within 6 months after parathyroidectomy. When initial postoperative iPTH was normal but returned to above normal range more than 6 months after successful surgery, the patient was defined as recurrent SHPT [ 16 ]. Patient demographics, imaging reports, laboratory values, and operative and pathological results were collected. Laboratory values included serum calcium, phosphorus, and iPTH, which were checked on 1st and 5th postoperative days and 6 months thereafter [ 18 ]. The primary endpoint of the study was the US detection rate of PG and analysis of the reason for missed PGs. The secondary endpoint was the association of the number of image-detectable PGs with surgery success rate and operating time. As part of our evaluation protocol, electrocardiography, echocardiography, and thallium scans were conducted before operation. If positive or equivocal thallium scan results were obtained, patients were referred to cardiologists for percutaneous coronary intervention (PCI). For safety, parathyroid surgery was postponed for at least two months in patients who underwent PCI stenting followed by dual anti-platelet therapy. US and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT) were used for preoperative localization, and both performed less than one month before surgery. The US was performed by one of three experienced endocrine surgeons with ultrasound diagnostic instruments (LOGIQ S8; GE Healthcare; USA) and line array high-frequency probes (8–10 mHz). The typical parathyroid image showed an oval or multilobulated hypoechoic mass with peripheral vascular arch and a parathyroid vascular pedicle (Fig. 2 ) [ 19 ]. The patient was placed in supine position with neck mildly extended. We searched four common gland locations, including the right upper, right lower, left upper, and left lower positions of the neck (Fig. 3 a to 3 d). The size of PG was measured in axial and transverse views. If the number of detected PGs was less than four, the regions of the carotid sheath, thyro-thymic trunk, and upper mediastinum were focused on to search for ectopic PGs. We did not perform a routine biopsy to confirm parathyroid hyperplasia. When an incidental thyroid nodule was detected on US, fine needle aspiration (FNA) was conducted according to current guidelines [ 20 ]. 99m Tc sestamibi SPECT/CT imaging was performed on a Siemens Symbia T SPECT/CT gamma camera (Siemens Medical Solutions, IL, USA). After intravenous administration of 1110 MBq (30 mCi) of 99m Tc sestamibi via a lower limb vein, each patient underwent early-phase planar imaging and delayed-phase planar imaging followed by SPECT/CT. The image was considered positive if it showed a focal area of increased uptake in the neck, mediastinum, or any potential ectopic site with either a progressive increase or a prolonged retention at the delayed phase. Surgical techniques US and parathyroidectomy were performed by the same surgical team. The results of US and SPECT/CT were read by surgeons at the time of surgery. Every patient underwent bilateral four-gland neck exploration via a transverse cervical incision under general anesthesia. When four or more enlarged PGs were removed, 100mg of the smallest gland was implanted into the subcutaneous layer of the limb. If fewer than three PGs were identified, no auto-transplantation would take place. We performed routine bilateral transcervical thymectomy. The location of PG was recorded during surgery (Fig. 3 e) and each gland was classified as true positive, false positive, true negative, or false negative based on US findings and pathology. Additionally, the surgeon defined the ectopic location and cause of US-missed PGs intraoperatively. The size and weight of PGs were measured immediately after removal. Hemithyroidectomy or total thyroidectomy was conducted in some patients with a large nodular goiter (> 2 cm), or a nodule suspected or confirmed malignancy via US or FNA. The removed PGs and/or thyroid were examined by pathologists for the final diagnosis. Postoperative follow-up was longer than six months to define SHP recurrence or relapse. Statistical analysis Numerical data are expressed as the mean (standard deviation) and categorical data are expressed as rates or proportions. Logistic regression and Spearman correlation were used for statistical analysis. Results were considered significant if the p value < 0.05. Statistical analysis was performed using SPSS software v.20 (Chicago, Illinois, USA) Results In all, 212 PGs of 54 uremic patients were removed with histological confirmation of parathyroid hyperplasia. The mean age of the patients was 58.7 ± 11.9 years. Male patients accounted for 61.1% (33/54) of this cohort. The mean duration of surgery was 83.5 ± 31.0 minutes (Table 1 ). Two patients (3.7%) were diagnosed with persistent SHPT after operation and no recurrent SHPT or permanent hypoparathyroidism after a mean follow-up period of 19.4 months. There were 28 (13.1%) ectopic PGs in this study. The locations of these ectopic PGs were as follows: thymus ( n = 15, 7.0%), intrathyroid ( n = 3, 1.4%), and others ( n = 10, 4.7%). Eleven patients underwent concurrent lobectomy (n = 5, 9.3%) or total thyroidectomy ( n = 6, 11.1%) for nodular goiter ( n = 7, 13.0%) or thyroid cancer ( n = 4, 7.4%). There were 2 surgical failures. We excised four extrathyroid nodules, but pathology proved that only three nodules were parathyroid hyperplasia and the other one was nodular goiter. The patient had persistent SHP (postoperative iPTH 261 pg/ml). In another case, we also excised four extrathyroid nodules, which all confirmed to be parathyroid hyperplasia. However, the postoperative iPTH was 665 pg/ml, therefore supernumerary PGs were suspected. The two patients did not undergo imaging evaluation after first operation. Table 1 Basic characteristics of the 54 ESRD patients with secondary hyperparathyroidism Total (n = 54) Age (year) 58.7 ± 11.9 Male sex, n (%) 33 (61.1%) Type of dialysis, n (%) Hemodialysis 40 (74.1%) Peritoneal dialysis 14 (25.9%) Years of dialysis (year) 7.6 ± 5.0 Pre-op iPTH level (pg/mL) 1797.9 ± 998.4 Post-op iPTH level (pg/mL) 19.7 ± 47.0 Pre-op Ca level (mg/dL) 10.4 ± 0.8 Concurrent thyroidectomy, n (%) 11 (20.4%) Lobectomy/total thyroidectomy 5 (9.3)/6 (11.1) Nodular goiter/thyroid cancer 7(13.0)/4(7.4) Eutopic PG 184 (86.8%) Ectopic PG 28 (13.2%) Thymus 15 (7.1%) Intrathyroid 3 (1.4%) Others* 10 (4.7%) US-missed ectopic PG 12 (5.7%) Small PG (< 1 cm) 12 (5.7%) US-missed small PG 6 (2.8%) Duration of surgery # (minutes) 83.5 ± 31.0 Postoperative follow-up (months) 19.4 ± 9.6 Recurrent or persistent SHP, n (%) 2 (3.7%) Values are expressed as means ± SD or numbers (percent) iPTH = intact parathyroid hormone, PG = parathyroid gland, SHP = secondary hyperparathyroidism * Parathyroid glands in mediastinum, retroesophageal, retropharyngeal locations # Exclude patients who underwent concurrent thyroidectomy In Table 2 , US showed all four PGs in 36 patients (66.7%), three PGs in 15 patients (27.8%), two PGs in 1 patient (1.9%), and only one PG in 2 patients (3.7%). SPECT/CT detected all four PGs in 19 patients (35.2%), three PGs in 23 patients (42.6%), and two PGs in 12 patients (22.2%). When analyzed by lesion number, the sensitivity of US, SPECT, and combination was 91.0% (193/212), 79.3% (169/212), and 95.8% (203/212), respectively. The specificity of US, SPECT, and combination was 75.0% (3/4), 33.3% (1/3), and 25.0% (1/4), respectively. The accuracy of US, SPECT, and combination was 90.7% (196/216), 78.7% (170/216), and 94.4% (204/216), respectively (Table 3 ). Table 2 Total number of parathyroid glands accurately identified on ultrasound and 99m Tc-MIBI SPECT/CT Numbers of glands identified* US, n (%) 99m Tc-MIBI SPECT/CT, n (%) 4 36 (66.7) 19 (35.2) 3 15 (27.8) 23 (42.6) 2 1 (1.9) 12 (22.2) 1 2 (3.7) 0 (0.0) * Exclude false positive parathyroid glands Table 3 Results of parathyroid glands localized on ultrasound and 99m Tc-MIBI SPECT/CT FP = false positive, FN = false negative, TP = true positive, TN = true negative TP FN TN FP Sensitivity (%) Specificity (%) Accuracy (%) US 193 19 3 1 91.0 75.0 90.7 99m Tc-MIBI SPECT/CT 169 44 1 2 79.3 33.3 78.7 US + 99m Tc-MIBI SPECT/CT 203 9 1 3 95.8 25.0 94.4 Compared with intraoperative findings and final pathology, one gland on US and two glands on SPECT/CT were false positives (Table 3 ). Meanwhile, 19 PGs (9.0%) were not shown on US and were categorized as false negatives. Table 4 summarizes the reason for