Surgery for sporadic primary hyperparathyroidism: controversies and evidence-based approach

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1 Langenbecks Arch Surg (2008) 393: DOI /s CURRENT CONCEPTS IN ENDOCRINE SURGERY Surgery for sporadic primary hyperparathyroidism: controversies and evidence-based approach Antonio Sitges-Serra & Prieto Rosa & Mónica Valero & Estela Membrilla & Joan J. Sancho Received: 20 July 2006 / Accepted: 18 January 2008 / Published online: 21 February 2008 # Springer-Verlag 2008 Abstract Introduction Sporadic primary hyperparathyroidism is due to single adenoma in over 90 95% of instances. Careful medical history and precise preoperative identification of the enlarged gland by parathyroid Tc-mibi scintigraphy and neck ultrasound allow selecting patients for minimally invasive parathyroidectomy, a focused intervention with minimal skin opening and tissue dissection. Small (<300 mg) adenomas continue to challenge preoperative imaging, and most of them will still require a bilateral exploration. Conclusion Surgery should never be indicated on the basis of positive or negative preoperative localization studies. Intraoperative quick parathyroid hormone measurements seem particularly helpful for cases with equivocal localization studies. The best minimal access approach is still a matter of debate, and options include small central incision, video-assisted parathyroidectomy, minimal lateral open approach, and purely endoscopic access via lateral approach. Radioguided surgery does not seem to have a role in routine cases but may be useful to find adenomas during reintervention on scarred difficult surgical fields. A. Sitges-Serra : P. Rosa : M. Valero : E. Membrilla : J. J. Sancho Department of Surgery, Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain A. Sitges-Serra (*) Department of Surgery, Hospital del Mar, Passeig Marítim, 25-29, Barcelona, Spain asitges@imas.imim.es Keywords Parathyroid adenoma. Focused parathyroidectomy. Controversies. Gamma probe. Endoscopy. Hyperparathyroidism Introduction Preoperative investigations and surgical approach to sporadic primary hyperparathyroidism (SPHPT) have changed substantially in the last two decades due to advances made in parathyroid imaging, quick parathyroid hormone (PTH) assays, and endoscopic techniques. Currently, parathyroid 99 Tc-sestamibi scintigraphy and neck ultrasound are carried out almost systematically in patients with SPHPT, and this makes preoperative localization of single adenomas possible in many patients. Precise localization of enlarged glands has, in turn, rendered selective or focused approach to single adenomas much more secure. When properly indicated and performed, the results of selective parathyroidectomy, as assessed by prospective randomized trials, are equivalent to bilateral parathyroid exploration in terms of persistence or recurrence of disease and superior in terms of cosmesis, duration of the intervention, postoperative stay, and hypocalcemia [1, 2]. Limited parathyroidectomy by a unilateral approach was pioneered by Sten Tibblin in the early 1980s [3] when localization techniques were still rudimentary. Some 10 years later, a positive scintigraphy made unilateral exploration much more secure [4]. Currently, the refinement of localization techniques has led to the focused or selective approach ignoring the normal ipsilateral gland which implies an even shorter intervention and further reduction of tissue dissection. New technologies, however, have given rise to several controversies regarding the yield of preoperative imaging techniques, the indications of selective parathyroidectomy,

2 240 Langenbecks Arch Surg (2008) 393: the advantages and failures of intraoperative PTH determination, and the use of other technological equipment. Furthermore, the issue is compounded by the fact that technology may be especially appealing to non-fully trained surgeons with the hope that it will protect them against the anatomical intricacies of parathyroid surgery. In this review, the authors summarize the critical issues regarding some of these hot topics. Although a whole article could be devoted to each of the subjects presented, a synthesis effort has been made to present to the reader the issues in a conceptualized rather than in an exhaustive review way. Preoperative localization techniques and indications of selective parathyroidectomy in SPHPT Before considering selective parathyroidectomy, a careful past medical history should be obtained to rule out conditions in which multiple gland disease is common or even any form of hereditary hyperparathyroidism, lithiumassociated hyperparathyroidism, or chronic renal failure. The coexistence of a goiter is a relative contraindication depending on thyroid size, need for thyroidectomy, and results of localizing techniques. SPHPT is due to a single adenoma in over 90% of the instances. This is the first evidence on which selective parathyroidectomy is based, the second one being the possibility of identifying the diseased gland by