- Email: [email protected]
CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism
Clinical Radiology 65 (2010) 278–287
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Original Paper
Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism C.N. Patel a, *, H.M. Salahudeen a, M. Lansdown b, A.F. Scarsbrook a a b
Department of Radiology and Nuclear Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK Department of Endocrine Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
article in formation Article history: Received 21 September 2009 Received in revised form 30 November 2009 Accepted 3 December 2009
AIM: To evaluate the accuracy of ultrasound and parathyroid scintigraphy using single photon-emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery. MATERIALS AND METHODS: Retrospective study of 63 consecutive patients with biochemical evidence of primary hyperparathyroidism referred for preoperative localization of parathyroid adenoma that proceeded to surgery in the same institution. All patients underwent high-resolution ultrasound and Technetium-99m sestamibi scintigraphy with planar and SPECT/CT imaging. The accuracy of preoperative imaging was compared to surgical and histological findings as the reference standard. RESULTS: Fifty-nine patients had solitary parathyroid adenomas, three patients had multiglandular hyperplasia, and one patient had multiple parathyroid adenomas confirmed at surgery and histology. Thirty-five solitary parathyroid adenomas were identified preoperatively with ultrasound (64%) and 53 with SPECT-CT (90%). Concordant ultrasound and SPECT/ CT findings were found in 35 cases (59%). An additional three adenomas were found with ultrasound alone and 18 adenomas with SPECT/CT alone. Fifty-one of the 56 adenomas localized using combined ultrasound and SPECT/CT were found at the expected sites during surgery. Combined ultrasound and SPECT/CT has an overall sensitivity of 95% and accuracy of 91% for the preoperative localization of solitary parathyroid adenomas. CONCLUSIONS: The combination of ultrasound and SPECT/CT has incremental value in accurately localizing solitary parathyroid adenomas over either technique alone, and allows selection of patients with primary hyperparathyroidism who would be suitable for minimally invasive surgery. Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Primary hyperparathyroidism is caused by a solitary parathyroid adenoma in approximately 85% of cases and * Guarantor and correspondent. C.N. Patel, Department of Nuclear Medicine, Bexley Wing, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK. Tel.: þ44 113 2068212; fax: þ44 113 2068228. E-mail address: [email protected] (C.N. Patel).
surgical resection of the pathological gland is curative. The remaining cases are usually secondary to glandular hyperplasia and less commonly, multiple adenomas with parathyroid carcinoma the rarest cause.1 The traditional surgical approach to treating patients was bilateral neck dissection with exploration of all four parathyroid glands to identify the pathological gland(s). As most patients with primary hyperparathyroidism have a solitary adenoma, many can be treated with unilateral minimally invasive surgical
0009-9260/$ – see front matter Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.12.005
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
techniques following accurate preoperative localization.2 The two most widely used imaging techniques are ultrasound and Technetium-99m sestamibi (99mTc MIBI) scintigraphy. These have similar sensitivities for the detection of solitary parathyroid adenomas, up to 88%, but when combined the overall sensitivity can be increased up to 95%.3 High-resolution ultrasound can accurately localize adenomas relative to the thyroid gland, whereas parathyroid scintigraphy is superior at detecting adenomas in the presence of nodular thyroid disease and at ectopic sites, which may be present in up to 20% of patients.4 Hybrid imaging with single photon-emission computed tomography/computed tomography (SPECT/CT), which combines anatomical (CT) and scintigraphic (SPECT) datasets has become increasingly available over the last few years. The CT component provides an attenuation map for the SPECT data and helps accurately localize sites of tracer activity. The incremental value of SPECT/CT has been described for a number of endocrine tumours with a significant impact on patient management.5 The accurate localization of parathyroid adenomas with SPECT/CT to anatomical landmarks should help improve the success of minimally invasive surgery of both non-ectopic and ectopic adenomas. However, the additional value of SPECT/CT for preoperative parathyroid adenoma localization has been equivocal in the studies reported to date.6–10 The purpose of this retrospective study was to compare the accuracy of high-resolution ultrasound and SPECT/CT for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery and to evaluate whether both techniques are necessary.
Material and methods Patients Sixty-three consecutive patients with biochemical evidence of primary hyperparathyroidism who underwent pre-operative imaging with ultrasound and SPECT/CT for localization of parathyroid adenoma and proceeded to surgery between January 2007 and March 2009 were included in the study. In this cohort, there were three patients with persistent hyperparathyroidism following previous unsuccessful surgery and two patients with recurrent hyperparathyroidism following prior resection of parathyroid adenomas. The local ethics committee confirmed that formal approval was not required for this retrospective audit of practice.
Imaging All patients underwent dual-phase parathyroid scintigraphy with 99mTc MIBI (Cardiolite; Bristol-Myers Squibb Medical Imaging, Brussels, Belgium). Anterior planar images of the neck and chest were acquired in a 256256 matrix at 10 min and 90 min following the injection of 800 MBq 99mTc MIBI. SPECT/CT of the neck and upper thorax
279
acquired following the delayed planar image with a dualhead gamma camera for the SPECT acquisition (using a 128128 matrix) and low-power CT system (2.5 mA and 140 kV with 10 mm sections reconstructed in a 256256 matrix) mounted on the same gantry (Infinia Hawkeye SPECT/CT system; GE Healthcare, Chalfont St Giles, Buckinghamshire, UK). The planar and SPECT/CT images were viewed and reported using XelerisÔ workstation software (GE Healthcare) by experienced nuclear medicine radiologists. As per departmental protocol, high-resolution ultrasound examinations of the neck were performed at the same attendance for the majority of patients unless a dedicated parathyroid ultrasound examination had been performed within the last 6 weeks. The thyroid and parathyroid glands were examined by one of two experienced ultrasonographers or one of three radiologists using a linear high-frequency (12–15 MHz) probe to document the presence of parathyroid adenoma(s) and characterize co-existing thyroid disease. The scintigraphic images were not available to review at the time of the ultrasound examination in the majority of cases.
Patient management Preoperative imaging was reviewed with the surgeon prior to each operation who documented the expected location of the parathyroid adenoma if localized. Patients with a solitary parathyroid adenoma localized using imaging underwent unilateral minimally invasive surgery by one of two experienced endocrine surgeons. Intraoperative parathyroid hormone assays were only undertaken in a small number of cases at the discretion of the operating surgeon. Bilateral exploratory surgery was performed when no adenoma was localized on preoperative imaging or at the expected site during a minimally invasive procedure. All resection specimens were sent for histological analysis to confirm the presence of parathyroid adenoma or hyperplasia.
