Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism
- Linwah Yip, MD
Linwah Yip, MD
- Assistant Professor of Surgery
- University of Pittsburgh School of Medicine
- Shonni J Silverberg, MD
Shonni J Silverberg, MD
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
- Ghada El-Hajj Fuleihan, MD, MPH
Ghada El-Hajj Fuleihan, MD, MPH
- Professor of Medicine
- American University of Beirut Medical Center, Lebanon
- Section Editors
- Sally E Carty, MD, FACS
Sally E Carty, MD, FACS
- Section Editor — Endocrine Surgery
- Professor, Chief, Division of Endocrine Surgery
- University of Pittsburgh School of Medicine
- Clifford J Rosen, MD
Clifford J Rosen, MD
- Section Editor — Bone Disease
- Professor of Nutrition
- University of Maine
- Professor of Medicine
- Tufts University School of Medicine
Primary hyperparathyroidism is usually caused by a solitary benign adenoma (80 to 85 percent), but can also be due to double adenomata (2 to 5 percent), diffuse or nodular hyperplasia (10 to 15 percent), or parathyroid carcinoma (<1 percent) . An open four gland parathyroid exploration has traditionally been considered the gold standard for patients undergoing surgery for primary hyperparathyroidism. However, a more focused, minimally invasive approach to parathyroid surgery is being adopted at many centers .
Localization techniques are primarily used in patients who have biochemically confirmed sporadic primary hyperparathyroidism to identify patients who are candidates for a minimally invasive approach. They are also important in patients undergoing remedial surgery for persistent or recurrent disease. Patients with hereditary primary hyperparathyroidism generally undergo bilateral parathyroid exploration, even in the event of a positive localizing study, because of the potential for asymmetric hyperplasia. Localization studies, in conjunction with intraoperative parathyroid hormone testing, can help minimize the extent of surgical dissection, identify concurrent thyroid pathology, and in patients with recurrent or persistent hyperparathyroidism, can help detect ectopic parathyroid tissue. However, localization studies should not be used to diagnose or confirm the diagnosis of hyperparathyroidism or determine the need for surgery. Localization studies do not supersede the recommendation that parathyroid surgery should only be performed by highly experienced surgeons .
The techniques and role of preoperative localization in patients with primary hyperparathyroidism will be reviewed here. Decision making regarding the role of surgical therapy and the details of surgical management in these patients and the role of surgery for secondary hyperparathyroidism in patients with end-stage renal disease is discussed elsewhere. (See "Indications for parathyroidectomy in end-stage renal disease" and "Parathyroid exploration for primary hyperparathyroidism", section on 'Focused parathyroid exploration' and "Primary hyperparathyroidism: Management", section on 'Candidates for surgery'.)
ROLE OF PREOPERATIVE LOCALIZATION
Imaging studies are not used in the diagnosis of primary hyperparathyroidism because of high false-positive rates, which can range from 5 to 25 percent (table 1). In addition, a single-focus positive imaging result does not reliably exclude the presence of multiglandular parathyroid disease . Rather, preoperative localization studies help plan the operative approach in patients who have a biochemically-confirmed diagnosis of primary hyperparathyroidism, and in whom other pathologies have been appropriately ruled out (eg, familial benign hypercalcemic hypocalciuria). With the growing acceptance of minimally invasive surgery, these studies are predominantly used to determine whether or not a patient is a candidate for a minimally invasive approach [5-7]. (See "Parathyroid hormone assays and their clinical use".)
Available radiologic expertise is an important factor in choosing the type of localization testing to be performed. Localization images should be displayed and available intraoperatively, since review during exploration often usefully guides successful surgery. (See 'Imaging modalities' below.)
Subscribers log in hereTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:Literature review current through: Jul 2017. | This topic last updated: Jul 06, 2015.References
- Kaplan EL, Yashiro T, Salti G. Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease. Ann Surg 1992; 215:300.
- Smith, SL, Van, Heerden, J. Conventional parathyroidectomy for priimary hyperparathyroidism. In: Mastery of Surgery, I, Fischer, JE (Eds), Lippincott, Philadelphia 2007. p.430.
- Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3561.
- Yip L, Pryma DA, Yim JH, et al. Can a lightbulb sestamibi SPECT accurately predict single-gland disease in sporadic primary hyperparathyroidism? World J Surg 2008; 32:784.
- Carty SE, Worsey J, Virji MA, et al. Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay. Surgery 1997; 122:1107.
- Arici C, Cheah WK, Ituarte PH, et al. Can localization studies be used to direct focused parathyroid operations? Surgery 2001; 129:720.
- Udelsman R. Six hundred fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 2002; 235:665.
