Scintigraphic techniques in primary hyperparathyroidism: from pre-operative localisation to intra-operative imaging

  • Domenico Rubello
  • Milton D. Gross
  • Giuliano Mariani
  • Adil AL-Nahhas
Occasional survey



Primary hyperparathyroidism (PHPT) is an increasingly diagnosed disease worldwide. In most cases, PHPT is related to the presence of a solitary parathyroid adenoma (PA). Fifty percent or more of newly diagnosed PHPT patients are asymptomatic, and there is debate among endocrinologists and endocrine surgeons about whether or not such patients should be treated.


Usually, in a PHPT patient with a solitary PA that is well localised pre-operatively, a parathyroidectomy with limited or minimally invasive neck exploration is offered. The diffusion of minimally invasive neck exploration procedures is a consequence of the significant improvement in the accuracy of pre-operative imaging (mainly scintigraphic) techniques; these techniques have changed the surgical strategy to PHPT, from the wide traditional bilateral neck exploration to limited neck exploration.


The present review considers developments during the past 10–15 years with regard to both the accuracy of pre-operative localising imaging techniques and intra-operative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary PA.


Primary hyperparathyroidism 99mTc-MIBI Minimally invasive parathyroidectomy Radio-guided surgery Gamma probe 


  1. 1.
    Heath H 3rd, Hodgson SF, Kennedy MA. Primary hyperparathyroidism. Incidence, morbidity, and potential economic impact in a community. N Engl J Med 1980;302:189–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Kaplan EL, Yashiro T, Salti G. Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease. Ann Surg 1992;215:301–17.CrossRefGoogle Scholar
  3. 3.
    Sofferman RA, Nathan MH, Fairbank JT, Foster RS Jr, Krag DN. Preoperative technetium 99m sestamibi imaging. Paving the way to minimal-access parathyroid surgery. Arch Otolaryngol Head Neck Surg 1996;122:369–74.PubMedGoogle Scholar
  4. 4.
    Norman J, Cheda H. Minimally invasive radioguided parathyroidectomy facilitated by intraoperative nuclear mapping. Surgery 1997;122:998–1004.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubello D, Pelizzo MR, Casara D. Nuclear medicine and minimally invasive surgery of parathyroid adenomas: a fair marriage [editorial]. Eur J Nucl Med Mol Imaging 2003;30:189–92.PubMedCrossRefGoogle Scholar
  6. 6.
    Sackett WR, Barraclough B, Reeve TS, Delbridge LW. Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy. Arch Surg 2002;137:1055–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Irvin GL 3rd. American Association of Endocrine Surgeons. Presidential address: chasin’ hormones. Surgery 1999;126:993–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Irvin GL 3rd, Carneiro DM. Rapid parathyroid hormone assay guided exploration. Operative Techniques Gen Surg 1999;1:18–27.CrossRefGoogle Scholar
  9. 9.
    Lloyd MN, Lees WR, Milroy EJ. Pre-operative localisation in primary hyperparathyroidism. Clin Radiol 1990; 41:239–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Ahuja AT, Wong KT, Ching AS, Fung MK, Lau JYW, Yuen EHY, et al. Imaging for primary hyperparathyroidism—what beginners should know. Clin Radiol 2004;59:967–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Miller DL, Doppman JL, Krudy AG, Shawker TH, Norton JA, Vucich JJ, et al. Localisation of parathyroid adenomas in patients who have undergone surgery. Radiology 1987;162:133–7.PubMedGoogle Scholar
  12. 12.
    Casara D, Rubello D, Pelizzo MR, Shapiro B. Role of preoperative imaging with 99mTc/MIBI scintigraphy combined with neck ultrasound, and of intraoperative 99mTc-sestamibi gamma probe technique in planning unilateral and minimally invasive surgery in primary hyperparathyroidism. Eur J Nucl Med 2001;28:1351–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Uden P, Aspelin P, Berglund J. Preoperative localization in unilateral parathyroid surgery. A cost-benefit study on ultrasound, computed tomography and scintigraphy. Acta Chir Scand 1990;156:29–35.PubMedGoogle Scholar
  14. 14.
