Minimally-Invasive Parathyroid Surgery
Brett Cordes, M.D.
June 8, 2006

The superior glands are derived from the fourth pharyngeal pouch and the inferior glands are derived from the third pharyngeal pouch, giving some clinical significance to the fact that the inferior glands are in a more variable position in the neck. The superior parathyroid glands are typically, about 80% of the time, found within 1cm of the cricothyroid junction and the inferior parathyroid glands are typically found within 1cm of the inferior thyroid pole. The anatomy of the parathyroid gland is typically described as bean-like, glistening, mahogany in color, and typically well-capsulated. It can sometimes be distinguished from the surrounding fat by the gliding sign.

Histologically, the parathyroid glands, as you can see, abut the thyroid gland intimately, and are made up of two main cells. The chief cells are the main endocrine cells of the parathyroid glands, which secrete the PTH, and the oxyphil cells, which are largely made up of mitochondria.

The parathyroid glands regulate serum calcium through the reabsorption of calcium from the bone as well as increased absorption from the gut and decreased renal excretion. It also stimulates the hydroxylate enzyme to produce vitamin D.

In 1880, Ivar Sandstrom identified and described the parathyroid glands for the first time. In 1892, Gley, from Paris, described the fact that the removal of the parathyroids caused tetany. In 1906, the Viennese pathologist Erdheim recognized the association between parathyroid glands and calcium metabolism, and he also reported pathologic diagnosis of parathyroid hyperplasia in the setting of osteomalacia. Dr. Felix Mandl, in 1925, was the first surgeon to perform parathyroidectomy. He was from the University of Vienna, and his patient was Albert Jahne from Austria.

Mr. Jahne was a 34-year-old streetcar conductor and had a progressive 5-year history of lower extremity pain, which subsequently terminated in spontaneous femur fracture in 1924. His head and neck exam was without abnormality. He went to the operating room and underwent a bilateral neck exploration under local anesthesia with excision of this parathyroid tumor. The macroscopic appearance is seen, as above, and histology were consistent with a parathyroid adenoma. This is the picture of the first page of Dr. Mandl’s manuscript describing this first case of a parathyroidectomy. Additionally, Mr. Jahne died 10 years later secondary to uremia. After his autopsy, there were three and only three normal parathyroid glands found. Additionally, in 1982, Tibbin performed the first unilateral parathyroidectomy for an adenoma. In 1996, the first endoscopic subtotal parathyroidectomy for four-gland hyperplasia was performed, and this is the picture of that first operation.

The indications for parathyroidectomy, as described by the NIH in 2002, include a serum calcium of greater than 11.4 mg/dL in a patient who is asymptomatic and less than 50 years old; and additionally, anyone who is symptomatic with renal, GI, or bone manifestations as well as calcinosis; and, sometimes, a patient with an elevated calcium simply requests surgery; or, if follow-up is difficult or impossible.

As for surgical options for the treatment of primary hyperparathyroidism, there are t wo main techniques. One is the bilateral neck exploration, which is the gold standard, and historical treatment. It ensures that all glands are visualized and the morphology as opposed to the function of the gland determines the need for resection. Cure rates of this technique are 90% to 95%, with a complication rate of about 1% to 3%, largely composed of recurrent laryngeal nerve injury, or temporary (and even permanent) hypocalcemia.

The other is focused parathyroidectomy, also known as minimally invasive parathyroid surgery. The definition can be described as the removal of a parathyroid adenoma through a small skin incision and, most importantly, without four-gland visualization. Two reasons for the evolution of the focus technique includes the fact that in 85% to 90% of cases, primary hyperparathyroidism is caused by a single adenoma. Also, the improved preoperative and intraoperative localization techniques have made this technique possible. Again, primary hyperparathyroidism is caused by a single adenoma in 85% of the cases, by four-gland hyperplasia in roughly 13% of the cases, with double adenoma or parathyroid carcinoma making up the remaining 2%. Contraindications for the minimally invasive technique include the presence of multiglandular disease, multiple endocrine neoplasia, malignancy, failure to localize the adenoma preoperatively. Some relative contraindications include the presence of concomitant thyroid disease as well as the patient’s body habitus or unfavorable surgical anatomy. Techniques for minimally invasive parathyroid surgeries include that of unilateral neck exploration as well as the endoscopic and video-assisted parathyroidectomy.