Data analysis Data analysis was performed to evaluate the sensitivity, specificity, and accuracy of preoperative imaging using ultrasound and SPECT/CT techniques alone and when combined for the detection and accurate localization of parathyroid adenomas using histological and surgical correlation, respectively. The data were analysed for statistical significance using Chi squared or Fisher’s exact test, as appropriate. The null hypothesis assumed that there was no statistical difference in solitary parathyroid adenoma localization between SPECT/CT and ultrasound. P<0.05 was considered statistically significant.
Results All 63 patients included in the study had surgical and histological correlation. The study group consisted of 42 women and 21 men with a median age of 59 years
280
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
(range 10–86 years). Patients had a mean corrected calcium of 2.83 mmol/l (median 2.77 mmol/l, range 2.53– 3.37 mmol/l) and mean parathyroid hormone level of 36 pmol/l (median 20.9 pmol/l, range 7.1–166.3 pmol/l). There were 59 cases of solitary parathyroid adenoma, three cases of multiglandular hyperplasia, and a single case of multiple adenomas. Preoperative imaging identified 56 of the 59 cases of solitary adenoma, but was negative in all three patients with multiglandular hyperplasia, and only localized a single adenoma in the patient who was subsequently found to have two adenomas following intraoperative parathyroid hormone assay. In contrast, there were two patients who were thought to have multiple adenomas on both ultrasound and SPECT/CT, who following surgical exploration and surgery had only solitary adenomas confirmed on histology.
Solitary parathyroid adenoma Preoperative imaging localized 56 of the 59 solitary parathyroid adenomas (95%) confirmed at surgery and histology. Of these, ultrasound identified 38 cases (64%) and SPECT/CT identified 53 cases (90%). There were two adenomas found at surgery, which were missed (false negatives) on both ultrasound and SPECT/CT. Statistical analysis confirmed a significant discordance between localization using ultrasound and SPECT/CT (p ¼ 0.005; Chi-square test). Surgical correlation was used to assess the accuracy of localization of solitary adenomas to the pathological gland. Both ultrasound and SPECT/CT correctly lateralized all adenomas and correctly localized the pathological gland (superior or inferior) in 90 and 91%, respectively. In four cases, both ultrasound and SPECT/CT incorrectly localized an adenoma to the inferior gland rather than the superior gland. In a further case, ultrasound alone also incorrectly localized an adenoma to the inferior gland rather than superior gland. Overall, preoperative imaging with combined ultrasound and SPECT/CT localized 95% of solitary parathyroid adenomas with an accuracy of 91% (Table 1).
Discordant imaging findings Combined ultrasound and SPECT/CT identified 56 solitary parathyroid adenomas with concordant findings in 35 cases (59%; Fig. 1). Discordant findings between ultrasound and SPECT/CT were found in 21 cases (Table 2). Eighteen solitary adenomas were missed at ultrasound, which were subsequently detected using SPECT/CT (Fig. 2). Table 1 Sensitivity and accuracy of localization for solitary parathyroid adenoma. Technique
Number
Sensitivity
Accuracy
Ultrasound SPECT/CT Ultrasound and SPECT/CT
38 53 56
64% 90% 95%
90% 91% 91%
SPECT/CT, single tomography.
photon-emission
computed
tomography/computed
Of these, the adenoma was deep-seated or ectopically located in 14 cases and there was co-existing nodular thyroid disease in eight cases. In a further case, SPECT/CT localized sestamibi uptake in an ectopic mediastinal parathyroid adenoma and a brown tumour (Fig. 3). Three adenomas were missed at SPECT/CT, which were demonstrated on ultrasound. There was no statistical significant difference between localization using SPECT/CT alone compared with SPECT/CT and ultrasound (p>0.05; Fisher’s exact test).
Discussion Surgical management is the mainstay of treatment for primary hyperparathyroidism. Whilst traditional bilateral neck exploration identifies the pathological gland(s) in most patients, there are risks of hypoparathyroidism in the immediate postoperative period and recurrent laryngeal nerve damage. Minimally invasive surgical techniques achieve similar cure rates with a lower risk of complications and a better cosmetic result in patients with solitary parathyroid adenomas.2,11 In addition, shorter operating times and hospital stays allow significant cost-savings to be achieved. As a result, minimally invasive surgical techniques have rapidly evolved over the past decade and radio-guided/endoscopic surgery has now gained wide acceptance amongst endocrine surgeons.12,13 The key to the success of these techniques lies in accurate preoperative localization of the pathological gland(s) and identifying patients suitable for minimally invasive surgery. Ultrasound allows anatomical detection of an enlarged parathyroid gland and accurate localization relative to the thyroid gland, although the presence of co-existing nodular thyroid disease reduces the sensitivity and specificity.14 Furthermore, deep-seated or ectopic adenomas in the neck are poorly visualized with ultrasound.15,16 In this study, ultrasound alone detected 64% of all solitary parathyroid adenomas, which is below the sensitivities quoted in the literature, which range between 72–89%.3 Eighteen solitary adenomas were missed at ultrasound, which were subsequently detected using SPECT/CT, the majority of which were deep-seated or in ectopic locations that would have been difficult to see at ultrasound. Similarly, the presence of co-existing multinodular thyroid disease can make differentiation of parathyroid and thyroid adenomas extremely difficult. In our department, there were a relatively large number of different operators/reporters (invariably with different levels of experience) involved in parathyroid ultrasound compared with parathyroid scintigraphy. This inevitably results in greater interobserver variability, which may explain the lower sensitivity of ultrasound in the present study. Our practice has subsequently been adapted so that all ultrasound examinations are performed at the time of scintigraphy by the same experienced radiologist(s) reporting the parathyroid SPECT/CT study. There are a variety of scintigraphic techniques that can be used in the evaluation of primary hyperparathyroidism.
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
281
Figure 1 Right inferior parathyroid adenoma accurately localized with (a) ultrasound and (b) SPECT/CT.
