Diagnostic Imaging Pathways - Hyperparathyroidism (Primary Suspected)
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This pathway provides guidance on the imaging of adult patients with suspected hyperparathyroidism.
Date reviewed: August 2018
Date of next review: August 2021
Published: July 2019
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The relative radiation level (RRL) of each imaging investigation is displayed in the pop up box.
| SYMBOL | RRL | EFFECTIVE DOSE RANGE |
 | None | 0 |
 | Minimal | < 1 millisieverts |
 | Low | 1-5 mSv |
 | Medium | 5-10 mSv |
 | High | >10 mSv |
Images
Image GalleryNote: These images open in a new page | ||
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| 1 |  |
Parathyroid Adenoma Image 1 (Ultrasound): A well circumscribed hypoechoic mass measuring up to 8mm is located deep to the inferior left thyroid pole. The appearances are consistent with a parathyroid adenoma. |
| 2a |  |
Parathyroid Adenoma Image 2a, 2b (Pertechnetate and Sestamibi Study), and 2c (SPECT): Initial pertechnetate images show uniform tracer distribution throughout both thyroid lobes apart from a small focal area of increased tracer uptake at the inferior pole of the left lobe of the thyroid gland. MIBI early and delayed images show increased uptake in the left and right lower poles of the thyroid. On subtraction images, there is an area of increased tracer activity near the inferior pole of the left lobe of the thyroid gland which represents abnormal parathyroid tissue (arrow). SPECT is used to help anatomically define the abnormal area. |
| 2b |  |
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| 2c |  |
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| 3 |  |
Parathyroid Adenoma Image 3 (H&E, x2.5): Histological section of a parathyroid adenoma showing sheets of monotonous oncocytic cells (blue arrows) and chief cells (green arrows) with no adipose tissue. |
Teaching Points
Teaching Points
- Imaging for preoperative localisation of the parathyroid glands remains controversial although it is generally recommended for minimally invasive or unilateral neck surgery
- Understanding the accuracy of each modality is vital in selecting the most appropriate preoperative imaging technique
- Ultrasound and Sestamibi scans are sensitive methods used as first line investigations, frequently in combination
- 4DCT has the advantage of superior anatomical localisation but is usually reserved for equivocal or negative ultrasound and nuclear medicine studies
- Preoperative imaging is required for recurrent or persistent hyperparathyroidism to minimise the risks of repeat surgery and to maximise the chances of successful treatment
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Primary Hyperparathyroidism
- Primary hyperparathyroidism is an endocrine disorder resulting from the autonomous functioning of one or more parathyroid glands 1,2
- The causes of primary hyperparathyroidism include a single parathyroid adenoma (80-85%), parathyroid hyperplasia (10-15%), multiple adenomas (2-3%), and very rarely, parathyroid adenocarcinoma (<1%) 1
- The role of imaging for preoperative localisation of the parathyroid glands remains controversial 1
- Traditionally, bilateral neck exploration with direct visualisation and evaluation of all four parathyroid glands has been the primary surgical method for treating primary hyperparathyroidism, with success rates >95% in experienced hands. Therefore, pre-operative localisation studies were not usually necessary 3
- Increasingly, surgeons prefer preoperative imaging, especially when considering minimally invasive surgery 1,3,4
- Imaging is usually required when there is recurrent disease as the success rates for repeat bilateral neck exploration after an initial failed surgery may be as low as 60%. In such cases of recurrent or persistent hyperparathyroidism, localisation studies have improved the ability to identify the site of the remaining abnormal parathyroid tissue 2,5
- The main advantages of preoperative imaging are 6,7
- The potential to reduce the time in surgery
- The ability to limit surgical exploration to the affected side
- The detection of ectopic abnormal parathyroid glands
- Technetium Tc-99m sestamibi imaging and sonography have been the most widely used imaging techniques for the localisation of parathyroid adenomas 1
- Invasive procedures such as selective venous sampling and selective angiography are expensive and technically difficult and therefore rarely used
