Comparison of first- and second-line imaging diagnostics (ultrasound + scintigraphy and PET + 4DCT) in visualizing parathyroid glands in primary hyperparathyroidism including ectopic foci
DOI:
https://doi.org/10.12775/JEHS.2025.82.60366Keywords
ectopic hyperparathyroidism, primary hyperparathyroidism imaging, hyperparathyroidism MIBI, hyperparathyroidism ultrasound, hyperparathyroidism PET/CT, hyperparathyroidism 4DCTAbstract
Introduction:
Primary hyperparathyroidism is an endocrine disorder that causes disturbances in calcium and phosphorus metabolism in the human body. The most effective permanent treatment is surgery, which involves the removal of the affected gland. To locate such small glands, various imaging diagnostic methods, including nuclear medicine, are currently used. This study aims to review current imaging protocols for hyperparathyroid glands and compare first- and second-line methods, particularly in cases of ectopic foci.
Material and methods:
This review was prepared based on articles available on PubMed. The literature review was conducted using the following keywords: primary hyperparathyroidism, primary hyperparathyroidism imaging, primary hyperparathyroidism US, primary hyperparathyroidism MIBI, primary hyperparathyroidism PET/CT, primary hyperparathyroidism 4DCT, ectopic hyperparathyroidism imaging.
The current state of knowledge:
Primary hyperparathyroidism is a condition that can go unnoticed for an extended period. The diagnosis of the disease is based on laboratory tests, followed by the crucial step of locating the gland responsible for progressively causing damage to the body over time. Identifying the hyperactive gland is essential for performing a successful surgery and curing the patient. However, this often poses a significant challenge, due to the potential for ectopic gland locations.
Summary:
It is hard to unequivocally state the superiority of one imaging line over the other, as each has specific pros and cons in specific cases. However, in the case of ectopic foci, the 2nd imaging line shows promising results.
References
1. Kowalski GJ, Buła G, Żądło D, Gawrychowska A, Gawrychowski J. Primary hyperparathyroidism. Endokrynol Pol. 2020;71(3):260-270. PMID: 32797471. https://doi.org/10.5603/EP.a2020.0028
2. Pokhrel B, Leslie SW, Levine SN. Primary Hyperparathyroidism. 2024 Mar 1. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK441895/ (access: 19.10.2024)
3. Georgakopoulos B, Al Khalili Y. Anatomy, Head and Neck, Parathyroid, Ectopic Glands. 2023 Jul 17. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK540972/ (access: 29.11.2024)
4. Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV. Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism. J Bone Miner Res. 2022 Nov;37(11):2315-2329. Epub 2022 Oct 17. PMID: 36245271; PMCID: PMC10092691. https://doi.org/10.1002/jbmr.4665
5. Galani A, Morandi R, Dimko M, Molfino S, Baronchelli C, Lai S, Gheza F, Cappelli C, Casella C. Atypical parathyroid adenoma: clinical and anatomical pathologic features. World J Surg Oncol. 2021 Jan 20;19(1):19. PMID: 33472651; PMCID: PMC7818751. https://doi.org/10.1186/s12957-021-02123-7
6. Guilmette J, Sadow PM. Parathyroid Pathology. Surg Pathol Clin. 2019 Dec;12(4):1007-1019. Epub 2019 Sep 27. PMID: 31672291; PMCID: PMC7395581. https://doi.org/10.1016/j.path.2019.08.006
7. Boccalatte LA, Gómez NL, Olivera López S, Yanzon A, Abuawad CY, Smith DE, Mazzaro EL, Figari MF. Hiperparatiroidismo ectópico. Detección de la localización mediastinal [Ectopic hyperparathyroidism. Detection of mediastinal localization]. Medicina (B Aires). 2020;80(1):39-47. Spanish. PMID: 32044740.