Dual-phase scintigraphy using a single radiopharmaceutical (99mTc MIBI) or dual-isotope substraction scintigraphy using 99m Tc MIBI and 99mTc-pertechnetate are the two most commonly performed. In addition, tomographic imaging with SPECT or SPECT/CT can be acquired with newer gamma cameras. There have been a number of studies in the literature comparing planar versus SPECT scintigraphy for preoperative localization of parathyroid adenomas and more
recently, SPECT versus SPECT/CT imaging.6–10,17–20 However, no consensus opinion has been reached on the optimum imaging technique.21 The overall sensitivity of planar, SPECT and SPECT/CT imaging does not vary significantly; however, the additional information gained from tomographic imaging often provides incremental value to the operating surgeon. SPECT imaging has greater contrast resolution, which can be important when there are subtle differences in
282
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Table 2 Discordant findings between ultrasound and SPECT/CT imaging. Case
Ultrasound findings
SPECT/CT findings
Discrepancy
PTH levela (pmol/l)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Multinodular thyroid No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid Multinodular thyroid No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid LIP LIP LIP and RIP
RIP Deep-seated LIP Retrotracheal LSP RIP Ectopic mediastinal Deep-seated RIP Deep-seated LIP Deep-seated LIP RIP Ectopic LIP (deep to head of lt clavicle) Deep-seated LIP Retrotracheal LIP LSP LIP Deep-seated RIP Deep-seated LSP Ectopic mediastinal Ectopic mediastinal No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma
Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound SPECT/CT SPECT/CT SPECT/CT
15 16 16 8 132 23 13 13 29 12 13 45 10 107 10 27 105 16 27 25 30
a PTH level: mean 36 pmol/l; median 21 pmol/l. SPECT/CT, single photon-emission computed tomography/computed tomography; PTH, parathyroid hormone; LIP, left inferior position; LSP, left superior position; RIP, right inferior position; RSP< right superior position.
pathological sestamibi uptake in parathyroid adenomas and physiological uptake in the thyroid gland. Furthermore, SPECT allows evaluation of depth, which is helpful for planning minimally invasive surgery.22 SPECT/CT allows more accurate localization of tracer activity demonstrated on SPECT imaging, with the CT component providing anatomical landmarks by which the endocrine surgeon can locate the intended target (Fig. 4). This is of particular benefit in deep-seated and ectopic adenomas, and in patients with altered neck anatomy following previous surgery.6,7 There were a number of cases in this series when planar imaging was equivocal but SPECT/CT demonstrated a clear focus of increased tracer uptake (Fig. 5), which lends support to the incremental value of SPECT/CT (and SPECT) over planar imaging. In this study, scintigraphy with dual-phase planar and delayed SPECT/CT imaging detected 90% of solitary parathyroid adenomas. The three adenomas (5%) identified with ultrasound and missed on scintigraphy did not show significant tracer uptake to allow detection and/or differentiation from physiological thyroid uptake. Sestamibi is a non-specific tracer that is taken up by mitochondria, and therefore, any mitochondria-rich cells may show uptake. The degree of sestamibi uptake in parathyroid adenomas has been reported to correlate with the size of gland and the cytological composition (greater uptake seen in adenomas with a predominance of oxyphil cells compared to chief cells).23 Histological analysis confirmed chief cell predominance in two of the three sestamibi negative parathyroid adenomas in the present study. More recently, expression of cell membrane proteins, multidrug resistance (MDR)-associated protein and P-glycoprotein (P-gp) by parathyroid adenomas has been shown to be associated with falsenegative sestamibi results, although this remains controversial.24,25
In keeping with previous studies, current imaging techniques remain poor at detecting multiglandular hyperplasia, which was confirmed in this study, where all three patients with hyperplasia had negative imaging. These patients requiring surgery should continue to have bilateral neck dissection and exploration. Combined ultrasound and parathyroid scintigraphy has been shown to increase the overall sensitivity for localization of solitary parathyroid adenomas, up to 95%.26–29 This study demonstrates a clear discrepancy between ultrasound and scintigraphy with SPECT/CT. The possible reasons for the lower sensitivity of ultrasound have already been discussed, but the sensitivity of the scintigraphic data is in line with the current literature. Similarly, the study has confirmed that the overall sensitivity of preoperative localization with combined ultrasound and SPECT/CT can be increased to 95% with an accuracy of 91%. Both ultrasound and SPECT/CT had similar rates of accuracy (90–91%) in localizing adenomas to the pathological gland, which is essential for the success of minimally invasive surgery. Although all adenomas were correctly lateralized, there were four cases where superior gland adenomas were incorrectly localized to the inferior glands on both ultrasound and SPECT/CT. This is likely to reflect the fact that superior glands tend to prolapse inferiorly as they enlarge.20 Surgeons should be aware that although both ultrasound and scintigraphy provide a high level of accuracy in localizing parathyroid adenoma, the differentiation of a low superior parathyroid adenoma and an inferior parathyroid adenoma remains a potential source of error. This study highlights the relative merits of SPECT/CT scintigraphy compared with ultrasound for localizing solitary parathyroid adenomas with greater sensitivity and comparable accuracy in the present patient cohort. Most centres advocate concordant imaging findings to achieve
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
283
Figure 2 Deep-seated parathyroid adenoma not visible with ultrasound due to acoustic shadowing from the trachea (a), but accurately localized with SPECT/CT (b).
the greatest accuracy for minimally invasive parathyroid surgery, usually with ultrasound and scintigraphy. Although most SPECT/CT machines have low-dose CT components, the latest systems have multidetector CT providing ‘‘diagnostic quality’’ images. The radiation exposure involved
with parathyroid SPECT/CT must also be considered. The effective dose of parathyroid scintigraphy (900 MBq 99mTc sestamibi) is 8 mSv.30 In our institution, for reasons of costeffectiveness, 800 MBq is used without significantly compromising image quality and as a result the effective
284
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Figure 3 Ectopic parathyroid adenoma in the posterior mediastinum and associated brown tumour in the left acromion demonstrated on planar scintigraphy (a), but accurately localized with SPECT/CT (b–c), which were confirmed at surgery and bone biopsy, respectively.
dose is marginally lower. The additional radiation exposure from the low-dose CT component is relatively small at approximately 0.1 mSv.31 This would be significantly greater with new multidetector SPECT/CT machines if highresolution images are acquired, although dose reductions could be achieved by only selecting patients for SPECT/CT who have not been adequately localized with ultrasound. An alternate strategy would be to perform SPECT/CT first and proceed to ultrasound only in patients with negative scintigraphy. In the present study, the additional adenomas
detected with ultrasound over SPECT/CT were quite small in number, with no statistically significant difference between SPECT/CT alone and when combined with ultrasound. Although a large number of ultrasound examinations could potentially be avoided, this would need to be evaluated in a prospective study to clarify if ultrasound may be safely withdrawn from the preoperative imaging algorithm of patients with primary hyperparathyroidism. In addition, the present study did not evaluate the additional information provided by ultrasound, such as characterizing
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
285
Figure 4 Ectopic parathyroid adenoma demonstrated on planar imaging (a), although the ectopic location is difficult to appreciate on these views but has been accurately localized with SPECT/CT to reside between the oesophagus and vertebral body (crosshairs), aiding surgical planning.
co-existing nodular thyroid disease, which may affect the surgical technique, precise measurement of depth from skin surface to adenoma, and the potential utility of skin marking prior to surgery. In conclusion the combined use of ultrasound and SPECT/ CT is advocated for the preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism. Concordant imaging findings increase
confidence in accurate localization and facilitate surgical planning for minimally invasive parathyroid surgery. In the present study, integrated SPECT/CT has been demonstrated to accurately detect and localize parathyroid adenomas. However, the inherent limitation of reduced or absent sestamibi tracer uptake in some adenomas, albeit a small number (5%), and the characterization of co-existing nodular thyroid disease, which is valuable for the operating surgeon,
286
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Figure 5 Right inferior parathyroid adenoma not clearly visible on planar imaging (a), but accurately localized with SPECT/CT (b) deep to the right lobe of the thyroid.
justifies the continued use of ultrasound with SPECT/CT in our institution at present. High-resolution imaging with multidetector SPECT/CT may allow a single technique approach in the near future.