preoperative imaging. In many institutions, single adenomas are currently being localized by neck ultrasound and/or parathyroid scintigraphy in over 75 80% of the patients. This has led surgeons to progressively implement selective parathyroidectomy [5, 6], which can now be regarded as a wellestablished procedure. The yield of imaging techniques, however, is dependent on the equipment, operator, and technique, and this has a major impact on local decisionmaking policies. For example, the methodology of parathyroid scintigraphy (collimator, dual-phase, subtraction, etc.) influences the rate of adenoma localization, this being highest for the single photon emission computed tomography (SPECT) technique and lower for simple anteroposterior planar projection [7 9]. In the study of Schachter et al., sensitivity for the planar projection was 78% and 96% for the SPECT study. Neck ultrasound requires an experienced operator to obtain the best results. Currently, there is a growing consensus that both techniques should be carried out because the best results of selective parathyroidectomy are obtained when both localize the adenoma in the same position. In recent series, this has happened in around 60% of cases [6, 10, 11]. When there is discrepancy between the two localization techniques, either a bilateral exploration should be carried out or a focused one with intraoperative PTH measurements [11]. In countries with a high prevalence of nodular thyroid disease, both parathyroid scintigraphy and ultrasound pose specific problems that make identification of parathyroid adenomas more difficult [12, 13]. In these circumstances where, in addition, thyroid resection may be considered, sound decision making in selecting the best approach on a case-to-case basis is essential to avoid surgical failures [14]. Preoperative imaging can, in addition, diagnose unsuspected multiple gland disease which contraindicates a selective approach. About 30 80% of patients with double adenomas will show a double uptake, and around 40 60% of patients with parathyroid hyperplasia will show at least two hot spots in the parathyroid scan [6, 15 17]. The small-adenoma paradox Despite the increasing accuracy of preoperative imaging, the current trend of earlier diagnosis of primary hyperparathyroidism implies that an increasing number of patients will present in the future with s-ca<11 mg/dl and small adenomas. Although some cellular metabolism factors influence the visualization of parathyroid adenomas in the Tc-mibi scan [18, 19], the positivity of parathyroid scintigraphy is very much dependent on the weight of the enlarged glands. Biertho et al. [20] classified Tc-mibi uptake by parathyroid adenomas from 0 (false negative) to 3 (high uptake). The 0-type adenomas had a median weight of 250 mg (interquartile range (IQR), mg) and accounted for 8% of their patients. The 1-type adenomas (equivocal uptake) were observed in 26% of cases and had a median weight of 340 mg (IQR, mg). PTH values were also lower in these two categories: 113 and 151 pg/ml, respectively. Thus, based on Tc-mibi uptake alone, one third of the patients would not have been eligible for a selective approach. Data from a recent study [21] are concordant with those of Biertho et al. [20]; about one third of 150 patients had a negative scan, and there was a clearcut relationship between mean gland weight and scan positivity: 1,180 vs. 517 mg for visualized vs. nonvisualized adenomas. The relationship between adenoma weight and localization also holds true for ultrasonography. At the Mayo Clinic, adenomas of 1,000 mg or more are visualized by neck ultrasonography in over 95% of instances. For adenomas weighing less than 200 mg, however, the localization rate is below 50% [6]. In the future, endocrine surgeons may thus face the paradox of operating on more patients with small adenomas and negative preoperative localization studies making bilateral exploration a must. In this setting, endocrinologists may be tempted to not refer patients for parathyroidectomy in the absence of preoperative localization of the adenoma. Surgeons should not let this occur because, first, a negative

3 Langenbecks Arch Surg (2008) 393: study does not necessarily imply a mild disease; second, it may indicate multiple gland disease; and, third, surgery is the only treatment for hyperparathyroidism. Furthermore, it has been shown that patients with negative scans also obtain a clear-cut benefit from parathyroidectomy [22]. Patients without preoperative localization of a parathyroid adenoma, however, should only be operated on by specialist surgeons having thorough knowledge of normal and pathological parathyroid anatomy. In expert hands, bilateral parathyroid exploration can be done with a short incision ensuring good cosmesis, low cost, few complications and, most importantly, a cure rate close to 100% [23, 24]. Intraoperative PTH measurements Controversies around quick intraoperative PTH assay involve its indications, the criteria for cure, and failures (false decline and false