Abstract
Surgical treatment is the primary approach in hyperparathyroidism, and today, minimally invasive parathyroidectomy is more frequently preferred over bilateral neck exploration in suitable patients. Preoperative localization of hyperfunctioning parathyroid glands is crucial for the application of these surgical approaches. Parathyroid imaging methods are not diagnostic but are used as complementary tools to guide surgical planning and aim to increase surgical success. The purpose of this review is to clarify the role of parathyroid imaging in the clinical practice of patients with biochemically confirmed hyperparathyroidism, to provide an overview of the main imaging methods used for preoperative localization, and to emphasize the importance of a patient-centered, step-by-step approach.
Keywords:
Hyperparathyroidism, parathyroid scintigraphy, sestamibi, SPECT/CT, preoperative localization
References
1
Çakır B, editor. Paratiroid hastalıkları. Ankara: Akademisyen Kitabevi; 2023. Available from: https://file.temd.org.tr/Uploads/publications/books/documents/PARATIROIDHASTALIKLARI.pdf
2
Siraj QH, editor. Radionuclide Parathyroid Imaging: Book and Atlas. Cham, Switzerland: Springer US; 2019.
3
Mallick R, Chen H. Diagnosis and management of hyperparathyroidism. Adv Surg. 2018;52:137-153.
4
Petranović Ovčariček P, Giovanella L, Carrió Gasset I, et al. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021;48:2801-2822.
5
Morris MA, Saboury B, Ahlman M, et al. Parathyroid imaging: past, present, and future. Front Endocrinol (Lausanne). 2022;12:760419.
6
Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151:959-968.
7
Westerdahl J, Bergenfelz A. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: five-year follow-up of a randomized controlled trial. Ann Surg. 2007;246:976-980; discussion 980-981.
8
Udelsman R, Lin Z, Donovan P. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. Ann Surg. 2011;253:585-591.
9
Ince S, Emer O, Deveci S, et al. Complementary role of parathormone washout test to 99m Tc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas. Rev Esp Med Nucl Imagen Mol (Engl Ed). 2018;37:205-210. English, Spanish.
10
Barbaros U, Erbil Y, Salmashoğlu A, et al. The characteristics of concomitant thyroid nodules cause false-positive ultrasonography results in primary hyperparathyroidism. Am J Otolaryngol. 2009;30:239-243.
11
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;43:133-143.
12
Frey S, Couëtte C, Trésallet C, et al. Utility of a second 99m Tc-MIBI scintigraphy before reoperation for patients with persistent sporadic primary hyperparathyroidism: results of a retrospective multicenter study. Ann Surg Oncol. 2020;27:3831-3839.
13
Patel SG, Saunders ND, Jamshed S, Weber CJ, Sharma J. Multimodal preoperative localization improves outcomes in reoperative parathyroidectomy: a 25-year surgical experience. Am Surg. 2019;85:939-943.
14
Parikh AM, Grogan RH, Morón FE. Localization of parathyroid disease in reoperative patients with primary hyperparathyroidism. Int J Endocrinol. 2020;2020:9649564.
15
Zander D, Bunch PM, Trout AT, et al. ACR appropriateness criteria ® parathyroid adenoma. J Am Coll Radiol. 2021;18:S406-S422.
16
Amadou C, Bera G, Ezziane M, et al. 18F-fluorocholine PET/CT and parathyroid 4D computed tomography for primary hyperparathyroidism: the challenge of reoperative patients. World J Surg. 2019;43:1232-1242.
17
Zafereo M, Yu J, Angelos P, et al. American Head and Neck Society Endocrine Surgery Section update on parathyroid imaging for surgical candidates with primary hyperparathyroidism. Head Neck. 2019;41:2398-2409.
18
Karakas E, Müller HH, Schlosshauer T, Rothmund M, Bartsch DK. Reoperations for primary hyperparathyroidism--improvement of outcome over two decades. Langenbecks Arch Surg. 2013;398:99-106.
19
Camenzuli C, DiMarco AN, Isaacs KE, et al. The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations. Ann R Coll Surg Engl. 2021;103:29-34.
20
Amjad W, Trerotola SO, Fraker DL, Wachtel H. Tricks of the trade: techniques for preoperative localization in reoperative parathyroidectomy. Am J Surg. 2023;226:207-212.
21
Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med. 2003;44:1443-1458.