References 1. Ruda JM, Hollenbeak CS, Stack Jr BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995–2003. Otolaryngol Head Neck Surg 2005;132:359–72.
2. Udelsman R. Six hundred and fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 2002;235:655–70. 3. Johnson NA, Tublin ME, Ogilvie JB. Parathyroid imaging: technique and role in the preoperative evaluation of primary hyperparathyroidism. AJR Am J Roentgenol 2007;188:1706–15. 4. Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surgery 1984;95:14–21. 5. Patel CN, Chowdhury FU, Scarsbrook AF. Clinical utility of hybrid SPECTCT in endocrine neoplasia. AJR Am J Roentgenol 2008;190:815–24. 6. Profanter C, Wetscher GJ, Gabriel M, et al. CT-MIBI image fusion: a new preoperative localization technique for primary, recurrent and persistent hyperparathyroidism. Surgery 2004;135:157–62.
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287 7. Krausz Y, Bettman L, Guralnik L, et al. Technetium-99 m-MIBI SPECT/CT in primary hyperparathyroidism. World J Surg 2006;30:76–83. 8. Gayed IW, Kim EE, Broussard WF, et al. The value of 99m Tc-sestamibi SPECT/CT over conventional SPECT in the evaluation of parathyroid adenomas or hyperplasia. J Nucl Med 2005;46:248–52. 9. Neumann DR, Obuchowski NA, Difilippo FP. Preoperative 123I/99mTcsestamibi subtraction SPECT and SPECT/CT in primary hyperparathyroidism. J Nucl Med 2008;49:2012–7. 10. Akram K, Parker JA, Donohoe K, et al. Role of single photon emission computed tomography/computed tomography in localization of ectopic parathyroid adenoma: a pictorial case series and review of the current literature. Clin Nucl Med 2009;34:500–2. 11. Norman J, Shheda H, Farrel C. Minimally invasive parathyroidectomy for primary hyperparathyroidism: decreasing operative time and potential complications while improving cosmetic results. Am Surg 1998;64:391–6. 12. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med 2003;44:1443–58. 13. Henry JF, Iacobone M, Mirallie E, et al. Indications and results of videoassisted parathyroidectomy by a lateral approach in patients with primary hyperparathyroidism. Surgery 2001;130:999–1004. 14. Kebapci M, Entok E, Kebapci N, et al. Preoperative evaluation of parathyroid lesions in patients with concomitant thyroid disease: role of high resolution ultrasonography and dual phase technetium 99m sestamibi scintigraphy. J Endocrinol Invest 2004;27:24–30. 15. Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99 m) technetium sestamibi scintigraphy. Clin Endocrinol 2002;57:241–9. 16. Tublin ME, Pryma DA, Yim JH, et al. Localization of parathyroid adenomas by sonography and technetium 99m sestamibi single-photon emission computed tomography before minimally invasive parathyroidectomy: are both studies really needed? J Ultrasound Med 2009;28:183–90. 17. Slater A, Gleeson FV. Increased sensitivity and confidence of SPECT over planar imaging in dual-phase sestamibi for parathyroid adenoma detection. Clin Nucl Med 2005;30:1–3. 18. Lavely WC, Goetze S, Friedman KP, et al. Comparison of SPECT/CT, SPECT, and planar imaging with single- and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy. J Nucl Med 2007;48:1084–9. 19. Sharma J, Mazzaglia P, Milas M, et al. Radionuclide imaging for hyperparathyroidism (HPT): which is the best technetium-99m sestamibi modality? Surgery 2006;140:856–63.
287
20. Civelek AC, Ozalp E, Donovan P, et al. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 2002;131: 149–57. 21. Hindie´ E, Ugur O, Fuster D, O’Doherty M, Grassetto G, Urena P. Parathyroid task group of the EANM. 2009 EANM parathyroid guidelines. Eur J Nucl Med Mol Imaging 2009;36:1201–16. 22. Harris L, Yoo J, Driedger A, et al. Accuracy of technetium-99m SPECT-CT hybrid images in predicting the precise intra-operative anatomical location of parathyroid adenomas. Head Neck 2008;30:509–17. 23. Mihai R, Gleeson F, Buley ID, et al. Negative imaging studies for primary hyperparathyroidism are unavoidable: correlation of sestamibi and high resolution ultrasound scanning with histological analysis in 150 patients. World J Surg 2006;30:697–704. 24. Gupta Y, Ahmed R, Happerfield L, et al. P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism. Br J Surg 2007;94:1491–5. 25. Jorna FH, Hollema H, Hendrikse HN, et al. P-gp and MRP1 expression in parathyroid tumors related to histology, weight and 99m Tc-sestamibi imaging results. Exp Clin Endocrinol Diabetes; 2009. doi: 10.1055/s-00281105925. 26. Lumachi F, Zucchetta P, Marzola MC, et al. Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism. Eur J Endocrinol 2000;143:755–60. 27. Siperstein A, Berber E, Mackey R, et al. Prospective evaluation of sestamibi scan, ultrasonography, and rapid PTH to predict the success of limited exploration for sporadic primary hyperparathyroidism. Surgery 2004;136:872–80. 28. Purcell GP, Dirbas FM, Jeffrey RB, et al. Parathyroid localization with high-resolution ultrasound and technetium 99mTc sestamibi. Arch Surg 1999;134:824–30. 29. De Feo ML, Colagrande S, Biagini C, et al. Parathyroid glands: combination of (99m) Tc MIBI scintigraphy and US for demonstration of parathyroid glands and nodules. Radiology 2000;214:393–402. 30. Administration of Radioactive Substances Advisory Committee (ARSAC). Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Oxon: ARSAC; 2006. 31. Sawyer LJ, Starritt HC, Hiscock SC, et al. Effective doses to patients from CT acquisition on the GE Infinia Hawkeye: a comparison of calculation methods. Nucl Med Commun 2008;29:144–9.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Original Paper
Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism C.N. Patel a, *, H.M. Salahudeen a, M. Lansdown b, A.F. Scarsbrook a a b
Department of Radiology and Nuclear Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK Department of Endocrine Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
article in formation Article history: Received 21 September 2009 Received in revised form 30 November 2009 Accepted 3 December 2009