- Hindié E, Mellière D, Perlemuter L, et al. Primary hyperparathyroidism: higher success rate of first surgery after preoperative Tc-99m sestamibi-I-123 subtraction scanning. Radiology 1997; 204:221.
- Ryan JA Jr, Eisenberg B, Pado KM, Lee F. Efficacy of selective unilateral exploration in hyperparathyroidism based on localization tests. Arch Surg 1997; 132:886.
- Martin RC 2nd, Greenwell D, Flynn MB. Initial neck exploration for untreated hyperparathyroidism. Am Surg 2000; 66:269.
- Carneiro DM, Solorzano CC, Nader MC, et al. Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate? Surgery 2003; 134:973.
- Riss P, Scheuba C, Asari R, et al. Is minimally invasive parathyroidectomy without QPTH monitoring justified? Langenbecks Arch Surg 2009; 394:875.
- Udelsman R, Åkerström G, Biagini C, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014; 99:3595.
- Jaskowiak N, Norton JA, Alexander HR, et al. A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma. Ann Surg 1996; 224:308.
- Shen W, Düren M, Morita E, et al. Reoperation for persistent or recurrent primary hyperparathyroidism. Arch Surg 1996; 131:861.
- Doherty GM, Weber B, Norton JA. Cost of unsuccessful surgery for primary hyperparathyroidism. Surgery 1994; 116:954.
- Henry JF. Reoperation for primary hyperparathyroidism: tips and tricks. Langenbecks Arch Surg 2010; 395:103.
- Caron NR, Sturgeon C, Clark OH. Persistent and recurrent hyperparathyroidism. Curr Treat Options Oncol 2004; 5:335.
- Udelsman R, Donovan PI. Remedial parathyroid surgery: changing trends in 130 consecutive cases. Ann Surg 2006; 244:471.
- Sacks BA, Pallotta JA, Cole A, Hurwitz J. Diagnosis of parathyroid adenomas: efficacy of measuring parathormone levels in needle aspirates of cervical masses. AJR Am J Roentgenol 1994; 163:1223.
- MacFarlane MP, Fraker DL, Shawker TH, et al. Use of preoperative fine-needle aspiration in patients undergoing reoperation for primary hyperparathyroidism. Surgery 1994; 116:959.
- Mihai R, Simon D, Hellman P. Imaging for primary hyperparathyroidism--an evidence-based analysis. Langenbecks Arch Surg 2009; 394:765.
- Shin JJ, Milas M, Mitchell J, et al. Impact of localization studies and clinical scenario in patients with hyperparathyroidism being evaluated for reoperative neck surgery. Arch Surg 2011; 146:1397.
- Hessman O, Stålberg P, Sundin A, et al. High success rate of parathyroid reoperation may be achieved with improved localization diagnosis. World J Surg 2008; 32:774.
- Alexander HR Jr, Chen CC, Shawker T, et al. Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism. J Bone Miner Res 2002; 17 Suppl 2:N133.
- Yen TW, Wang TS, Doffek KM, et al. Reoperative parathyroidectomy: an algorithm for imaging and monitoring of intraoperative parathyroid hormone levels that results in a successful focused approach. Surgery 2008; 144:611.
- Yip L, Ogilvie JB, Challinor SM, et al. Identification of multiple endocrine neoplasia type 1 in patients with apparent sporadic primary hyperparathyroidism. Surgery 2008; 144:1002.
- Mitchell BK, Kinder BK, Cornelius E, Stewart AF. Primary hyperparathyroidism: preoperative localization using technetium-sestamibi scanning. J Clin Endocrinol Metab 1995; 80:7.
- Summers GW. Parathyroid exploration. A review of 125 cases. Arch Otolaryngol Head Neck Surg 1991; 117:1237.
- Bilezikian JP, Potts JT Jr, Fuleihan Gel-H, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 2002; 87:5353.
- Sosa JA, Powe NR, Levine MA, et al. Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons. J Clin Endocrinol Metab 1998; 83:2658.
- Schell SR, Dudley NE. Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques. Surgery 2003; 133:32.
- Udelsman R, Pasieka JL, Sturgeon C, et al. Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009; 94:366.
- Eslamy HK, Ziessman HA. Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99mTc sestamibi SPECT and SPECT/CT. Radiographics 2008; 28:1461.
- Lew JI, Solorzano CC. Surgical management of primary hyperparathyroidism: state of the art. Surg Clin North Am 2009; 89:1205.
- 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.
- Prommegger R, Wimmer G, Profanter C, et al. Virtual neck exploration: a new method for localizing abnormal parathyroid glands. Ann Surg 2009; 250:761.