- Image-guided biopsy is performed in cases where percutaneous ethanol ablation as a first line therapy is considered or when the results of imaging procedures are equivocal 8
- Note: It is important to consider and exclude Familial Hypocalciuric Hypercalcaemia (FHH) in mild cases of primary hyperparathyroidism. FHH does not require surgery and is a major cause of "failed" neck exploration in primary hyperparathyroidism
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Sestamibi Nuclear Medicine Scan and Subtraction Pertechnetate Scan
- Used for preoperative localisation of abnormal parathyroid glands in the following cases
- Includes the neck and the mediastinum for detection of ectopic abnormal parathyroid glands
- High sensitivity (50-75%) and specificity (>90%) for the detection of abnormal parathyroid glands 13-17
- Correlating the functional imaging provided by sestamibi scan with a technique with superior anatomical resolution such as SPECT, SPECT-CT, US or 4DCT improves the sensitivity for detection of abnormal parathyroid tissue 10,11,14,15,18-20
- Sestamibi accumulates in both parathyroid tissue and thyroid nodules and anatomical localisation of the abnormality is based on washout properties 21
- 99mTc-pertechnetate is a thyroid selective radioisotope that can be used in combination with sestamibi. It is especially useful in patients with suspected or known thyroid disease or previous thyroid surgery. Digital subtraction methods can be used as an aid in identifying sestamibi accumulation due to abnormal parathyroid tissue 18,20,21
- Limitations
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Ultrasound
- Used for identification and localisation of parathyroid adenomas in patients with primary hyperparathyroidism who undergo minimally invasive surgery 6,7,10
- Its sensitivity for detecting parathyroid neoplasms ranges between 36% to 78%. 7,10,13-15 In view of this, many authors now propose the use of ultrasound in combination with another imaging modality, most commonly scintigraphy 22
- Advantages 23
- Superior anatomical resolution (provides more detailed information of adenoma characteristics and relationships to other structures in the neck)
- Useful in evaluation of thyroid abnormalities
- Relatively inexpensive
- Does not emit ionising radiation
- Limitations 22,23
- Inability to localise the small percentage (2%) of parathyroid adenomas, particularly intrathyroidal, deeply located and ectopic mediastinal lesions
- Low sensitivity in recurrent or persistent primary hyperparathyroidism
- Operator dependent and subjective
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Persistent or Recurrent Hyperparathyroidism
- The incidence of persistent or recurrent disease following surgery for hyperparathyroidism is 5-10% 26,27
- Multiple potential causes could lead to recurrent disease including but not limited to inadequate excision, a second adenoma, multigland hyperplasia or hyperactive ectopic parathyroid tissue 26
- In such cases, the diagnosis of primary hyperparathyroidism should be re-confirmed and the indications for surgery should be reviewed 27
- Preoperative localisation is required in patients being considered for repeat surgery to more precisely define the site of abnormal parathyroid tissue and to minimise the risks associated with repeat surgery due to fibrosis
- Preoperative localisation improves the success rate from 60 to more than 95% 28
- It is still debated which combination of imaging modalities represents the optimum assessment. However, most agree that at least two modalities should be performed, one of which should be a sestamibi scan 27
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Four-dimensional computed tomography (4DCT)
- CT of the neck and mediastinum is generally considered second line investigation in the assessment of primary hyperparathyroidism, following on from equivocal or negative ultrasound or nuclear medicine studies 22
- The main advantage is superior spatial resolution and the detailed anatomical localisation of ectopic mediastinal lesions for surgical planning 22
- The sensitivity of CT for preoperative localisation of abnormal parathyroid tissue ranges from 78% to 92% 9,26,29,30
- Four-dimensional computed tomography involves acquisition of CT images during two or more contrast enhancement phases usually non-contrast, arterial and delayed phase 2
- 4DCT is able to provide detailed anatomical and functional information 26,31
- Several recent studies have shown 4DCT to be more sensitive than US and 99m Tc-MIBI scanning for localizing parathyroid tissue 26,29
