Online first
Review paper
Published online: 2025-03-31
Contemporary localization diagnostics in primary hyperparathyroidism. Review of visualization techniques including ultrasonography, PTH washout, 99mTc-MIBI scintigraphy, and 18F-choline PET
1
, 1, 1, 1, 1, 1
, 1, 1, 1, 1, 1
Abstract
Introduction: Primary hyperparathyroidism is a set of symptoms caused by overproduction of parathormone (PTH), leading to impaired calcium and phosphorus metabolism. Proper diagnosis and detection of a parathyroid adenoma, including ectopic ones, is crucial to confirm the diagnosis and to tailor further treatment. In clinical practice, preoperative localization of parathyroid adenomas is a difficult task. Conventional imaging studies such as ultrasonography (US) and 99mTc-MIBI scintigraphy often cause unequivocal results; therefore, additional examinations are needed. The following paper discusses currently available diagnostic methods that could help in doubtful cases, and which should be considered during localization of parathyroid lesions.
Material and methods: When writing the following paper, we researched medical databases, such as PubMed and Google Scholar, for papers published in 2000–2024 with special attention paid to the latest articles published in the past 5 years. The presented data are gathered from 66 selected publications on primary hyperparathyroidism and contemporary methods of localization diagnostics by keywords: “primary hyperparathyroidism”, “parathyroids”, “parathormone”, “MIBI”, “scintigraphy”, “parathyroids ultrasonography”, “parathyroid adenoma”, “parathyroid localization diagnostics”, “imaging studies in hyperparathyroidism”, “minimally invasive surgery in hyperparathyroidism”, “18F-choline”, “PET”, and “PTH washout.”
Results: Use of positron emission tomography with 18F-choline (18F-FCH PET/CT) or parathormone washout from ultrasound-guided fine-needle aspiration (FNA) increases the effectiveness of localization diagnostics. Due to the high sensitivity of those tests, contemporary reports emphasize their value more often than ever. These examinations have a great impact on the accurate identification of parathyroid lesions, and in some cases they allow minimally invasive surgery to be performed.
Conclusions: The following paper underlines a need for determination of a perfect tool for primary hyperparathyroidism localization diagnostics based on its sensitivity and availability; however, contemporary available tests and exams when combined may bring great results and allow a patient to be qualified for a minimally invasive surgical treatment.
Keywords: primary hyperparathyroidismMIBIscintigraphyparathyroids ultrasonographyparathyroid adenomaparathyroid localization diagnosticsimaging studies in hyperparathyroidismminimally invasive surgery in hyperparathyroidismPETPTH washout
References
- Kowalski G, Buła G, Żądło D, et al. Primary hyperparathyroidism. Endokrynol Pol. 2020; 71(3): 260–270.
- Gopinath P, Mihai R. Hyperparathyroidism. Surgery (Oxford). 2011; 29(9): 451–458.
- Yu N, Donnan PT, Murphy MJ, et al. Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK. Clin Endocrinol (Oxf). 2009; 71(4): 485–493.
- Yeh MW, Ituarte PHG, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013; 98(3): 1122–1129.
- Twigt BA, Scholten A, Valk GD, et al. Differences between sporadic and MEN related primary hyperparathyroidism; clinical expression, preoperative workup, operative strategy and follow-up. Orphanet J Rare Dis. 2013; 8: 50.
- Oberger Marques JV, Moreira CA. Primary hyperparathyroidism. Best Pract Res Clin Rheumatol. 2020; 34(3): 101514.
- Griebeler ML, Kearns AE, Ryu E, et al. Secular trends in the incidence of primary hyperparathyroidism over five decades (1965-2010). Bone. 2015; 73: 1–7.
- Weber T, Hillenbrand A, Peth S, et al. Symptoms of Primary Hyperparathyroidism in Men and Women: The Same but Different? Visc Med. 2020; 36(1): 41–47.
- Dandurand K, Ali DS, Khan AA. Primary Hyperparathyroidism: A Narrative Review of Diagnosis and Medical Management. J Clin Med. 2021; 10(8).
- Pallan S, Rahman MO, Khan AA, et al. Primary hyperparathyroidism: Update on presentation, diagnosis, and management in primary care. Can Fam Physician. 2011; 57(2): 184–189.
- Udelsman R, Åkerström G, Biagini C, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99(10): 3595–3606.
- Urkan M, Peker YS, Ozturk E. MINIMALLY INVASIVE PARATHYROIDECTOMY FOR PRIMARY HYPERPARATHYROIDISM. Acta Endocrinol (Buchar). 2019; 15(2): 182–186.
- 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(10): 959–968.
- Gierach M, Skowrońska A, Mirlak I, et al. [The method of secondary hyperparathyroidism imaging]. Forum Nefrol. 2014, vol7, no; 7(3): 141–145.