- Moure D, Larrañaga E, Domínguez-Gadea L, et al. 99MTc-sestamibi as sole technique in selection of primary hyperparathyroidism patients for unilateral neck exploration. Surgery 2008; 144:454.
- Lindqvist V, Jacobsson H, Chandanos E, et al. Preoperative 99Tc(m)-sestamibi scintigraphy with SPECT localizes most pathologic parathyroid glands. Langenbecks Arch Surg 2009; 394:811.
- Gilat H, Cohen M, Feinmesser R, et al. Minimally invasive procedure for resection of a parathyroid adenoma: the role of preoperative high-resolution ultrasonography. J Clin Ultrasound 2005; 33:283.
- Rodgers SE, Hunter GJ, Hamberg LM, et al. Improved preoperative planning for directed parathyroidectomy with 4-dimensional computed tomography. Surgery 2006; 140:932.
- Palestro CJ, Tomas MB, Tronco GG. Radionuclide imaging of the parathyroid glands. Semin Nucl Med 2005; 35:266.
- Lal A, Chen H. The negative sestamibi scan: is a minimally invasive parathyroidectomy still possible? Ann Surg Oncol 2007; 14:2363.
- Chiu B, Sturgeon C, Angelos P. What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy. Surgery 2006; 140:418.
- Civelek AC, Ozalp E, Donovan P, Udelsman R. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 2002; 131:149.
- Wheeler MH. Preoperative parathyroid scanning in secondary hyperparathyroidism. Lancet 1999; 353:2174.
- 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.
- Pappu S, Donovan P, Cheng D, Udelsman R. Sestamibi scans are not all created equally. Arch Surg 2005; 140:383.
- Friedman K, Somervell H, Patel P, et al. Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism. Surgery 2004; 136:1199.
- Mehta NY, Ruda JM, Kapadia S, et al. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg 2005; 131:493.
- Stephen AE, Roth SI, Fardo DW, et al. Predictors of an accurate preoperative sestamibi scan for single-gland parathyroid adenomas. Arch Surg 2007; 142:381.
- Gómez-Ramírez J, Sancho-Insenser JJ, Pereira JA, et al. Impact of thyroid nodular disease on 99mTc-sestamibi scintigraphy in patients with primary hyperparathyroidism. Langenbecks Arch Surg 2010; 395:929.
- Nichols KJ, Tomas MB, Tronco GG, et al. Preoperative parathyroid scintigraphic lesion localization: accuracy of various types of readings. Radiology 2008; 248:221.
- Wimmer G, Profanter C, Kovacs P, et al. CT-MIBI-SPECT image fusion predicts multiglandular disease in hyperparathyroidism. Langenbecks Arch Surg 2010; 395:73.
- Schachter PP, Issa N, Shimonov M, et al. Early, postinjection MIBI-SPECT as the only preoperative localizing study for minimally invasive parathyroidectomy. Arch Surg 2004; 139:433.
- Spanu A, Falchi A, Manca A, et al. The usefulness of neck pinhole SPECT as a complementary tool to planar scintigraphy in primary and secondary hyperparathyroidism. J Nucl Med 2004; 45:40.
- 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.
- Solorzano CC, Carneiro-Pla DM, Irvin GL 3rd. Surgeon-performed ultrasonography as the initial and only localizing study in sporadic primary hyperparathyroidism. J Am Coll Surg 2006; 202:18.
- Hindié E, Mellière D, Jeanguillaume C, et al. Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning. Arch Surg 2000; 135:1461.
- Singh N, Krishna BA. Role of radionuclide scintigraphy in the detection of parathyroid adenoma. Indian J Cancer 2007; 44:12.
- McBiles M, Lambert AT, Cote MG, Kim SY. Sestamibi parathyroid imaging. Semin Nucl Med 1995; 25:221.
- 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; 57:241.
- Erbil Y, Barbaros U, Tükenmez M, et al. Impact of adenoma weight and ectopic location of parathyroid adenoma on localization study results. World J Surg 2008; 32:566.
- Powell AC, Alexander HR, Chang R, et al. Reoperation for parathyroid adenoma: a contemporary experience. Surgery 2009; 146:1144.
- Siperstein A, Berber E, Barbosa GF, et al. Predicting the success of limited exploration for primary hyperparathyroidism using ultrasound, sestamibi, and intraoperative parathyroid hormone: analysis of 1158 cases. Ann Surg 2008; 248:420.
- Barbaros U, Erbil Y, Salmashoğlu A, et al. The characteristics of concomitant thyroid nodules cause false-positive ultrasonography results in primary hyperparathyroidism. Am J Otolaryngol 2009; 30:239.