    De Feo ML, Colagrande S, Biagini C, Tonarelli A, Bisi G, Vaggelli L, et al. Parathyroid glands: combination of 99mTc-MIBI scintigraphy and US for demonstration of parathyroid glands and nodules. Radiology 2000;214:393–402.PubMedGoogle Scholar
  15. 15.
    Casara D, Rubello D, Pelizzo MR, Shapiro B. Clinical role of 99mTcO4/MIBI scan, ultrasound and intra-operative gamma probe in the performance of unilateral and minimally invasive surgery in primary hyperparathyroidism. Eur J Nucl Med 2001;28:1351–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Eisenberg H, Pallotta J, Sacks B, Brickman AS. Parathyroid localisation, three dimensional modelling and percutaneous ablation techniques. Endocrin Metab Clinics North Am 1989;18:659–700.Google Scholar
  17. 17.
    Mitchell BK, Merrell RC, Kinder BK. Localization studies in patients with hyperparathyroidism. Surg Clin North Am 1995;75:483–98.PubMedGoogle Scholar
  18. 18.
    Koong HN, Choong LH, Soo KC. The role of preoperative localisation techniques in surgery for hyperparathyroidism. Ann Acad Med Singapore 1998;27:192–5.PubMedGoogle Scholar
  19. 19.
    Weber AL, Randolph G, Aksoy FG. The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. Radiol Clin North Am 2000;38:1105–29.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee VS, Spritzer CE. MR imaging of abnormal parathyroid glands. Am J Roentgenol 1998;170:1097–103.Google Scholar
  21. 21.
    Hishibashi M, Nishida H, Hiromatsu Y, Kojima K, Tabuchi E, Hayabuchi N. Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound, and MRI for localization of abnormal parathyroid glands. J Nucl Med 1988;39:320–4.Google Scholar
  22. 22.
    Fayet P, Hoeffel C, Fulla Y, Legmann P, Hazebroucq V, Luton JP, et al. Techetium-99m-sestamibi, magnetic resonance imaging and venous blood sampling in persistent and recurrent hyperparathyroidism. Br J Radiol 1997;70:459–64.PubMedGoogle Scholar
  23. 23.
    Gotway MB, Reddy GP, Webb WR, Morita ET, Clark OH, Higgins CB. Comparison between MR imaging and 99mTc-MIBI scintigraphy in the evaluation of recurrent or persistent hyperparathyroidism. Radiology 2001;218:783–90.PubMedGoogle Scholar
  24. 24.
    Seehofer D, Steinmuller T, Rayes N, Podrabsky P, Riethmuller J, Klupp J, et al. Parathyroid hormone venous sampling before reoperative surgery in renal hyperparathyroidism: comparison with noninvasive localization procedures and review of the literature. Arch Surg 2004;139:1331–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Waldorf JC, van Heerden JA, Gorman CA, Grant CS, Wahner HW. [75Se]Selenomethionine scanning for parathyroid localization should be abandoned. Mayo Clin Proc 1984;59:534–7.PubMedGoogle Scholar
  26. 26.
    Samanta A, Wilson B, Iqbal J, Burden AC, Walls J, Cosgriff P. A clinical audit of thallium-technetium subtraction parathyroid scans. Postgrad Med J 1990;66:441–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Coakley AJ, Kettle AG, Wells CP, O’Doherty MJ, Collings REC. 99mTc-sestamibi—a new agent for parathyroid imaging. Nucl Med Commun 1989;10:791–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Hetrakul N, Civelek AC, Stag CA, Udelsman R. In vitro accumulation of technetium-99m sestamibi in human parathyroid mitochondria. Surgery 2001;130:1011–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Bhatnagar A, Vezza PR, Bryan JA, Atkins FB, Ziessman HA. Technetium-99m-sestamibi parathyroid scintigraphy: effect of P-glycoprotein, histology and tumor size on detectability. J Nucl Med 1998;39:1617–20.PubMedGoogle Scholar
  30. 30.