8. Petranović Ovčariček P, Giovanella L, Carrió Gasset I, Hindié E, Huellner MW, Luster M, Piccardo A, Weber T, Talbot JN, Verburg FA. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2801-2822. Epub 2021 Apr 10. PMID: 33839893; PMCID: PMC8263421. https://doi.org/10.1007/s00259-021-05334-y
9. Hindié E, Schwartz P, Avram AM, Imperiale A, Sebag F, Taïeb D. Primary Hyperparathyroidism: Defining the Appropriate Preoperative Imaging Algorithm. J Nucl Med. 2021 Jul;62(Suppl 2):3S-12S. PMID: 34230072. https://doi.org/10.2967/jnumed.120.245993
10. Chakrabarty N, Mahajan A, Basu S, D'Cruz AK. Imaging Recommendations for Diagnosis and Management of Primary Parathyroid Pathologies: A Comprehensive Review. Cancers (Basel). 2024 Jul 19;16(14):2593. PMID: 39061231; PMCID: PMC11274996. https://doi.org/10.3390/cancers16142593
11. Walker MD, Bilezikian JP. Primary Hyperparathyroidism. [Updated 2021 Apr 19]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK278923/ (access: 21.10.2024)
12. Pappachan JM, Lahart IM, Viswanath AK, Borumandi F, Sodi R, Metzendorf MI, Bongaerts B. Parathyroidectomy for adults with primary hyperparathyroidism. Cochrane Database Syst Rev. 2023 Mar 8;3(3):CD013035. PMID: 36883976; PMCID: PMC9995748. https://doi.org/10.1002/14651858.CD013035.pub2
13. Weber T, Hillenbrand A, Peth S, Hummel R. Symptoms of Primary Hyperparathyroidism in Men and Women: The Same but Different? Visc Med. 2020 Feb;36(1):41-47. Epub 2020 Jan 22. PMID: 32110656; PMCID: PMC7036559. https://doi.org/10.1159/000505497
14. Fieber J, Goodsell K, Kelz RR, Ermer JP, Wirtalla C, Fraker DL, Wachtel H. Racial Disparities in Primary Hyperparathyroidism. World J Surg. 2021 Jan;45(1):180-187. Epub 2020 Sep 25. PMID: 32978665; PMCID: PMC7906108. https://doi.org/10.1007/s00268-020-05791-w
15. Leslie SW, Levine SN. Normocalcemic Hyperparathyroidism. [Updated 2024 Mar 4]. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK555967/ (access: 23.10.2024)
16. Kochman M. Primary hyperparathyroidism: clinical manifestations, diagnosis and evaluation according to the Fifth International Workshop guidelines. Reumatologia. 2023;61(4):256-263. Epub 2023 Aug 31. PMID: 37745146; PMCID: PMC10515122. https://doi.org/10.5114/reum/170705
17. Fiz F, Bottoni G, Massollo M, Trimboli P, Catrambone U, Bacigalupo L, Righi S, Treglia G, Imperiale A, Piccardo A. [18F]F-Choline PET/CT and 4D-CT in the evaluation of primary hyperparathyroidism: rivals or allies? Q J Nucl Med Mol Imaging. 2023 Jun;67(2):130-137. PMID: 37232932. https://doi.org/10.23736/S1824-4785.23.03514-8
18. Noltes ME, Cottrell J, Madani A, Rotstein L, Gomez-Hernandez K, Devon K, Boggild MK, Goldstein DP, Wong EM, Brouwers AH, Kruijff S, Eskander A, Monteiro E, Pasternak JD. Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism. JAMA Otolaryngol Head Neck Surg. 2022 Mar 1;148(3):209-219. PMID: 34989783; PMCID: PMC8739767. https://doi.org/10.1001/jamaoto.2021.3858
19. Mifsud S, Montanaro G, Craus S, Mifsud EL, Gruppetta M. Thiazide diuretics and primary hyperparathyroidism. Br J Hosp Med (Lond). 2023 Dec 2;84(12):1-8. Epub 2023 Dec