- Currently 4DCT is more widely accepted as a second-line investigation or in patients undergoing repeat surgery 2
- Benefits include the speed and simplicity in image acquisition while limitations to consider include
- Exposure to ionising radiation
- The use of intravenous contrast
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Selective Venous Sampling
- Selective venous sampling is an invasive procedure which is generally only considered in the preoperative localisation of abnormal parathyroid tissue for recurrent or persistent hyperparathyroidism when non-invasive imaging methods have failed 26,32
- It involves selective cannulation of cervical and mediastinal veins to sample venous PTH levels. Local elevations of serum PTH compared to peripheral levels allow target areas to be defined for surgery (at least a two-fold gradient is required). Therefore, the effectiveness of this procedure depends upon production of PTH by the parathyroid glands and not on their size 32
- In the setting of recurrent or persistent hyperparathyroidism, the sensitivity for the localisation of abnormal parathyroid tissue ranges from 80 to 94% and the specificity from 85 to 100% 32,33
- The disadvantages of selective venous sampling include its
- Invasiveness with risks of haemorrhage and infection
- Exposure to ionising radiation and intravenous contrast
- Inability to direct the surgeon to an exact anatomical location
References
References
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
- Loevner LA. Imaging of the parathyroid glands. Semin Ultrasound CT MR. 1996;17:563-75. (Review article). View the reference
- Hoang JK, Sung WK, Bahl M, Phillips CD. How to perform parathyroid 4D CT: tips and traps for technique and interpretation. Radiology. 2014;270(1):15-24. (Review article). View the reference
- Howe JR. Minimally invasive parathyroid surgery. The Surgical clinics of North America. 2000;80(5):1399-426. (Review article). View the reference
- Mohebati A, Shaha AR. Imaging techniques in parathyroid surgery for primary hyperparathyroidism. American journal of otolaryngology. 2012;33(4):457-68. (Review article). View the reference
- Numerow LM, Morita ET, Clark OH, Higgins CB. Persistent/recurrent hyperparathyroidism: a comparison of sestamibi scintigraphy, MRI, and ultrasonography. Journal of magnetic resonance imaging : JMRI. 1995;5(6):702-8. (Level III evidence). View the reference
- Smit PC, Borel Rinkes IH, van Dalen A, van Vroonhoven TJ. Direct, minimally invasive adenomectomy for primary hyperparathyroidism: An alternative to conventional neck exploration? Annals of surgery. 2000;231(4):559-65. (Level II evidence). View the reference
- van Dalen A, Smit CP, van Vroonhoven TJ, Burger H, de Lange EE. Minimally invasive surgery for solitary parathyroid adenomas in patients with primary hyperparathyroidism: role of US with supplemental CT. Radiology. 2001;220(3):631-9. (Level II evidence). View the reference
- Gritzmann N, Koischwitz D, Rettenbacher T. Sonography of the thyroid and parathyroid glands. Radiologic clinics of North America. 2000;38(5):1131-45. (Review article). View the reference
- Harari A, Zarnegar R, Lee J, Kazam E, Inabnet WB, 3rd, Fahey TJ, 3rd. Computed tomography can guide focused exploration in select patients with primary hyperparathyroidism and negative sestamibi scanning. Surgery. 2008;144(6):970-6. (Level III evidence). View the reference
- Purcell GP, Dirbas FM, Jeffrey RB, Lane MJ, Desser T, McDougall IR, et al. Parathyroid localization with high-resolution ultrasound and technetium Tc 99m sestamibi. Archives of surgery (Chicago, Ill : 1960). 1999;134(8):824-8. (Level II evidence). View the reference
- 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 of persistent hyperparathyroidism. Radiology. 2001;218(3):783-90. (Level II evidence). View the reference
- Lee VS, Wilkinson RH, Jr., Leight GS, Jr., Coogan AC, Coleman RE. Hyperparathyroidism in high-risk surgical patients: evaluation with double-phase technetium-99m sestamibi imaging. Radiology. 1995;197(3):627-33. (Level III evidence). View the reference
- Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Annals of surgical oncology. 2012;19(2):577-83. (Level II evidence). View the reference
- Krubsack AJ, Wilson SD, Lawson TL, Kneeland JB, Thorsen MK, Collier BD, et al. Prospective comparison of radionuclide, computed tomographic, sonographic, and magnetic resonance localization of parathyroid tumors. Surgery. 1989;106(4):639-44. (Level II evidence). View the reference