    Chudzinski W, Niderla J, Lasiecka Z, Wilczynski G, Gornicka B, Wasiutynshi A, et al. P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism. Int J Mol Med 2005;16:215–9.PubMedGoogle Scholar
  31. 31.
    Grzela T, Chudzinski W, Lazarczyk M, Niderla J, Dziunycz P, Milewski L, et al. Persisted/recurrent hyperparathyroidism associated with development of multi-drug resistance phenotype and proliferation of parathyroid transplants. Int J Mol Med 2004;14:559–99.Google Scholar
  32. 32.
    Grzela T, Chudzinski W, Lasiecka Z, Niderla J, Wilczynski G, Gornicka B, et al. The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism. Int J Mol Med 2006;17:779–83.PubMedGoogle Scholar
  33. 33.
    Taillefer R, Boucher Y, Potvin C, Lambert R. Detection and localization of parathyroid adenomas in patients with hyperparathyroidism using a single radionuclide imaging procedure with technetium-99m-sestamibi (double phase study). J Nucl Med 1992;33:1801–7.PubMedGoogle Scholar
  34. 34.
    Casara D, Rubello D, Piotto A, Pelizzo MR. 99mTc–MIBI radio–guided minimally invasive parathyroid surgery planned on the basis of a preoperative combined 99mTc-pertechnetate/99mTc–MIBI and ultrasound imaging protocol. Eur J Nucl Med 2000;27:1300–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Perrier ND, Ituarte PHG, Morita E, Hamill T, Gielow R, Duh QY, et al. Parathyroid surgery: separating promise from reality. J Clin Endocrinol Metab 2002;87:1024–8, discussion 1028–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Bénard F, Lefebvre B, Beuvon F, Langlois MF, Bisson G. Rapid wash-out of technetium-99m-MIBI from a large parathyroid adenoma. J Nucl Med 1995;36:241–3.PubMedGoogle Scholar
  37. 37.
    Geatti O, Shapiro B, Orsolon P, Proto G, Guerra UP, Antonucci F, et al. Localization of parathyroid enlargement: experience with technetium 99m methoxyisobutylisonitrile and thallium-201 scintigraphy, ultrasound and computed tomography. Eur J Nucl Med 1994;21:17–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Rubello D, Saladini G, Casara D, Borsato N, Toniato A, Piotto A, et al. Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction scintigraphy. A fast and effective technique. Clin Nucl Med 2000;25:527–31.PubMedCrossRefGoogle Scholar
  39. 39.
    Sfakianakis GN, Irvin GL III, Foss J, Mallin W, Georgiou M, Deriso GT, et al. Efficient parathyroidectomy guided by SPECT-MIBI and hormonal measurements. J Nucl Med 1996;37:798–804.PubMedGoogle Scholar
  40. 40.
    Hindie E, Melliere D, Jeanguillame C, Perlemuter L, Chehade F, Galle P. Parathyroid imaging using simultaneous double window recording of technetium-99m-sestamibi and iodine-123. J Nucl Med 1998;39:1100–5.PubMedGoogle Scholar
  41. 41.
    Moka D, Eschner W, Voth E, Dietlein M, Larena-Avellaneda A, Schicha H. Iterative reconstruction: an improvement of technetium-99m-MIBI SPECT for the detection of parathyroid adenoma? Eur J Nucl Med 2000;27:485–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Rubello D, Casara D, Giannini S, Piotto A, De Carlo E, Muzzio PC, et al. Importance of radio-guided minimally invasive parathyroidectomy using hand-held gamma probe and low 99mTc-MIBI dose: technical considerations and long-term clinical results. Q J Nucl Med 2003;47:224–32.Google Scholar
  43. 43.
    Billotey C, Sarfati E, Aurengo A, Duet M, Mundler O, Toubert ME, et al. Advantages of SPECT in technetium-99m-sestamibi parathyroid scintigraphy. J Nucl Med 1996;37:1773–8.PubMedGoogle Scholar
  44. 44.
