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Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis

  • Giorgio TregliaEmail author
  • Arnoldo Piccardo
  • Alessio Imperiale
  • Klaus Strobel
  • Philipp A. Kaufmann
  • John O. Prior
  • Luca Giovanella
Original Article

Abstract

Purpose

Hyperparathyroidism (HPT) is a common endocrine disorder caused by hyperfunctioning parathyroid glands (HP). The correct detection and localization of HP is challenging but crucial, as it may guide surgical treatment, particularly in patients with primary HPT. There is a growing body of data regarding the role of radiolabelled choline positron emission tomography (PET) in this setting. Therefore, we performed a systematic review and meta-analysis of the diagnostic performance of this method in detecting HP in patients with HPT.

Methods

This systematic review and meta-analysis was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE and Cochrane Library databases for studies published through May 2018 was performed using the following search algorithm: (a) “choline” or “fluorocholine” or “F-choline” or “C-choline” or “FCH” or “CH” or “FECH” or “FMCH” and (b) “PET” or “positron emission tomography” and (c) “parathyroid” or “hyperparathyroidism”. The diagnostic performance of radiolabelled choline PET was expressed as sensitivity and positive predictive value (PPV) on a per-patient and per-lesion basis and as detection rate (DR) on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI) obtained using a random-effects model.

Results

Eighteen studies were included in the systematic review. Fourteen articles (517 patients) were selected for the meta-analysis. The meta-analysis provided the following results on a per-patient analysis analysis: sensitivity 95% (95% CI: 92–97%), PPV 97% (95% CI: 95–98%) and DR 91% (95% CI: 87–94%). On a per-lesion analysis, pooled sensitivity and PPV were 92% (95% CI: 88–96) and 92% (95% CI: 89–95%), respectively. No significant heterogeneity was found among the selected studies.

Conclusions

Radiolabelled choline PET demonstrated excellent diagnostic performance in detecting HP in patients with HPT. Large multicentre studies and cost-effectiveness analyses are needed to better define the role of this imaging method in this setting.