22
Fukunaga M, Morita R, Yonekura Y, et al. Accumulation of 201Tl-chloride in a parathyroid adenoma. Clin Nucl Med. 1979;4:229-230.
23
Ferlin G, Borsato N, Camerani M, Conte N, Zotti D. New perspectives in localizing enlarged parathyroids by technetium-thallium subtraction scan. J Nucl Med. 1983;24:438-441.
24
Coakley AJ, Kettle AG, Wells CP, O’Doherty MJ, Collins RE. 99Tcm sestamibi--a new agent for parathyroid imaging. Nucl Med Commun. 1989;10:791-794.
25
Palestro CJ, Tomas MB, Tronco GG. Radionuclide imaging of the parathyroid glands. Semin Nucl Med. 2005;35:266-276.
26
Greenspan BS, Dillehay G, Intenzo C, et al. SNM practice guideline for parathyroid scintigraphy 4.0. J Nucl Med Technol. 2012;40:111-118.
27
Erdil TY, Beşli LU. Clinical value of single photon emission computed tomography/computed tomography in the evaluation of Tc-99m MIBI parathyroid scintigraphy. Nucl Med Semin. 2016;1:49-56.
28
Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19:577-583.
29
Yeh R, Tay YD, Tabacco G, et al. Diagnostic performance of 4D CT and sestamibi SPECT/CT in localizing parathyroid adenomas in primary hyperparathyroidism. Radiology. 2019;291:469-476.
30
Wong KK, Fig LM, Gross MD, Dwamena BA. Parathyroid adenoma localization with 99mTc-sestamibi SPECT/CT: a meta-analysis. Nucl Med Commun. 2015;36:363-375.
31
Treglia G, Sadeghi R, Schalin-Jäntti C, 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-E2172.
32
McCoy KL, Ghodadra AG, Hiremath TG, et al. Sestamibi SPECT/CT versus SPECT only for preoperative localization in primary hyperparathyroidism: a single institution 8-year analysis. Surgery. 2018;163:643-647.
33
Pata G, Casella C, Magri GC, et al. Financial and clinical implications of low-energy CT combined with 99m technetium-sestamibi SPECT for primary hyperparathyroidism. Ann Surg Oncol. 2011;18:2555-2563.
34
Perez-Monte JE, Brown ML, Shah AN, et al. Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT. Radiology. 1996;201:85-91.
35
Lorberboym M, Minski I, Macadziob S, Nikolov G, Schachter P. Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma. J Nucl Med. 2003;44:904-908.
36
García-Talavera San Miguel P, Gómez-Caminero López F, Villanueva Curto JG, Tamayo Alonso MP, Martín Gómez ME. Update of the role of Nuclear Medicine techniques in the pre-surgical localization of primary hyperparathyroidism. Rev Esp Med Nucl Imagen Mol (Engl Ed). 2019;38:123-135. English, Spanish.
37
Lal A, Chen H. The negative sestamibi scan: is a minimally invasive parathyroidectomy still possible? Ann Surg Oncol. 2007;14:2363-2366.
38
Chiu B, Sturgeon C, Angelos P. What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy. Surgery. 2006;140:418-422.
39
Cho NL, Gawande AA, Sheu EG, Moore FD Jr, Ruan DT. Critical role of identification of the second gland during unilateral parathyroid surgery: a prospective review of 119 patients with concordant localization. Arch Surg. 2011;146:512-516.
40
Westreich RW, Brandwein M, Mechanick JI, Bergman DA, Urken ML. Preoperative parathyroid localization: correlating false-negative technetium 99m sestamibi scans with parathyroid disease. Laryngoscope. 2003;113:567-572.
41
Erbil Y, Kapran Y, Işsever H, et al. The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism. Am J Surg. 2008;195:34-39.
42
Pons F, Torregrosa JV, Fuster D. Biological factors influencing parathyroid localization. Nucl Med Commun. 2003;24:121-124.
43
Erovic BM, Goldstein DP, Asa SL, Janik S, Mete O, Irish JC. VEGFR-2 is downregulated in sestamibi-negative parathyroid adenomas. Head Neck. 2019;41:3564-3569.
44
Friedman K, Somervell H, Patel P, et al. Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism. Surgery. 2004;136:1199-1204.
45
Sung JY. Parathyroid ultrasonography: the evolving role of the radiologist. Ultrasonography. 2015;34:268-274.
