Parathyroid adenoma other imaging findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]
Overview
Imaging modalities may be helpful in preoperative localization of hyper-functioning parathyroid glands. This includes both non-invasive and invasive modalities. Non-invasive imaging modalities for preoperative localization of hyper-functioning parathyroid glands include Tc-99m sestamibi scintigraphy (sestamibi or MIBI), single photon emission computed tomography (SPECT), positron emission tomography (PET). Invasive modalities used for preoperative localization of hyper-functioning parathyroid glands include selective arteriography and angiography. Dual energy X-ray absorptiometry is helpful in detecting low bone mineral density (BMD) caused by hyperparathyroidism.
Other Imaging Findings
Other imaging modalities are used for preoperative localization of hyper-functioning parathyroid glands. This includes both non-invasive and invasive modalities. Another modality used in hyperparathyroidism is dual energy X-ray absorptiometry (DXA). DXA is helpful in detecting low bone mineral density (BMD) caused by hyperparathyroidism.
Non-invasive modalities
TC-99m Sestamibi Scintigraphy
- Technetium-99m-methoxyisobutylisonitrile (99mTc-sestamibi or MIBI) scintigraphy is the most popular investigation for preoperative localization of hyper-functioning parathyroid glands.[1]
- Most of the sestamibi is retained in mitochondria of thyroid and abnormal parathyroid tissue and is a function of mitochondrial activity.[2]
- Single-isotope, double-phase technique is used. The basis of "single-isotope, double-phase technique" is that sestamibi washes out of the thyroid more rapidly than from abnormal parathyroid tissue.[3]
- Multiple planar images are obtained, typically one shortly after injection of 99mTc-sestamibi and another after two hours to identify the areas of retained sestamibi showing hyper-functioning parathyroid tissue.
- As all parathyroid lesions does not retain sestamibi nor all thyroid tissue washes out quickly, subtraction imaging may be beneficial.[4]
- Subtraction technique uses dual contrast Tc-99m sestamibi along with iodine-123 or 99m-technicium pertechnetate, which are taken by thyroid tissue only. Iodine-123/99m-technicium pertechnetate images of thyroid are later digitally subtracted from Tc-99m sestamibi images leading to visualization of parathyroid tissue only.[5]
- Presence of solid thyroid nodule is the most common cause of false positive results. Other causes of false positive results may include thyroid carcinoma, lymphoma, and lymphadenopathy.
- The sensitivity of sestamibi scintigraphy can be increased by using it concomitantly with neck ultrasound and/or SPECT. [6][7]
- The sensitivity of sestamibi scintigraphy is 80% - 90%.[8][9][10]
| Factors influencing sensitivity of Tc-99m sestamibi scintigraphy | ||
|---|---|---|
| Factors | Sensitivity | |
| Biochemical factors | High serum calcium level[11] | Increased |
| High serum parathyroid hormone level[11][12] | Increased | |
| Hypovitaminosis D [13]
(only in primary hyperparathyroidism) |
Increased | |
| Calcium channel blocker use[14]
(only in primary hyperparathyroidism) |
Decreased | |
| Gross and architectural factors | Size (Large)[15][16] | Increased |
| Multi-glandular disease[17] | Decreased | |
| Cytological factors | Increased amount of cellular content[15][16]
(Chief cells and oxyphil cells) |
Increased |
| Immunohistochemical factors | Increased P-glycoprotien expression[18] | Decreased |
| Note: P-glycoprotein (Pgp) is a plasma membrane protein encoded by mammalian multidrug resistance gene (MDRI). Many drugs that are lipophilic and cationic at physiological pH interact with P-gp. Sestamibi is a lipophilic cationic on physioligical pH. P-gp acts as ATP-dependent efflux pump and prevents accumulation of sestamibi in parathyroid tissue. So, the uptake of sestamibi into parathyroid adenoma cells depends on the activity of the P-gp[19]. | ||
 |
 |
Single photon emission computed tomography (SPECT)
- Single photon emission computed tomography may be used along with Tc-99m sestamibi scintigraphy for preoperative evaluation of hyper-functioning parathyroid gland.[20][21]
- Sestamibi-SPECT is also called pinhone-SPECT (P-SPECT). P-SPECT uses cone beam collimator in contrast to parallel-hole collimator used in SPECT. cone bean collimator possess more suitable geometric properties leading to high spatial resolution.[22][23]
- Using SPECT with sestamibi scintigraphy improves detection and localization of hyper-functioning parathyroid gland.[24][25]
- P-SPECT provides more precise result of sestamibi scitigraphy allowing surgeon to choose best route for surgical intervention.
