Downloaded from www.ajronline.org by UCSF LIB & CKM/RSCS MGMT on 12/12/14 from IP address 169.230.243.252. Copyright ARRS. For personal use only; all rights reserved
Letters Reply to “Imaging Secondary Hyperparathyroidism” We thank Taïeb and Hindié [1] for the comments on our article [2] and for their insightful opinions and suggestions related to parathyroid scanning in secondary hyperparathyroidism (sHPT). First, the aim of our study was to compare the diagnostic value of dual-phase (early and delayed), early, and delayed phase 99mTc-sestamibi SPECT/CT in the detection of parathyroid tissue in patients with sHPT. It was not our main purpose to calculate or compare the exact sensitivity of dual-phase, early, and delayed phase 99mTcsestamibi SPECT/CT. Second, Table 2 in our article compared the diagnostic value of the early phase of 99mTc-MIBI SPECT/CT scintigraphy with that of the delayed phase. The table showed 99mTc-MIBI SPECT/CT scintigraphy of 12 patients with sHPT who were negative in both the early and delayed phase; it did not show that one or two parathyroid glands could not be identified by the surgeon in 12 patients. On the early phase, 99mTc-sestamibi SPECT/CT was negative in 19 patients, on the delayed phase in 18 patients, and on both phases in 12 patients. Thus, when considering all included patients (not only those with positive imaging), the number of lesions depicted was 2.73 (218/80) per patient on the early phase and 2.75 (220/80) for the delayed phase. At surgery, 278 abnormal glands were identified and resected. It seems that the sensitivity of this study was higher than that of previous studies, which may be caused by several reasons. First, all patients in our study were resistant to medical therapy (including cinacalcet and conventional medical treatment, such as calcium supplements, phosphate binders, and active vitamin D analogs). Sumida et al. [3] investigated the effects of cinacalcet for histopathologic alterations on the parathyroid glands in sHPT patients. They found the percentage of oxyphil cell area to the total area was significantly higher in the cinacalcet group (treated with cinacalcet in combination with conventional medical treatment, such as calcium supplements, phosphate binders, and active vitamin D analogs) compared with the conventional group. Addition-
ally, a number of studies have investigated the relationship of parathyroid scintigraphy with pathohistologic findings and oxyphil cell content of parathyroid glands in parathyroid hyperplasia patients. These studies have shown a positive correlation of parathyroid scintigraphy with oxyphil cell content in the parathyroid gland [4–6]. Fuster et al. [7] also reported that the detection rate with delayed phase pinhole imaging was 89% in the patients who were poorly controlled using cinacalcet. Second, Mshelia et al. [8] investigated the relationship of serum calcium levels with the results of dual-phase 99mTc-sestamibi parathyroid scintigraphy. They showed that 99mTc-MIBI parathyroid scintigraphy is most likely to yield identification and localization of a parathyroid adenoma when both parathyroid hormone (PTH) concentration and calcium are elevated. In our study, the mean PTH concentration was greater than 600 pg/ mL and calcium concentration was greater than 10.4 mg/dL. Third, although Fuster et al. [7] reported that the delayed phase pinhole collimator acquisition showed the highest detection rate of hyperfunctioning parathyroid glands using 99mTc-MIBI scintigraphy in sHPT patients, the delayed phase images were planar images, not tomographic images as our study. Ali et al. [9] investigated whether the use of a pinhole collimator in parathyroid scintigraphy would enhance lesion detectability and delineation more than a parallel-hole collimator or SPECT in sHPT patients. This study concluded that pinhole imaging better delineates and detects lesions in parathyroid scintigraphy than parallel-hole imaging or SPECT [9]. However, the SPECT images were acquired only in the delayed phase, not both early and delayed phase as in our study. On the other hand, their tomographic images were SPECT images, not SPECT/CT images as in our study. Our study team evaluated the role of 99mTc-sestamibi SPECT/CT in the detection of parathyroid in sHPT patients. We found the sensitivity, specificity, and accuracy of 99mTc-sestamibi SPECT/CT in detecting parathyroid were 78.9%, 100%, and 78.9%, respectively, compared with 55.6%, 100%, and 55.6% for static planar 99mTc-