Keywords

PET Positron emission tomography Choline Hyperparathyroidism Parathyroid 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no financial or non-financial competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168–78.CrossRefPubMedGoogle Scholar
  2. 2.
    Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Portillo MR, Rodríguez-Ortiz ME. Secondary hyperparthyroidism: pathogenesis, diagnosis, preventive and therapeutic strategies. Rev Endocr Metab Disord. 2017;18(1):79–95.CrossRefPubMedGoogle Scholar
  4. 4.
    Cocchiara G, Fazzotta S, Palumbo VD, Damiano G, Cajozzo M, Maione C, et al. The medical and surgical treatment in secondary and tertiary hyperparathyroidism. Review. Clin Ter. 2017;168(2):e158–67.PubMedGoogle Scholar
  5. 5.
    Udelsman R, Åkerström G, Biagini C, Duh QY, Miccoli P, Niederle B, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab. 2014;99:3595–606.CrossRefPubMedGoogle Scholar
  6. 6.
    Stephen AE, Mannstadt M, Hodin RA. Indications for surgical management of hyperparathyroidism: a review. JAMA Surg. 2017;152(9):878–82.CrossRefPubMedGoogle Scholar
  7. 7.
    Treglia G, Trimboli P, Huellner M, Giovanella L. Imaging in primary hyperparathyroidism: focus on the evidence-based diagnostic performance of different methods. Minerva Endocrinol. 2018;43(2):133–43.PubMedGoogle Scholar
  8. 8.
    Liddy S, Worsley D, Torreggiani W, Feeney J. Preoperative imaging in primary hyperparathyroidism: literature review and recommendations. Can Assoc Radiol J. 2017;68(1):47–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Kuzminski SJ, Sosa JA, Hoang JK. Update in parathyroid imaging. Magn Reson Imaging Clin N Am. 2018;26(1):151–66.CrossRefPubMedGoogle Scholar
  10. 10.
    Kluijfhout WP, Pasternak JD, Drake FT, Beninato T, Gosnell JE, Shen WT, et al. Use of PET tracers for parathyroid localization: a systematic review and meta-analysis. Langenbeck’s Arch Surg. 2016;401(7):925–35.CrossRefGoogle Scholar
  11. 11.
    Caldarella C, Treglia G, Isgrò MA, Giordano A. Diagnostic performance of positron emission tomography using 11C-methionine in patients with suspected parathyroid adenoma: a meta-analysis. Endocrine. 2013;43(1):78–83.CrossRefPubMedGoogle Scholar
  12. 12.
    Imperiale A, Taïeb D, Hindié E. (18)F-Fluorocholine PET/CT as a second line nuclear imaging technique before surgery for primary hyperparathyroidism. Eur J Nucl Med Mol Imaging. 2018;45(4):654–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Prior JO. New scintigraphic methods for parathyroid imaging. Ann Endocrinol. 2015;76(2):145–7.CrossRefGoogle Scholar
  14. 14.
    Treglia G, Giovannini E, Di Franco D, Calcagni ML, Rufini V, Picchio M, et al. The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review. Ann Nucl Med. 2012;26(6):451–61.CrossRefPubMedGoogle Scholar
  15. 15.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Sadeghi R, Treglia G. Systematic reviews and meta-analyses of diagnostic studies: a practical guideline. Clin Transl Imaging. 2017;5:83–7.CrossRefGoogle Scholar
  17. 17.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. Bossuyt PM; QUADAS-2 group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36.CrossRefPubMedGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25(20):3443–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Morland D, Richard C, Godard F, Deguelte S, Delemer B. Temporal uptake patterns of 18F-Fluorocholine among hyperfunctioning parathyroid glands. Clin Nucl Med. 2018;43(7):504–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Alharbi AA, Alshehri FM, Albatly AA, Sah BR, Schmid C, Huber GF, et al. [(18)F]Fluorocholine uptake of parathyroid adenoma is correlated with parathyroid hormone level. Mol Imaging Biol. 2018;  https://doi.org/10.1007/s11307-018-1179-x.
  22. 22.
    Grimaldi S, Young J, Kamenicky P, Hartl D, Terroir M, Leboulleux S, et al. Challenging pre-surgical localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism: the added value of (18)F-Fluorocholine PET/CT. Eur J Nucl Med Mol Imaging. 2018;  https://doi.org/10.1007/s00259-018-4018-z.
  23. 23.
    Beheshti M, Hehenwarter L, Paymani Z, Rendl G, Imamovic L, Rettenbacher R, et al. (18)F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with (99m)Tc-MIBI or (99m)Tc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients. Eur J Nucl Med Mol Imaging. 2018;  https://doi.org/10.1007/s00259-018-3980-9.
  24. 24.
    Fischli S, Suter-Widmer I, Nguyen BT, Müller W, Metzger J, Strobel K, et al. The significance of 18F-Fluorocholine-PET/CT as localizing imaging technique in patients with primary hyperparathyroidism and negative conventional imaging. Front Endocrinol. 2018;8:380.  https://doi.org/10.3389/fendo.2017.00380.CrossRefGoogle Scholar
  25. 25.
    Huber GF, Hüllner M, Schmid C, Brunner A, Sah B, Vetter D, et al. Benefit of (18)F-fluorocholine PET imaging in parathyroid surgery. Eur Radiol. 2018;28(6):2700–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Parvinian A, Martin-Macintosh EL, Goenka AH, Durski JM, Mullan BP, Kemp BJ, et al. (11)C-choline PET/CT for detection and localization of parathyroid adenomas. AJR Am J Roentgenol. 2018;210(2):418–22.CrossRefPubMedGoogle Scholar
  27. 27.