- P-SPECT may detect glands not visible on planer images leading to increased sensitivity. It is very useful in case of uncertain result from conventional sestamibi scitigraphy.[26][27]
- P-SPECT also enables accurate interpretation sestamibi uptake in upper mediastinum leading to a higher specificity.
- In difficult cases, P-SPECT may also be adjuncted with subtraction Tc-99m sestamibi and I-123 scintigraphy or positron emission tomography.[28]
- P-SPECT is approximately 84% sensitive, 91% specific with positive predictive value of around 91% and negative predictive value of around 84%.[29]
- Fusion images of CT-MIBI-SPECT is superior to CT scan or MIBI-SPECT alone in preoperative localization of hyper-functioning parathyroid gland.[30]
Positron Emission Tomography (PET)
- 11C-methionine PET along with CT scan (MET-PET/CT) may be used for preoperative localization of hyper-functioning parathyroid glands.[31][32]
- MET-PET/CT may be used as an complimentary imaging modality for localizing hyper-functioning parathyroid glands in patients with negative Tc-99m sestamibi scintigraphy/SPECT results.[33]
Invasive modalities
Selective arteriography
- Selective transarterial hypocalcemic stimulation is combined with nonselective venous sampling to perform selective arteriography.[34]
- Sodium citrate is injected to induce hypocalcemia. Simultaneous arteriography is performed.
- Samples are taken for superior vena cava at basaeline and timed intervals (20 sec, 40 sec, and 60 sec).
- An increase in the parathyroid hormone level to 1.4 times above the baseline or a clear blush observed on arteriography is considered as positive localization.
- Arterial stimulation venous sampling is performed simultaneously with arteriogram due to similarly high PPV.
Angiography
- Superselective arterial digital subtraction angiography (DSA) and superselective conventional angiography (CA) may be used for preoperative localization of hyper-functioning parathyroid glands in which noninvasive imaging modalities are negative or inconclusive.[35]
- Sensitivity of superselective digital subtraction angiography appears to be similar to conventional angiography.
- Superselective arterial digital subtraction angiography may be more sensitive than conventional angiography for preoperative localization of mediastinal hyper-functioning parathyroid glands.
Dual Energy X-ray Absorptiometry (DXA)
- Low bone mineral density (BMD) is caused by primary hyperparathyroidism. Distal forearm is affected most commonly.
- DXA of distal forearm should be done in all patients of primary hyperparathyroidism. Very low T-score of distal forearm is observed in patients with primary hyperparathyroidism.[36]
References
- ↑ Palestro CJ, Tomas MB, Tronco GG (2005). "Radionuclide imaging of the parathyroid glands". Semin Nucl Med. 35 (4): 266–76. doi:10.1053/j.semnuclmed.2005.06.001. PMID 16150247.
- ↑ Hetrakul N, Civelek AC, Stagg CA, Udelsman R (2001). "In vitro accumulation of technetium-99m-sestamibi in human parathyroid mitochondria". Surgery. 130 (6): 1011–8. doi:10.1067/msy.2001.118371. PMID 11742331.
- ↑ Taillefer R, Boucher Y, Potvin C, Lambert R (1992). "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. 33 (10): 1801–7. PMID 1328564.
- ↑ Thulé P, Thakore K, Vansant J, McGarity W, Weber C, Phillips LS (1994). "Preoperative localization of parathyroid tissue with technetium-99m sestamibi 123I subtraction scanning". J Clin Endocrinol Metab. 78 (1): 77–82. doi:10.1210/jcem.78.1.8288719. PMID 8288719.
- ↑ Ryhänen EM, Schildt J, Heiskanen I, Väisänen M, Ahonen A, Löyttyniemi E; et al. (2015). "(99m)Technetium Sestamibi-(123)Iodine Scintigraphy Is More Accurate Than (99m)Technetium Sestamibi Alone before Surgery for Primary Hyperparathyroidism". Int J Mol Imaging. 2015: 391625. doi:10.1155/2015/391625. PMC 4333274. PMID 25722888.
- ↑ Eslamy HK, Ziessman HA (2008). "Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99mTc sestamibi SPECT and SPECT/CT". Radiographics. 28 (5): 1461–76. doi:10.1148/rg.285075055. PMID 18794320.
- ↑ Haber RS, Kim CK, Inabnet WB (2002). "Ultrasonography for preoperative localization of enlarged [[parathyroid]] glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy". Clin Endocrinol (Oxf). 57 (2): 241–9. PMID 12153604. URL–wikilink conflict (help)
- ↑ Chapuis Y, Fulla Y, Bonnichon P, Tarla E, Abboud B, Pitre J, Richard B (1996). "Values of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of 1-84 PTH for unilateral neck exploration of primary hyperparathyroidism". World J Surg. 20 (7): 835–9, discussion 839–40. PMID 8678959.