non-decline). An in-depth review of the subject is available [25]. For the sake of clarity, the authors refer in the following paragraphs to the most used and tested Miami criteria for cure: a drop of PTH values at least 50% below the highest PTH value (at induction of anesthesia or pre-excision) 10 min after adenoma resection. Indications Intraoperative PTH assay should have an accuracy superior to the expected failure rate when not implemented. In addition, it should not spuriously prolong the surgical intervention by waiting for results that will not alter the surgical strategy or that will alter it erroneously. These are the main reasons why some experts feel that intraoperative PTH measurement is not indicated when adenoma localization is unequivocal, that is, when both ultrasound and scintigraphy are concordant. In these circumstances, surgical failure is less than 2 3% [11, 26], and PTH measurement only adds potential confusion due to the inherent limitations of the technique. It will be unable to reduce this minimal failure rate while, at the same time, it may lead the surgeon to unnecessarily explore the contralateral side in 5 10% of cases [11, 26, 27]. Others, based on preoperative localization by scintigraphy alone, [28 30] have found that intraoperative PTH measurement is essential to attain the best results from a selective approach. Again, this may be the case or, as an alternative explanation, there may be a crucial problem in the selection of patients. To date, no randomized studies have been published on the benefits of PTH measurement depending on the accuracy of preoperative localization studies. Equivocal localization studies could be the most powerful reason to implement intraoperative PTH measurements [11, 27, 28, 30]. In this circumstance, starting the operation on the suspicious location would be appropriate and then, if the adenoma is correctly identified, a 50% PTH decline should be required. If the adenoma is not found in the suspected location or PTH fails to decline, the surgeon should proceed to a bilateral exploration. Criteria for cure Some refinements of criteria for cure and persistence may still be needed to increase the accuracy of intraoperative PTH measurement. False declines are probably rare if patients have been properly selected for focused parathyroidectomy but still occur in 1 3% of cases [6, 30, 31]. In a series of bilateral explorations validating intraoperative PTH testing, some 50 75% of patients with multiglandular disease have shown an inappropriate 50% drop of PTH values [31 36]. This may be due to the initial removal of the most active gland (which, in addition, may be the only one showing on the scan) or to latent multiple endocrine neoplasia type 1 disease [31, 32]. Others have suggested that concomitant thyroid surgery, by interfering with the adenoma blood supply, may also be a reason for some of these PTH false declines [37]. Finally, Irvin et al. [38] have controversially put forward that there may be enlarged nonfunctioning glands that will be disclosed only if a bilateral exploration is performed. In these circumstances, selective parathyroidectomy based on a purely immediate functional basis (>50% PTH decline) would be appropriate. Furthermore, this would be the explanation for the lower incidence of multiglandular disease found in series of selective parathyroidectomies implementing PTH measurements compared to that reported in a series of bilateral cervical exploration [28, 38]. To avoid false non-declines, two alternatives have been proposed and are currently under evaluation: (1) extending the sampling period to min after the resection of the adenoma [39, 40] and/or (2) requiring normalization of the PTH values (<60 pg/ml). Both may increase the specificity of the intraoperative PTH testing at the expense of unduly prolonging the anesthesia time thus losing one of the main advantages of selective parathyroidectomy. The endoscopic approach Minimally invasive techniques have also interested endocrine surgeons. What this exactly means in thyroid and parathyroid surgery, however, is far from clear [24, 41]. Simple extrapolation from abdominal procedures has led some authors to propose a purely endoscopic approach to (selected) neck endocrine pathologies. Others have combined the open with the endoscopic approach (videoassisted surgery). Although there are a number of studies