US-missed PGs. The most common cause was an ectopic position ( n = 12, 3.2%), including thymus ( n = 6, 2.8%) (Fig. 4 a), intrathyroid ( n = 1, 0.5%) (Fig. 4 b), and others (located at mediastinum, retroesophageal, and retropharyngeal area; n = 5, 2.4%). The second most common cause was small size ( n = 6, 2.8%), which all was less than 1 cm in maximal length and weighed less than 200 µg. One upper PG overlap with the ipsilateral lower PG ( n = 1, 0.5%) (Fig. 4 c) also led to a missed US cause. Table 4 Causes of US-missed parathyroid glands Causes n (%*) Ectopic location 12 (5.7) Thymus 6 (2.8) Intrathyroid 1 (0.5) Others # 5 (2.4) Small size (< 1 cm) 6 (2.8) Overlap with ipsilateral parathyroid gland 1 (0.5) Overall 19 (9.0) * Divided by total parathyroid glands identified by pathology (n = 212) # Ectopic parathyroid glands at upper mediastinum, retroesophageal, and retropharyngeal area The analysis of the association between the number of US, SPECT/CT, or US + SPECT/CT detected PGs and the surgical success rate showed no significance ( p = 0.671, 0.625, and 0.335, respectively) (Table 5 ). The number of SPECT/CT detected PGs was not correlated with surgical time ( rs = -0.225, p = 0.147), but the number of US- or US + SPECTCT-detected PGs was negatively associated with surgical time ( rs = -0.459 and − 0.519, p = 0.002 and < 0.001, respectively), as shown in Table 6 . Table 5 Correlation between number of image-detected parathyroid glands with surgical success rate Imaging modality Odds ratio P value US-detectable PG number NA 0.671 99m Tc-MIBI SPECT/CT detectable PG number NA 0.625 US + 99m Tc-MIBI SPECT/CT detectable PG number NA 0.335 NA = not available Table 6 Correlation between number of image-detected parathyroid glands with surgical time* Imaging modality rs P value US-detectable PG number -0.459 0.002 99m Tc-MIBI SPECT/CT-detectable PG number -0.225 0.147 US + 99m Tc-MIBI SPECT/CT detectable PG number -0.519 < 0.001 * Exclude patients who underwent concurrent thyroidectomy Discussion Ultrasonography is one of the most common modalities for localization of hyperfunctioning PGs. However, several studies have noted that the sensitivity of US varies greatly, and the reason for missed gland has not been discussed in detail. In this study, we found that US for preoperative localization had 90% sensitivity and accuracy. Visualizing all four parathyroid hyperplasia can be achieved in 66.7% and 35.2% of SHPT patients by US and SPECT/CT, respectively. PGs located in an ectopic position or of a small size (< 1 cm) might cause negative results on US. Furthermore, if we could completely map the hyperplastic glands, the surgical time could be reduced. Ectopic position was the most common cause of US-missed localization. In our study, the incidence of ectopic glands was 13.2%, 42.9% of which could not be recognized on US. The study by Andrade et al. corroborated these findings [ 15 ]. They recruited 166 secondary and tertiary HPT patients. Thirteen percent of hyperfunctioning PGs were located in ectopic positions, and 61.5% of these ectopic PGs failed to be localized by US and Tc99m-Sestamibi scintigraphy (MIBI). A study by Alkhalili et al. concluded that half of ectopic PGs were not detected by US or MIBI [ 14 ]. Several different definitions of ectopic glands have led to variation in the incidence. The most common ectopic sites included the thymus, retroesophageal, retropharyngeal, intrathyroid, mediastinum, and carotid sheath [ 9 , 14 , 15 ]. Hyperfunctioning PGs within the mediastinum or in retroesophageal locations where bone and air, respectively, prevent visualization of deeper structures. Because missed PGs in ectopic positions were the leading cause of failed surgery, awareness of the disadvantages of US is important for surgical planning. Small PGs (< 1 cm) were determined to be a limitation for US detection. Perie et al. found that false-negative results on ultrasonography correlated with low gland weight [ 19 ]. A small gland was considered equally as low weight. Although we found that not all small glands are undetectable on US, all the missed PGs that was in eutopic positions were smaller than one centimeter. In a prospective study of 1000 consecutive patients with primary HPT, body mass index and gland size independently predicted the accurate detection of PGs by US and MIBI [ 21 ]. Furthermore, when the maximal length was smaller than 1 cm, more than half of PGs were undetectable [ 21 ]. Either in primary or secondary HTP, abnormal PG with less than 1 cm in length were associated with false negatives on US. The overwhelming majority of individuals have 4 PGs, 2 superiors and 2 inferiors, whereas between 2.5–13.0% have supernumerary glands, and 3% have fewer than 4 glands [ 22 , 23 ]. We did not find any supernumerary PGs, but there was one suspicious case because of persistent HPT after excision of four parathyroid hyperplasia. Our protocol for parathyroid US consisted of searching four common positions for PGs, and supernumerary glands would therefore miss. Furthermore, surgical failure is mainly due to resect not all the PGs, coming from the existence of ectopic or supernumerary PGs [ 12 , 24 , 25 ]. To improve the surgical success rate, precise preoperative imaging localization is crucial. Andrade et al. noted that US and MIBI could not detect supernumerary PGs [ 15 ]. EI-Sageer et al. recommended that neck exploration was the best reliable method for localization than imaging modalities [ 7 ]. However, from our experience, ectopic PGs in the thyroid, carotid sheath or mediastinum were difficult to detect during operation and the searching of neck prolonged the operative time. Preoperative mapping for parathyroid surgery is rational and recommended. Recent studies have found that concurrent nodular goiter or thyroid cancer was not uncommon in SHP patients, and the prevalence of incidental nodular goiter and thyroid cancer were approximately 20–30% and 6–8%, respectively [ 14 , 26 – 28 ], both of which corresponded with our results. The prevalence of concurrent papillary carcinoma (PTC) was higher in SHP patients than in general population. Although most of those concomitant PTCs were microcarcinomas (> 70%), they may express more aggressive tumor features [ 27 ]. Therefore, it is necessary to perform a thorough examination to avoid missing the coexistence of malignancy. Limitations of the study The study has several limitations. First, 99m Tc-MIBI SPECT/CT provided additional information for preoperative localization. Second, the judgement of US-missed PG was decided by endocrine surgeons who were not blinded. Third, two surgical failure cases with persistent HPT did not undergo imaging survey and reoperation until now. Finally, the study was a retrospective design with a small sample size. More prospective studies with larger groups are needed. Conclusions Our findings demonstrated that US localization was accurate in 90% of our patients. Awareness of the limitations of US is important for surgeons searching for hyperplastic PGs, especially those situated in ectopic positions and small sizes. US provided a useful guide for localization, and therefore, shortened the operation time. Abbreviations CKD – chronic kidney disease ESRD – end-stage renal disease FNA – fine needle aspiration HPT – hyperparathyroidism iPTH – intact parathyroid hormone MIBI – Tc99m-Sestamibi scintigraphy PCI – percutaneous coronary intervention PG – parathyroid gland PTC – papillary thyroid carcinoma SHPT – secondary hyperparathyroidism SPECT/CT – single-photon-emission-computed tomography/computed tomography US – ultrasound Declarations Funding This study was supported by National Science and Technology Council, Taiwan (111-2314-B-182A-158 -) Conflict of interest statement The authors have declared that no conflicts of interests exist. Ethical approval The study was approved by Change Gung Medical Foundation Institutional Review Board (number: 202300239B0) Informed consent The need for informed consent from patients was waived because of the retrospective design of the study Acknowledgements We thank the Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, for their statistics work. Availability of data and materials The dataset supporting the conclusions of this article are included within the article and files. The dataset used during the current study are available from the corresponding author on reasonable request. Authors contribution: YCC, SEC, and SYC designed this project. SEC and YCC analyzed data and wrote the manuscript. FFC and YJW analyzed the data and modified this paper. YCC, SYC, and YHC recruited patients and revised the paper. All authors read and approved the final manuscript. References Kumar R, Thompson JR. The regulation of parathyroid hormone secretion and synthesis. J Am Soc Nephrol. 