20. PMID: 38153014. https://doi.org/10.12968/hmed.2023.0228
20. Sell J, Ramirez S, Partin M. Parathyroid Disorders. Am Fam Physician. 2022 Mar 1;105(3):289-298. PMID: 35289573.
21. Lorenz FJ, Beauchamp-Perez F, Manni A, Chung T, Goldenberg D, Goyal N. Analysis of Time to Diagnosis and Outcomes Among Adults With Primary Hyperparathyroidism. JAMA Netw Open. 2022 Dec 1;5(12):e2248332. PMID: 36574247; PMCID: PMC9857508. https://doi.org/10.1001/jamanetworkopen.2022.48332
22. Morris MA, Saboury B, Ahlman M, Malayeri AA, Jones EC, Chen CC, Millo C. Parathyroid Imaging: Past, Present, and Future. Front Endocrinol (Lausanne). 2022 Feb 25;12:760419. PMID: 35283807; PMCID: PMC8914059. https://doi.org/10.3389/fendo.2021.760419
23. Karunaratne D, Karunaratne N, Vasanthan R, Ojofeitimi O, Owens E, Sathiskumar P, Till D, Kirkland P, Howlett D. Primary Hyperparathyroidism: Outcomes of Repeated Imaging After Initial Negative Radiological Localization. Cureus. 2023 Aug 3;15(8):e42889. PMID: 37664265; PMCID: PMC10474611. https://doi.org/10.7759/cureus.42889
24. Salhi H, Bouziane T, Maaroufi M, Alaoui NI, El Ouahabi H. Primary hyperparathyroidism: Correlation between cervical ultrasound and MIBI scan. Ann Afr Med. 2022 Apr-Jun;21(2):161-164. PMID: 35848650; PMCID: PMC9383011. https://doi.org/10.4103/aam.aam_73_20
25. Kim WW, Lee YM, Sung TY, Chung KW, Hong SJ. Selection of parathyroidectomy methods for primary hyperparathyroidism according to concordance between ultrasonography and MIBI scan results. Gland Surg. 2021 Jan;10(1):298-306. PMID: 33633986; PMCID: PMC7882318. https://doi.org/10.21037/gs-20-611
26. Quak E, Lasne-Cardon A, Cavarec M, Lireux B, Bastit V, Roudaut N, Salaun PY, Keromnes N, Potard G, Vaduva P, Esvant A, Jegoux F, de Crouy-Chanel O, Devillers A, Guery C, Lasnon C, Ciappuccini R, Legrand B, Estienne A, Christy F, Grellard JM, Bardet S, Clarisse B. F18-Choline PET/CT or MIBI SPECT/CT in the Surgical Management of Primary Hyperparathyroidism: A Diagnostic Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2024 Aug 1;150(8):658-665. PMID: 38900416; PMCID: PMC11190825. https://doi.org/10.1001/jamaoto.2024.1421
27. Tay D, Das JP, Yeh R. Preoperative Localization for Primary Hyperparathyroidism: A Clinical Review. Biomedicines. 2021 Apr 6;9(4):390. PMID: 33917470; PMCID: PMC8067482. https://doi.org/10.3390/biomedicines9040390
28. Poh BR, Nagadia RH, Tay GC. Ectopic parathyroid gland within carotid sheath. Clin Case Rep. 2020 Nov 22;9(1):578-579. PMID: 33505697; PMCID: PMC7813128. https://doi.org/10.1002/ccr3.3476
29. Zajíčková K, Včelák J, Lešková Z, Grega M, Goltzman D, Zogala D. Multiglandular Parathyroid Disease in Primary Hyperparathyroidism With Inconclusive Conventional Imaging. Physiol Res. 2022 Apr 30;71(2):233-240. Epub 2022 Apr 11. PMID: 35275696; PMCID: PMC9150553. https://doi.org/10.33549/physiolres.934851