- De Feo ML, Colagrande S, Biagini C, Tonarelli A, Bisi G, Vaggelli L, et al. Parathyroid glands: combination of (99m)Tc MIBI scintigraphy and US for demonstration of parathyroid glands and nodules. Radiology. 2000;214(2):393-402. (Level II/III evidence). View the reference
- Moralidis E. Radionuclide parathyroid imaging: a concise, updated review. Hellenic journal of nuclear medicine. 2013;16(2):125-33. (Review article). View the reference
- Madkhali T, Alhefdhi A, Chen H, Elfenbein D. Primary hyperparathyroidism. Ulusal cerrahi dergisi. 2016;32(1):58-66. (Review article). View the reference
- Lorberboym M, Minski I, Macadziob S, Nikolov G, Schachter P. Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2003;44(6):904-8. (Level II evidence). View the reference
- Ozkan ZG, Unal SN, Kuyumcu S, Sanli Y, Gecer MF, Ozcinar B, et al. Clinical Utility of Tc-99m MIBI SPECT/CT for Preoperative Localization of Parathyroid Lesions. The Indian journal of surgery. 2017;79(4):312-8. (Level IV evidence). View the reference
- Neumann DR, Esselstyn CB, Jr., Go RT, Wong CO, Rice TW, Obuchowski NA. Comparison of double-phase 99mTc-sestamibi with 123I-99mTc-sestamibi subtraction SPECT in hyperparathyroidism. AJR American journal of roentgenology. 1997;169(6):1671-4. (Level II evidence). View the reference
- Smith JR, Oates ME. Radionuclide imaging of the parathyroid glands: patterns, pearls, and pitfalls. Radiographics : a review publication of the Radiological Society of North America, Inc. 2004;24(4):1101-15. (Review article). View the reference
- Hindie E, Ugur O, Fuster D, O'Doherty M, Grassetto G, Urena P, et al. 2009 EANM parathyroid guidelines. European journal of nuclear medicine and molecular imaging. 2009;36(7):1201-16. (Guidelines). View the reference
- Reeder SB, Desser TS, Weigel RJ, Jeffrey RB. Sonography in primary hyperparathyroidism: review with emphasis on scanning technique. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2002;21(5):539-52. (Review article). View the reference
- 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. European journal of nuclear medicine and molecular imaging. 2018;45(10):1762-71. (Level II/III evidence). View the reference
- Lezaic L, Rep S, Sever MJ, Kocjan T, Hocevar M, Fettich J. (1)(8)F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study. European journal of nuclear medicine and molecular imaging. 2014;41(11):2083-9. (Level III/IV evidence). View the reference
- Ginsburg M, Christoforidis GA, Zivin SP, Obara P, Wroblewski K, Angelos P, et al. Adenoma localization for recurrent or persistent primary hyperparathyroidism using dynamic four-dimensional CT and venous sampling. Journal of vascular and interventional radiology : JVIR. 2015;26(1):79-86. (Review article). View the reference
- Linwah Yip, Shonni Silverberg, Fuleihan G. reoperative localization for parathyroid surgery in patients with primary hyperparathyroidism. Waltham, MA: UpToDate Inc View the reference
- Shen W, Duren M, Morita E, Higgins C, Duh QY, Siperstein AE, et al. Reoperation for persistent or recurrent primary hyperparathyroidism. Archives of surgery (Chicago, Ill : 1960). 1996;131(8):861-7. (Level III evidence). View the reference
- Brown SJ, Lee JC, Christie J, Maher R, Sidhu SB, Sywak MS, et al. Four-dimensional computed tomography for parathyroid localization: a new imaging modality. ANZ journal of surgery. 2015;85(6):483-7. (Level III evidence). View the reference
- Mazzeo S, Cappelli C, Caramella D, Belcari A, Forasassi F, Battaglia V, et al. Multidetector CT in diagnostic work-up of patients with primary hyperparathyroidism. La Radiologia medica. 2007;112(5):763-75. (Level III evidence). View the reference
- Rodgers SE, Hunter GJ, Hamberg LM, Schellingerhout D, Doherty DB, Ayers GD, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery. 2006;140(6):932-40; (Review article). View the reference
- Chaffanjon PC, Voirin D, Vasdev A, Chabre O, Kenyon NM, Brichon PY. Selective venous sampling in recurrent and persistent hyperparathyroidism: indication, technique, and results. World journal of surgery. 2004;28(10):958-61. (Level III evidence). View the reference
- Reidel MA, Schilling T, Graf S, Hinz U, Nawroth P, Buchler MW, et al. Localization of hyperfunctioning parathyroid glands by selective venous sampling in reoperation for primary or secondary hyperparathyroidism. Surgery. 2006;140(6):907-13. (Level II evidence). View the reference
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