2011;22(2). https://DOI.org/10.1681/ASN.2010020186 . 216 – 24. Ketteler M, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. Kidney Int. 2017;92(1):26–36. https://DOI.org/10.1016/j.kint.2017.04.006 . Komaba H, et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 2015;88(2):350–9. https://DOI.org/10.1038/ki.2015.72 . Apetrii M, et al. Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD) - A systematic review and meta-analysis. PLoS ONE. 2017;12(11):e0187025. https://DOI.org/10.1371/journal.pone.0187025 . Madorin C, et al. The surgical management of renal hyperparathyroidism. Eur Arch Otorhinolaryngol. 2012;269(6):1565–76. https://DOI.org/10.1007/s00405-011-1833-2 . Steinl GK, Kuo JH. Surgical Management of Secondary Hyperparathyroidism. Kidney Int Rep. 2021;6(2):254–64. https://DOI.org/10.1016/j.ekir.2020.11.023 . El-Sageer EM, et al. Neck Exploration Versus Imaging Localization of Parathyroid in Secondary Hyperparathyroidism. Indian J Surg. 2018;81(5):457–61. https://DOI.org/10.1007/s12262-018-1842-0 . Petranovic Ovcaricek P, et al. An essential practice summary of the new EANM guidelines for parathyroid imaging. Q J Nucl Med Mol Imaging. 2022;66(2):93–103. https://DOI.org/10.23736/S1824-4785.22.03427-6 . Reitz RJ 3, et al. Ectopic and supernumerary parathyroid glands in patients with refractory renal hyperparathyroidism. Surgery. 2021;169(3):513–8. https://DOI.org/10.1016/j.surg.2020.08.007 . Sung JY. Parathyroid ultrasonography: the evolving role of the radiologist. Ultrasonography. 2015;34(4). https://DOI.org/10.14366/usg.14071 . 268 – 74. Mohammadi A, Moloudi F, Ghasemi-Rad M. Preoperative localization of parathyroid lesion: diagnostic usefulness of color doppler ultrasonography. Int J Clin Exp Med. 2012;5(1):80–6. Hiramitsu T, et al. Pre-operative Localisation of the Parathyroid Glands in Secondary Hyperparathyroidism: A Retrospective Cohort Study. Sci Rep. 2019;9(1):14634. https://DOI.org/10.1038/s41598-019-51265-y . Zhang R, et al. Diagnostic performance of ultrasonography, dual-phase (99m)Tc-MIBI scintigraphy, early and delayed (99m)Tc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism. BMC Med Imaging. 2020;20(1):91. https://DOI.org/10.1186/s12880-020-00490-3 . Alkhalili E, et al. The utility of neck ultrasound and sestamibi scans in patients with secondary and tertiary hyperparathyroidism. World J Surg. 2015;39(3):701–5. https://DOI.org/10.1007/s00268-014-2878-3 . Andrade JS, et al. 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. Braz J Otorhinolaryngol. 2014;80(1):29–34. https://DOI.org/10.5935/1808-8694.20140008 . Tominaga Y. Surgical treatment of secondary hyperparathyroidism due to chronic kidney disease. Ups J Med Sci. 2006;111(3). https://DOI.org/10.3109/2000-1967-047 . 277 – 92. Phitayakorn R, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006;191(3). https://DOI.org/10.1016/j.amjsurg.2005.10.049 . 418 – 23. Chou YC, et al. Being elderly is not a contraindication of parathyroidectomy for renal hyperparathyroidism and chronic kidney disease-mineral and bone disorder. Asian J Surg. 2021;44(1):321–8. https://DOI.org/10.1016/j.asjsur.2020.07.022 . Perie S, et al. Usefulness of combination of high-resolution ultrasonography and dual-phase dual-isotope iodine 123/technetium Tc 99m sestamibi scintigraphy for the preoperative localization of hyperplastic parathyroid glands in renal hyperparathyroidism. Am J Kidney Dis. 2005;45(2):344–52. https://DOI.org/10.1053/j.ajkd.2004.10.021 . Haugen BR et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 2016. 26(1): p. 1-133. https://DOI.org/10.1089/thy.2015.0020 . Berber E, et al. Factors contributing to negative parathyroid localization: an analysis of 1000 patients. Surgery. 2008;144(1). https://DOI.org/10.1016/j.surg.2008.03.019 . 74 – 9. Akerström G, Malmaeus J, Bergström R. Surgical anatomy of human parathyroid glands. Surgery. 1984;95(1):14–21. Nakatsuka K, et al. The fifth hyperfunctioning parathyroid gland in end-stage renal disease. Nephron. 1989;51(1):140–2. https://DOI.org/10.1159/000185277 . Schneider R, et al. 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. https://DOI.org/10.1007/s00268-011-1079-6 . Taterra D, et al. The prevalence and anatomy of parathyroid glands: a meta-analysis with implications for parathyroid surgery. Langenbecks Arch Surg. 2019;404(1):63–70. https://DOI.org/10.1007/s00423-019-01751-8 . Preda C, et al. Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics. BMC Surg. 2019;19(1):94. https://DOI.org/10.1186/s12893-019-0556-y . Jeong C, et al. Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study. Endocrinol Metab (Seoul). 2020;35(4):925–32. https://DOI.org/10.3803/EnM.2020.725 . Ma J, et al. Coexistence of papillary thyroid carcinoma in secondary hyperparathyroidism. BMC Surg. 2021;21(1):335. https://DOI.org/10.1186/s12893-021-01330-z . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3970012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":273804057,"identity":"462a5a76-ec73-4ca5-88f2-9f344f3f174e","order_by":0,"name":"Shen-En Chou","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shen-En","middleName":"","lastName":"Chou","suffix":""},{"id":273804058,"identity":"c2eaf4bb-f728-4dba-be45-b39ce7410f06","order_by":1,"name":"Cheng-Hsi Yeh","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cheng-Hsi","middleName":"","lastName":"Yeh","suffix":""},{"id":273804059,"identity":"2292d68f-f037-40b6-97d0-cb46f6b6a988","order_by":2,"name":"Shun-Yu Chi","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shun-Yu","middleName":"","lastName":"Chi","suffix":""},{"id":273804060,"identity":"61901ce3-c8a9-4dc7-b550-5d874e601d06","order_by":3,"name":"Fong-Fu Chou","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fong-Fu","middleName":"","lastName":"Chou","suffix":""},{"id":273804061,"identity":"5caec3ff-a0af-4f9f-ac08-973e2d0b3b1d","order_by":4,"name":"Yi-Ju Wu","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Ju","middleName":"","lastName":"Wu","suffix":""},{"id":273804062,"identity":"53ea7855-038b-428e-aab0-aee210f87356","order_by":5,"name":"Yen-Hsiang Chang","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yen-Hsiang","middleName":"","lastName":"Chang","suffix":""},{"id":273804063,"identity":"bbf181ec-3dff-4c2f-ac6f-da48970d8ceb","order_by":6,"name":"Yi-Chia Chan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYJACxoYCBjkGhgQwJ4FILQYMxmhaCOgEaUlsIFqL/OzmZx9nGNik97dnJzD8+LUtj4G99/ELxh+HcWoxuHPMeOYGg7TcGWfebmDs7btdzMBz3MyCIQGPFokEY8YHBodzG27kbmBm7Lmd2CCRxmbAkHAbt8NmpH8GavmfLk+0FoYbOcaMGwwOJBiAtDD8AGthfoBPi8GdM8WMMwySDTcC/XKwt+F2YhvPMTaGhLT/uB02u30zY0+Fnbzc8dyND378uZ3Yz97G/OGDTRpuh0kgsQ8wtjEwsAGRRAJuDahaGBj+gEnmD/h0jIJRMApGwYgDAOjsXa2WnbIlAAAAAElFTkSuQmCC","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yi-Chia","middleName":"","lastName":"Chan","suffix":""}],"badges":[],"createdAt":"2024-02-19 12:52:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3970012/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3970012/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51506526,"identity":"263d3d1a-99a0-49f6-ae1f-6b47045aa796","added_by":"auto","created_at":"2024-02-22 19:31:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":228678,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of screening for eligible cases.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3970012/v1/54976143906a11e18c687acb.png"},{"id":51506527,"identity":"12bc34ea-6d79-4c6e-a6f5-912ff44e22f0","added_by":"auto","created_at":"2024-02-22 19:31:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":395957,"visible":true,"origin":"","legend":"\u003cp\u003eParathyroid hyperplasia was shown on ultrasound in transversal (\u003cstrong\u003eA\u003c/strong\u003e) and longitudinal (\u003cstrong\u003eB\u003c/strong\u003e) views. Typical characteristics include homogenous hypoechogenicity, oval or multilobulated shape, and peripheral vascularity.