- Taubman ML, Goldfarb M, Lew JI. Role of SPECT and SPECT/CT in the Surgical Treatment of Primary Hyperparathyroidism. Int J Mol Imaging. 2011; 2011: 141593.
- Lee B, Chung SR, Choi YJ, et al. Diagnosis of parathyroid incidentaloma detected on thyroid ultrasonography: the role of fine-needle aspiration cytology and washout parathyroid hormone measurements. Ultrasonography. 2023; 42(1): 129–135.
- Broos WAM, van der Zant FM, Knol RJJ. Incidental Detection of Parathyroid Adenoma on 18F-PSMA PET/CT. Clin Nucl Med. 2023; 48(12): 1082–1083.
- Suzuki A, Hirokawa M, Kanematsu R, et al. Fine-needle aspiration of parathyroid adenomas: Indications as a diagnostic approach. Diagn Cytopathol. 2021; 49(1): 70–76.
- Güneş E, Koca N, Tufanoğlu FH. Tissue Parathyroid Hormone Washout: A Reliable Method for the Localization and Exclusion of Parathyroid Adenomas. Cureus. 2023; 15(9): e45814.
- Cansu GB, Taşkıran B, Dizen H, et al. Parathyroid hormone in washout fluid seems to be superior to cytology for localization of the lesion in MIBI-negative patients with primary hyperparathyroidism. Turk J Med Sci. 2017; 47(6): 1703–1707.
- Aygün N, İşgör A, Uludağ M. The Effectiveness of Preoperative Ultrasonography and Scintigraphy in the Pathological Gland Localization in Primary Hyperparathyroidism Patients. Sisli Etfal Hastan Tip Bul. 2019; 53(4): 379–384.
- Amaral S, Rego T, Palha A, et al. Preoperative Location Of Parathyroid Adenomas In Primary Hyperparathyroidism: The Role of Cervical Doppler Ultrasound. Acta Med Port. 2023; 36(4): 246–253.
- Salhi H, Bouziane T, Maaroufi M, et al. Primary hyperparathyroidism: Correlation between cervical ultrasound and MIBI scan. Ann Afr Med. 2022; 21(2): 161–164.
- Shi Y, Brandler TC, Yee-Chang M, et al. Application of GATA 3 and TTF-1 in differentiating parathyroid and thyroid nodules on cytology specimens. Diagn Cytopathol. 2020; 48(2): 128–137.
- Takada N, Hirokawa M, Suzuki A, et al. Diagnostic value of GATA-3 in cytological identification of parathyroid tissues. Endocr J. 2016; 63(7): 621–626.
- Schilsky JB, Ni Ai, Ahn L, et al. Prognostic impact of TTF-1 expression in patients with stage IV lung adenocarcinomas. Lung Cancer. 2017; 108: 205–211.
- Doppman JL, Krudy AG, Marx SJ, et al. Aspiration of enlarged parathyroid glands for parathyroid hormone assay. Radiology. 1983; 148(1): 31–35.
- Salameh OM, Gul W, Al-Thani N, et al. Novel Method in Performing PTH Washout for Localizing Parathyroid Adenoma: Case Report & an Institute Experience in Qatar. J Endocr Soc. 2021; 5(Supplement_1): A265–A266.
- Szczepanek-Parulska E, Filipowicz D, Czepczyński R, et al. Clinical, Biochemical, and Sonographic Factors Influencing Performance of Parathormone Washout Measurement vs. Tc-MIBI Scintigraphy in the Preoperative Diagnostics of Parathyroid Adenomas. J Clin Med. 2023; 12(12).
- Castellana M, Virili C, Palermo A, et al. Primary hyperparathyroidism with surgical indication and negative or equivocal scintigraphy: safety and reliability of PTH washout. A systematic review and meta-analysis. Eur J Endocrinol. 2019; 181(3): 245–253.
- Sardana R, Abi-Raad R, Adeniran AJ, et al. Utility of parathyroid hormone immunocytochemistry in fine needle aspiration diagnosis of parathyroid tissue. Cytopathology. 2023; 34(6): 597–602.
- Centello R, Sesti F, Feola T, et al. The Dark Side of Ultrasound Imaging in Parathyroid Disease. J Clin Med. 2023; 12(7).
- Jasim S, Dean DS, Gharib H. Fine-Needle Aspiration of the Thyroid Gland. In: Feingold KR, Anawalt BS, Blackman MR. et al. ed. Endotext. , South Dartmouth 2000.
- Obołończyk Ł, Karwacka I, Wiśniewski P, et al. The Current Role of Parathyroid Fine-Needle Biopsy (P-FNAB) with iPTH-Washout Concentration (iPTH-WC) in Primary Hyperparathyroidism: A Single Center Experience and Literature Review. Biomedicines. 2022; 10(1).