    Carty SE, Worsey MJ, Virji MA, Brown ML, Watson CG. Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay. Surgery 1997;122:1107–16.PubMedCrossRefGoogle Scholar
  45. 45.
    Gallowitsch JH, Mikosch P, Kresnik E, Gomez I, Lind P. Technetium-99m-tetrofosmin parathyroid imaging: results with double-phase study and SPECT in primary and secondary hyperparathyroidism. Invest Radiol 1997;32:459–65.PubMedCrossRefGoogle Scholar
  46. 46.
    Neumann DR, Esselstyn CB Jr, Go RT, Wong CO, Rice TW, Obuchowsky NA. Comparison of double-phase 99mTc-sestamibi with 123I-99mTc-sestamibi subtraction SPECT in hyperparathyroidism. Am J Roentgenol 1997;169:1671–4.Google Scholar
  47. 47.
    Francis IS, Loney EL, Buscombe JR, Thakrar DS, Berger L, Hilson AJW. Technetium-99m-sestamibi dual-phase SPECT imaging: concordance with ultrasound. Nucl Med Commun 1999;20:487–8.CrossRefGoogle Scholar
  48. 48.
    O’Doherty MJ, Kettle AG, Wells P, Collins REC, Coakley AJ. Parathyroid imaging with technetium-99m-sestamibi: preoperative localization and tissue uptake studies. J Nucl Med 1992;33:313–8.PubMedGoogle Scholar
  49. 49.
    Spanu A, Falchi A, Manca A, Marongiu P, Cossu A, Pisu N, et al. The usefulness of neck pinhole SPECT as a complementary tool to planar scintigraphy in primary and secondary hyperparathyroidism. J Nucl Med 2004;45:40–8.PubMedGoogle Scholar
  50. 50.
    Gayed IW, Kim EE, Broussard WF, Evans D, Lee J, Broemeling LD, et al. The value of 99mTc-sestamibi SPECT/CT over conventional SPECT in the evaluation of parathyroid adenomas or hyperplasia. J Nucl Med 2005;46:248–52.PubMedGoogle Scholar
  51. 51.
    Denham DW, Norman J. Cost-effectiveness of preoperative sestamibi scan for primary hyperparathyroidism is dependent solely upon the surgeons choice of operative procedure. J Am Coll Surg 1998;186:293–304.PubMedCrossRefGoogle Scholar
  52. 52.
    George EF, Komisar A, Scharf SC, Ferracci A, Blaugrund S. Diagnostic value of the preoperative sestamibi scan in intraoperative localisation of parathyroid adenomas: a case study. Laryngoscope 1998;108:627–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Chen H, Sokoll LJ, Udelsman R. Outpatient minimally invasive parathyroidectomy: a combination of sestamibi-SPECT localisation, cervical block anaesthesia, and intraoperative parathyroid hormone assay. Surgery 1999;126:1016–21.PubMedCrossRefGoogle Scholar
  54. 54.
    Kumar A, Cozens NJA, Nash JR. Sestamibi scan-directed unilateral neck exploration for primary hyperparathyroidism due to a solitary adenoma. Eur J Surg Oncol 2000;26:785–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Froberg AC, Valkema R, Bonjer HJ, Krenning EP. 99mTc-tetrofosmin or 99mTc-sestamibi for double-phase parathyroid scintigraphy? Eur J Nucl Med Mol Imaging 2003;30:193–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Gallowitsch HJ, Mikosch P, Kresnik E, Unterweger O, Lind P. Comparison between 99mTc-tetrofosmin/pertechnetate subtraction scintigraphy and 99mTc-tetrofosmin SPECT for preoperative localization of parathyroid adenoma in an endemic goiter area. Invest Radiol 2000;35:453–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Neumann DR, Esselstyn CB, MacIntyre WJ, Go RT, Obuchowski NA, Chen EQ, et al. Comparison of FDG-PET and sestamibi SPECT in primary hyperparathyroidism. J Nucl Med 1996;37:1809–15.PubMedGoogle Scholar
  58. 58.