Unilateral neck explorations are by far the most widely used. It is performed via a 2cm to 3cm incision. This incision can either be made in the midline of the neck or unilaterally. The advantages of the unilateral neck exploration as compared to the other techniques include the fact that there is no insufflation, a shorter duration of surgery, and the possibility of performing techniques through local anesthesia in an outpatient setting. Endoscopic parathyroidectomy can be performed via cervical, axillary, or anterior chest wall approaches. Trocar incisions typically number 3 to 4. The advantages of the endoscopic technique are cosmesis (this could be argued as well as access to mediastinum.) This is the approach of the first parathyroidectomy performed endoscopically. Here, you can see the left upper parathyroid gland being excised from the operative basin. Feeding vessels are typically clipped with 5mm clip applier. This is the patient on postoperative day 3. Notably, on postoperative day 2, his subcutaneous emphysema resolved. The video-assisted technique is typically performed by central or lateral approach with a 1cm to 2cm incision. The one being shown was made approximately 2cm superior to the sternal notch. The advantages of the video-assisted technique include the possibility of a bilateral neck exploration, cosmesis, and no insufflation. Here you can see the recurrent laryngeal nerve as it is greatly magnified with the camera. This is the parathyroid adenoma being excised from the operative basin, which is the thyroid in the right upper quadrant. And finally, the skin incision, in this case, was closed with Dermabond.

Preoperative localizations in the setting of minimally invasive parathyroidectomy is absolutely required. Your options include a sestamibi scan with the SPECT imaging, which we will look at later, as well as neck ultrasonography. We will also talk about the cost-effectiveness of these preoperative localization studies.

In the literature the sensitivity of sestamibi is widely reported to be between 85% to 95%. Logistically, the test is performed by taking anterior planar images of the neck and chest at 10 minutes and 2 hours after IV injection of sestamibi. In this picture, the top arrow actually shows increased uptake in the left thyroid basin, which turned out to be a papillary thyroid carcinoma, and the left inferior pole was parathyroid adenoma. The sestamibi has been shown to have one weakness: it is less accurate in the presence of multinodular goiter, with a sensitivity of 68%.

SPECT imaging, single positron emitted CT, is basically a 3-D CT image of the uptake of the sestamibi and has been shown to have no increased sensitivity in the detection of parathyroid adenoma over sestamibi scan. However, it has been shown to improve the localization and also facilitates surgical exploration in the settings of ectopic glands, which have been shown to occur anywhere from 8% to 11% of the time, and in the setting of previous neck surgery. It has, however, been shown to have an increased sensitivity, upwards of 95%, with concomitant multinodular goiter.

This is a depiction of a SPECT scan. On the left column, is a typical CAT scan imaging. The middle column is a 3-D reconstruction of the SPECT image with increased uptake in the left posterior paratracheal region and the left column is the fusion of the two images. This patient, interestingly, had this left posterior paratracheal adenoma excised after previously failed four-gland exploration, and a 400mg adenoma was removed.

The remainder of the data will be about the surgeon-performed neck ultrasonography, which can be an office-based procedure, with a learning curve stage of between 20 to 25 examinations. The normal glands are typically not visualized while the abnormal glands are visualized, as you see here, as a large hypoechoic, typically mobile mass. The important thing is that the majority of these masses are behind the thyroid gland. Neck ultrasonography is less affected by thyroid abnormalities and the sensitivity is reported to be between 76% and 89%. As you can see here, they are typically also hypervascular on color Doppler studies. A few studies have compared surgeon-performed ultrasonography with sestamibi scanning, with sensitivity and specificity being 76% and 97% respectively, and with an overall accuracy of 91% and 92%. The study on the right lower corner of the slide goes a step further, and looks at the sensitivity of localizing the parathyroid adenoma to the specific side and quadrant of the neck. In this particular study, ultrasound was shown to be a bit superior to sestamibi scanning. An ultrasound costs roughly $200 while the sestamibi is approximately $1300. In a study done this year, published in the Archives, patients with primary hyperparathyroidism and negative findings on sestamibi scans, showed that using additional preoperative ultrasound imaging appears to be cost-effective compared with SPECT of BNE.