4 242 Langenbecks Arch Surg (2008) 393: showing the feasibility of these approaches, a few have reported data hard enough to demonstrate that they are really minimally invasive and that they offer advantages over conventional minimal incision surgery. Miccoli et al. [42] have published a feasibility uncontrolled study based on their experience in 370 cases of video-assisted selective parathyroidectomy study. They used a central cm incision (at the beginning of the procedure) with external lateral retraction through which endoscopic instruments are introduced. The operation was accomplished in 36 min, and patients were discharged the day after with a complication rate of 2.7%, a cure rate of 98.3%, and a 6.2% conversion rate. No data are given concerning the superiority of this approach over the conventional mini-incision central or lateral selective approach. The first randomized study comparing videoassisted vs. open central (Kocher incision) parathyroidectomy has been recently published by Barczynski et al. [43]. Although they state that central incision for the open procedure was 2 3 cm long, their follow-up data indicate that patients finally had a conventional 3.8±4-cm scar probably because using a central approach, a more extensive muscular dissection, and thyroid mobilization is required in comparison with targeted lateral approaches in which the infrahyoidal muscles are minimally retracted and the thyroid lobe is left almost untouched. This on its own could explain the minimal (five to eight points on a scale of 100) albeit significant differences found in the pain score and analgesic requirements. At 6 months, there were no significant differences in cosmetic satisfaction. The operating time for both procedures was similar, but the costs were higher for the video-assisted procedure. Henry et al. [44] have published a feasibility uncontrolled study based on their experience in 279 cases of purely endoscopic selective/unilateral parathyroidectomy study. They used a central 1.5-cm gasless approach (at the beginning of the procedure) for inferior/anterior adenomas and a lateral three-trochar approach with neck insufflation for the remaining adenomas. The operation was accomplished in 49 min, and there was a 13.4% conversion rate. No precise data are given on day of discharge nor on morbidity. The authors of the present review see no reason to approach inferior parathyroid adenomas through a central (either open or video-assisted) or a lateral endoscopic approach. These adenomas can be safely and expeditiously resected through a lateral minimal incision between the strap and the sternocleidomastoid muscles. The issue is more debatable for deep-seated superior adenomas that are anyway more difficult to excise whatever the approach. Perhaps, in those cases, vision is better by a purely endoscopic approach, but a vertical incision along the anterior border of the sternocleidomastoid muscle would also be appropriate [45]. Potential disadvantages for minimally invasive parathyroid surgery, which may apply to open and/or endoscopic approaches, are capsular rupture of adenomas (more likely to occur when small surgical fields or long-range instruments are used), increased expenses due to single-use instruments, neck insufflation, need for conversion, and unexpected findings related to concomitant thyroid disease or complex parathyroid anatomy. Large adenomas (>3 cm) may be difficult to excise through a small skin opening because they occupy almost all the available working space. Finally, some will find the term minimally invasive difficult to accept for central approaches (either open or video-assisted) and, even more, for the endoscopic lateral approach with gas insufflation. In terms of duration, tissue dissection, and structure mobilization, they may be at least as minimally aggressive as conventional bilateral parathyroidectomy. Has radioguided parathyroidectomy a future? Intravenous injection of Tc-mibi before parathyroid surgery allows identification of parathyroid tumors and imaging them with a gamma camera (MIBI Scan) as well as with a hand-held gamma detector intraoperatively. This is the basis for the so-called minimally invasive radioguided parathyroidectomy (MIRP). In both cases, the key limiting factor lies in the fact that thyroid tumors can also retain the radioisotope, reducing both sensitivity and specificity of the technique. Repeated scans and comparison with a thyroid scan allows parathyroid scintigraphy to attain a sensitivity of 75 85% [46], whereas there is no way to avoid false-positive results due to concomitant thyroid pathology when using MIRP. The technique involves injecting 2 to 20 mci TC-99m sestamibi a few hours before surgery and performing a parathyroid scan. If the scan is considered positive for a single adenoma, patients are taken to the operating room and surgery is performed through a small incision; the dissection down to the adenoma is guided by a miniature hand-held probe [47], a similar approach used to localize the sentinel node in breast cancer or melanoma excision. In brief, any excised tissue containing more than 20% of background radioactivity in a patient with a positive sestamibi scan is considered a solitary parathyroid adenoma. Theoretically, this alleviates the need to identify other glands, obtain frozen sections, or measure serum parathyroid hormone levels intraoperatively. The majority of reports assessing the use of MIRP are either retrospective series with no control group or prospective but nonrandomized trials with erratic inclusion criteria, including in one study [48] the exclusion of every patient with thyroid pathology (up to 68% of the screened population).