    Melon P, Luxen A, Hamoir E, Meurisse M. Fluorine-18-fluorodeoxyglucose positron emission tomography for preoperative parathyroid imaging in primary hyperparathyroidism. Eur J Nucl Med 1995;22:556–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Sundin A, Johansson C, Hellman P, Bergstrom M, Ahlstrom H, Jacobson GB, et al. PET and parathyroid L-[carbon-11]methionine accumulation in hyperparathyroidism. J Nucl Med 1996;37:1766–70.PubMedGoogle Scholar
  60. 60.
    Beggs A, Hain SF. Localization of parathyroid adenomas using 11C-methionine positron emission tomography. Nucl Med Commun 2005:26:133–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Norman JG. Minimally invasive radioguided parathyroidectomy: an endocrine surgeon’s perspective. J Nucl Med 1998;39:15N–24N.PubMedGoogle Scholar
  62. 62.
    Casara D, Rubello D, Cauzzo C, Pelizzo MR. 99mTc-MIBI radio-guided minimally invasive parathyroidectomy: experience with patients with normal thyroids and nodular goiters. Thyroid 2002;12:53–61.PubMedCrossRefGoogle Scholar
  63. 63.
    Rubello D, Casara D, Pelizzo MR. Symposium on parathyroid localization. Optimization of peroperative procedures. Nucl Med Commun 2003;24:133–40.PubMedCrossRefGoogle Scholar
  64. 64.
    Flynn MB, Bumpous JM, Schill K, McMasters KM. Minimally invasive radioguided parathyroidectomy. J Am Coll Surg 2000;191:24–31.PubMedCrossRefGoogle Scholar
  65. 65.
    Goldstein RE, Blevins L, Delbeke D, Martin WH. Effect of minimally invasive radioguided parathyroidectomy on efficacy, length of stay, and costs in the management of primary hyperparathyroidism. Ann Surg 2000;231:732–42.PubMedCrossRefGoogle Scholar
  66. 66.
    Koong HN, Choong LH, Soo KC. The role of preoperative localisation techniques in surgery for hyperparathyroidism. Ann Acad Med Singapore 1998;27:192–5.PubMedGoogle Scholar
  67. 67.
    Norman J, Denham D. Minimally invasive radioguided parathyroidectomy in the reoperative neck. Surgery 1998;124:1088–93.PubMedCrossRefGoogle Scholar
  68. 68.
    Bonjer HJ, Bruining HA, Pols HAP, de Herder WW, van Eijck CH, Breeman WA, et al. Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer. Eur J Nucl Med 1997;24:246–51.PubMedGoogle Scholar
  69. 69.
    Chapius Y, Fulla Y, Bonnichon P, Tarla E, Abbound B, Pitre J, et al. Values of ultrasonography, sestamibi scintigraphy and intraoperative measurement of 1–84 PTH for unilateral neck exploration of primary hyperparathyroidism. World J Surg 1996;20:835–40.CrossRefGoogle Scholar
  70. 70.
    Giordano A, Rubello D, Casara D. New trends in parathyroid scintigraphy. Eur J Nucl Med 2001;28:1409–20.PubMedCrossRefGoogle Scholar
  71. 71.
    Rubello D, Casara D, Shapiro B. Recent advances in preoperative and intraoperative nuclear medicine procedures in patients with primary hyperparathyroidism. Panminerva Med 2002;44:99–105.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Domenico Rubello
    • 1
  • Milton D. Gross
    • 2
  • Giuliano Mariani
    • 3
  • Adil AL-Nahhas
    • 4
  1. 1.Service of Nuclear MedicineS. Maria della Misericordia HospitalRovigoItaly
  2. 2.Nuclear Medicine ServiceDepartment of Veterans Affairs Health SystemAnn ArborUSA
  3. 3.Regional Center of Nuclear MedicineUniversity of PisaPisaItaly
  4. 4.Department of Nuclear MedicineHammersmith HospitalLondonUK

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