AIM: To evaluate the accuracy of ultrasound and parathyroid scintigraphy using single photon-emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery. MATERIALS AND METHODS: Retrospective study of 63 consecutive patients with biochemical evidence of primary hyperparathyroidism referred for preoperative localization of parathyroid adenoma that proceeded to surgery in the same institution. All patients underwent high-resolution ultrasound and Technetium-99m sestamibi scintigraphy with planar and SPECT/CT imaging. The accuracy of preoperative imaging was compared to surgical and histological findings as the reference standard. RESULTS: Fifty-nine patients had solitary parathyroid adenomas, three patients had multiglandular hyperplasia, and one patient had multiple parathyroid adenomas confirmed at surgery and histology. Thirty-five solitary parathyroid adenomas were identified preoperatively with ultrasound (64%) and 53 with SPECT-CT (90%). Concordant ultrasound and SPECT/ CT findings were found in 35 cases (59%). An additional three adenomas were found with ultrasound alone and 18 adenomas with SPECT/CT alone. Fifty-one of the 56 adenomas localized using combined ultrasound and SPECT/CT were found at the expected sites during surgery. Combined ultrasound and SPECT/CT has an overall sensitivity of 95% and accuracy of 91% for the preoperative localization of solitary parathyroid adenomas. CONCLUSIONS: The combination of ultrasound and SPECT/CT has incremental value in accurately localizing solitary parathyroid adenomas over either technique alone, and allows selection of patients with primary hyperparathyroidism who would be suitable for minimally invasive surgery. Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Primary hyperparathyroidism is caused by a solitary parathyroid adenoma in approximately 85% of cases and * Guarantor and correspondent. C.N. Patel, Department of Nuclear Medicine, Bexley Wing, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK. Tel.: þ44 113 2068212; fax: þ44 113 2068228. E-mail address: [email protected] (C.N. Patel).
surgical resection of the pathological gland is curative. The remaining cases are usually secondary to glandular hyperplasia and less commonly, multiple adenomas with parathyroid carcinoma the rarest cause.1 The traditional surgical approach to treating patients was bilateral neck dissection with exploration of all four parathyroid glands to identify the pathological gland(s). As most patients with primary hyperparathyroidism have a solitary adenoma, many can be treated with unilateral minimally invasive surgical
0009-9260/$ – see front matter Ó 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.12.005
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
techniques following accurate preoperative localization.2 The two most widely used imaging techniques are ultrasound and Technetium-99m sestamibi (99mTc MIBI) scintigraphy. These have similar sensitivities for the detection of solitary parathyroid adenomas, up to 88%, but when combined the overall sensitivity can be increased up to 95%.3 High-resolution ultrasound can accurately localize adenomas relative to the thyroid gland, whereas parathyroid scintigraphy is superior at detecting adenomas in the presence of nodular thyroid disease and at ectopic sites, which may be present in up to 20% of patients.4 Hybrid imaging with single photon-emission computed tomography/computed tomography (SPECT/CT), which combines anatomical (CT) and scintigraphic (SPECT) datasets has become increasingly available over the last few years. The CT component provides an attenuation map for the SPECT data and helps accurately localize sites of tracer activity. The incremental value of SPECT/CT has been described for a number of endocrine tumours with a significant impact on patient management.5 The accurate localization of parathyroid adenomas with SPECT/CT to anatomical landmarks should help improve the success of minimally invasive surgery of both non-ectopic and ectopic adenomas. However, the additional value of SPECT/CT for preoperative parathyroid adenoma localization has been equivocal in the studies reported to date.6–10 The purpose of this retrospective study was to compare the accuracy of high-resolution ultrasound and SPECT/CT for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery and to evaluate whether both techniques are necessary.
Material and methods Patients Sixty-three consecutive patients with biochemical evidence of primary hyperparathyroidism who underwent pre-operative imaging with ultrasound and SPECT/CT for localization of parathyroid adenoma and proceeded to surgery between January 2007 and March 2009 were included in the study. In this cohort, there were three patients with persistent hyperparathyroidism following previous unsuccessful surgery and two patients with recurrent hyperparathyroidism following prior resection of parathyroid adenomas. The local ethics committee confirmed that formal approval was not required for this retrospective audit of practice.
Imaging All patients underwent dual-phase parathyroid scintigraphy with 99mTc MIBI (Cardiolite; Bristol-Myers Squibb Medical Imaging, Brussels, Belgium). Anterior planar images of the neck and chest were acquired in a 256256 matrix at 10 min and 90 min following the injection of 800 MBq 99mTc MIBI. SPECT/CT of the neck and upper thorax
279
acquired following the delayed planar image with a dualhead gamma camera for the SPECT acquisition (using a 128128 matrix) and low-power CT system (2.5 mA and 140 kV with 10 mm sections reconstructed in a 256256 matrix) mounted on the same gantry (Infinia Hawkeye SPECT/CT system; GE Healthcare, Chalfont St Giles, Buckinghamshire, UK). The planar and SPECT/CT images were viewed and reported using XelerisÔ workstation software (GE Healthcare) by experienced nuclear medicine radiologists. As per departmental protocol, high-resolution ultrasound examinations of the neck were performed at the same attendance for the majority of patients unless a dedicated parathyroid ultrasound examination had been performed within the last 6 weeks. The thyroid and parathyroid glands were examined by one of two experienced ultrasonographers or one of three radiologists using a linear high-frequency (12–15 MHz) probe to document the presence of parathyroid adenoma(s) and characterize co-existing thyroid disease. The scintigraphic images were not available to review at the time of the ultrasound examination in the majority of cases.
Patient management Preoperative imaging was reviewed with the surgeon prior to each operation who documented the expected location of the parathyroid adenoma if localized. Patients with a solitary parathyroid adenoma localized using imaging underwent unilateral minimally invasive surgery by one of two experienced endocrine surgeons. Intraoperative parathyroid hormone assays were only undertaken in a small number of cases at the discretion of the operating surgeon. Bilateral exploratory surgery was performed when no adenoma was localized on preoperative imaging or at the expected site during a minimally invasive procedure. All resection specimens were sent for histological analysis to confirm the presence of parathyroid adenoma or hyperplasia.
Data analysis Data analysis was performed to evaluate the sensitivity, specificity, and accuracy of preoperative imaging using ultrasound and SPECT/CT techniques alone and when combined for the detection and accurate localization of parathyroid adenomas using histological and surgical correlation, respectively. The data were analysed for statistical significance using Chi squared or Fisher’s exact test, as appropriate. The null hypothesis assumed that there was no statistical difference in solitary parathyroid adenoma localization between SPECT/CT and ultrasound. P<0.05 was considered statistically significant.
Results All 63 patients included in the study had surgical and histological correlation. The study group consisted of 42 women and 21 men with a median age of 59 years
280
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
(range 10–86 years). Patients had a mean corrected calcium of 2.83 mmol/l (median 2.77 mmol/l, range 2.53– 3.37 mmol/l) and mean parathyroid hormone level of 36 pmol/l (median 20.9 pmol/l, range 7.1–166.3 pmol/l). There were 59 cases of solitary parathyroid adenoma, three cases of multiglandular hyperplasia, and a single case of multiple adenomas. Preoperative imaging identified 56 of the 59 cases of solitary adenoma, but was negative in all three patients with multiglandular hyperplasia, and only localized a single adenoma in the patient who was subsequently found to have two adenomas following intraoperative parathyroid hormone assay. In contrast, there were two patients who were thought to have multiple adenomas on both ultrasound and SPECT/CT, who following surgical exploration and surgery had only solitary adenomas confirmed on histology.
Solitary parathyroid adenoma Preoperative imaging localized 56 of the 59 solitary parathyroid adenomas (95%) confirmed at surgery and histology. Of these, ultrasound identified 38 cases (64%) and SPECT/CT identified 53 cases (90%). There were two adenomas found at surgery, which were missed (false negatives) on both ultrasound and SPECT/CT. Statistical analysis confirmed a significant discordance between localization using ultrasound and SPECT/CT (p ¼ 0.005; Chi-square test). Surgical correlation was used to assess the accuracy of localization of solitary adenomas to the pathological gland. Both ultrasound and SPECT/CT correctly lateralized all adenomas and correctly localized the pathological gland (superior or inferior) in 90 and 91%, respectively. In four cases, both ultrasound and SPECT/CT incorrectly localized an adenoma to the inferior gland rather than the superior gland. In a further case, ultrasound alone also incorrectly localized an adenoma to the inferior gland rather than superior gland. Overall, preoperative imaging with combined ultrasound and SPECT/CT localized 95% of solitary parathyroid adenomas with an accuracy of 91% (Table 1).
Discordant imaging findings Combined ultrasound and SPECT/CT identified 56 solitary parathyroid adenomas with concordant findings in 35 cases (59%; Fig. 1). Discordant findings between ultrasound and SPECT/CT were found in 21 cases (Table 2). Eighteen solitary adenomas were missed at ultrasound, which were subsequently detected using SPECT/CT (Fig. 2). Table 1 Sensitivity and accuracy of localization for solitary parathyroid adenoma. Technique
Number
Sensitivity
Accuracy
Ultrasound SPECT/CT Ultrasound and SPECT/CT
38 53 56
64% 90% 95%
90% 91% 91%
SPECT/CT, single tomography.
photon-emission
computed
tomography/computed
Of these, the adenoma was deep-seated or ectopically located in 14 cases and there was co-existing nodular thyroid disease in eight cases. In a further case, SPECT/CT localized sestamibi uptake in an ectopic mediastinal parathyroid adenoma and a brown tumour (Fig. 3). Three adenomas were missed at SPECT/CT, which were demonstrated on ultrasound. There was no statistical significant difference between localization using SPECT/CT alone compared with SPECT/CT and ultrasound (p>0.05; Fisher’s exact test).
Discussion Surgical management is the mainstay of treatment for primary hyperparathyroidism. Whilst traditional bilateral neck exploration identifies the pathological gland(s) in most patients, there are risks of hypoparathyroidism in the immediate postoperative period and recurrent laryngeal nerve damage. Minimally invasive surgical techniques achieve similar cure rates with a lower risk of complications and a better cosmetic result in patients with solitary parathyroid adenomas.2,11 In addition, shorter operating times and hospital stays allow significant cost-savings to be achieved. As a result, minimally invasive surgical techniques have rapidly evolved over the past decade and radio-guided/endoscopic surgery has now gained wide acceptance amongst endocrine surgeons.12,13 The key to the success of these techniques lies in accurate preoperative localization of the pathological gland(s) and identifying patients suitable for minimally invasive surgery. Ultrasound allows anatomical detection of an enlarged parathyroid gland and accurate localization relative to the thyroid gland, although the presence of co-existing nodular thyroid disease reduces the sensitivity and specificity.14 Furthermore, deep-seated or ectopic adenomas in the neck are poorly visualized with ultrasound.15,16 In this study, ultrasound alone detected 64% of all solitary parathyroid adenomas, which is below the sensitivities quoted in the literature, which range between 72–89%.3 Eighteen solitary adenomas were missed at ultrasound, which were subsequently detected using SPECT/CT, the majority of which were deep-seated or in ectopic locations that would have been difficult to see at ultrasound. Similarly, the presence of co-existing multinodular thyroid disease can make differentiation of parathyroid and thyroid adenomas extremely difficult. In our department, there were a relatively large number of different operators/reporters (invariably with different levels of experience) involved in parathyroid ultrasound compared with parathyroid scintigraphy. This inevitably results in greater interobserver variability, which may explain the lower sensitivity of ultrasound in the present study. Our practice has subsequently been adapted so that all ultrasound examinations are performed at the time of scintigraphy by the same experienced radiologist(s) reporting the parathyroid SPECT/CT study. There are a variety of scintigraphic techniques that can be used in the evaluation of primary hyperparathyroidism.
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
281
Figure 1 Right inferior parathyroid adenoma accurately localized with (a) ultrasound and (b) SPECT/CT.
Dual-phase scintigraphy using a single radiopharmaceutical (99mTc MIBI) or dual-isotope substraction scintigraphy using 99m Tc MIBI and 99mTc-pertechnetate are the two most commonly performed. In addition, tomographic imaging with SPECT or SPECT/CT can be acquired with newer gamma cameras. There have been a number of studies in the literature comparing planar versus SPECT scintigraphy for preoperative localization of parathyroid adenomas and more
recently, SPECT versus SPECT/CT imaging.6–10,17–20 However, no consensus opinion has been reached on the optimum imaging technique.21 The overall sensitivity of planar, SPECT and SPECT/CT imaging does not vary significantly; however, the additional information gained from tomographic imaging often provides incremental value to the operating surgeon. SPECT imaging has greater contrast resolution, which can be important when there are subtle differences in
282
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Table 2 Discordant findings between ultrasound and SPECT/CT imaging. Case
Ultrasound findings
SPECT/CT findings
Discrepancy
PTH levela (pmol/l)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Multinodular thyroid No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid Multinodular thyroid No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma Multinodular thyroid Multinodular thyroid LIP LIP LIP and RIP
RIP Deep-seated LIP Retrotracheal LSP RIP Ectopic mediastinal Deep-seated RIP Deep-seated LIP Deep-seated LIP RIP Ectopic LIP (deep to head of lt clavicle) Deep-seated LIP Retrotracheal LIP LSP LIP Deep-seated RIP Deep-seated LSP Ectopic mediastinal Ectopic mediastinal No parathyroid adenoma No parathyroid adenoma No parathyroid adenoma
Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound Ultrasound SPECT/CT SPECT/CT SPECT/CT
15 16 16 8 132 23 13 13 29 12 13 45 10 107 10 27 105 16 27 25 30
a PTH level: mean 36 pmol/l; median 21 pmol/l. SPECT/CT, single photon-emission computed tomography/computed tomography; PTH, parathyroid hormone; LIP, left inferior position; LSP, left superior position; RIP, right inferior position; RSP< right superior position.
pathological sestamibi uptake in parathyroid adenomas and physiological uptake in the thyroid gland. Furthermore, SPECT allows evaluation of depth, which is helpful for planning minimally invasive surgery.22 SPECT/CT allows more accurate localization of tracer activity demonstrated on SPECT imaging, with the CT component providing anatomical landmarks by which the endocrine surgeon can locate the intended target (Fig. 4). This is of particular benefit in deep-seated and ectopic adenomas, and in patients with altered neck anatomy following previous surgery.6,7 There were a number of cases in this series when planar imaging was equivocal but SPECT/CT demonstrated a clear focus of increased tracer uptake (Fig. 5), which lends support to the incremental value of SPECT/CT (and SPECT) over planar imaging. In this study, scintigraphy with dual-phase planar and delayed SPECT/CT imaging detected 90% of solitary parathyroid adenomas. The three adenomas (5%) identified with ultrasound and missed on scintigraphy did not show significant tracer uptake to allow detection and/or differentiation from physiological thyroid uptake. Sestamibi is a non-specific tracer that is taken up by mitochondria, and therefore, any mitochondria-rich cells may show uptake. The degree of sestamibi uptake in parathyroid adenomas has been reported to correlate with the size of gland and the cytological composition (greater uptake seen in adenomas with a predominance of oxyphil cells compared to chief cells).23 Histological analysis confirmed chief cell predominance in two of the three sestamibi negative parathyroid adenomas in the present study. More recently, expression of cell membrane proteins, multidrug resistance (MDR)-associated protein and P-glycoprotein (P-gp) by parathyroid adenomas has been shown to be associated with falsenegative sestamibi results, although this remains controversial.24,25
In keeping with previous studies, current imaging techniques remain poor at detecting multiglandular hyperplasia, which was confirmed in this study, where all three patients with hyperplasia had negative imaging. These patients requiring surgery should continue to have bilateral neck dissection and exploration. Combined ultrasound and parathyroid scintigraphy has been shown to increase the overall sensitivity for localization of solitary parathyroid adenomas, up to 95%.26–29 This study demonstrates a clear discrepancy between ultrasound and scintigraphy with SPECT/CT. The possible reasons for the lower sensitivity of ultrasound have already been discussed, but the sensitivity of the scintigraphic data is in line with the current literature. Similarly, the study has confirmed that the overall sensitivity of preoperative localization with combined ultrasound and SPECT/CT can be increased to 95% with an accuracy of 91%. Both ultrasound and SPECT/CT had similar rates of accuracy (90–91%) in localizing adenomas to the pathological gland, which is essential for the success of minimally invasive surgery. Although all adenomas were correctly lateralized, there were four cases where superior gland adenomas were incorrectly localized to the inferior glands on both ultrasound and SPECT/CT. This is likely to reflect the fact that superior glands tend to prolapse inferiorly as they enlarge.20 Surgeons should be aware that although both ultrasound and scintigraphy provide a high level of accuracy in localizing parathyroid adenoma, the differentiation of a low superior parathyroid adenoma and an inferior parathyroid adenoma remains a potential source of error. This study highlights the relative merits of SPECT/CT scintigraphy compared with ultrasound for localizing solitary parathyroid adenomas with greater sensitivity and comparable accuracy in the present patient cohort. Most centres advocate concordant imaging findings to achieve
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
283
Figure 2 Deep-seated parathyroid adenoma not visible with ultrasound due to acoustic shadowing from the trachea (a), but accurately localized with SPECT/CT (b).
the greatest accuracy for minimally invasive parathyroid surgery, usually with ultrasound and scintigraphy. Although most SPECT/CT machines have low-dose CT components, the latest systems have multidetector CT providing ‘‘diagnostic quality’’ images. The radiation exposure involved
with parathyroid SPECT/CT must also be considered. The effective dose of parathyroid scintigraphy (900 MBq 99mTc sestamibi) is 8 mSv.30 In our institution, for reasons of costeffectiveness, 800 MBq is used without significantly compromising image quality and as a result the effective
284
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Figure 3 Ectopic parathyroid adenoma in the posterior mediastinum and associated brown tumour in the left acromion demonstrated on planar scintigraphy (a), but accurately localized with SPECT/CT (b–c), which were confirmed at surgery and bone biopsy, respectively.
dose is marginally lower. The additional radiation exposure from the low-dose CT component is relatively small at approximately 0.1 mSv.31 This would be significantly greater with new multidetector SPECT/CT machines if highresolution images are acquired, although dose reductions could be achieved by only selecting patients for SPECT/CT who have not been adequately localized with ultrasound. An alternate strategy would be to perform SPECT/CT first and proceed to ultrasound only in patients with negative scintigraphy. In the present study, the additional adenomas
detected with ultrasound over SPECT/CT were quite small in number, with no statistically significant difference between SPECT/CT alone and when combined with ultrasound. Although a large number of ultrasound examinations could potentially be avoided, this would need to be evaluated in a prospective study to clarify if ultrasound may be safely withdrawn from the preoperative imaging algorithm of patients with primary hyperparathyroidism. In addition, the present study did not evaluate the additional information provided by ultrasound, such as characterizing
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
285
Figure 4 Ectopic parathyroid adenoma demonstrated on planar imaging (a), although the ectopic location is difficult to appreciate on these views but has been accurately localized with SPECT/CT to reside between the oesophagus and vertebral body (crosshairs), aiding surgical planning.
co-existing nodular thyroid disease, which may affect the surgical technique, precise measurement of depth from skin surface to adenoma, and the potential utility of skin marking prior to surgery. In conclusion the combined use of ultrasound and SPECT/ CT is advocated for the preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism. Concordant imaging findings increase
confidence in accurate localization and facilitate surgical planning for minimally invasive parathyroid surgery. In the present study, integrated SPECT/CT has been demonstrated to accurately detect and localize parathyroid adenomas. However, the inherent limitation of reduced or absent sestamibi tracer uptake in some adenomas, albeit a small number (5%), and the characterization of co-existing nodular thyroid disease, which is valuable for the operating surgeon,
286
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287
Figure 5 Right inferior parathyroid adenoma not clearly visible on planar imaging (a), but accurately localized with SPECT/CT (b) deep to the right lobe of the thyroid.
justifies the continued use of ultrasound with SPECT/CT in our institution at present. High-resolution imaging with multidetector SPECT/CT may allow a single technique approach in the near future.
