{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:32:17Z","timestamp":1792715537580,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>We sought to systematically evaluate diagnostic performance of four-dimensional computed tomography (4D-CT) in the localization of hyperfunctioning parathyroid glands (HPGs) in patients with primary hyperparathyroidism (pHPT). We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratios (DOR) of 4D-CT on a per-lesion level, as well as pooled sensitivity and positive predictive value (PPV) on a per-patient level with 95% confidence intervals (CIs). Additionally, we plotted summary receiver operating characteristic (SROC) curves and evaluated the areas under the curves (AUC). A total of 16 studies were included in the analysis. Their pooled sensitivity, specificity, PLR, NLR, and DOR of 4D-CT on per-lesion level were 75% (95%CI: 66\u201382%), 85% (95%CI: 50\u201397%), 4.9 (95%CI: 1.1\u201321.3), 0.30 (95%CI: 0.19\u20130.45), and 17 (95%CI: 3\u2013100), respectively, with an AUC of 81% (95%CI: 77\u201384%). We also observed heterogeneity in sensitivity (I2 = 79%) and specificity (I2 = 94.7%), and obtained a pooled sensitivity of 81% (95%CI: 70\u201390%) with heterogeneity of 81.9% (p &lt; 0.001) and PPV of 91% (95%CI: 82\u201398%) with heterogeneity of 80.8% (p &lt; 0.001), based on a per-patient level. Overall, 4D-CT showed moderate sensitivity and specificity for preoperative localization of HPG(s) in patients with pHPT. The diagnostic performance may improve with 4D-CT\u2019s promotion to first-line use on a lesion-based level, further research is needed to confirm the results.<\/jats:p>","DOI":"10.3390\/diagnostics11040664","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T21:49:06Z","timestamp":1617832146000},"page":"664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Diagnostic Role of Four-Dimensional Computed Tomography for Preoperative Parathyroid Localization in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-6741","authenticated-orcid":false,"given":"Lixin","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Radiology, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1001\/jamaoto.2018.1671","article-title":"Preoperative Imaging Techniques in Primary Hyperparathyroidism: A Review","volume":"144","author":"Bunch","year":"2018","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0140-6736(09)60507-9","article-title":"Hyperparathyroidism","volume":"374","author":"Fraser","year":"2009","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1210\/jc.2012-4022","article-title":"Incidence and prevalence of primary hyperparathyroidism in a racially mixed population","volume":"98","author":"Yeh","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1148\/rg.2020190190","article-title":"Parathyroid 4D CT: What the Surgeon Wants to Know","volume":"40","author":"Bunch","year":"2020","journal-title":"Radiographics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1001\/jamasurg.2016.2310","article-title":"The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism","volume":"151","author":"Wilhelm","year":"2016","journal-title":"JAMA Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1210\/jc.2014-1413","article-title":"Guidelines for the management of asymptomatic primary hyperparathyroidism: Summary statement from the Fourth International Workshop","volume":"99","author":"Bilezikian","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00198-016-3716-2","article-title":"Primary hyperparathyroidism: Review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus","volume":"28","author":"Khan","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1007\/s00268-004-7600-4","article-title":"Open minimally invasive parathyroid surgery","volume":"28","author":"Udelsman","year":"2004","journal-title":"World J. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.surg.2006.07.028","article-title":"Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography","volume":"140","author":"Rodgers","year":"2006","journal-title":"Surgery"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1148\/radiol.13122661","article-title":"How to perform parathyroid 4D CT: Tips and traps for technique and interpretation","volume":"270","author":"Hoang","year":"2014","journal-title":"Radiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1308\/rcsann.2019.0182","article-title":"Diagnostic value of four-dimensional computed tomography and four-dimensional magnetic resonance imaging in primary hyperparathyroidism when first-line imaging was inadequate","volume":"102","author":"Acar","year":"2020","journal-title":"Ann. R Coll. Surg. Engl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.amjsurg.2010.08.033","article-title":"Mild hypercalcemia: An indication to select 4-dimensional computed tomography scan for preoperative localization of parathyroid adenomas","volume":"201","author":"Carlin","year":"2011","journal-title":"Am. J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1148\/radiol.2019182122","article-title":"Diagnostic