5 Langenbecks Arch Surg (2008) 393: To assess the value of this technique, a case control study was performed with 62 patients having MIRP and 60 patients having conventional parathyroid explorations. The sensitivity rates of the MIBI probe in single and multiple gland disease were 84.6% and 63.0%, respectively [49], illustrating the narrow margin of usefulness of MIRP. In another comparative study, a directed operation was facilitated by sestamibi scan in 22 of 24 patients, by intraoperative gamma probe detection in only five of 23 patients, and by the rapid intraoperative parathyroid hormone assay in 15 of 15 patients [50]. The experience reported by Costello and Norman [51] in which radio guidance eliminated the need for preoperative imaging could not be reproduced by other groups with a large experience in parathyroid surgery [52], while others found the information given by the probe confusing or inaccurate [53]. Regarding the impact of the MIRP on final results, the rates of success, temporary and permanent hypoparathyroidism, and injury of the recurrent laryngeal nerve were at best similar in patients who underwent probe-guided surgery and those who had conventional surgery. In addition, controversies persist on the best dose of MIBI, as well as on how to achieve the optimal time interval between injection and exploration. It has been suggested by some investigators that intraoperative probe may facilitate a directed operation when preoperative imaging is equivocal, and no concomitant thyroid pathology exists, as in two out of eight patients in a Mayo Clinic prospective nonrandomized study [52]; but this narrow scope of use has to be assessed in future studies. In conclusion, although the MIRP probe may seem to be a useful tool in parathyroid surgery, its use has not improved the outcome of such surgery. The enthusiasm and results that elicited in some teams could not be shared and reproduced by the remaining majority. References 1. Bergenfelz A, Lindblom P, Tibblin S, Westerdahl J (2002) Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial. Ann Surg 236: Russell CF, Dolan SJ, Laird JD (2006) Randomized clinical trial comparing scan-directed unilateral versus bilateral cervical exploration for primary hyperparathyroidism due to solitary adenoma. Br J Surg 93: Tiblin S, Bondeson AG, Ljunberg O (1982) Unilateral parathyroidectomy due to single adenoma. Ann Surg 195: Russell CF, Laird JD, Ferguson WR (1990) Scan-directed unilateral cervical exploration for parathyroid adenoma: a legitimate approach. World J Surg 14: Sackett WR, Barraclough B, Reeve TS, Delbridge LW (2002) Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy. Arch Surg 137: Grant CS, Thompson G, Farley D, van Heerden J (2005) Primary hyperparathyroidism surgical management since the introduction of minimally invasive parathyroidectomy: Mayo Clinic experience. Arch Surg 140: Schachter PP, Issa N, Shimonov M, Czerniak A, Lorberboym M (2004) Early, postinjection MIBI-SPECT as the only preoperative localizing study for minimally invasive parathyroidectomy. Arch Surg 139: O Doherty MJ, Kettle AG (2003) Parathyroid imaging: preoperative localization. Nucl Med Comm 24: Civelek AC, Ozalp E, Donovan P, Udelsman R (2002) Prospective evaluation of delayed technetium-99 m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 131: Siperstein A, Berber E, Mackey R, Alghoul M, Wagner K, Milas M (2004) Prospective evaluation of sestamibi scan, ultrasonography, and rapid PTH to predict the success of limited exploration for sporadic primary hyperparathyroidism. Surgery 136: Gawande AA, Monchik JM, Abbruzzese TA, Iannuccilli JD, Ibrahim SI, Moore