References 1. Ruda JM, Hollenbeak CS, Stack Jr BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995–2003. Otolaryngol Head Neck Surg 2005;132:359–72.
2. Udelsman R. Six hundred and fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 2002;235:655–70. 3. Johnson NA, Tublin ME, Ogilvie JB. Parathyroid imaging: technique and role in the preoperative evaluation of primary hyperparathyroidism. AJR Am J Roentgenol 2007;188:1706–15. 4. Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surgery 1984;95:14–21. 5. Patel CN, Chowdhury FU, Scarsbrook AF. Clinical utility of hybrid SPECTCT in endocrine neoplasia. AJR Am J Roentgenol 2008;190:815–24. 6. Profanter C, Wetscher GJ, Gabriel M, et al. CT-MIBI image fusion: a new preoperative localization technique for primary, recurrent and persistent hyperparathyroidism. Surgery 2004;135:157–62.
C.N. Patel et al. / Clinical Radiology 65 (2010) 278–287 7. Krausz Y, Bettman L, Guralnik L, et al. Technetium-99 m-MIBI SPECT/CT in primary hyperparathyroidism. World J Surg 2006;30:76–83. 8. Gayed IW, Kim EE, Broussard WF, et al. The value of 99m Tc-sestamibi SPECT/CT over conventional SPECT in the evaluation of parathyroid adenomas or hyperplasia. J Nucl Med 2005;46:248–52. 9. Neumann DR, Obuchowski NA, Difilippo FP. Preoperative 123I/99mTcsestamibi subtraction SPECT and SPECT/CT in primary hyperparathyroidism. J Nucl Med 2008;49:2012–7. 10. Akram K, Parker JA, Donohoe K, et al. Role of single photon emission computed tomography/computed tomography in localization of ectopic parathyroid adenoma: a pictorial case series and review of the current literature. Clin Nucl Med 2009;34:500–2. 11. Norman J, Shheda H, Farrel C. Minimally invasive parathyroidectomy for primary hyperparathyroidism: decreasing operative time and potential complications while improving cosmetic results. Am Surg 1998;64:391–6. 12. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med 2003;44:1443–58. 13. Henry JF, Iacobone M, Mirallie E, et al. Indications and results of videoassisted parathyroidectomy by a lateral approach in patients with primary hyperparathyroidism. Surgery 2001;130:999–1004. 14. Kebapci M, Entok E, Kebapci N, et al. Preoperative evaluation of parathyroid lesions in patients with concomitant thyroid disease: role of high resolution ultrasonography and dual phase technetium 99m sestamibi scintigraphy. J Endocrinol Invest 2004;27:24–30. 15. Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99 m) technetium sestamibi scintigraphy. Clin Endocrinol 2002;57:241–9. 16. Tublin ME, Pryma DA, Yim JH, et al. Localization of parathyroid adenomas by sonography and technetium 99m sestamibi single-photon emission computed tomography before minimally invasive parathyroidectomy: are both studies really needed? J Ultrasound Med 2009;28:183–90. 17. Slater A, Gleeson FV. Increased sensitivity and confidence of SPECT over planar imaging in dual-phase sestamibi for parathyroid adenoma detection. Clin Nucl Med 2005;30:1–3. 18. Lavely WC, Goetze S, Friedman KP, et al. Comparison of SPECT/CT, SPECT, and planar imaging with single- and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy. J Nucl Med 2007;48:1084–9. 19. Sharma J, Mazzaglia P, Milas M, et al. Radionuclide imaging for hyperparathyroidism (HPT): which is the best technetium-99m sestamibi modality? Surgery 2006;140:856–63.
287
20. Civelek AC, Ozalp E, Donovan P, et al. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 2002;131: 149–57. 21. Hindie´ E, Ugur O, Fuster D, O’Doherty M, Grassetto G, Urena P. Parathyroid task group of the EANM. 2009 EANM parathyroid guidelines. Eur J Nucl Med Mol Imaging 2009;36:1201–16. 22. Harris L, Yoo J, Driedger A, et al. Accuracy of technetium-99m SPECT-CT hybrid images in predicting the precise intra-operative anatomical location of parathyroid adenomas. Head Neck 2008;30:509–17. 23. Mihai R, Gleeson F, Buley ID, et al. Negative imaging studies for primary hyperparathyroidism are unavoidable: correlation of sestamibi and high resolution ultrasound scanning with histological analysis in 150 patients. World J Surg 2006;30:697–704. 24. Gupta Y, Ahmed R, Happerfield L, et al. P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism. Br J Surg 2007;94:1491–5. 25. Jorna FH, Hollema H, Hendrikse HN, et al. P-gp and MRP1 expression in parathyroid tumors related to histology, weight and 99m Tc-sestamibi imaging results. Exp Clin Endocrinol Diabetes; 2009. doi: 10.1055/s-00281105925. 26. Lumachi F, Zucchetta P, Marzola MC, et al. Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism. Eur J Endocrinol 2000;143:755–60. 27. Siperstein A, Berber E, Mackey R, et al. Prospective evaluation of sestamibi scan, ultrasonography, and rapid PTH to predict the success of limited exploration for sporadic primary hyperparathyroidism. Surgery 2004;136:872–80. 28. Purcell GP, Dirbas FM, Jeffrey RB, et al. Parathyroid localization with high-resolution ultrasound and technetium 99mTc sestamibi. Arch Surg 1999;134:824–30. 29. De Feo ML, Colagrande S, Biagini C, et al. Parathyroid glands: combination of (99m) Tc MIBI scintigraphy and US for demonstration of parathyroid glands and nodules. Radiology 2000;214:393–402. 30. Administration of Radioactive Substances Advisory Committee (ARSAC). Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Oxon: ARSAC; 2006. 31. Sawyer LJ, Starritt HC, Hiscock SC, et al. Effective doses to patients from CT acquisition on the GE Infinia Hawkeye: a comparison of calculation methods. Nucl Med Commun 2008;29:144–9.