- ↑ Prasannan S, Davies G, Bochner M, Kollias J, Malycha P (2007). "Minimally invasive parathyroidectomy using surgeon-performed ultrasound and sestamibi". ANZ J Surg. 77 (9): 774–7. doi:10.1111/j.1445-2197.2007.04227.x. PMID 17685957.
- ↑ Gómez-Ramírez J, Sancho-Insenser JJ, Pereira JA, Jimeno J, Munné A, Sitges-Serra A (2010). "Impact of thyroid nodular disease on 99mTc-sestamibi scintigraphy in patients with primary hyperparathyroidism". Langenbecks Arch Surg. 395 (7): 929–33. doi:10.1007/s00423-010-0680-8. PMID 20625763.
- ↑ 11.0 11.1 Parikshak M, Castillo ED, Conrad MF, Talpos GB (2003). "Impact of [[hypercalcemia]] and [[parathyroid hormone]] level on the sensitivity of preoperative sestamibi scanning for primary hyperparathyroidism". Am Surg. 69 (5): 393–8, discussion 399. PMID 12769210. URL–wikilink conflict (help)
- ↑ Siegel A, Alvarado M, Barth RJ, Brady M, Lewis J (2006). "Parameters in the prediction of the sensitivity of parathyroid scanning". Clin Nucl Med. 31 (11): 679–82. doi:10.1097/01.rlu.0000242212.23936.a7. PMID 17053383.
- ↑ Kandil E, Tufaro AP, Carson KA, Lin F, Somervell H, Farrag T; et al. (2008). "Correlation of plasma 25-hydroxyvitamin D levels with severity of primary hyperparathyroidism and likelihood of parathyroid adenoma localization on sestamibi scan". Arch Otolaryngol Head Neck Surg. 134 (10): 1071–5. doi:10.1001/archotol.134.10.1071. PMID 18936353.
- ↑ Friedman K, Somervell H, Patel P, Melton GB, Garrett-Mayer E, Dackiw AP; et al. (2004). "Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism". Surgery. 136 (6): 1199–204. doi:10.1016/j.surg.2004.06.047. PMID 15657576.
- ↑ 15.0 15.1 Mehta NY, Ruda JM, Kapadia S, Boyer PJ, Hollenbeak CS, Stack BC (2005). "Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue". Arch Otolaryngol Head Neck Surg. 131 (6): 493–8. doi:10.1001/archotol.131.6.493. PMID 15967881.
- ↑ 16.0 16.1 Takebayashi S, Hidai H, Chiba T, Takagi Y, Nagatani Y, Matsubara S (1999). "Hyperfunctional parathyroid glands with 99mTc-MIBI scan: semiquantitative analysis correlated with histologic findings". J Nucl Med. 40 (11): 1792–7. PMID 10565772.
- ↑ Haciyanli M, Lal G, Morita E, Duh QY, Kebebew E, Clark OH (2003). "Accuracy of preoperative localization studies and intraoperative [[parathyroid hormone]] assay in patients with primary hyperparathyroidism and double [[adenoma]]". J Am Coll Surg. 197 (5): 739–46. doi:10.1016/S1072-7515(03)00676-8. PMID 14585407. URL–wikilink conflict (help)
- ↑ Gupta Y, Ahmed R, Happerfield L, Pinder SE, Balan KK, Wishart GC (2007). "P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism". Br J Surg. 94 (12): 1491–5. doi:10.1002/bjs.5882. PMID 17929232.
- ↑ Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM (1993). "Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex". Cancer Res. 53 (5): 977–84. PMID 8094997.
- ↑ Billotey C, Sarfati E, Aurengo A, Duet M, Mündler O, Toubert ME; et al. (1996). "Advantages of SPECT in technetium-99m-sestamibi parathyroid scintigraphy". J Nucl Med. 37 (11): 1773–8. PMID 8917173.
- ↑ Civelek AC, Ozalp E, Donovan P, Udelsman R (2002). "Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism". Surgery. 131 (2): 149–57. PMID 11854692.
- ↑ Strand SE, Ivanovic M, Erlandsson K, Franceschi D, Button T, Sjögren K; et al. (1994). "Small animal imaging with pinhole single-photon emission computed tomography". Cancer. 73 (3 Suppl): 981–4. PMID 8306288.
- ↑ Jaszczak RJ, Li J, Wang H, Zalutsky MR, Coleman RE (1994). "Pinhole collimation for ultra-high-resolution, small-field-of-view SPECT". Phys Med Biol. 39 (3): 425–37. PMID 15551591.
- ↑ Schachter PP, Issa N, Shimonov M, Czerniak A, Lorberboym M (2004). "Early, postinjection MIBI-SPECT as the only preoperative localizing study for minimally invasive parathyroidectomy". Arch Surg. 139 (4): 433–7. doi:10.1001/archsurg.139.4.433. PMID 15078713.
- ↑ Perez-Monte JE, Brown ML, Shah AN, Ranger NT, Watson CG, Carty SE; et al. (1996). "Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT". Radiology. 201 (1): 85–91. doi:10.1148/radiology.201.1.8816526. PMID 8816526.
- ↑ Spanu A, Falchi A, Manca A, Marongiu P, Cossu A, Pisu N; et al. (2004). "The usefulness of neck pinhole SPECT as a complementary tool to planar scintigraphy in primary and secondary hyperparathyroidism". J Nucl Med. 45 (1): 40–8. PMID 14734671.
- ↑ Carlier T, Oudoux A, Mirallié E, Seret A, Daumy I, Leux C, Bodet-Milin C, Kraeber-Bodéré F, Ansquer C (2008). "99mTc-MIBI pinhole SPECT in primary hyperparathyroidism: comparison with conventional SPECT, planar scintigraphy and ultrasonography". Eur. J. Nucl. Med. Mol. Imaging. 35 (3): 637–43. doi:10.1007/s00259-007-0625-9. PMC 2964350. PMID 17960377.
- ↑ Nguyen BD (1999). "Parathyroid imaging with Tc-99m sestamibi planar and SPECT scintigraphy". Radiographics. 19 (3): 601–14, discussion 615-6. doi:10.1148/radiographics.19.3.g99ma10601. PMID 10336191.
- ↑ Lindqvist V, Jacobsson H, Chandanos E, Bäckdahl M, Kjellman M, Wallin G (2009). "Preoperative 99Tc(m)-sestamibi scintigraphy with SPECT localizes most pathologic parathyroid glands". Langenbecks Arch Surg. 394 (5): 811–5. doi:10.1007/s00423-009-0536-2. PMID 19578871.
- ↑ Wimmer G, Profanter C, Kovacs P, Sieb M, Gabriel M, Putzer D; et al. (2010). "CT-MIBI-SPECT image fusion predicts multiglandular disease in hyperparathyroidism". Langenbecks Arch Surg. 395 (1): 73–80. doi:10.1007/s00423-009-0545-1. PMID 19705144.
- ↑ Tang BN, Moreno-Reyes R, Blocklet D, Corvilain B, Cappello M, Delpierre I; et al. (2008). "Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT". Contrast Media Mol Imaging. 3 (4): 157–63. doi:10.1002/cmmi.243. PMID 18781582.
- ↑ Weber T, Maier-Funk C, Ohlhauser D, Hillenbrand A, Cammerer G, Barth TF; et al. (2013). "Accurate preoperative localization of parathyroid adenomas with C-11 methionine PET/CT". Ann Surg. 257 (6): 1124–8. doi:10.1097/SLA.0b013e318289b345. PMID 23478517.
- ↑ Traub-Weidinger T, Mayerhoefer ME, Koperek O, Mitterhauser M, Duan H, Karanikas G; et al. (2014). "11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/CT-negative patients with primary hyperparathyroidism and previous neck surgery". J Clin Endocrinol Metab. 99 (11): 4199–205. doi:10.1210/jc.2014-1267. PMID 25029418.
- ↑ Powell AC, Alexander HR, Chang R, Marx SJ, Skarulis M, Pingpank JF; et al. (2009). "Reoperation for parathyroid adenoma: a contemporary experience". Surgery. 146 (6): 1144–55. doi:10.1016/j.surg.2009.09.015. PMC 3467310. PMID 19958942.
- ↑ Miller DL, Chang R, Doppman JL, Norton JA (1989). "Localization of parathyroid adenomas: superselective arterial DSA versus superselective conventional angiography". Radiology. 170 (3 Pt 2): 1003–6. doi:10.1148/radiology.170.3.2644666. PMID 2644666.
- ↑ Wood K, Dhital S, Chen H, Sippel RS (2012). "What is the utility of distal forearm DXA in primary hyperparathyroidism?". Oncologist. 17 (3): 322–5. doi:10.1634/theoncologist.2011-0285. PMC 3316917. PMID 22258698.