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Original Article |

Minimally Invasive/Focused Parathyroidectomy in Patients With Negative Sestamibi Scan Results FREE

Emad Kandil, MD; Ahmed Jan Malazai, MD; Saud Alrasheedi, MD; Ralph P. Tufano, MD
[+] Author Affiliations

Author Affiliations: Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana (Drs Kandil, Malazai, and Alrasheedi); and Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr Tufano).


Arch Otolaryngol Head Neck Surg. 2012;138(3):223-225. doi:10.1001/archoto.2011.1419.
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Published online

Objective To examine the feasibility of minimally invasive/focused parathyroidectomy in patients with primary hyperparathyroidism and negative results on preoperative sestamibi scanning.

Design Retrospective review.

Setting Hospital.

Patients A total of 452 patients with primary hyperparathyroidism underwent parathyroidectomy between January 2005 and December 2009.

Main Outcome Measures Preoperative sestamibi scans were reviewed, and their influence on the surgical outcome was examined. Records of the intraoperative and postoperative findings were also reviewed.

Results Seventy-seven patients (17.0%) were found to have negative results on preoperative sestamibi scans, and these patients formed our cohort study group. In this group, neck ultrasonography performed as an adjunct was able to preoperatively localize an area that was suggestive of a single adenoma in 61 patients (79.2%), 53 of whom were confirmed to have a single adenoma intraoperatively (sensitivity, 80.3%; specificity, 27.3%; positive predictive value, 86.9%; and negative predictive value, 18.8%). In total, 66 of 77 patients (85.7%) were confirmed to have a single adenoma at the time of surgery.

Conclusions Negative results on sestamibi scans should not be used as exclusion criteria for minimally invasive/focused parathyroidectomy in patients with primary hyperparathyroidism. In our study, 66 patients with negative results on preoperative scans were found to have a single adenoma and were surgically cured by minimally invasive/focused parathyroidectomy.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient setting. Preoperative localization and the intraoperative parathyroid hormone (PTH) assay have revolutionized the surgical management of these cases. Over the years, minimally invasive/focused parathyroidectomy (MIFP) has rapidly gained popularity as the procedure of choice for patients with PHPT.1,2 It has been shown to have many advantages over traditional bilateral 4-gland parathyroid exploration, including decreased pain, small incisions, lower morbidity, and decreased length of hospital stay.1,35 This procedure, however, relies on perioperative imaging techniques to identify the affected parathyroid gland. Before surgery, technetium 99 sestamibi scanning is most commonly used to determine whether the patient has a single adenoma and, if so, to identify its location. When the results of the scans are negative, surgeons often recommend bilateral 4-gland parathyroid exploration to identify affected glands. Therefore, false-negative results on sestamibi scans may preclude patients from targeted minimally invasive parathyroidectomy, although a single-gland adenoma may still be discovered at the time of bilateral neck exploration. The objective of this study was to examine the feasibility of intraoperative PTH monitoring–guided MIFP in patients with PHPT and negative results on preoperative sestamibi scanning. Intraoperative PTH monitoring was used to evaluate the intraoperative success of the procedure. The intraoperative criterion for successful parathyroidectomy was defined as follows: intact PTH levels should decrease by more than 50% and fall into the normal range from the highest preincisional or preexcisional hormone levels in a peripheral blood sample obtained 10 minutes after removal of abnormal parathyroid tissue.6,7 We have also used this criterion to treat double adenomas in PHPT.8

A total of 452 consecutive patients with PHPT underwent parathyroidectomy at Johns Hopkins Hospital, Baltimore, Maryland, between January 2005 and December 2009. All patients underwent preoperative technetium 99 sestamibi scintigraphy at our institution using single-photon emission computed tomography. Images were performed at 15 minutes and 2 hours after injection, as described previously.9

All patients also underwent concomitant cervical ultrasonography as an additional localization study. Patients with a positive results on ultrasonography of the neck underwent MIFP with intraoperative PTH testing. None of the patients in our study had previously undergone thyroid or parathyroid surgery. All patients underwent PTH testing in the operating room to confirm removal of all affected glands. A failure of PTH levels to decrease by 50% and fall into the normal range 10 minutes after resection of the image-identified adenoma was an indication for bilateral neck exploration.