- Farley DR. Technetium-99m 2-methoxyisobutyl isonitrile-scintigraphy: preoperative and intraoperative guidance for primary hyperparathyroidism. World J Surg. 2004; 28(12): 1207–1211.
- Liu Y, Yang L, Xu H, et al. Analysis of false-positive and false-negative results in Tc-MIBI SPECT/CT parathyroid imaging. Quant Imaging Med Surg. 2023; 13(12): 8669–8680.
- Gladić Nenadić V, Šiško Markoš I, Punda M, et al. Tc-MIBI SPECT/CT scintigraphy and ultrasound of the anterior neck region in diagnosing parathyroid gland pathology in patients with thyroid nodules. Acta Clin Croat. 2022; 60(3): 423–428.
- Wilson MP, Katlariwala P, Abele J, et al. A review of 99mTc-sestamibi SPECT/CT for renal oncocytomas: A modified diagnostic algorithm. Intractable Rare Dis Res. 2022; 11(2): 46–51.
- Zhang R, Zhang Z, Huang P, et al. Diagnostic performance of ultrasonography, dual-phase Tc-MIBI scintigraphy, early and delayed Tc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism. BMC Med Imaging. 2020; 20(1): 91.
- Zhang R, Zhang Z, Huang P, et al. Diagnostic performance of ultrasonography, dual-phase Tc-MIBI scintigraphy, early and delayed Tc-MIBI SPECT/CT in preoperative parathyroid gland localization in secondary hyperparathyroidism. BMC Med Imaging. 2020; 20(1): 91.
- Silov G, Erdogan Ozbodur S. The Relationship between Planar and SPECT/CT Parameters and Functional Markers in Primary Hyperparathyroidism. Diagnostics (Basel). 2023; 13(20).
- Park HS, Hong N, Jeong JJu, et al. Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism. Endocrinol Metab (Seoul). 2022; 37(5): 744–755.
- Rizk TH, Nagalli S. Technetium 99m Sestamibi. StatPearls, Treasure Island 2024.
- Uslu-Beşli L, Sonmezoglu K, Teksoz S, et al. Performance of F-18 Fluorocholine PET/CT for Detection of Hyperfunctioning Parathyroid Tissue in Patients with Elevated Parathyroid Hormone Levels and Negative or Discrepant Results in conventional Imaging. Korean J Radiol. 2020; 21(2): 236–247.
- Wolf HW, Nebiker CA. Preoperative identification of small parathyroid adenomas-better done by fluorocholine positron emission tomography/computed tomography. Gland Surg. 2023; 12(12): 1686–1695.
- Broos WAM, van der Zant FM, Knol RJJ, et al. Choline PET/CT in parathyroid imaging: a systematic review. Nucl Med Commun. 2019; 40(2): 96–105.
- Rep S, Hocevar M, Vaupotic J, et al. 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): 343–356.
- Cegla P, Scibisz-Dziedzic K, Witkowska K, et al. Detection of a second primary cancer in a 18F-fluorocholine PET/CT - multicentre retrospective analysis on a group of 1345 prostate cancer patients. Nucl Med Rev Cent East Eur. 2022; 25(1): 25–30.
- Boudousq V, Guignard N, Gilly O, et al. Diagnostic Performance of Cervical Ultrasound, (99m)Tc-Sestamibi Scintigraphy, and Contrast-Enhanced (18)F-Fluorocholine PET in Primary Hyperparathyroidism. J Nucl Med. J Nucl Med. 2022; 63(7): 1081–1086.
- Quak E, Lasne Cardon A, Ciappuccini R, et al. Upfront F18-choline PET/CT versus Tc99m-sestaMIBI SPECT/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2. BMC Endocr Disord. 2021; 21(1): 3.
- Acar N, Haciyanli M, Coskun M, et al. Diagnostic value of four-dimensional computed tomography and four-dimensional magnetic resonance imaging in primary hyperparathyroidism when first-line imaging was inadequate. Ann R Coll Surg Engl. 2020; 102(4): 294–299.
- Scheepers MH, Al-Difaie Z, Brandts L, et al. Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review. Diagnostics (Basel). 2023; 14(1).
- Becker JL, Patel V, Johnson KJ, et al. 4D-Dynamic Contrast-Enhanced MRI for Preoperative Localization in Patients with Primary Hyperparathyroidism. AJNR Am J Neuroradiol. 2020; 41(3): 522–528.
- Ron E, Lubin J, Shore R, et al. Thyroid Cancer after Exposure to External Radiation: A Pooled Analysis of Seven Studies. Radiat Res. 1995; 141(3): 259.