30. Haciyanli SG, Karaisli S, Erdogan N, Turgut B, Gur EO, Haciyanli M. Intrathyroidal Parathyroid Adenomas in Primary Hyperparathyroidism: Clinical and Imaging Findings. Sisli Etfal Hastan Tip Bul. 2022 Jun 28;56(2):256-261. PMID: 35990304; PMCID: PMC9350060. https://doi.org/10.14744/SEMB.2022.82584
31. Lala M. Management of Primary Hyperparathyroidism. Indian J Surg Oncol. 2022 Mar;13(1):143-151. Epub 2021 Apr 27. PMID: 35462664; PMCID: PMC8986895. https://doi.org/10.1007/s13193-021-01319-3
32. Chen Z, Cheng L, Zhang W, He W. Ultrasound-guided thermal ablation for hyperparathyroidism: current status and prospects. Int J Hyperthermia. 2022;39(1):466-474. PMID: 35271788. https://doi.org/10.1080/02656736.2022.2028907
33. Liu Y, Dang Y, Huo L, Hu Y, Wang O, Liu H, Chang X, Liu Y, Xing X, Li F, Liao Q, Hacker M, Li X, Kreissl MC. Preoperative Localization of Adenomas in Primary Hyperparathyroidism: The Value of 11C-Choline PET/CT in Patients with Negative or Discordant Findings on Ultrasonography and 99mTc-Sestamibi SPECT/CT. J Nucl Med. 2020 Apr;61(4):584-589. Epub 2019 Oct 10. PMID: 31601698. https://doi.org/10.2967/jnumed.119.233213
34. Hargitai L, Schefner M, Traub-Weidinger T, Haug A, Arikan M, Scheuba C, Riss P. Accessing the influence of 99mTc-Sesta-MIBI-positive thyroid nodules on preoperative localisation studies in patients with primary hyperparathyroidism. Langenbecks Arch Surg. 2022 May;407(3):1183-1191. Epub 2022 Jan 21. PMID: 35061094; PMCID: PMC9151570. https://doi.org/10.1007/s00423-022-02442-7
35. Gladić Nenadić V, Šiško Markoš I, Punda M, Blažeković I, Franceschi M, Fröbe A, Jukić T. 99mTc-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 Feb;60(3):423-428. PMID: 35282495; PMCID: PMC8907962. https://doi.org/10.20471/acc.2021.60.03.12
36. Manyalich-Blasi M, Domínguez-Garijo P, Saavedra-Pérez D, Sánchez-Izquierdo N, Casanueva Eliceiry S, Perissinotti A, Mora Porta M, de Hollanda A, Hanzu FA, López-Boado Serrat MA, Rull Ortuño AR, Ardid J, Vidal-Sicart S, Vidal Pérez Ò. Comparison of [18F]fluorocholine PET/CT with [99mTc]sestamibi and ultrasonography to detect parathyroid lesions in primary hyperparathyroidism: a prospective study. Gland Surg. 2022 Nov;11(11):1764-1771. PMID: 36518798; PMCID: PMC9742049. https://doi.org/10.21037/gs-22-198
37. Crișan G, Moldovean-Cioroianu NS, Timaru DG, Andrieș G, Căinap C, Chiș V. Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. Int J Mol Sci. 2022 Apr 30;23(9):5023. PMID: 35563414; PMCID: PMC9103893. https://doi.org/10.3390/ijms23095023
38. Zhu M, He Y, Liu T, Tao B, Zhan W, Zhang Y, Xie J, Chen X, Zhao H, Sun L, Liu J. Factors That Affect the Sensitivity of Imaging Modalities in Primary Hyperparathyroidism. Int J Endocrinol. 2021 Feb 20;2021:3108395. PMID: 34840566; PMCID: PMC8616673. https://doi.org/10.1155/2021/3108395
39. Battistella E, Pomba L, Toniato R, Burei M, Gregianin M, Watutantrige Fernando S, Toniato A. Evolution of the Diagnosis and Treatment of Primary Hyperparathyroidism. J Clin Med. 2023 Mar 6;12(5):2057. PMID: 36902844; PMCID: PMC10004239. https://doi.org/10.3390/jcm12052057