sestamibi [10]. Schalin-Jäntti et al. [11] prospectively compared the performance of planar scintigraphy with 123I/ 99mTc-sestamibi and 99mTc-sestamibi SPECT/CT in primary hyperparathyroidism. This study concluded that 99mTc-sestamibi SPECT/CT provided no additional information compared with the combined results of 123I/ 99mTc-sestamibi and 11C-methionine PET/CT. However, only delayed 99mTc-sestamibi SPECT/CT images were acquired [11]. Both early and delayed phase (dual-phase) 99mTc-sestamibi SPECT/ CT images were acquired in our study. Ciappuccini et al. [12] assessed the diagnostic value of dual-phase 99mTc-sestamibi scintigraphy with neck and thorax SPECT/CT in patients with primary hyperparathyroidism. They found dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT enabled them to identify a parathyroid adenoma in about two thirds of patients with primary hyperparathyroidism and enabled the surgeon to plan appropriate surgery. However, only delayed phase 99mTc-sestamibi scintigraphy with SPECT/CT was performed, which differed from our study. In conclusion, our study showed that both early and delayed phase 99mTc-sestamibi SPECT/CT can show more parathyroid gland than single early or delayed phase 99mTc-sestamibi SPECT/CT. However, we could not perform 123I thyroid scanning because no commercial 123I nuclear medicine tracer is currently available in our country. Therefore, we did not compare the head-tohead diagnostic value of dual-phase 99mTcsestamibi SPECT/CT with dual-radiopharmaceutical 123I/ 99mTc-sestamibi subtraction pinhole imaging followed by SPECT/CT. To date, the optimal scintigraphic protocol for 99mTc-sestamibi parathyroid scanning has not been established for primary hyperparathyroidism or sHPT. Each method has advantages and disadvantages. For example, 11C-methionine PET/CT can provide valuable additional information if 123I/ 99mTcsestamibi results remain negative in primary hyperparathyroidism patients. However, 11Cmethionine PET is not available in all centers, and the complicated labeling procedure also can be regarded as a limitation [11]. Nuclear medicine physicians should select
AJR 2014; 203:W553 0361–803X/14/2035–W553 © American Roentgen Ray Society
AJR:203, November 2014 W553
Downloaded from www.ajronline.org by UCSF LIB & CKM/RSCS MGMT on 12/12/14 from IP address 169.230.243.252. Copyright ARRS. For personal use only; all rights reserved
Letters the optimal scintigraphic protocol according to the available scanner (PET, SPECT, or SPECT/CT), the available the radiopharmaceuticals (123I, 99mTc-sestamibi, dual tracer, or 11C-methionine). If the diagnostic value of dual-radiopharmaceutical 123I/ 99mTc-sestamibi subtraction pinhole imaging followed by SPECT/CT is found to be better than that of dual phase 99mTc-sestamibi SPECT/CT in primary hyperparathyroidism or sHPT patients, we suggest that SPECT/CT should be performed at both the early and delayed phase. The CT acquisition data in the early phase can be used for the reconstruction of delayed phase SPECT/CT. This protocol will not increase the radiation dose compared with early or delayed imaging alone. Jigang Yang Beijing Friendship Hospital, Capital Medical University, Beijing, China Jue Yan Lishi Zhen China-Japan Friendship Hospital, Beijing, China DOI:10.2214/AJR.14.12923 WEB—This is a web exclusive article.