- Tay D, Das JP, Yeh R. Preoperative Localization for Primary Hyperparathyroidism: A Clinical Review. Biomedicines. 2021; 9(4).
- Champendal M, Jreige M, Nicod Lalonde M, et al. Feasibility and Performance of Free-Hand Single-Photon Computed Tomography/Ultrasonography for Preoperative Parathyroid Adenoma Localization: A Pilot Study. Diagnostics (Basel). 2023; 13(13).
- Starker LF, Mahajan A, Björklund P, et al. 4D parathyroid CT as the initial localization study for patients with de novo primary hyperparathyroidism. Ann Surg Oncol. 2011; 18(6): 1723–1728.
- Eichhorn-Wharry LI, Carlin AM, Talpos GB. Mild hypercalcemia: an indication to select 4-dimensional computed tomography scan for preoperative localization of parathyroid adenomas. Am J Surg. 2011; 201(3): 334–8; discussion 338.
- Murruste M, Kivilo M, Kase K, et al. The Utility of 4D-CT Imaging in Primary Hyperparathyroidism Management in a Low-Volume Center. Medicina (Kaunas). 2023; 59(8).
- Al-Difaie Z, Scheepers MH, Engelen SME, et al. Diagnostic Value of Four-Dimensional Dynamic Computed Tomography for Primary Hyperparathyroidism in Patients with Low Baseline Parathyroid Hormone Levels. Diagnostics (Basel). 2023; 13(16).
- Andryszak N, Świniuch D, Wójcik E, et al. Head-to-Head Comparison of [F]PSMA-1007 and [F]FDG PET/CT in Patients with Triple-Negative Breast Cancer. Cancers (Basel). 2024; 16(3).
- Tsechelidis I, Vrachimis A. PSMA PET in Imaging Prostate Cancer. Front Oncol. 2022; 12: 831429.
- Cieślewicz M, Andryszak N, Pełka K, et al. Parathyroid Adenoma Detected in Ga-PSMA PET/CT but Not in the Dedicated Imaging Modalities. Diagnostics (Basel). 2024; 14(15).
- Prades JM, Lelonge Y, Farizon B, et al. Positive predictive values of ultrasound-guided fine-needle aspiration with parathyroid hormone assay and Tc-99m sestamibi scintigraphy in sporadic primary hyperparathyroidism. Eur Ann Otorhinolaryngol Head Neck Dis. 2023; 140(1): 3–7.
- Carral F, Jiménez AI, Tomé M, et al. Safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate in suspicious parathyroid adenomas. Endocrinol Diabetes Nutr (Engl Ed). 2021; 68(7): 481–488.
- Pekkolay Z, Altun Tuzcu Ş. Importance of Parathyroid Hormone Needle Aspiration Washout in Adenoma Localization in Primary Hyperparathyroidism. Med Sci Monit. 2019; 25: 1694–1698.
- Aydın C, Polat SB, Dellal FD, et al. The diagnostic value of parathyroid hormone washout in primary hyperparathyroidism patients with negative or equivocal 99 m Tc-MIBI results. Diagn Cytopathol. 2019; 47(2): 94–99.
- Gökçay Canpolat A, Şahin M, Ediboğlu E, et al. Diagnostic accuracy of parathyroid hormone levels in washout samples of suspicious parathyroid adenomas: A single-centre retrospective cohort study. Clin Endocrinol (Oxf). 2018; 89(4): 489–495.
- Ozderya A, Temizkan S, Gul AE, et al. Correlation of BRAF mutation and SUV levels in thyroid cancer patients incidentally detected in F-fluorodeoxyglucose positron emission tomography. Endocrine. 2017; 55(1): 215–222.
- Kuzu F, Arpaci D, Cakmak GK, et al. Focused parathyroidectomy without intra-operative parathormone monitoring: The value of PTH assay in preoperative ultrasound guided fine needle aspiration washout. Ann Med Surg (Lond). 2016; 6: 64–67.
- Bancos I, Grant CS, Nadeem S, et al. Risks and benefits of parathyroid fine-needle aspiration with parathyroid hormone washout. Endocr Pract. 2012; 18(4): 441–449.
- Giusti M, Dolcino M, Vera L, et al. Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue. J Zhejiang Univ Sci B. 2009; 10(5): 323–330.
- Erbil Y, Salmaslioğlu A, Kabul E, et al. Use of preoperative parathyroid fine-needle aspiration and parathormone assay in the primary hyperparathyroidism with concomitant thyroid nodules. Am J Surg. 2007; 193(6): 665–671.
- Abraham D, Sharma PK, Bentz J, et al. Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomy. Endocr Pract. 2007; 13(4): 333–337.
- Barczynski M, Golkowski F, Konturek A, et al. Technetium-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. Clin Endocrinol (Oxf). 2006; 65(1): 106–113.