performance of 4D CT and sestamibi SPECT\/CT in localizing parathyroid adenomas in primary hyperparathyroidism","volume":"291","author":"Yeh","year":"2019","journal-title":"Radiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1245\/s10434-011-1870-5","article-title":"A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism","volume":"19","author":"Cheung","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/MNM.0000000000001331","article-title":"Comparing the diagnostic accuracy of 4D CT and 99mTc-MIBI SPECT\/CT for localizing hyperfunctioning parathyroid glands: A systematic review and meta-analysis","volume":"42","author":"Wan","year":"2021","journal-title":"Nucl. Med. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gotzsche, P.C., Ioannidis, J.P., Clarke, M., Devereaux, P.J., Kleijnen, J., and Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med., 6.","DOI":"10.2427\/5768"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0895-4356(03)00177-X","article-title":"The diagnostic odds ratio: A single indicator of test performance","volume":"56","author":"Glas","year":"2003","journal-title":"J. Clin. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1136\/bmj.309.6965.1351","article-title":"Why sources of heterogeneity in meta-analysis should be investigated","volume":"309","author":"Thompson","year":"1994","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jclinepi.2005.01.016","article-title":"The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed","volume":"58","author":"Deeks","year":"2005","journal-title":"J. Clin. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1007\/s00268-019-04910-6","article-title":"18F-Fluorocholine PET\/CT and Parathyroid 4D Computed Tomography for Primary Hyperparathyroidism: The Challenge of Reoperative Patients","volume":"43","author":"Amadou","year":"2019","journal-title":"World J. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/ans.14374","article-title":"A rural perspective on minimally invasive parathyroidectomy: Optimal preoperative imaging and patient outcomes","volume":"89","author":"Binks","year":"2018","journal-title":"ANZ J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3174\/ajnr.A2805","article-title":"Diagnostic accuracy of 4D-CT for parathyroid adenomas and hyperplasia","volume":"33","author":"Chazen","year":"2012","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.surg.2014.11.010","article-title":"The utility of 4-dimensional computed tomography for preoperative localization of primary hyperparathyroidism in patients not localized by sestamibi or ultrasonography","volume":"157","author":"Day","year":"2015","journal-title":"Surgery"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jss.2020.07.055","article-title":"Accuracy of 4-Dimensional Computed Tomography for Localization in Primary Hyperparathyroidism","volume":"257","author":"Eller","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jvir.2014.09.019","article-title":"Adenoma localization for recurrent or persistent primary hyperparathyroidism using dynamic four-dimensional CT and venous sampling","volume":"26","author":"Ginsburg","year":"2015","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1177\/0194599815599372","article-title":"Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT","volume":"153","author":"Hinson","year":"2015","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_27","first-page":"93","article-title":"A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism","volume":"41","author":"Krakauer","year":"2016","journal-title":"J. Med. Imaging Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102683","DOI":"10.1016\/j.amjoto.2020.102683","article-title":"4D-CT facilitates focused parathyroidectomy in patients with primary hyperparathyroidism by maintaining a high negative-predictive value for uninvolved quadrants","volume":"41","author":"Naqvi","year":"2020","journal-title":"Am. J. Otolaryngol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1007\/s00259-018-4147-4","article-title":"Additional value of integrated F-18-choline PET\/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile","volume":"46","author":"Piccardo","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pretet, V., Rotania, M., Helali, M., Ignat, M., Vix, M., and Imperiale, A. (2020). F-18-Fluorocholine PET and Multiphase CT Integrated in Dual Modality PET\/4D-CT for Preoperative Evaluation of Primary Hyperparathyroidism. J. Clin. Med., 9.","DOI":"10.3390\/jcm9062005"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1002\/lary.26201","article-title":"Four-dimensional computed tomography scan utility in parathyroidectomy for primary hyperparathyroidism with low baseline intact parathyroid hormone","volume":"127","author":"Rameau","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1177\/0194599814562195","article-title":"Comparison of 4D CT, Ultrasonography, and Tc-99m Sestamibi SPECT\/CT in Localizing Single-Gland Primary Hyperparathyroidism","volume":"152","author":"Suh","year":"2015","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/MNM.0000000000000262","article-title":"Parathyroid adenoma localization with 99mTc-sestamibi SPECT\/CT: A meta-analysis","volume":"36","author":"Wong","year":"2015","journal-title":"Nucl. Med. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mortenson, M.M., Evans, D.B., Lee, J.E., Hunter, G.J., Shellingerhout, D., Vu, T., Edeiken, B.S., Feng, L., and Perrier, N.D. (2008). Parathyroid exploration in the reoperative neck: Improved preoperative localization with 4D-computed tomography. J. Am. Coll. Surg., 206.","DOI":"10.1016\/j.jamcollsurg.2007.12.044"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1245\/s10434-018-6367-z","article-title":"4D-CT is Superior to Ultrasound and Sestamibi for Localizing Recurrent Parathyroid Disease","volume":"25","author":"Hamidi","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/j.1445-2197.2006.03931.x","article-title":"Reoperative parathyroid surgery: The importance of ectopic location and multigland disease","volume":"76","author":"Gough","year":"2006","journal-title":"ANZ J. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/00000658-199609000-00007","article-title":"A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma","volume":"224","author":"Jaskowiak","year":"1996","journal-title":"Ann. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00423-010-0724-0","article-title":"Results of surgery for sporadic primary hyperparathyroidism in patients with preoperatively negative sestamibi scintigraphy and ultrasound","volume":"396","author":"Bergenfelz","year":"2011","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1245\/s10434-017-6115-9","article-title":"Four-Dimensional Computed Tomography: Clinical Impact for Patients with Primary Hyperparathyroidism","volume":"25","author":"Tian","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1097\/RCT.0000000000000442","article-title":"Dual-Energy CT Characteristics of Parathyroid Adenomas on 25-and 55-Second 4D-CT Acquisitions: Preliminary Experience","volume":"40","author":"Forghani","year":"2016","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.surg.2010.09.002","article-title":"Accuracy of 4-dimensional computed tomography in poorly localized patients with primary hyperparathyroidism","volume":"148","author":"Lubitz","year":"2010","journal-title":"Surgery"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.3174\/ajnr.A3978","article-title":"Dynamic CT for parathyroid disease: Are multiple phases necessary?","volume":"35","author":"Raghavan","year":"2016","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ijsu.2015.01.005","article-title":"Two-phase (low-dose) computed tomography is as effective as 4D-CT for identifying enlarged parathyroid glands","volume":"14","author":"Campbell","year":"2015","journal-title":"Int. J. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3801902","DOI":"10.1155\/2020\/3801902","article-title":"Shear Wave Elastography versus Strain Elastography in Diagnosing Parathyroid Adenomas","volume":"2020","author":"Cotoi","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.ejrad.2016.06.009","article-title":"Shear wave elastography and parathyroid adenoma: A new tool for diagnosing parathyroid adenomas","volume":"85","author":"Azizi","year":"2016","journal-title":"Eur. J. Radiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s40618-017-0694-y","article-title":"Can ARFI elastography be used to differentiate parathyroid from thyroid lesions?","volume":"41","author":"Chandramohan","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2967\/jnumed.119.229914","article-title":"(18)F-Fluorocholine PET\/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands","volume":"61","author":"Cuderman","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1210\/jc.2014-1267","article-title":"11C-methionine PET\/CT imaging of 99mTc-MIBI-SPECT\/CT-negative patients with primary hyperparathyroidism and previous neck surgery","volume":"99","author":"Mayerhoefer","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00259-018-4123-z","article-title":"Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: A systematic review and meta-analysis","volume":"46","author":"Treglia","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s12020-012-9746-4","article-title":"Diagnostic performance of positron emission tomography using (1)(1)C-methionine in patients with suspected parathyroid adenoma: A meta-analysis","volume":"43","author":"Caldarella","year":"2013","journal-title":"Endocrine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1007\/s00330-018-5437-8","article-title":"Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: Comparison with ultrasound and 99mTc-sestamibi scans","volume":"28","author":"Argiro","year":"2018","journal-title":"Eur. 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