- Bentrem DJ, Angelos P, Talamonti MS, Nayar R. Is preoperative investigation of the thyroid justified in patients undergoing parathyroidectomy for hyperparathyroidism? Thyroid 2002; 12:1109.
- Elaraj DM, Sippel RS, Lindsay S, et al. Are additional localization studies and referral indicated for patients with primary hyperparathyroidism who have negative sestamibi scan results? Arch Surg 2010; 145:578.
- Kunstman JW, Kirsch JD, Mahajan A, Udelsman R. Clinical review: Parathyroid localization and implications for clinical management. J Clin Endocrinol Metab 2013; 98:902.
- Patel CN, Salahudeen HM, Lansdown M, Scarsbrook AF. Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism. Clin Radiol 2010; 65:278.
- Kwon JH, Kim EK, Lee HS, et al. Neck ultrasonography as preoperative localization of primary hyperparathyroidism with an additional role of detecting thyroid malignancy. Eur J Radiol 2013; 82:e17.
- Milas M, Mensah A, Alghoul M, et al. The impact of office neck ultrasonography on reducing unnecessary thyroid surgery in patients undergoing parathyroidectomy. Thyroid 2005; 15:1055.
- Lubitz CC, Stephen AE, Hodin RA, Pandharipande P. Preoperative localization strategies for primary hyperparathyroidism: an economic analysis. Ann Surg Oncol 2012; 19:4202.
- Haciyanli M, Lal G, Morita E, et al. Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. J Am Coll Surg 2003; 197:739.
- Berber E, Parikh RT, Ballem N, et al. Factors contributing to negative parathyroid localization: an analysis of 1000 patients. Surgery 2008; 144:74.
- Mortenson MM, Evans DB, Lee JE, et al. Parathyroid exploration in the reoperative neck: improved preoperative localization with 4D-computed tomography. J Am Coll Surg 2008; 206:888.
- Mahajan A, Starker LF, Ghita M, et al. Parathyroid four-dimensional computed tomography: evaluation of radiation dose exposure during preoperative localization of parathyroid tumors in primary hyperparathyroidism. World J Surg 2012; 36:1335.
- Gotway MB, Reddy GP, Webb WR, et al. Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism. Radiology 2001; 218:783.
- Jayender J, Lee TC, Ruan DT. Real-Time Localization of Parathyroid Adenoma during Parathyroidectomy. N Engl J Med 2015; 373:96.
- Wakamatsu H, Noguchi S, Yamashita H, et al. Parathyroid scintigraphy with 99mTc-MIBI and 123I subtraction: a comparison with magnetic resonance imaging and ultrasonography. Nucl Med Commun 2003; 24:755.
- Lopez Hänninen E, Vogl TJ, Steinmüller T, et al. Preoperative contrast-enhanced MRI of the parathyroid glands in hyperparathyroidism. Invest Radiol 2000; 35:426.
- Tang BN, Moreno-Reyes R, Blocklet D, et al. Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT. Contrast Media Mol Imaging 2008; 3:157.
- Herrmann K, Takei T, Kanegae K, et al. Clinical value and limitations of [11C]-methionine PET for detection and localization of suspected parathyroid adenomas. Mol Imaging Biol 2009; 11:356.
- Weber T, Cammerer G, Schick C, et al. C-11 methionine positron emission tomography/computed tomography localizes parathyroid adenomas in primary hyperparathyroidism. Horm Metab Res 2010; 42:209.
- Weber T, Maier-Funk C, Ohlhauser D, et al. Accurate preoperative localization of parathyroid adenomas with C-11 methionine PET/CT. Ann Surg 2013; 257:1124.
- Lebastchi AH, Aruny JE, Donovan PI, et al. Real-Time Super Selective Venous Sampling in Remedial Parathyroid Surgery. J Am Coll Surg 2015; 220:994.
- Chan RK, Ruan DT, Gawande AA, Moore FD Jr. Surgery for hyperparathyroidism in image-negative patients. Arch Surg 2008; 143:335.
- ROLE OF PREOPERATIVE LOCALIZATION
- Minimally invasive and unilateral parathyroidectomy
- Reoperation for recurrent or persistent hyperparathyroidism
- Bilateral neck exploration
- IMAGING MODALITIES
- Sestamibi scintigraphy
- - SPECT
- - SPECT and CT fusion
- - Subtraction thyroid scan
- Four dimensional computed tomography
- Magnetic resonance imaging
- Positron emission tomography and CT
- Invasive localization
- - Selective venous sampling
- - Selective arteriography
- NEGATIVE IMAGING
- SUMMARY AND RECOMMENDATIONS