W554
References 1. Taïeb D, Hindié E. Imaging secondary hyperparathyroidism. (letter) AJR 2014; 203:[web] W552 2. Yang J, Hao R, Yuan L, Li C, Yan J, Zhen L. Value of dual-phase 99mTc-sestamibi scintigraphy with neck and thoracic SPECT/CT in secondary hyperparathyroidism. AJR 2014; 202:180–184 3. Sumida K, Nakamura M, Ubara Y, et al. Histopathological alterations of the parathyroid glands in haemodialysis patients with secondary hyperparathyroidism refractory to cinacalcet hydrochloride. J Clin Pathol 2011; 64:756–760 4. Nishida H, Ishibashi M, Hiromatsu Y, et al. Comparison of histological findings and parathyroid scintigraphy in hemodialysis patients with secondary hyperparathyroid glands. Endocr J 2005; 52:223–228 5. Arbab AS, Ueki J, Koizumi K, Araki T. Effects of extracellular Na+ and Ca2+ ions and Ca2+ channel modulators on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin in tumour cells. Nucl Med Commun 2003; 24:155–166 6. Tanaka Y, Funahashi H, Imai T, Seo H, Tominaga Y, Takagi H. Oxyphil cell function in secondary parathyroid hyperplasia. Nephron 1996; 73:580–586 7. Fuster D, Depetris M, Torregrosa JV, et al. Advantages of pinhole collimator double-phase scin-
tigraphy with 99mTc-MIBI in secondary hyperparathyroidism. Clin Nucl Med 2013; 38:878–881 8. Mshelia DS, Hatutale AN, Mokgoro NP, Nchabaleng ME, Buscombe JR, Sathekge MM. Correlation between serum calcium levels and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy in primary hyperparathyroidism. Clin Physiol Funct Imaging 2012; 32:19–24 9. Ali L, Loutfi I, Biswas G, Hadi G, Grigis T. Improved delineation of parathyroid lesions in patients with chronic renal failure using magnified pinhole imaging. J Nucl Med Technol 2011; 39:35–39 10. Zhen L, Li H, Liu X, Ge BH, Yan J, Yang J. The application of SPECT/CT for preoperative planning in patients with secondary hyperparathyroidism. Nucl Med Commun 2013; 34:439–444 11. Schalin-Jäntti C, Ryhänen E, Heiskanen I, et al. Planar scintigraphy with 123I/ 99mTc-sestamibi, 99mTc-sestamibi SPECT/CT, 11C-methionine PET/CT, or selective venous sampling before reoperation of primary hyperparathyroidism? J Nucl Med 2013; 54:739–747 12. Ciappuccini R, Morera J, Pascal P, et al. Dualphase 99mTc sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience. Clin Nucl Med 2012; 37:223–228
AJR:203, November 2014
Letters Reply to “Imaging Secondary Hyperparathyroidism” We thank Taïeb and Hindié [1] for the comments on our article [2] and for their insightful opinions and suggestions related to parathyroid scanning in secondary hyperparathyroidism (sHPT). First, the aim of our study was to compare the diagnostic value of dual-phase (early and delayed), early, and delayed phase 99mTc-sestamibi SPECT/CT in the detection of parathyroid tissue in patients with sHPT. It was not our main purpose to calculate or compare the exact sensitivity of dual-phase, early, and delayed phase 99mTcsestamibi SPECT/CT. Second, Table 2 in our article compared the diagnostic value of the early phase of 99mTc-MIBI SPECT/CT scintigraphy with that of the delayed phase. The table showed 99mTc-MIBI SPECT/CT scintigraphy of 12 patients with sHPT who were negative in both the early and delayed phase; it did not show that one or two parathyroid glands could not be identified by the surgeon in 12 patients. On the early phase, 99mTc-sestamibi SPECT/CT was negative in 19 patients, on the delayed phase in 18 patients, and on both phases in 12 patients. Thus, when considering all included patients (not only those with positive imaging), the number of lesions depicted was 2.73 (218/80) per patient on the early phase and 2.75 (220/80) for the delayed phase. At surgery, 278 abnormal glands were identified and resected. It seems that the sensitivity of this study was higher than that of previous studies, which may be caused by several reasons. First, all patients in our study were resistant to medical therapy (including cinacalcet and conventional medical treatment, such as calcium supplements, phosphate binders, and active vitamin D analogs). Sumida et al. [3] investigated the effects of cinacalcet for histopathologic alterations on the parathyroid glands in sHPT patients. They found the percentage of oxyphil cell area to the total area was significantly higher in the cinacalcet group (treated with cinacalcet in combination with conventional medical treatment, such as calcium supplements, phosphate binders, and active vitamin D analogs) compared with the conventional group. Addition-