FD Jr. (2006) Reassessment of parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism after 2 preoperative localization studies. Arch Surg 141: Krausz Y, Lebensart PD, Klein M, Weininger J, Blachar A, Chisin R, Shiloni E (2000) Preoperative localization of parathyroid adenoma in patients with concomitant thyroid nodular disease. World J Surg 24: Rink T, Schroth HJ, Holle LH, Garth LH (2002) Limited sensitivity of parathyroid imaging with 99m Tc-sestamibi/ 123 I subtraction in an endemic goiter area. J Nucl Med 43: Prager G, Czerny C, Ofluoglu S, Kurtaran A, Passler C, Kaczirek K, Scheuba C, Niederle B (2003) Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region. J Am Coll Surg 196: Pattou F, Huglo D, Proye C (1998) Radionuclide scanning in parathyroid diseases. Br J Surg 85: Perrier ND, Ituarte PH, Morita E, Hamill T, Gielow R, Duh QY, Clark OH (2002) Parathyroid surgery: separating promise from reality. J Clin Endocrinol Metab 87: Haciyanli M, Lal G, Morita E, Duh QY, Kebebew E, Clark OH (2003) Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. J Am Coll Surg 197: Piñero A, Rodriguez JM, Martinez-Barba E, Canteras M, Sitges- Serra A, Parrilla P (2003) Tc99 m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship. Surgery 134: Pons F, Torregrosa JV, Fuster D (2003) Biological factors influencing parathyroid localization. Nucl Med Commun 24: Biertho LD, Kim C, Wu HS, Unger P, Inabnet WB (2004) Relationship between sestamibi uptake, parathyroid hormone assay, and nuclear morphology in primary hyperparathyroidism. J Am Coll Surg 199: Mihai R, Gleeson F, Buley ID, Roskell DE, Sadler GP (2006) 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 30: Slitt GT, Lavery H, Morgan A, Bernstein B, Slavin J, Karimeddini MK, Kozol RA (2005) Hyperparathyroidism but a negative sestamibi scan: a clinical dilemma. Am J Surg 190:

6 244 Langenbecks Arch Surg (2008) 393: Lowney JK, Weber B, Johnson S, Doherty GM (2000) Minimal incision parathyroidectomy: cure, cosmesis, and cost. World J Surg 24: Brunaud L, Zarnegar R, Wada N, Ituarte P, Clark OH, Duh QY (2003) Incision length for standard thyroidectomy and parathyroidectomy: when is it minimally invasive. Arch Surg 138: Carter AB, Howanitz PJ (2003) Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Pathol Lab Med 127: Stalberg P, Sidhu S, Sywak M, Robinson B, Wilkinson M, Delbridge L (2006) Intraoperative Parathyroid hormone measurement during minimally invasive parathyroidectomy: does it value-add to decision-making. J Am Coll Surg 203: Miura D, Wada N, Arici C, Morita E, Duh QY, Clark OH (2002) Does intraoperative quick parathyroid hormone assay improve the results of parathyroidectomy. World J Surg 26: Carneiro-Pla DM, Solorzano CC, Irvin GL 3rd (2006) Consequences of targeted parathyroidectomy guided by localization studies without intraoperative parathyroid hormone monitoring. J Am Coll Surg 202: Chen H, Pruhs Z, Starling JR, Mack E (2005) Intraoperative parathyroid hormone testing improves cure rates in patients undergoing minimally invasive parathyroidectomy. Surgery 138: Goldstein RE, Carter WM, Fleming M, Bumpous J, Lentsch E, Rice M, Flynn M (2006) Unilateral cervical surgical exploration aided by intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism and equivocal sestamibi scan results. Arch Surg 141: Zettinig G, Kurtaran A, Prager G, Kaserer K, Dudczak R, Niederle B (2002) Suppressed double adenoma a rare pitfall in minimally invasive parathyroidectomy. Horm Res 57: Westerdahl J, Bergenfelz A (2006) Parathyroid surgical failures with sufficient decline of intraoperative parathyroid hormone levels. Unobserved multiple endocrine neoplasia as