We identified 77 patients (17.0%) in our database with PHPT and negative results on sestamibi scanning. The mean age of the patients was 54 years; 25.9% were male; the average preoperative calcium level was 11.1 mg/dL (to convert to millimoles per liter, multiply by 0.25); and the average preoperative PTH level was 113.4 mg/dL (to convert to nanograms per liter, multiply by 1.0). To investigate further localization, all patients underwent cervical ultrasonography in the Department of Radiology at Johns Hopkins Hospital. Sixty-one of them (79.2%) had results that suggested an adenoma, and 53 of the 61 patients were confirmed to have a single adenoma at the time of surgery (sensitivity, 80.3%; specificity, 27.3%; positive predictive value, 86.9%; and negative predictive value, 18.8%). The sensitivity, specificity, positive predictive value, and negative predictive value of sestamibi scanning in localizing a single adenoma in our study were 83.5%, 23.4%, 90.2%, and 14.3%, respectively

Of the 77 patients with negative results on sestamibi scans, 66 (85.7%) were found to have a single adenoma at the time of surgery. Of the remaining patients, 8 (10.4%) had a double adenoma, and 3 (3.9%) had 4-gland hyperplasia. Fifty-three patients who were found to have a single adenoma underwent MIFP alone, and the remaining 13 patients underwent 4-gland exploration that confirmed the evidence of single-gland disease.

Primary hyperparathyroidism has been recognized as a disease process since the 1920s, when it was discovered in both Europe and the United States1,10 Since that time, the recognition, diagnosis, and treatment of PHPT have evolved because of improved laboratory testing, accurate preoperative localization, and less invasive surgical procedures. Once a diagnosis of PHPT is made and the patient is deemed an appropriate surgical candidate, preoperative localization of the involved gland(s) aids in the choice of operation (MIFP vs bilateral 4-gland exploration). Preoperative localization of the abnormal gland(s) has become even more important in the era of minimally invasive parathyroid surgery. The 2 most common imaging modalities are ultrasonography and technetium 99m sestamibi scintigraphy. The sensitivity of sestamibi–single-photon computed tomographic scanning in the present study was similar to that reported in the literature (range, 71% to 88%).1113

Ultrasonography is particularly beneficial because it is inexpensive, can be performed by the surgeon in office settings, can be repeated easily, and does not involve ionizing radiation. A point of concern with preoperative imaging is the case involving PHPT and a negative sestamibi scan result. Such cases represent an important subset in which traditional 4-gland operative exploratory surgery is widely advocated at the expense of MIFP. However, MIFP is rapidly gaining popularity as the procedure of choice for patients with PHPT as well as the preferred treatment option in patients with PHPT and negative results on sestamibi scans.1,2,14 It has been shown to have many advantages over traditional bilateral 4-gland parathyroid exploration, including decreased pain, small incisions, improved cosmetic results, lower morbidity, and decreased length of hospital stay.35 In contrast, parathyroid exploratory surgery often and unpredictably requires more extensive neck exploration, including paratracheal dissection, thymectomy, and partial thyroidectomy. Intraoperative PTH monitoring can help confirm a successful operation, leaving little to no suspicion of multiglandular disease and thereby avoiding bilateral neck exploration.14 We and others have shown that intraoperative PTH monitoring is of value not only in cases involving single-gland disease but also in cases involving double adenoma and multiglandular disease.8,14,15 Therefore, it has been our goal to consider more patients with PHPT as candidates for MIFP. However, it is important to emphasize that an experienced parathyroid surgeon should perform the operation after a comprehensive preoperative workup, either with an MIFP approach or with a conventional bilateral neck exploration. Treatment using the bilateral approach results in a greater than 95% cure, with a complication rate of less than 4%.16