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3970012/v1/d22fa6a3e2e40edb9aacd56a.png"},{"id":51506525,"identity":"a5a60c8c-caa2-49e0-805a-7988728d7db8","added_by":"auto","created_at":"2024-02-22 19:31:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":649729,"visible":true,"origin":"","legend":"\u003cp\u003eUltrasound in transverse (\u003cstrong\u003e3A\u003c/strong\u003e for right upper PG, \u003cstrong\u003e3B\u003c/strong\u003e for right lower PG, \u003cstrong\u003e3C\u003c/strong\u003efor left upper PG, \u003cstrong\u003e3D\u003c/strong\u003e for left lower PG) views of an ESRD patient showing secondary parathyroid hyperplasia compared with intraoperative findings (\u003cstrong\u003e3E\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eC – carotid artery; J – internal jugular vein; LLP – left lower parathyroid gland; LUP – left upper parathyroid gland; NG – nodular goiter; RUP – right upper parathyroid gland; RLP – right lower parathyroid gland; T – trachea; TH – thymus\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3970012/v1/79d7295d393822c355d5472a.png"},{"id":51506528,"identity":"6ef0a2c0-edbf-45c8-ae10-380aa1706959","added_by":"auto","created_at":"2024-02-22 19:31:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2200551,"visible":true,"origin":"","legend":"\u003cp\u003eCauses of ultrasound-missed parathyroid hyperplasia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4A\u003c/strong\u003e: Ectopic bilateral lower parathyroid glands in the thymus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4B\u003c/strong\u003e: (Left) The left upper parathyroid gland was misdiagnosed as part of the thyroid nodule (NG), compared to the intraoperative findings (right)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4C\u003c/strong\u003e: (Left) The right upper parathyroid gland overlapped with right lower one, compared to the intraoperative finding (right)\u003c/p\u003e\n\u003cp\u003eC – carotid artery; LLP – left lower parathyroid gland; LUP – left upper parathyroid gland; NG –nodular goiter; RUP – right upper parathyroid gland; RLP – right lower parathyroid gland; TH – thymus\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3970012/v1/5c8a308d041ee6d54c30ad06.png"},{"id":51922671,"identity":"07383a00-533b-409e-bb38-cc2a389ca197","added_by":"auto","created_at":"2024-03-03 23:17:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3555537,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3970012/v1/0d0e6bc7-e8d8-428b-9a1a-a7047f93e566.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Addressing the challenges of missed parathyroid glands in ultrasonography for secondary hyperparathyroidism.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic kidney disease (CKD) is a major burden on global health. Patients with CKD stage III or higher often develop secondary parathyroid hyperplasia, caused by hyperphosphatemia and hypocalcemia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Secondary hyperparathyroidism (SHPT) results in abnormal calcium deposition, osteoporosis, bone deformity, or fracture [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Surgical resection is the treatment option for severe SHPT when drug regimens fail. Several studies have confirmed that parathyroidectomy provides better quality of life, fewer major cardiovascular events, and lower risk of postoperative recurrence [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the success of parathyroidectomy relies on localization with imaging and the experience of surgeon [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the incidence of surgical failure, defined as persistent and recurrent SHPT after operation, is estimated to be 10\u0026ndash;30%, largely due to incomplete localization. Therefore, thorough localization by imaging might prevent surgical failure [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUltrasound (US) localization for SHPT is commonly practiced in various centers due to its widespread availability, real-time imaging, lack of contrast requirement, absence of renal dysfunction risk, and cost-effectiveness [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Compared with normal PGs, four-gland hyperplasia in SHPT may be more easily detected because of enlarged size. However, the preoperative imaging modality did not have high sensitivity in the detection of all the glands. The sensitivity of US localization ranges from 54\u0026ndash;76% [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The reported rate of ultrasound-detection of four parathyroid glands ranges from 7.8\u0026ndash;47.5% [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur objective aimed to assess the use of US and determine the reason for echo-detection failure. We may improve our technique accordingly to reduce surgical time and surgical failure rate.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003ePatients and methods\u003c/h2\u003e\n \u003cp\u003eWe retrospectively reviewed all SHPT patients who underwent total parathyroidectomy\u0026thinsp;\u0026plusmn;\u0026thinsp;auto-transplantation between September 2020 and March 2022 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. The indications for surgery were SHPT with any of the following: (1) age\u0026thinsp;\u0026gt;\u0026thinsp;18 years old; (2) serum intact parathyroid hormone (iPTH)\u0026thinsp;\u0026ge;\u0026thinsp;800 pg/mL; (3) associated symptoms (pruritis, bone pain, fracture, calciphylaxis); (4) refractory hypercalcemia (\u0026ge;\u0026thinsp;10.2 mg/dL) and/or hyperphosphatemia (\u0026ge;\u0026thinsp;6.0 mg/dL) despite pharmacologic therapy [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. Initially, 63 SHPT patients were enrolled. Patients who had recurrent SHPT (n\u0026thinsp;=\u0026thinsp;5), a history of thyroidectomy (n\u0026thinsp;=\u0026thinsp;2), no preoperative US (n\u0026thinsp;=\u0026thinsp;1), or were lost to follow-up (n\u0026thinsp;=\u0026thinsp;1) were excluded, thus leaving 54 patients for the final analysis (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThis study was approved by the Change Gung Medical Foundation Institutional Review Board (number: 202300239B0). The need for informed consent from patients was waived because of the study\u0026rsquo;s retrospective design.\u003c/p\u003e\n \u003cp\u003eThe PGs were determined to be eutopic or ectopic during operation [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. An intrathyroidal PG was defined as a gland that was completely surrounded by thyroid tissue [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. The normal range for iPTH is 15\u0026ndash;76 pg/ml. Early surgical success was defined as the iPTH\u0026thinsp;\u0026le;\u0026thinsp;normal range on the 5th postoperative day. Persistent SHPT was defined as the lowest iPTH exceeding the normal range within 6 months after parathyroidectomy. When initial postoperative iPTH was normal but returned to above normal range more than 6 months after successful surgery, the patient was defined as recurrent SHPT [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003ePatient demographics, imaging reports, laboratory values, and operative and pathological results were collected. Laboratory values included serum calcium, phosphorus, and iPTH, which were checked on 1st and 5th postoperative days and 6 months thereafter [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. The primary endpoint of the study was the US detection rate of PG and analysis of the reason for missed PGs. The secondary endpoint was the association of the number of image-detectable PGs with surgery success rate and operating time.\u003c/p\u003e\n \u003cp\u003eAs part of our evaluation protocol, electrocardiography, echocardiography, and thallium scans were conducted before operation. If positive or equivocal thallium scan results were obtained, patients were referred to cardiologists for percutaneous coronary intervention (PCI). For safety, parathyroid surgery was postponed for at least two months in patients who underwent PCI stenting followed by dual anti-platelet therapy. US and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT) were used for preoperative localization, and both performed less than one month before surgery.\u003c/p\u003e\n \u003cp\u003eThe US was performed by one of three experienced endocrine surgeons with ultrasound diagnostic instruments (LOGIQ S8; GE Healthcare; USA) and line array high-frequency probes (8\u0026ndash;10 mHz). The typical parathyroid image showed an oval or multilobulated hypoechoic mass with peripheral vascular arch and a parathyroid vascular pedicle (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. The patient was placed in supine position with neck mildly extended. We searched four common gland locations, including the right upper, right lower, left upper, and left lower positions of the neck (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea to \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ed). The size of PG was measured in axial and transverse views. If the number of detected PGs was less than four, the regions of the carotid sheath, thyro-thymic trunk, and upper mediastinum were focused on to search for ectopic PGs. We did not perform a routine biopsy to confirm parathyroid hyperplasia. When an incidental thyroid nodule was detected on US, fine needle aspiration (FNA) was conducted according to current guidelines [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc sestamibi SPECT/CT imaging was performed on a Siemens Symbia T SPECT/CT gamma camera (Siemens Medical Solutions, IL, USA). After intravenous administration of 1110 MBq (30 mCi) of\u0026nbsp;\u003csup\u003e99m\u003c/sup\u003eTc sestamibi via a lower limb vein, each patient underwent early-phase planar imaging and delayed-phase planar imaging followed by SPECT/CT. The image was considered positive if it showed a focal area of increased uptake in the neck, mediastinum, or any potential ectopic site with either a progressive increase or a prolonged retention at the delayed phase.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eSurgical techniques\u003c/h2\u003e\n \u003cp\u003eUS and parathyroidectomy were performed by the same surgical team. The results of US and SPECT/CT were read by surgeons at the time of surgery. Every patient underwent bilateral four-gland neck exploration via a transverse cervical incision under general anesthesia. When four or more enlarged PGs were removed, 100mg of the smallest gland was implanted into the subcutaneous layer of the limb. If fewer than three PGs were identified, no auto-transplantation would take place. We performed routine bilateral transcervical thymectomy. The location of PG was recorded during surgery (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ee) and each gland was classified as true positive, false positive, true negative, or false negative based on US findings and pathology. Additionally, the surgeon defined the ectopic location and cause of US-missed PGs intraoperatively. The size and weight of PGs were measured immediately after removal. Hemithyroidectomy or total thyroidectomy was conducted in some patients with a large nodular goiter (\u0026gt;\u0026thinsp;2 cm), or a nodule suspected or confirmed malignancy via US or FNA. The removed PGs and/or thyroid were examined by pathologists for the final diagnosis. Postoperative follow-up was longer than six months to define SHP recurrence or relapse.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eNumerical data are expressed as the mean (standard deviation) and categorical data are expressed as rates or proportions. Logistic regression and Spearman correlation were used for statistical analysis. Results were considered significant if the p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analysis was performed using SPSS software v.20 (Chicago, Illinois, USA)\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn all, 212 PGs of 54 uremic patients were removed with histological confirmation of parathyroid hyperplasia. The mean age of the patients was 58.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 years. Male patients accounted for 61.1% (33/54) of this cohort. The mean duration of surgery was 83.5\u0026thinsp;\u0026plusmn;\u0026thinsp;31.0 minutes (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Two patients (3.7%) were diagnosed with persistent SHPT after operation and no recurrent SHPT or permanent hypoparathyroidism after a mean follow-up period of 19.4 months.\u003c/p\u003e\n\u003cp\u003eThere were 28 (13.1%) ectopic PGs in this study. The locations of these ectopic PGs were as follows: thymus (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15, 7.0%), intrathyroid (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3, 1.4%), and others (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;10, 4.7%). Eleven patients underwent concurrent lobectomy (n\u0026thinsp;=\u0026thinsp;5, 9.3%) or total thyroidectomy (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6, 11.1%) for nodular goiter (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7, 13.0%) or thyroid cancer (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4, 7.4%).\u003c/p\u003e\n\u003cp\u003eThere were 2 surgical failures. We excised four extrathyroid nodules, but pathology proved that only three nodules were parathyroid hyperplasia and the other one was nodular goiter. The patient had persistent SHP (postoperative iPTH 261 pg/ml). In another case, we also excised four extrathyroid nodules, which all confirmed to be parathyroid hyperplasia. However, the postoperative iPTH was 665 pg/ml, therefore supernumerary PGs were suspected. The two patients did not undergo imaging evaluation after first operation.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBasic characteristics of the 54 ESRD patients with secondary hyperparathyroidism\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (61.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of dialysis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemodialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (74.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeritoneal dialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (25.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYears of dialysis (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-op iPTH level (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1797.9\u0026thinsp;\u0026plusmn;\u0026thinsp;998.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost-op iPTH level (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-op Ca level (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent thyroidectomy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLobectomy/total thyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (9.3)/6 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNodular goiter/thyroid cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(13.0)/4(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEutopic PG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e184 (86.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEctopic PG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (13.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThymus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntrathyroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-missed ectopic PG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (5.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall PG (\u0026lt;\u0026thinsp;1 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (5.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-missed small PG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDuration of surgery\u003csup\u003e#\u003c/sup\u003e (minutes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.5\u0026thinsp;\u0026plusmn;\u0026thinsp;31.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePostoperative follow-up (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecurrent or persistent SHP, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eValues are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or numbers (percent)\u003c/p\u003e\n\u003cp\u003eiPTH\u0026thinsp;=\u0026thinsp;intact parathyroid hormone, PG\u0026thinsp;=\u0026thinsp;parathyroid gland, SHP\u0026thinsp;=\u0026thinsp;secondary hyperparathyroidism\u003c/p\u003e\n\u003cp\u003e* Parathyroid glands in mediastinum, retroesophageal, retropharyngeal locations\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e Exclude patients who underwent concurrent thyroidectomy\u003c/p\u003e\n\u003cp\u003eIn Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, US showed all four PGs in 36 patients (66.7%), three PGs in 15 patients (27.8%), two PGs in 1 patient (1.9%), and only one PG in 2 patients (3.7%). SPECT/CT detected all four PGs in 19 patients (35.2%), three PGs in 23 patients (42.6%), and two PGs in 12 patients (22.2%). When analyzed by lesion number, the sensitivity of US, SPECT, and combination was 91.0% (193/212), 79.3% (169/212), and 95.8% (203/212), respectively. The specificity of US, SPECT, and combination was 75.0% (3/4), 33.3% (1/3), and 25.0% (1/4), respectively. The accuracy of US, SPECT, and combination was 90.7% (196/216), 78.7% (170/216), and 94.4% (204/216), respectively (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTotal number of parathyroid glands accurately identified on ultrasound and \u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumbers of glands identified*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUS, n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT, n (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (35.