46
Nafisi Moghadam R, Amlelshahbaz AP, Namiranian N, et al. Comparative diagnostic performance of ultrasonography and 99mTc-sestamibi scintigraphy for parathyroid adenoma in primary hyperparathyroidism; systematic review and meta- analysis. Asian Pac J Cancer Prev. 2017;18:3195-3200.
47
Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005;132:359-372.
48
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;84:1745-1751.
49
Ilgan S, Ozbas S, Bilezikci B, et al. Radioguided occult lesion localization for minimally invasive parathyroidectomy: technical consideration and feasibility. Nucl Med Commun. 2014;35:1167-1174.
50
Li W, Zhu Q, Lai X, et al. Value of preoperative ultrasound-guided fine-needle aspiration for localization in Tc-99m MIBI-negative primary hyperparathyroidism patients. Medicine (Baltimore). 2017;96:e9051.
51
Trimboli P, D’Aurizio F, Tozzoli R, Giovanella L. Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids. Clin Chem Lab Med. 2017;55:914-925.
52
Kunstman JW, Kirsch JD, Mahajan A, Udelsman R. Clinical review: parathyroid localization and implications for clinical management. J Clin Endocrinol Metab. 2013;98:902-912.
53
Treglia G, Giovannini E, Di Franco D, 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;26:451-461.
54
Treglia G, Piccardo A, Imperiale A, et al. Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2019;46:751-765.
55
Quak E, Blanchard D, Houdu 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;45:658-666.
56
Lezaic L, Rep S, Sever MJ, Kocjan T, Hocevar M, Fettich J. 18 F-fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study. Eur J Nucl Med Mol Imaging. 2014;41:2083-2089.
57
Kluijfhout WP, Pasternak JD, Surg. 2016;401:925-935.
58
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;45:654-657.
59
Gotway MB, Higgins CB. MR imaging of the thyroid and parathyroid glands. Magn Reson Imaging Clin N Am. 2000;8:163-182.
60
Beland MD, Mayo-Smith WW, Grand DJ, Machan JT, Monchik JM. Dynamic MDCT for localization of occult parathyroid adenomas in 26 patients with primary hyperparathyroidism. AJR Am J Roentgenol. 2011;196:61-65.
61
Welling RD, Olson JA Jr, Kranz PG, Eastwood JD, Hoang JK. Bilateral retropharyngeal parathyroid hyperplasia detected with 4D multidetector row CT. AJNR Am J Neuroradiol. 2011;32:E80-E82.
62
Mahajan A, Starker LF, Ghita M, Udelsman R, Brink JA, Carling T. Parathyroid four-dimensional computed tomography: evaluation of radiation dose exposure during preoperative localization of parathyroid tumors in primary hyperparathyroidism. World J Surg. 2012;36:1335-1339.
63
Kedarisetty S, Fundakowski C, Ramakrishnan K, Dadparvar S. Clinical value of Tc99m-MIBI SPECT/CT versus 4D-CT or US in management of patients with hyperparathyroidism. Ear Nose Throat J. 2019;98:149-157.
64
Yanar C, Kostek M, Unlu MT, et al. The role of 4D-CT for pre-operative localization in patients with primary hyperparathyroidism with negative ultrasonography and/or sestamibi SPECT/CT. Sisli Etfal Hastan Tip Bul. 2023;57:238-244.
65
Bunch PM, Kelly HR. Preoperative imaging techniques in primary hyperparathyroidism: a review. JAMA Otolaryngol Head Neck Surg. 2018;144:929-937.
66
Yip L, Pryma DA, Yim JH, Virji MA, Carty SE, Ogilvie JB. Can a lightbulb sestamibi SPECT accurately predict single-gland disease in sporadic primary hyperparathyroidism? World J Surg. 2008;32:784-792; discussion 793-794.
67
Mehta NY, Ruda JM, Kapadia S, Boyer PJ, Hollenbeak CS, Stack BC Jr. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg. 2005;131:493-498.
68
Bilezikian JP, Khan AA, Silverberg SJ, et al.; International Workshop on Primary Hyperparathyroidism. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022;37:2293-2314.
69
Bilezikian JP, Silverberg SJ, Bandeira F, et al. Management of primary hyperparathyroidism. J Bone Miner Res. 2022;37:2391-2403.
70
Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery. 2006;140:932-940; discussion 940-941.