an explanation.. Arch Surg 141: Gauger PG, Agarwal G, England BG, Delbridge LW, Matz KA, Wilkinson M, Robinson BG, Thompson NW (2003) Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience. Surgery 130: Milas M, Wagner K, Easley KA, Siperstein A, Weber CJ (2003) Double adenomas revisited: nonuniform distribution favors enlarged superior parathyroids (fourth pouch disease). Surgery 134: Haciyanli M, Lal G, Morita E, Duh QY, Kebebew E, Clark OH (2003) Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. J Am Coll Surg 197: Jaskowiak NT, Sugg SL, Helke J, Koka MR, Kaplan EL (2002) Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism. Arch Surg 137: Horanyi J, Duffek L, Szlavik R, Darvas K, Lakatos P, Toth M, Racz K (2003) Parathyroid surgical failures with misleading falls of intraoperative parathyroid hormone levels. J Endocrinol Invest 6: Irvin GL 3rd, Solorzano CC, Carneiro DM (2004) Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome. World J Surg 28: Westerdahl J, Lindblom P, Bergenfelz A (2002) Measurement of intraoperative parathyroid hormone predicts long-term operative success. Arch Surg 137: Gurnell EM, Thomas SK, McFarlane I, Munday I, Balan KK, Berman L, Chatterjee VK, Wishart GC (2004) Focused parathyroid surgery with intraoperative parathyroid hormone measurement as a day-case procedure. Br J Surg 91: Duh QY (2003) Presidential address: minimally invasive endocrine surgery standard of treatment or hype. Surgery 134: Miccoli P, Berti P, Materazzi G, Massi M, Picone A, Minuto MN (2004) Results of video-assisted parathyroidectomy: single institution s six-year experience. World J Surg 28: Barczynski M, Cichon S, Konturek A, Cichon W (2006) Minimally invasive video-assisted parathyroidectomy versus open minimally invasive parathyroidectomy for a solitary parathyroid adenoma: a prospective, randomized, blinded trial. World J Surg 30: Henry JF, Sebag F, Tamagnini P, Forman C, Silaghi H (2004) Endoscopic parathyroid surgery: results of 365 consecutive procedures. World J Surg 28: Udelsman R, Donovan PI (2004) Open minimally invasive parathyroid surgery. World J Surg 28: Ishibashi M, Nishida H, Hiromatsu Y, Kojima K, Tabuchi E, Hayabuchi N (1998) Comparison of technetium-99 m-mibi, technetium-99 m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands. J Nucl Med 39: Murphy C, Norman J (1999) The 20% rule: a simple, instantaneous radioactivity measurement defines cure and allows elimination of frozen sections and hormone assays during parathyroidectomy. Surgery 126: Rubello D, Giannini S, Martini C, Piotto A, Rampin L, Fanti S (2006) Minimally invasive radio-guided parathyroidectomy. Biomed Pharmacother 260: Bonjer HJ, Bruining HA, Pols HA, de Herder WW, Proye CA, Carnaille BM, Mohamedammin DS, Steyerberg EW, Breeman WA, Krening EP (1998) 2-Methoxyisobutylisonitrile probe during parathyroid surgery: tool or gadget. World J Surg 22: Dackiw AP, Sussman JJ, Fritsche HA Jr, Delpassand ES, Stanford P, Hoff A (2000) Relative contributions of technetium Tc 99 m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay to the surgical management of hyperparathyroidism. Arch Surg 135: Costello D, Norman J (1999) Minimally invasive radioguided parathyroidectomy. Surg Oncol Clin N Am 8: Burkey SH, Van Heerden JA, Farley DR, Thompson GB, Grant CS, Curlee KJ (2002) Will directed parathyroidectomy utilizing the gamma probe or intraoperative parathyroid hormone assay replace bilateral cervical exploration as the preferred operation for primary hyperparathyroidism. World J Surg 26: Inabnet WB 3rd, Kim CK, Haber RS, Lopchinsky RA (2002) Radioguidance is not necessary during parathyroidectomy. Arch Surg 137: