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Факторы, ассоциированные со степенью накопления 99mTc-МИБИ при планарной сцинтиграфии и ОФЭКТ/КТ в опухолях околощитовидных желез при первичном гиперпаратиреозе: одномоментное сравнительное исследование
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Slashchuk KYu, Degtyarev MV, Rumyantsev PO, Rebrova OYu, Elfimova AR, Selivanova LS, Mokrysheva NG. Factors associated with the degree of 99mTc-MIBI accumulation in parathyroid glands neoplasms during planar scintigraphy and SPECT/CT in primary hyperparathyroidism: cross-sectional comparative study. Journal of Modern Oncology. 2022;24(1):98–105. DOI: 10.26442/18151434.2022.1.201252
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Цель. Определить факторы, ассоциированные со степенью накопления (интенсивностью захвата) 99mTc-МИБИ в ОЩЖ у пациентов с первичным гиперпаратиреозом при планарной сцинтиграфии и ОФЭКТ/КТ.
Материалы и методы. В одномоментное сравнительное исследование были включены 186 пациентов с первичным гиперпаратиреозом, которым выполнена планарная сцинтиграфия и ОФЭКТ/КТ с целью топической диагностики образований ОЩЖ с последующим хирургическим лечением в объеме минимально инвазивной паратиреоидэктомии, гистологическим и иммуногистохимическим исследованиями удаленных образований ОЩЖ. Пациенты разделены на 3 группы в зависимости от интенсивности накопления РФП, накопление РФП оценивалось экспертом как низко-, умеренно- и высоко-интенсивное.
Результаты. Установлена ассоциация объема образований ОЩЖ, определенного при ультразвуковом исследовании, и интенсивности захвата РФП. При объеме ОЩЖ<0,215 см3, что соответствует линейному размеру образований ОЩЖ≤5 мм, вероятность низкого накопления или его отсутствия составила 80%. Фактором, препятствующим накоплению РФП, являются сопутствующие структурные заболевания щитовидной железы. Ассоциации содержания паратгормона, кальция в крови, локализации и клеточного состава образований ОЩЖ, индекса пролиферативной активности Ki67, экспрессии паратиреоидного гормона, П-гликопротеина или циклина D1 в ткани ОЩЖ с интенсивностью накопления 99mTc-МИБИ не обнаружено.
Заключение. Фактором, положительно ассоциированным со степенью накопления РФП при планарной сцинтиграфии и ОФЭКТ/КТ, является объем образований ОЩЖ. Сопутствующая патология щитовидной железы имеет статистическую тенденцию к ассоциации с низким накоплением РФП.
Ключевые слова: первичный гиперпаратиреоз, визуализация околощитовидных желез, планарная сцинтиграфия, ОФЭКТ/КТ, объем околощитовидных желез, сопутствующая патология щитовидной железы
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Background. Primary hyperparathyroidism (PHPT) is the third most common endocrine disease, after diabetes mellitus and thyroid gland disorders. Surgical removal of the hyperfunctioning parathyroid glands is the only radical treatment. Various methods of preoperative imaging and intraoperative navigation are developed. Planar scintigraphy with 99mTc-MIBI is used for visualization and it is the most frequently performed radionuclide study in PHPT, while it has a relatively low sensitivity and specificity. Single photon emission computed tomography and computed tomography (SPECT/CT) can reduce false-negative and false-positive results, and combines the advantages of radionuclide diagnostic methods and computed tomography. However, the factors that prevent the accumulation of 99mTc-MIBI in patients with PHPT are not clear enough.
Aim. To identify the factors associated with the degree of accumulation (uptake rate) of 99mTc-MIBI in the parathyroid glands during planar scintigraphy and SPECT/CT.
Materials and methods. The cross-sectional comparative study included 186 patients with PHPT who underwent planar scintigraphy and SPECT/CT for topical diagnosis of parathyroid glands and minimally invasive parathyroidectomy followed by histological and immunohistochemical examination of parathyroid glands. The patients were divided into 3 groups depending on the accumulation of 99mTc-MIBI. The accumulation of 99mTc-MIBI was assessed by the expert as low- , moderate- , and high-intensity.
Results. The association between the volume of the parathyroid glands on ultrasound and the intensity of the capture of the radiopharmaceutical was revealed, and 80% of low uptake is observed if volume is less than 0.215 cm3 (it corresponds to the linear size of the parathyroid gland ≤5 mm). Next factor that complicate the interpretation of the results of planar scintigraphy and SPECT/CT in patients with PHPT is thyroid diseases. The associations of the level of PTH, calcium in the blood, the localization and cellular composition of the parathyroid glands, the index of proliferative activity (Ki67), the expression of PTH, P-glycoprotein, cyclin D1 in the PTG tissue with the intensity of 99mTc-MIBI accumulation were not found.
Conclusion. The main factor that positively associates with the degree of 99mTc-MIBI accumulation with planar scintigraphy and SPECT/CT is the volume of the parathyroid glands according to ultrasound data. Comorbidity of the thyroid gland has tendency to be associated with a negative result of radionuclide diagnostics.
Keywords: primary hyperparathyroidism, visualization of parathyroid glands, sestamibi scintigraphy, SPECT/CT, volume of parathyroid glands, concomitant thyroid disease
2. Wong KK, Fig LM, Gross MD, et al. Parathyroid adenoma localization with 99mTc-sestamibi SPECT/CT: a meta-analysis. Nucl Med Comm. 2015;36(4):363‑75. DOI:10.1097/MNM.0000000000000262
3. Taieb D, Hindie E, Grassetto G., et al. Parathyroid scintigraphy: When, how, and why? A concise systematic review. Clin Nucl Med. 2012;37(6):568-74. DOI:10.1097/RLU.0b013e318251e408
4. Zhou J, Lu DY, Xia L, Cheng XJ. Diagnosis performance of 99mTc-MIBI and multimodality imaging for hyperparathyroidism. J Huazhong Univ Sci Technolog Med Sci. 2017;37(4):582‑6. DOI:10.1007/s11596-017-1776-y
5. Robin P, Klein R, Gardner J, et al. Quantitative analysis of technetium-99m-sestamibi uptake and washout in parathyroid scintigraphy supports dual mechanisms of lesion conspicuity. Nucl Med Commun. 2019;40(5):469-76. DOI:10.1097/MNM.0000000000000996
6. Parathyroid Scintigraphy A Technologist’s Guide Contributors. EANM Guidelines, 2005. Available at: https://www.eanm.org/content-eanm/uploads/2016/11/tech_guide_pt_scint.pdf/ Accessed: 14.02.2022.
7. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med. 2003;44(9):1443-58.
8. Pons F, Torregrosa JV, Fuster D. Biological factors influencing parathyroid localization. Nucl Med Commun. 2003;24(2):121-4. DOI:10.1097/00006231-200302000-00003
9. Sencar ME, Sakiz D, Unsal IO, et al. Serum Vitamin D Level Does not Affect The Sensitivity of Parathyroid Adenoma Localization Tests. Sci Rep. 2019;9(1):12035.
DOI:10.1038/s41598-019-48536-z
10. 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):959-68. DOI:10.1001/jamasurg.2016.2310
11. Calva-Cerqueira D, Smith BJ, Hostetler ML, et al. Minimally invasive parathyroidectomy and preoperative MIBI scans: correlation of gland weight and preoperative PTH. J Am Coll Surg. 2007;205(4 Suppl.):38-44. DOI:10.1016/j.jamcollsurg.2007.06.322
12. 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(1):34-9. DOI:10.1016/j.amjsurg.2007.01.040
13. Elgazzar AH, Anim JT, Dannoon SF, Farghaly MM. Ultrastructure of Hyperfunctioning Parathyroid Glands: Does it Explain Various Patterns of 99mTc-sestamibi Uptake. World J Nucl Med. 2017;16(2):145-9. DOI:10.4103/1450-1147.203073
14. Bleier BS, LiVolsi VA, Chalian AA, et al. Technetium Tc 99m sestamibi sensitivity in oxyphil cell-dominant parathyroid adenomas. Arch Otolaryngol Head Neck Surg. 2006;132(7):779‑82. DOI:10.1001/archotol.132.7.779
15. Mehta NY, Ruda JM, Kapadia S, et al. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg. 2005;131:493-8. DOI:10.1001/archotol.131.6.493
16. Gupta Y, Ahmed R, Happerfield L, et al. P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism. Br J Surg. 2007;94(12):1491-5. DOI:10.1002/bjs.5882
17. Pinero A, Rodríguez JM, Martínez-Barba E, et al. Tc99m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship? Surgery. 2003;134(1):41-4. DOI:10.1067/msy.2003.158
18. Sun SS, Shiau YC, Lin CC, et al. Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings. Nucl Med Biol. 2001;28(8):929‑33. DOI:10.1016/s0969-8051(01)00259-1
19. Yamaguchi S, Yachiku S, Hashimoto H, et al. Relation between technetium 99m-methoxyisobutylisonitrile accumulation and multidrug resistance protein in the parathyroid glands. World J Surg. 2002;26(1):29-34. DOI:10.1007/s00268-001-0177-2
20. Mshelia DS, Hatutale AN, Mokgoro NP, et al. Correlation between serum calcium levels and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy in primary hyperparathyroidism. Clin Physiol Funct Imaging. 2012;32(1):19-24. DOI:10.1111/j.1475-097X.2011.01048.x
21. Silov G, Ozdal A, Erdoğan Z, et al. The relationship between technetium-99m-methoxyisobutylisonitrile parathyroid scintigraphy and hormonal and biochemical markers in suspicion of primary hyperparathyroidism. Mol Imaging Radionucl Ther. 2013;22(1):8-13. DOI:10.4274/Mirt.21931
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1. Sudhaker D. Epidemiology of parathyroid disorders. Best Pract Res Clin Endocrinol Metab. 2018;32(6):773-80. DOI:10.1016/j.beem.2018.12.003
2. Wong KK, Fig LM, Gross MD, et al. Parathyroid adenoma localization with 99mTc-sestamibi SPECT/CT: a meta-analysis. Nucl Med Comm. 2015;36(4):363‑75. DOI:10.1097/MNM.0000000000000262
3. Taieb D, Hindie E, Grassetto G., et al. Parathyroid scintigraphy: When, how, and why? A concise systematic review. Clin Nucl Med. 2012;37(6):568-74. DOI:10.1097/RLU.0b013e318251e408
4. Zhou J, Lu DY, Xia L, Cheng XJ. Diagnosis performance of 99mTc-MIBI and multimodality imaging for hyperparathyroidism. J Huazhong Univ Sci Technolog Med Sci. 2017;37(4):582‑6. DOI:10.1007/s11596-017-1776-y
5. Robin P, Klein R, Gardner J, et al. Quantitative analysis of technetium-99m-sestamibi uptake and washout in parathyroid scintigraphy supports dual mechanisms of lesion conspicuity. Nucl Med Commun. 2019;40(5):469-76. DOI:10.1097/MNM.0000000000000996
6. Parathyroid Scintigraphy A Technologist’s Guide Contributors. EANM Guidelines, 2005. Available at: https://www.eanm.org/content-eanm/uploads/2016/11/tech_guide_pt_scint.pdf/ Accessed: 14.02.2022.
7. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med. 2003;44(9):1443-58.
8. Pons F, Torregrosa JV, Fuster D. Biological factors influencing parathyroid localization. Nucl Med Commun. 2003;24(2):121-4. DOI:10.1097/00006231-200302000-00003
9. Sencar ME, Sakiz D, Unsal IO, et al. Serum Vitamin D Level Does not Affect The Sensitivity of Parathyroid Adenoma Localization Tests. Sci Rep. 2019;9(1):12035.
DOI:10.1038/s41598-019-48536-z
10. 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):959-68. DOI:10.1001/jamasurg.2016.2310
11. Calva-Cerqueira D, Smith BJ, Hostetler ML, et al. Minimally invasive parathyroidectomy and preoperative MIBI scans: correlation of gland weight and preoperative PTH. J Am Coll Surg. 2007;205(4 Suppl.):38-44. DOI:10.1016/j.jamcollsurg.2007.06.322
12. 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(1):34-9. DOI:10.1016/j.amjsurg.2007.01.040
13. Elgazzar AH, Anim JT, Dannoon SF, Farghaly MM. Ultrastructure of Hyperfunctioning Parathyroid Glands: Does it Explain Various Patterns of 99mTc-sestamibi Uptake. World J Nucl Med. 2017;16(2):145-9. DOI:10.4103/1450-1147.203073
14. Bleier BS, LiVolsi VA, Chalian AA, et al. Technetium Tc 99m sestamibi sensitivity in oxyphil cell-dominant parathyroid adenomas. Arch Otolaryngol Head Neck Surg. 2006;132(7):779‑82. DOI:10.1001/archotol.132.7.779
15. Mehta NY, Ruda JM, Kapadia S, et al. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg. 2005;131:493-8. DOI:10.1001/archotol.131.6.493
16. Gupta Y, Ahmed R, Happerfield L, et al. P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism. Br J Surg. 2007;94(12):1491-5. DOI:10.1002/bjs.5882
17. Pinero A, Rodríguez JM, Martínez-Barba E, et al. Tc99m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship? Surgery. 2003;134(1):41-4. DOI:10.1067/msy.2003.158
18. Sun SS, Shiau YC, Lin CC, et al. Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings. Nucl Med Biol. 2001;28(8):929‑33. DOI:10.1016/s0969-8051(01)00259-1
19. Yamaguchi S, Yachiku S, Hashimoto H, et al. Relation between technetium 99m-methoxyisobutylisonitrile accumulation and multidrug resistance protein in the parathyroid glands. World J Surg. 2002;26(1):29-34. DOI:10.1007/s00268-001-0177-2
20. Mshelia DS, Hatutale AN, Mokgoro NP, et al. Correlation between serum calcium levels and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy in primary hyperparathyroidism. Clin Physiol Funct Imaging. 2012;32(1):19-24. DOI:10.1111/j.1475-097X.2011.01048.x
21. Silov G, Ozdal A, Erdoğan Z, et al. The relationship between technetium-99m-methoxyisobutylisonitrile parathyroid scintigraphy and hormonal and biochemical markers in suspicion of primary hyperparathyroidism. Mol Imaging Radionucl Ther. 2013;22(1):8-13. DOI:10.4274/Mirt.21931
1 ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия;
2 Международный медицинский центр «СОГАЗ», Санкт-Петербург, Россия;
3 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*slashuk911@gmail.com
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Konstantin Yu. Slashchuk*1, Mikhail V. Degtyarev1, Pavel O. Rumyantsev2, Olga Yu. Rebrova1,3, Alina R. Elfimova1, Lilia S. Selivanova1, Nataliya G. Mokrysheva1
1 National Medical Research Center for Endocrinology, Moscow, Russia;
2 International Medical Center «SOGAZ», Saint-Petersburg, Russia;
3 Pirogov Russian National Research Medical University, Moscow, Russia
*slashuk911@gmail.com