40. Mathey C, Keyzer C, Blocklet D, Van Simaeys G, Trotta N, Lacroix S, Corvilain B, Goldman S, Moreno-Reyes R. 18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism. J Nucl Med. 2022 May;63(5):785-791. Epub 2021 Aug 19. PMID: 34413141. https://doi.org/10.2967/jnumed.121.262395
41. Evangelista L, Ravelli I, Magnani F, Iacobone M, Giraudo C, Camozzi V, Spimpolo A, Cecchin D. 18F-choline PET/CT and PET/MRI in primary and recurrent hyperparathyroidism: a systematic review of the literature. Ann Nucl Med. 2020 Sep;34(9):601-619. Epub 2020 Aug 7. PMID: 32767248; PMCID: PMC7438295. https://doi.org/10.1007/s12149-020-01507-1
42. Boudousq V, Guignard N, Gilly O, Chambert B, Mamou A, Moranne O, Zemmour M, Sharara H, Lallemant B. Diagnostic Performance of Cervical Ultrasound, 99mTc-Sestamibi Scintigraphy, and Contrast-Enhanced 18F-Fluorocholine PET in Primary Hyperparathyroidism. J Nucl Med. 2022 Jul;63(7):1081-1086. Epub 2021 Dec 2. PMID: 34857659. https://doi.org/10.2967/jnumed.121.261900
43. Aphale R, Dharmashaktu Y, Damle NA, Singareddy CR, Behera A, Wakankar R, Kumar P, Bal C, Khadgawat R, Chumber S. Odd Sites of Parathyroid Adenomas: 18F-fluorocholine PET/CT Pointing to the Right Place. Indian J Nucl Med. 2024 Mar-Apr;39(2):123-125. Epub 2024 May 29. PMID: 38989306; PMCID: PMC11232731. https://doi.org/10.4103/ijnm.ijnm_13_23
44. Imperiale A, Bani J, Bottoni G, Latgé A, Heimburger C, Catrambone U, Vix M, Treglia G, Piccardo A. Does 18F-Fluorocholine PET/CT add value to positive parathyroid scintigraphy in the presurgical assessment of primary hyperparathyroidism? Front Med (Lausanne). 2023 Apr 27;10:1148287. PMID: 37181366; PMCID: PMC10172498. https://doi.org/10.3389/fmed.2023.1148287
45. Uslu-Beşli L, Sonmezoglu K, Teksoz S, Akgun E, Karayel E, Pehlivanoglu H, Khosroshahi BR, Ocak M, Kabasakal L, Sager S, Bukey Y. 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 Feb;21(2):236-247. PMID: 31997599; PMCID: PMC6992441. https://doi.org/10.3348/kjr.2019.0268
46. Latge A, Riehm S, Vix M, Bani J, Ignat M, Pretet V, Helali M, Treglia G, Imperiale A. 18F-Fluorocholine PET and 4D-CT in Patients with Persistent and Recurrent Primary Hyperparathyroidism. Diagnostics (Basel). 2021 Dec 17;11(12):2384. PMID: 34943620; PMCID: PMC8700343. https://doi.org/10.3390/diagnostics11122384
47. Suntornlohanakul O, Leelawattana R. A case report of successful identification of ectopic parathyroid adenomas with a sequence of selective parathyroid venous sampling and 4D-computed tomography in a patient with recurrent hyperparathyroidism. Int J Surg Case Rep. 2020;71:183-186. Epub 2020 May 7. PMID: 32464540; PMCID: PMC7256430. https://doi.org/10.1016/j.ijscr.2020.04.021
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Laura Loryś, Klaudia Klimczak, Kamila Budzyńska, Marcin Narloch, Stanisław Kasprzak, Karolina Kasprzak, Jakub Kamiński, Norbert Kandefer

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 251
Number of citations: 0