Intraoperative adjuncts in the setting of minimally invasive parathyroid surgery include a rapid parathyroid hormone level, frozen section, and the use of gamma probe. The PTH assay is arguably the most important listed event of parathyroid surgery. It provides immediate feedback regarding adequacy of the resection with a half-life of 2 to 4 minutes and a greater than 50% reduction in postexcision values over the preexcision values being compared to an adequate resection. Postexcision sample at 10 minutes has been shown to have an accuracy of 82% upwards to 100%. The cost of a PTH assay ranges from $28 to $295. The price discrepancy results from the fact that some hospitals purchase a central laboratory machine that performs other lab functions, which can also perform the assay, which then costs approximately $30 to $60 per patient; whereas some purchase a specialized machine that is in the operating room, in which case the cost can be approximately $300 per patient. Frozen section is, in fact, classically used with the bilateral neck exploration with an excellent cure rate. The top images is a high-powered images of parathyroid adenoma with increased cellularity and again, decreased parenchymal fat. The lower image shows individual parathyroid cells, which are typical cells and have chromatin pattern. It is widely known that frozen section has a difficult time distinguishing between diagnoses of adenoma and hyperplasia. Iacobone, in a 2005 study, looked at 102 patients and showed that frozen section would have predicted the diagnosis in 81% of the surgeries. Costs of frozen section range from $195 to $314 per specimen.

At this time, the question is, is routine frozen section necessary? In Iacobon’s study, they predicted, by a frozen section, in 83 out of 102 patients. But more impressively, the PTH level predicted adequacy of resection in 100% of the specimens. What are the recommendations for the acquisition of frozen section intraoperatively? They include: when the PTH levels fail to decline appropriately and in the setting of an atypical appearance of the parathyroid gland. This parathyroid gland is obviously long at 4cm to 5cm in length: this would be an example when you might want to do a frozen section. Additionally, frozen section is recommended in the setting of multiglandular disease, revision surgery, and if a parathyroid adenoma is found in an ectopic location. The final recommendation for the use of frozen section is in the setting of surgeon inexperience.

The gamma probe is the final intraoperative adjunctive we will talk about this morning. It requires a preoperative injection of low dose sestamibi with or without methylene blue dye, which in the past has been shown to localize these adenomas, and may or may not help with the resection. It is performed with the unilateral resection technique via transverse midline or unilateral neck incision, typically 2cm, and an 11mm diameter probe is most widely used. The radioactivity is measured on the parathyroid adenoma and is used to guide the excision. Performance of a gamma probe is based on the 20% rule, which was originally described by Murphy and Norman, which states that any lesion that is removed from the operative basin with a greater than 20% radioactivity as compared to the background radioactivity, can be assumed to be a parathyroid adenoma. A gamma probe study by Ugur in 2006, showed that it could differentiate between an adenoma and hyperplasia with a sensitivity of 82.5% and with an accuracy of 74.4%. However, the sensitivity for differentiating an adenoma or a hyperplastic parathyroid gland decreased to 44.2% when compared with other tissues such as lymph node or thyroid. So, using the gamma probe when performing minimally invasive parathyroid surgery is also known as minimally invasive radio-guided parathyroidectomy. A study by Rubello in 2006, which is the largest series using a gamma probe that I found, 263 patients, surgeons who were polled stated that the gamma probe was slightly useful in 8.7%, discretely useful in 75.9%, and particularly useful in 15.4%. Surgeons usually stated that the gamma probe was particularly useful in the setting of ectopic glands. Cohen, in a study of 140 patients, compared intraoperative and preoperative adjuncts and showed that generally the PTH assay was by far the single most useful test. Again sensitivity, positive predictive value, and accuracy of the PTH are upwards of 96% to 98%, as compared to sestamibi and gamma probe.