Our study aimed to assess the feasibility of MIFP in patients with PHPT who have negative results on preoperative sestamibi scanning. The results of our study emphasize several important points. First, in patients who had negative sestamibi scan results, we found a high incidence of single parathyroid gland disease. Most of these patients (85.7%) had a single adenoma. This finding contradicts the common perception that a negative sestamibi scan result indicates a diagnosis of parathyroid hyperplasia/multiglandular disease and thus requires 4-gland operative exploratory surgery.17 Second, further localization with comprehensive cervical ultrasonography will reveal a single adenoma in most cases, as in our study, in which cervical ultrasonography demonstrated a positive predictive value of 86.9% in the preoperative detection of a single adenoma when the results of sestamibi scanning were negative. Comprehensive neck ultrasonography is beneficial because it allows more patients who were previously excluded to be candidates for MIFP. This concept was advocated in some previous studies, but little has been done to evaluate its efficacy in cases involving negative sestamibi scan results.1821 Furthermore, we are able to achieve a success rate of 98.4% in resolving PHPT by starting with MIFP in this challenging patient subgroup. One of the limitations of our current study involved the difficulty in reporting an accurate cure rate in our study cohort. Therefore, we used intraoperative PTH testing as a predictor of cure. However, most surgeons agree that a decrease of more than 50% in PTH level from the highest preincision or preexcision level is associated with a predictive cure in 94% to 97% of cases.6,7,22 Future studies are needed to specifically address the cure rate in this interesting group of patients with negative preoperative sesatmibi scan results.

We recently reported on independently evaluating both ultrasonography and sestamibi scanning as single-modality preoperative screening tools in cases of PHPT. We reported that the sensitivity for correct localization of a single parathyroid adenoma was 83% for sestamibi scanning vs 72% for ultrasonography.23 Therefore, when patients have negative results on a sestamibi scan, we recommend that they undergo comprehensive cervical ultrasonography before the option of MIFP is excluded. Using this approach, many more patients with PHPT will be considered for MIFP.

Correspondence: Ralph P. Tufano, MD, Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD 21287 (rtufano@jhmi.edu).

Submitted for Publication: March 18, 2011; final revision received September 10, 2011; accepted November 17, 2011.

Published Online: February 20, 2012. doi:10.1001/archoto.2011.1419

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kandil and Tufano. Acquisition of data: Kandil and Alrasheedi. Analysis and interpretation of data: Malazai and Alrasheedi. Drafting of the manuscript: Kandil and Malazai. Critical revision of the manuscript for important intellectual content: Alrasheedi and Tufano. Study supervision: Tufano.

Financial Disclosure: None reported.

Previous Presentation: This study was presented in part at the American Head and Neck Society 2011 Annual Meeting; April 27, 2011; Chicago, Illinois.

Felger EA, Kandil E. Primary hyperparathyroidism.  Otolaryngol Clin North Am. 2010;43(2):417-432, x
PubMed   |  Link to Article
Sackett WR, Barraclough B, Reeve TS, Delbridge LW. Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy.  Arch Surg. 2002;137(9):1055-1059
PubMed   |  Link to Article
Udelsman R. Six hundred fifty-six consecutive explorations for primary hyperparathyroidism.  Ann Surg. 2002;235(5):665-672
PubMed   |  Link to Article
Bergenfelz A, Lindblom P, Tibblin S, Westerdahl J. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial.  Ann Surg. 2002;236(5):543-551
PubMed   |  Link to Article
Goldstein RE, Blevins L, Delbeke D, Martin WH. Effect of minimally invasive radioguided parathyroidectomy on efficacy, length of stay, and costs in the management of primary hyperparathyroidism.  Ann Surg. 2000;231(5):732-742
PubMed   |  Link to Article
Irvin GL III, Solorzano CC, Carneiro DM. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome.  World J Surg. 2004;28(12):1287-1292
PubMed   |  Link to Article
Carneiro DM, Solorzano CC, Nader MC, Ramirez M, Irvin GL III. Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate?  Surgery. 2003;134(6):973-981
PubMed   |  Link to Article
Kandil E, Alabbas HH, Bansal A, Islam T, Tufaro AP, Tufano RP. Intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma.  Arch Otolaryngol Head Neck Surg. 2009;135(12):1206-1208
PubMed   |  Link to Article
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(7):1084-1089
PubMed   |  Link to Article
Ahmad R, Hammond JM. Primary, secondary, and tertiary hyperparathyroidism.  Otolaryngol Clin North Am. 2004;37(4):701-713, vii-viii
PubMed   |  Link to Article
Eslamy HK, Ziessman HA. Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99m Tc sestamibi SPECT and SPECT/CT.  Radiographics. 2008;28(5):1461-1476
PubMed   |  Link to Article
Caixàs A, Bernà L, Hernández A,  et al.  Efficacy of preoperative diagnostic imaging localization of technetium 99m-sestamibi scintigraphy in hyperparathyroidism.  Surgery. 1997;121(5):535-541
PubMed   |  Link to Article
Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003.  Otolaryngol Head Neck Surg. 2005;132(3):359-372
PubMed   |  Link to Article
Lew JI, Irvin GL III. Focused parathyroidectomy guided by intra-operative parathormone monitoring does not miss multiglandular disease in patients with sporadic primary hyperparathyroidism: a 10-year outcome.  Surgery. 2009;146(6):1021-1027
PubMed   |  Link to Article
Kandil E, Carson KA, Tufaro AP,  et al.  Role of preoperative intact parathyroid hormone levels in predicting the likelihood of multiglandular disease in primary hyperparathyroidism.  Head Neck. 2010;33(4):543-546
PubMed   |  Link to Article
Allendorf J, DiGorgi M, Spanknebel K, Inabnet W, Chabot J, Logerfo P. 1112 consecutive bilateral neck explorations for primary hyperparathyroidism.  World J Surg. 2007;31(11):2075-2080
PubMed   |  Link to Article
Chan RK, Ruan DT, Gawande AA, Moore FD Jr. Surgery for hyperparathyrodism in image-negative patients.  Arch Surg. 2008;143(4):335-337
PubMed   |  Link to Article
Solorzano CC, Lee TM, Ramirez MC, Carneiro DM, Irvin GL. Surgeon-performed ultrasound improves localization of abnormal parathyroid glands.  Am Surg. 2005;71(7):557-563
PubMed
Casas AT, Burke GJ, Sathyanarayana , Mansberger AR Jr, Wei JP. Prospective comparison of technetium-99m-sestamibi/iodine-123 radionuclide scan versus high-resolution ultrasonography for the preoperative localization of abnormal parathyroid glands in patients with previously unoperated primary hyperparathyroidism.  Am J Surg. 1993;166:369-373
PubMed   |  Link to Article
Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy.  Clin Endocrinol (Oxf). 2002;57(2):241-249
PubMed   |  Link to Article
Lal A, Chen H. The negative sestamibi scan: is a minimally invasive parathyroidectomy still possible?  Ann Surg Oncol. 2007;14(8):2363-2366
PubMed   |  Link to Article
Chiu B, Sturgeon C, Angelos P. Which intraoperative parathyroid hormone assay criterion best predicts operative success? a study of 352 consecutive patients.  Arch Surg. 2006;141(5):483-488
PubMed   |  Link to Article
Levy JM, Kandil E, Yau LC, Cuda JD, Sheth SN, Tufano RP. Can ultrasound be used as the primary screening modality for the localization of parathyroid disease prior to surgery for primary hyperparathyroidism? a review of 440 cases.  ORL J Otorhinolaryngol Relat Spec. 2011;73(2):116-120
PubMed   |  Link to Article

Figures

Tables

References

Felger EA, Kandil E. Primary hyperparathyroidism.  Otolaryngol Clin North Am. 2010;43(2):417-432, x
PubMed   |  Link to Article
Sackett WR, Barraclough B, Reeve TS, Delbridge LW. Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy.  Arch Surg. 2002;137(9):1055-1059
PubMed   |  Link to Article
Udelsman R. Six hundred fifty-six consecutive explorations for primary hyperparathyroidism.  Ann Surg. 2002;235(5):665-672
PubMed   |  Link to Article
Bergenfelz A, Lindblom P, Tibblin S, Westerdahl J. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial.  Ann Surg. 2002;236(5):543-551
PubMed   |  Link to Article
Goldstein RE, Blevins L, Delbeke D, Martin WH. Effect of minimally invasive radioguided parathyroidectomy on efficacy, length of stay, and costs in the management of primary hyperparathyroidism.  Ann Surg. 2000;231(5):732-742
PubMed   |  Link to Article
Irvin GL III, Solorzano CC, Carneiro DM. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome.  World J Surg. 2004;28(12):1287-1292
PubMed   |  Link to Article
Carneiro DM, Solorzano CC, Nader MC, Ramirez M, Irvin GL III. Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate?  Surgery. 2003;134(6):973-981
PubMed   |  Link to Article
Kandil E, Alabbas HH, Bansal A, Islam T, Tufaro AP, Tufano RP. Intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma.  Arch Otolaryngol Head Neck Surg. 2009;135(12):1206-1208
PubMed   |  Link to Article
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(7):1084-1089
PubMed   |  Link to Article
Ahmad R, Hammond JM. Primary, secondary, and tertiary hyperparathyroidism.  Otolaryngol Clin North Am. 2004;37(4):701-713, vii-viii
PubMed   |  Link to Article
Eslamy HK, Ziessman HA. Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99m Tc sestamibi SPECT and SPECT/CT.  Radiographics. 2008;28(5):1461-1476
PubMed   |  Link to Article
Caixàs A, Bernà L, Hernández A,  et al.  Efficacy of preoperative diagnostic imaging localization of technetium 99m-sestamibi scintigraphy in hyperparathyroidism.  Surgery. 1997;121(5):535-541
PubMed   |  Link to Article
Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003.  Otolaryngol Head Neck Surg. 2005;132(3):359-372
PubMed   |  Link to Article
Lew JI, Irvin GL III. Focused parathyroidectomy guided by intra-operative parathormone monitoring does not miss multiglandular disease in patients with sporadic primary hyperparathyroidism: a 10-year outcome.  Surgery. 2009;146(6):1021-1027
PubMed   |  Link to Article
Kandil E, Carson KA, Tufaro AP,  et al.  Role of preoperative intact parathyroid hormone levels in predicting the likelihood of multiglandular disease in primary hyperparathyroidism.  Head Neck. 2010;33(4):543-546
PubMed   |  Link to Article
Allendorf J, DiGorgi M, Spanknebel K, Inabnet W, Chabot J, Logerfo P. 1112 consecutive bilateral neck explorations for primary hyperparathyroidism.  World J Surg. 2007;31(11):2075-2080
PubMed   |  Link to Article
Chan RK, Ruan DT, Gawande AA, Moore FD Jr. Surgery for hyperparathyrodism in image-negative patients.  Arch Surg. 2008;143(4):335-337
PubMed   |  Link to Article
Solorzano CC, Lee TM, Ramirez MC, Carneiro DM, Irvin GL. Surgeon-performed ultrasound improves localization of abnormal parathyroid glands.  Am Surg. 2005;71(7):557-563
PubMed
Casas AT, Burke GJ, Sathyanarayana , Mansberger AR Jr, Wei JP. Prospective comparison of technetium-99m-sestamibi/iodine-123 radionuclide scan versus high-resolution ultrasonography for the preoperative localization of abnormal parathyroid glands in patients with previously unoperated primary hyperparathyroidism.  Am J Surg. 1993;166:369-373
PubMed   |  Link to Article
Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy.  Clin Endocrinol (Oxf). 2002;57(2):241-249
PubMed   |  Link to Article
Lal A, Chen H. The negative sestamibi scan: is a minimally invasive parathyroidectomy still possible?  Ann Surg Oncol. 2007;14(8):2363-2366
PubMed   |  Link to Article
Chiu B, Sturgeon C, Angelos P. Which intraoperative parathyroid hormone assay criterion best predicts operative success? a study of 352 consecutive patients.  Arch Surg. 2006;141(5):483-488
PubMed   |  Link to Article
Levy JM, Kandil E, Yau LC, Cuda JD, Sheth SN, Tufano RP. Can ultrasound be used as the primary screening modality for the localization of parathyroid disease prior to surgery for primary hyperparathyroidism? a review of 440 cases.  ORL J Otorhinolaryngol Relat Spec. 2011;73(2):116-120
PubMed   |  Link to Article

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