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (27.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e* Exclude false positive parathyroid glands\u003c/p\u003e\n\u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eResults of parathyroid glands localized on ultrasound and \u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT FP\u0026thinsp;=\u0026thinsp;false positive, FN\u0026thinsp;=\u0026thinsp;false negative, TP\u0026thinsp;=\u0026thinsp;true positive, TN\u0026thinsp;=\u0026thinsp;true negative\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecificity (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAccuracy (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u0026thinsp;+\u0026thinsp;\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e94.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eCompared with intraoperative findings and final pathology, one gland on US and two glands on SPECT/CT were false positives (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Meanwhile, 19 PGs (9.0%) were not shown on US and were categorized as false negatives. Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the reason for US-missed PGs. The most common cause was an ectopic position (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;12, 3.2%), including thymus (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6, 2.8%) (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ea), intrathyroid (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1, 0.5%) (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eb), and others (located at mediastinum, retroesophageal, and retropharyngeal area; \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5, 2.4%). The second most common cause was small size (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6, 2.8%), which all was less than 1 cm in maximal length and weighed less than 200 \u0026micro;g. One upper PG overlap with the ipsilateral lower PG (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1, 0.5%) (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ec) also led to a missed US cause.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCauses of US-missed parathyroid glands\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCauses\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en (%*)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEctopic location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThymus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntrathyroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall size (\u0026lt;\u0026thinsp;1 cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverlap with ipsilateral parathyroid gland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e* Divided by total parathyroid glands identified by pathology (n\u0026thinsp;=\u0026thinsp;212)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e Ectopic parathyroid glands at upper mediastinum, retroesophageal, and retropharyngeal area\u003c/p\u003e\n\u003cp\u003eThe analysis of the association between the number of US, SPECT/CT, or US\u0026thinsp;+\u0026thinsp;SPECT/CT detected PGs and the surgical success rate showed no significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.671, 0.625, and 0.335, respectively) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). The number of SPECT/CT detected PGs was not correlated with surgical time (\u003cem\u003ers\u003c/em\u003e= -0.225, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.147), but the number of US- or US\u0026thinsp;+\u0026thinsp;SPECTCT-detected PGs was negatively associated with surgical time (\u003cem\u003ers\u003c/em\u003e= -0.459 and \u0026minus;\u0026thinsp;0.519, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002 and \u0026lt;\u0026thinsp;0.001, respectively), as shown in Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation between number of image-detected parathyroid glands with surgical success rate\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eImaging modality\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u0026thinsp;+\u0026thinsp;\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eNA\u0026thinsp;=\u0026thinsp;not available\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation between number of image-detected parathyroid glands with surgical time*\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eImaging modality\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ers\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT-detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u0026thinsp;+\u0026thinsp;\u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT detectable PG number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e* Exclude patients who underwent concurrent thyroidectomy\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eUltrasonography is one of the most common modalities for localization of hyperfunctioning PGs. However, several studies have noted that the sensitivity of US varies greatly, and the reason for missed gland has not been discussed in detail. In this study, we found that US for preoperative localization had 90% sensitivity and accuracy. Visualizing all four parathyroid hyperplasia can be achieved in 66.7% and 35.2% of SHPT patients by US and SPECT/CT, respectively. PGs located in an ectopic position or of a small size (\u0026lt;\u0026thinsp;1 cm) might cause negative results on US. Furthermore, if we could completely map the hyperplastic glands, the surgical time could be reduced.\u003c/p\u003e \u003cp\u003eEctopic position was the most common cause of US-missed localization. In our study, the incidence of ectopic glands was 13.2%, 42.9% of which could not be recognized on US. The study by Andrade et al. corroborated these findings [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. They recruited 166 secondary and tertiary HPT patients. Thirteen percent of hyperfunctioning PGs were located in ectopic positions, and 61.5% of these ectopic PGs failed to be localized by US and Tc99m-Sestamibi scintigraphy (MIBI). A study by Alkhalili et al. concluded that half of ectopic PGs were not detected by US or MIBI [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Several different definitions of ectopic glands have led to variation in the incidence. The most common ectopic sites included the thymus, retroesophageal, retropharyngeal, intrathyroid, mediastinum, and carotid sheath [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Hyperfunctioning PGs within the mediastinum or in retroesophageal locations where bone and air, respectively, prevent visualization of deeper structures. Because missed PGs in ectopic positions were the leading cause of failed surgery, awareness of the disadvantages of US is important for surgical planning.\u003c/p\u003e \u003cp\u003eSmall PGs (\u0026lt;\u0026thinsp;1 cm) were determined to be a limitation for US detection. Perie et al. found that false-negative results on ultrasonography correlated with low gland weight [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A small gland was considered equally as low weight. Although we found that not all small glands are undetectable on US, all the missed PGs that was in eutopic positions were smaller than one centimeter. In a prospective study of 1000 consecutive patients with primary HPT, body mass index and gland size independently predicted the accurate detection of PGs by US and MIBI [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Furthermore, when the maximal length was smaller than 1 cm, more than half of PGs were undetectable [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Either in primary or secondary HTP, abnormal PG with less than 1 cm in length were associated with false negatives on US.\u003c/p\u003e \u003cp\u003eThe overwhelming majority of individuals have 4 PGs, 2 superiors and 2 inferiors, whereas between 2.5\u0026ndash;13.0% have supernumerary glands, and 3% have fewer than 4 glands [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. We did not find any supernumerary PGs, but there was one suspicious case because of persistent HPT after excision of four parathyroid hyperplasia. Our protocol for parathyroid US consisted of searching four common positions for PGs, and supernumerary glands would therefore miss. Furthermore, surgical failure is mainly due to resect not all the PGs, coming from the existence of ectopic or supernumerary PGs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. To improve the surgical success rate, precise preoperative imaging localization is crucial. Andrade et al. noted that US and MIBI could not detect supernumerary PGs [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. EI-Sageer et al. recommended that neck exploration was the best reliable method for localization than imaging modalities [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, from our experience, ectopic PGs in the thyroid, carotid sheath or mediastinum were difficult to detect during operation and the searching of neck prolonged the operative time. Preoperative mapping for parathyroid surgery is rational and recommended.\u003c/p\u003e \u003cp\u003eRecent studies have found that concurrent nodular goiter or thyroid cancer was not uncommon in SHP patients, and the prevalence of incidental nodular goiter and thyroid cancer were approximately 20\u0026ndash;30% and 6\u0026ndash;8%, respectively [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], both of which corresponded with our results. The prevalence of concurrent papillary carcinoma (PTC) was higher in SHP patients than in general population. Although most of those concomitant PTCs were microcarcinomas (\u0026gt;\u0026thinsp;70%), they may express more aggressive tumor features [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, it is necessary to perform a thorough examination to avoid missing the coexistence of malignancy.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLimitations of the study\u003c/h2\u003e \u003cp\u003eThe study has several limitations. First, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI SPECT/CT provided additional information for preoperative localization. Second, the judgement of US-missed PG was decided by endocrine surgeons who were not blinded. Third, two surgical failure cases with persistent HPT did not undergo imaging survey and reoperation until now. Finally, the study was a retrospective design with a small sample size. More prospective studies with larger groups are needed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings demonstrated that US localization was accurate in 90% of our patients. Awareness of the limitations of US is important for surgeons searching for hyperplastic PGs, especially those situated in ectopic positions and small sizes. US provided a useful guide for localization, and therefore, shortened the operation time.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCKD \u0026ndash; chronic kidney disease\u003c/p\u003e\n\u003cp\u003eESRD \u0026ndash; end-stage renal disease\u003c/p\u003e\n\u003cp\u003eFNA \u0026ndash; fine needle aspiration\u003c/p\u003e\n\u003cp\u003eHPT \u0026ndash; hyperparathyroidism \u003c/p\u003e\n\u003cp\u003eiPTH \u0026ndash; intact parathyroid hormone\u003c/p\u003e\n\u003cp\u003eMIBI \u0026ndash; Tc99m-Sestamibi scintigraphy\u003c/p\u003e\n\u003cp\u003ePCI \u0026ndash; percutaneous coronary intervention\u003c/p\u003e\n\u003cp\u003ePG \u0026ndash; parathyroid gland\u003c/p\u003e\n\u003cp\u003ePTC \u0026ndash; papillary thyroid carcinoma\u003c/p\u003e\n\u003cp\u003eSHPT \u0026ndash; secondary hyperparathyroidism\u003c/p\u003e\n\u003cp\u003eSPECT/CT \u0026ndash; single-photon-emission-computed tomography/computed tomography\u003c/p\u003e\n\u003cp\u003eUS \u0026ndash; ultrasound\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Science and Technology Council, Taiwan (111-2314-B-182A-158 -)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have declared that no conflicts of interests exist.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by Change Gung Medical Foundation Institutional Review Board (number: 202300239B0)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe need for informed consent from patients was waived because of the retrospective design of the study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, for\u0026nbsp;their\u0026nbsp;statistics work.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset supporting the conclusions of this article are included within the article and files. The dataset used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYCC, SEC, and SYC designed this project. SEC and YCC analyzed data and wrote the manuscript. FFC and YJW analyzed the data and modified this paper. YCC, SYC, and YHC recruited patients and revised the paper. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKumar R, Thompson JR. The regulation of parathyroid hormone secretion and synthesis. J Am Soc Nephrol. 2011;22(2). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1681/ASN.2010020186\u003c/span\u003e\u003cspan address=\"https://DOI.10.1681/ASN.2010020186\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 216\u0026thinsp;\u0026ndash;\u0026thinsp;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKetteler M, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. Kidney Int. 2017;92(1):26\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.kint.2017.04.006\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.kint.2017.04.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKomaba H, et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 2015;88(2):350\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1038/ki.2015.72\u003c/span\u003e\u003cspan address=\"https://DOI.10.1038/ki.2015.72\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApetrii M, et al. Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD) - A systematic review and meta-analysis. PLoS ONE. 2017;12(11):e0187025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1371/journal.pone.0187025\u003c/span\u003e\u003cspan address=\"https://DOI.10.1371/journal.pone.0187025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadorin C, et al. The surgical management of renal hyperparathyroidism. Eur Arch Otorhinolaryngol. 2012;269(6):1565\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1007/s00405-011-1833-2\u003c/span\u003e\u003cspan address=\"https://DOI.10.1007/s00405-011-1833-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteinl GK, Kuo JH. Surgical Management of Secondary Hyperparathyroidism. Kidney Int Rep. 2021;6(2):254\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.ekir.2020.11.023\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.ekir.2020.11.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Sageer EM, et al. Neck Exploration Versus Imaging Localization of Parathyroid in Secondary Hyperparathyroidism. Indian J Surg. 2018;81(5):457\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1007/s12262-018-1842-0\u003c/span\u003e\u003cspan address=\"https://DOI.10.1007/s12262-018-1842-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetranovic Ovcaricek P, et al. An essential practice summary of the new EANM guidelines for parathyroid imaging. Q J Nucl Med Mol Imaging. 2022;66(2):93\u0026ndash;103. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.23736/S1824-4785.22.03427-6\u003c/span\u003e\u003cspan address=\"https://DOI.10.23736/S1824-4785.22.03427-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReitz RJ 3, et al. Ectopic and supernumerary parathyroid glands in patients with refractory renal hyperparathyroidism. Surgery. 2021;169(3):513\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.surg.2020.08.007\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.surg.2020.08.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung JY. Parathyroid ultrasonography: the evolving role of the radiologist. Ultrasonography. 2015;34(4). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.14366/usg.14071\u003c/span\u003e\u003cspan address=\"https://DOI.10.14366/usg.14071\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 268\u0026thinsp;\u0026ndash;\u0026thinsp;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohammadi A, Moloudi F, Ghasemi-Rad M. Preoperative localization of parathyroid lesion: diagnostic usefulness of color doppler ultrasonography. Int J Clin Exp Med. 2012;5(1):80\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiramitsu T, et al. Pre-operative Localisation of the Parathyroid Glands in Secondary Hyperparathyroidism: A Retrospective Cohort Study. Sci Rep. 2019;9(1):14634. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1038/s41598-019-51265-y\u003c/span\u003e\u003cspan address=\"https://DOI.10.1038/s41598-019-51265-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang R, et al. Diagnostic performance of ultrasonography, dual-phase (99m)Tc-MIBI scintigraphy, early and delayed (99m)Tc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism. BMC Med Imaging. 2020;20(1):91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1186/s12880-020-00490-3\u003c/span\u003e\u003cspan address=\"https://DOI.10.1186/s12880-020-00490-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlkhalili E, et al. The utility of neck ultrasound and sestamibi scans in patients with secondary and tertiary hyperparathyroidism. World J Surg. 2015;39(3):701\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1007/s00268-014-2878-3\u003c/span\u003e\u003cspan address=\"https://DOI.10.1007/s00268-014-2878-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndrade JS, et al. 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. Braz J Otorhinolaryngol. 2014;80(1):29\u0026ndash;34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.5935/1808-8694.20140008\u003c/span\u003e\u003cspan address=\"https://DOI.10.5935/1808-8694.20140008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTominaga Y. Surgical treatment of secondary hyperparathyroidism due to chronic kidney disease. Ups J Med Sci. 2006;111(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.3109/2000-1967-047\u003c/span\u003e\u003cspan address=\"https://DOI.10.3109/2000-1967-047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 277\u0026thinsp;\u0026ndash;\u0026thinsp;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhitayakorn R, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006;191(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.amjsurg.2005.10.049\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.amjsurg.2005.10.049\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 418\u0026thinsp;\u0026ndash;\u0026thinsp;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChou YC, et al. Being elderly is not a contraindication of parathyroidectomy for renal hyperparathyroidism and chronic kidney disease-mineral and bone disorder. Asian J Surg. 2021;44(1):321\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.asjsur.2020.07.022\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.asjsur.2020.07.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerie S, et al. Usefulness of combination of high-resolution ultrasonography and dual-phase dual-isotope iodine 123/technetium Tc 99m sestamibi scintigraphy for the preoperative localization of hyperplastic parathyroid glands in renal hyperparathyroidism. Am J Kidney Dis. 2005;45(2):344\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1053/j.ajkd.2004.10.021\u003c/span\u003e\u003cspan address=\"https://DOI.10.1053/j.ajkd.2004.10.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaugen BR et al. 2015 \u003cem\u003eAmerican Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.\u003c/em\u003e Thyroid, 2016. 26(1): p. 1-133. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1089/thy.2015.0020\u003c/span\u003e\u003cspan address=\"https://DOI.10.1089/thy.2015.0020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerber E, et al. Factors contributing to negative parathyroid localization: an analysis of 1000 patients. Surgery. 2008;144(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1016/j.surg.2008.03.019\u003c/span\u003e\u003cspan address=\"https://DOI.10.1016/j.surg.2008.03.019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 74\u0026thinsp;\u0026ndash;\u0026thinsp;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkerstr\u0026ouml;m G, Malmaeus J, Bergstr\u0026ouml;m R. Surgical anatomy of human parathyroid glands. Surgery. 1984;95(1):14\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakatsuka K, et al. The fifth hyperfunctioning parathyroid gland in end-stage renal disease. Nephron. 1989;51(1):140\u0026ndash;2. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1159/000185277\u003c/span\u003e\u003cspan address=\"https://DOI.10.1159/000185277\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchneider R, et al. 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\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1007/s00268-011-1079-6\u003c/span\u003e\u003cspan address=\"https://DOI.10.1007/s00268-011-1079-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaterra D, et al. The prevalence and anatomy of parathyroid glands: a meta-analysis with implications for parathyroid surgery. Langenbecks Arch Surg. 2019;404(1):63\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1007/s00423-019-01751-8\u003c/span\u003e\u003cspan address=\"https://DOI.10.1007/s00423-019-01751-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePreda C, et al. Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics. BMC Surg. 2019;19(1):94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1186/s12893-019-0556-y\u003c/span\u003e\u003cspan address=\"https://DOI.10.1186/s12893-019-0556-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeong C, et al. Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study. Endocrinol Metab (Seoul). 2020;35(4):925\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.3803/EnM.2020.725\u003c/span\u003e\u003cspan address=\"https://DOI.10.3803/EnM.2020.725\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa J, et al. Coexistence of papillary thyroid carcinoma in secondary hyperparathyroidism. BMC Surg. 2021;21(1):335. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://DOI.org/10.1186/s12893-021-01330-z\u003c/span\u003e\u003cspan address=\"https://DOI.10.1186/s12893-021-01330-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ultrasonography, renal hyperparathyroidism, secondary hyperparathyroidism, localization","lastPublishedDoi":"10.21203/rs.3.rs-3970012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3970012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePreoperative localization plays an important role in secondary hyperparathyroidism (SHPT) surgery. The advantages of neck ultrasound (US) include high availability and low cost. However, the reported sensitivity of US is 54\u0026ndash;76%, and the reason for missed PG on US has been rarely addressed.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFifty-four patients who were diagnosed with renal SHPT from September 2020 to March 2022 were included in this retrospective study. Preoperative localization included surgeon-oriented US and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 212 parathyroid glands (PGs) were pathologically confirmed, resulting in success rate of 96.2% (52/54). Using echo, 193 (91.0%) PGs were accurately localized, while 19 (9.0%) glands were not identified, including those in ectopic positions (n\u0026thinsp;=\u0026thinsp;12, at thymus or intra-thyroid or others), of a small size (\u0026lt;\u0026thinsp;1 cm, n\u0026thinsp;=\u0026thinsp;6), or overlapping with an ipsilateral PG (n\u0026thinsp;=\u0026thinsp;1). US accurately detected four PGs in 36 (66.7%) patients, while SPECT/CT localized four glands in 19 (35.2%) patients. Although the number of US-detectable PGs was not associated with success rate, it showed significant negative correlation with surgical time (\u003cem\u003er\u003c/em\u003e\u003csub\u003es\u003c/sub\u003e=-0.459, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eUS detected four glands in 66% of SHPT patients with a sensitivity of 90% for localization. Ectopic position and small size were the most common reasons of failing to detect PG on US. Complete preoperative echo localization might shorten the operating time.\u003c/p\u003e","manuscriptTitle":"Addressing the challenges of missed parathyroid glands in ultrasonography for secondary hyperparathyroidism.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-22 19:30:55","doi":"10.21203/rs.3.rs-3970012/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ffb8cdb8-6d83-4aeb-b24e-0a14cfbf330d","owner":[],"postedDate":"February 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-19T09:36:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-22 19:30:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3970012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3970012","identity":"rs-3970012","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}