ally, a number of studies have investigated the relationship of parathyroid scintigraphy with pathohistologic findings and oxyphil cell content of parathyroid glands in parathyroid hyperplasia patients. These studies have shown a positive correlation of parathyroid scintigraphy with oxyphil cell content in the parathyroid gland [4–6]. Fuster et al. [7] also reported that the detection rate with delayed phase pinhole imaging was 89% in the patients who were poorly controlled using cinacalcet. Second, Mshelia et al. [8] investigated the relationship of serum calcium levels with the results of dual-phase 99mTc-sestamibi parathyroid scintigraphy. They showed that 99mTc-MIBI parathyroid scintigraphy is most likely to yield identification and localization of a parathyroid adenoma when both parathyroid hormone (PTH) concentration and calcium are elevated. In our study, the mean PTH concentration was greater than 600 pg/ mL and calcium concentration was greater than 10.4 mg/dL. Third, although Fuster et al. [7] reported that the delayed phase pinhole collimator acquisition showed the highest detection rate of hyperfunctioning parathyroid glands using 99mTc-MIBI scintigraphy in sHPT patients, the delayed phase images were planar images, not tomographic images as our study. Ali et al. [9] investigated whether the use of a pinhole collimator in parathyroid scintigraphy would enhance lesion detectability and delineation more than a parallel-hole collimator or SPECT in sHPT patients. This study concluded that pinhole imaging better delineates and detects lesions in parathyroid scintigraphy than parallel-hole imaging or SPECT [9]. However, the SPECT images were acquired only in the delayed phase, not both early and delayed phase as in our study. On the other hand, their tomographic images were SPECT images, not SPECT/CT images as in our study. Our study team evaluated the role of 99mTc-sestamibi SPECT/CT in the detection of parathyroid in sHPT patients. We found the sensitivity, specificity, and accuracy of 99mTc-sestamibi SPECT/CT in detecting parathyroid were 78.9%, 100%, and 78.9%, respectively, compared with 55.6%, 100%, and 55.6% for static planar 99mTc-
sestamibi [10]. Schalin-Jäntti et al. [11] prospectively compared the performance of planar scintigraphy with 123I/ 99mTc-sestamibi and 99mTc-sestamibi SPECT/CT in primary hyperparathyroidism. This study concluded that 99mTc-sestamibi SPECT/CT provided no additional information compared with the combined results of 123I/ 99mTc-sestamibi and 11C-methionine PET/CT. However, only delayed 99mTc-sestamibi SPECT/CT images were acquired [11]. Both early and delayed phase (dual-phase) 99mTc-sestamibi SPECT/ CT images were acquired in our study. Ciappuccini et al. [12] assessed the diagnostic value of dual-phase 99mTc-sestamibi scintigraphy with neck and thorax SPECT/CT in patients with primary hyperparathyroidism. They found dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT enabled them to identify a parathyroid adenoma in about two thirds of patients with primary hyperparathyroidism and enabled the surgeon to plan appropriate surgery. However, only delayed phase 99mTc-sestamibi scintigraphy with SPECT/CT was performed, which differed from our study. In conclusion, our study showed that both early and delayed phase 99mTc-sestamibi SPECT/CT can show more parathyroid gland than single early or delayed phase 99mTc-sestamibi SPECT/CT. However, we could not perform 123I thyroid scanning because no commercial 123I nuclear medicine tracer is currently available in our country. Therefore, we did not compare the head-tohead diagnostic value of dual-phase 99mTcsestamibi SPECT/CT with dual-radiopharmaceutical 123I/ 99mTc-sestamibi subtraction pinhole imaging followed by SPECT/CT. To date, the optimal scintigraphic protocol for 99mTc-sestamibi parathyroid scanning has not been established for primary hyperparathyroidism or sHPT. Each method has advantages and disadvantages. For example, 11C-methionine PET/CT can provide valuable additional information if 123I/ 99mTcsestamibi results remain negative in primary hyperparathyroidism patients. However, 11Cmethionine PET is not available in all centers, and the complicated labeling procedure also can be regarded as a limitation [11]. Nuclear medicine physicians should select
AJR 2014; 203:W553 0361–803X/14/2035–W553 © American Roentgen Ray Society
AJR:203, November 2014 W553
Downloaded from www.ajronline.org by UCSF LIB & CKM/RSCS MGMT on 12/12/14 from IP address 169.230.243.252. Copyright ARRS. For personal use only; all rights reserved
Letters the optimal scintigraphic protocol according to the available scanner (PET, SPECT, or SPECT/CT), the available the radiopharmaceuticals (123I, 99mTc-sestamibi, dual tracer, or 11C-methionine). If the diagnostic value of dual-radiopharmaceutical 123I/ 99mTc-sestamibi subtraction pinhole imaging followed by SPECT/CT is found to be better than that of dual phase 99mTc-sestamibi SPECT/CT in primary hyperparathyroidism or sHPT patients, we suggest that SPECT/CT should be performed at both the early and delayed phase. The CT acquisition data in the early phase can be used for the reconstruction of delayed phase SPECT/CT. This protocol will not increase the radiation dose compared with early or delayed imaging alone. Jigang Yang Beijing Friendship Hospital, Capital Medical University, Beijing, China Jue Yan Lishi Zhen China-Japan Friendship Hospital, Beijing, China DOI:10.2214/AJR.14.12923 WEB—This is a web exclusive article.
W554
References 1. Taïeb D, Hindié E. Imaging secondary hyperparathyroidism. (letter) AJR 2014; 203:[web] W552 2. Yang J, Hao R, Yuan L, Li C, Yan J, Zhen L. Value of dual-phase 99mTc-sestamibi scintigraphy with neck and thoracic SPECT/CT in secondary hyperparathyroidism. AJR 2014; 202:180–184 3. Sumida K, Nakamura M, Ubara Y, et al. Histopathological alterations of the parathyroid glands in haemodialysis patients with secondary hyperparathyroidism refractory to cinacalcet hydrochloride. J Clin Pathol 2011; 64:756–760 4. Nishida H, Ishibashi M, Hiromatsu Y, et al. Comparison of histological findings and parathyroid scintigraphy in hemodialysis patients with secondary hyperparathyroid glands. Endocr J 2005; 52:223–228 5. Arbab AS, Ueki J, Koizumi K, Araki T. Effects of extracellular Na+ and Ca2+ ions and Ca2+ channel modulators on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin in tumour cells. Nucl Med Commun 2003; 24:155–166 6. Tanaka Y, Funahashi H, Imai T, Seo H, Tominaga Y, Takagi H. Oxyphil cell function in secondary parathyroid hyperplasia. Nephron 1996; 73:580–586 7. Fuster D, Depetris M, Torregrosa JV, et al. Advantages of pinhole collimator double-phase scin-
tigraphy with 99mTc-MIBI in secondary hyperparathyroidism. Clin Nucl Med 2013; 38:878–881 8. Mshelia DS, Hatutale AN, Mokgoro NP, Nchabaleng ME, Buscombe JR, Sathekge MM. Correlation between serum calcium levels and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy in primary hyperparathyroidism. Clin Physiol Funct Imaging 2012; 32:19–24 9. Ali L, Loutfi I, Biswas G, Hadi G, Grigis T. Improved delineation of parathyroid lesions in patients with chronic renal failure using magnified pinhole imaging. J Nucl Med Technol 2011; 39:35–39 10. Zhen L, Li H, Liu X, Ge BH, Yan J, Yang J. The application of SPECT/CT for preoperative planning in patients with secondary hyperparathyroidism. Nucl Med Commun 2013; 34:439–444 11. Schalin-Jäntti C, Ryhänen E, Heiskanen I, et al. Planar scintigraphy with 123I/ 99mTc-sestamibi, 99mTc-sestamibi SPECT/CT, 11C-methionine PET/CT, or selective venous sampling before reoperation of primary hyperparathyroidism? J Nucl Med 2013; 54:739–747 12. Ciappuccini R, Morera J, Pascal P, et al. Dualphase 99mTc sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience. Clin Nucl Med 2012; 37:223–228
AJR:203, November 2014