    Quak E, Blanchard D, Houdu B, Le Roux Y, Ciappuccini R, Lireux B, et al. F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study. Eur J Nucl Med Mol Imaging. 2018;45(4):658–66.CrossRefPubMedGoogle Scholar
  28. 28.
    Rep S, Hocevar M, Vaupotic J, Zdesar U, Zaletel K, Lezaic L. (18)F-choline PET/CT for parathyroid scintigraphy: significantly lower radiation exposure of patients in comparison to conventional nuclear medicine imaging approaches. J Radiol Prot. 2018;38(1):343–56.CrossRefPubMedGoogle Scholar
  29. 29.
    Hocevar M, Lezaic L, Rep S, Zaletel K, Kocjan T, Sever MJ, et al. Focused parathyroidectomy without intraoperative parathormone testing is safe after pre-operative localization with (18)F-Fluorocholine PET/CT. Eur J Surg Oncol. 2017;43(1):133–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Kluijfhout WP, Pasternak JD, Gosnell JE, Shen WT, Duh QY, Vriens MR, et al. (18)F Fluorocholine PET/MR imaging in patients with primary hyperparathyroidism and inconclusive conventional imaging: a prospective pilot study. Radiology. 2017;284(2):460–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Taywade SK, Damle NA, Behera A, Devasenathipathy K, Bal C, Tripathi M, et al. Comparison of 18F-Fluorocholine positron emission tomography/computed tomography and four-dimensional computed tomography in the preoperative localization of parathyroid adenomas-initial results. Indian J Endocrinol Metab. 2017;21(3):399–403.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Thanseer N, Bhadada SK, Sood A, Mittal BR, Behera A, Gorla AKR, et al. Comparative effectiveness of ultrasonography, 99mTc-Sestamibi, and 18F-Fluorocholine PET/CT in detecting parathyroid adenomas in patients with primary hyperparathyroidism. Clin Nucl Med. 2017;42(12):e491–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Kluijfhout WP, Vorselaars WM, van den Berk SA, Vriens MR, Borel Rinkes IH, Valk GD, et al. Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging: a multicenter study from the Netherlands. Nucl Med Commun. 2016;37(12):1246–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Kluijfhout WP, Vorselaars WM, Vriens MR, Borel Rinkes IH, Valk GD, de Keizer B. Enabling minimal invasive parathyroidectomy for patients with primary hyperparathyroidism using Tc-99m-sestamibi SPECT-CT, ultrasound and first results of (18)F-fluorocholine PET-CT. Eur J Radiol. 2015;84(9):1745–51.CrossRefPubMedGoogle Scholar
  35. 35.
    Michaud L, Balogova S, Burgess A, Ohnona J, Huchet V, Kerrou K, et al. A pilot comparison of 18F-fluorocholine PET/CT, ultrasonography and 123I/99mTc-sestaMIBI dual-phase dual-isotope scintigraphy in the preoperative localization of Hyperfunctioning parathyroid glands in primary or secondary hyperparathyroidism: influence of thyroid anomalies. Medicine (Baltimore). 2015;94(41):e1701.CrossRefGoogle Scholar
  36. 36.
    Rep S, Lezaic L, Kocjan T, Pfeifer M, Sever MJ, Simoncic U, et al. Optimal scan time for evaluation of parathyroid adenoma with [(18)F]-fluorocholine PET/CT. Radiol Oncol. 2015;49(4):327–33.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lezaic L, Rep S, Sever MJ, Kocjan T, Hocevar M, Fettich J. 18F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study. Eur J Nucl Med Mol Imaging. 2014;41(11):2083–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Michaud L, Burgess A, Huchet V, Lefèvre M, Tassart M, Ohnona J, et al. Is 18F-fluorocholine-positron emission tomography/computerized tomography a new imaging tool for detecting hyperfunctioning parathyroid glands in primary or secondary hyperparathyroidism? J Clin Endocrinol Metab. 2014;99(12):4531–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Orevi M, Freedman N, Mishani E, Bocher M, Jacobson O, Krausz Y. Localization of parathyroid adenoma by 11C-choline PET/CT: preliminary results. Clin Nucl Med. 2014;39(12):1033–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Treglia G, Sadeghi R, Schalin-Jäntti C, Caldarella C, Ceriani L, Giovanella L, et al. Detection rate of (99m) Tc-MIBI single photon emission computed tomography (SPECT)/CT in preoperative planning for patients with primary hyperparathyroidism: a meta-analysis. Head Neck. 2016;38(Suppl 1):E2159–72.CrossRefPubMedGoogle Scholar
  41. 41.
    Kluijfhout WP, Pasternak JD, Beninato T, Drake FT, Gosnell JE, Shen WT, et al. Diagnostic performance of computed tomography for parathyroid adenoma localization; a systematic review and meta-analysis. Eur J Radiol. 2017;88:117–28.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinic of Nuclear Medicine and PET/CT Center, Ente Ospedaliero CantonaleOncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  2. 2.Health Technology Assessment UnitEnte Ospedaliero CantonaleBellinzonaSwitzerland
  3. 3.Clinical Trial UnitEnte Ospedaliero CantonaleBellinzonaSwitzerland
  4. 4.Department of Nuclear Medicine and Molecular ImagingLausanne University HospitalLausanneSwitzerland
  5. 5.Department of Biophysics and Nuclear MedicineHôpital de Hautepierre-Hôpitaux Universitaires de StrasbourgStrasbourgFrance
  6. 6.Faculty of Medicine, ICubeUniversity of Strasbourg/CNRS (UMR 7357) and FMTSStrasbourgFrance
  7. 7.Department of Radiology and Nuclear MedicineLucerne Cantonal HospitalLucerneSwitzerland
  8. 8.Department of Nuclear MedicineUniversity Hospital ZurichZurichSwitzerland

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