Minimally invasive parathyroid surgery can be used via unilateral exploration, endoscopic, and video-assisted techniques. Preoperative localization can be sought by sestamibi scanning, + or – SPECT sestamibi scanning and surgeon-performed ultrasound. Intraoperative adjuncts include parathyroid hormone level, frozen section, and the use of a gamma probe. The advantages of the minimally invasive technique include decreased pain, improved cosmesis, and, more importantly, decreased complication rates. Again, in the Rubello study, he had an 8.5% rate of hypocalcemia and there were no recurrent laryngeal nerve injuries. There was also shorter hospital stay, an average of 1.2 days, in the same study. In the Cohen study, 84% of his minimally invasive surgeries were performed using local anesthesia and, of those patients, 86% were discharged on the same day. With regard to morbidity of the local anesthesia to patients, there was only one complication, which was neck swelling, which was subsequently determined not to be hematoma but edema, and that patient was discharged home on postoperative day #1. The minimally invasive technique has been shown to have a shorter operative time, 35 to 56 minutes in the two studies, and it has also been shown to be less expensive, as discussed previously.

One of the concerns with the minimally invasive technique is having to convert to a bilateral neck exploration intraoperatively, which is more of an issue when a patient is under local anesthesia. In the Cohen study, they only had this complication in 4 of 139 cases, and the Rubello study only had 10 of 263 cases that had to be converted to a bilateral neck exploration. In the Rubello study, the reasons included two patients that had frozen section diagnosis of parathyroid carcinoma, four patients that had failure of the rapid PTH level to fall appropriately, and four other patients with which they encountered technical difficulties. The final concern with minimally invasive technique is the failure to routinely identify the recurrent laryngeal nerve. In all the studies that I saw, surgeons did encourage the active studying and tracing of the recurrent laryngeal nerve during the surgeries. However, in the Cohen study, although he had no complications of nerve injury, he stated that if he were to remove the gland without seeing the nerves, he could do so and suggested dissecting directly on the adenoma capsule. In this particular photo, you can see the first arrow points to the parathyroid adenoma prior to excision and the second arrow points to the recurrent laryngeal nerve following direct loop over the adenoma. This adenoma was safely excised.

The proposed algorithm for the workup of patients with primary hyperparathyroidism, should they be referred to you, is first, obviously, looking at their preoperative laboratory values, which may include 24-hour urine calcium with vitamin D levels. Sestamibi scanning could be the first test that you order and, if this is positive, going on to the minimally invasive technique using the rapid PTH monitoring. If there is a greater than 50% drop in that PTH level, you can assume that you have performed an adequate operation. If there is a less than 50% drop, consider further exploration versus converting to a bilateral exploration as an option. If the sestamibi scan is negative or equivocal, either an ultrasound and/or SPECT image can be obtained and, if either one of these is positive, going on with a minimally invasive technique is appropriate. If all studies are negative, a bilateral neck exploration is suggested.

In summary, minimally invasive parathyroid surgery is yet to become the gold standard of treatment for primary hyperparathyroidism. However, it is the procedure of choice of 92% of members of the International Association of Endocrine Surgeons in the setting of localized single gland disease and the cure rate has been estimated at 96% to 98.6%.

Case Presentation:

TC is a 28-year-old female who was referred by the Endocrinology Service for surgical evaluation for primary hyperparathyroidism. She was found to have an elevated calcium level on routine physical exam and laboratory screening, and a subsequent PTH level was also found to be elevated. She denied any signs or symptoms of hypercalcemia. Her past medical and surgical history was significant only for hypertension and she had a noncontributory social history. Her mediations included enalapril. Her family history was significant for no previous parathyroid disease or multiple endocrine neoplasia syndromes. Her calcium was found to be 10.4 and 6.4 mg/dL, and her PTH level was 64. Notably, her 24-hour urine calcium and vitamin D levels were within normal limits.

On physical exam, she was afebrile. Her blood pressure was 158/100 and the rest of her vital signs were stable. Her head and neck exam was unremarkable. Her Planar sestamibi scan was significant for increased uptake in the left inferior pole of the thyroid, which was consistent with a parathyroid adenoma.

She went for a focal parathyroidectomy and underwent a unilateral neck incision under general endotracheal anesthesia. Operation was performed without difficulty and a 670 mg parathyroid gland was excised. Her intraoperative parathyroid hormone level dropped from 76 to 24 and the diagnosis of a parathyroid adenoma was confirmed by frozen section. Again, the frozen section was able to say that it was definitively an adenoma because of this discrete capsule around the gland. This is a higher magnification and again hypercellular gland with decreased parenchymal fat. Her postoperative course was largely insignificant. She was admitted for 23-hour observation and then discharged home the following day. Her follow-up 2-moth labs were significant for normalization of her calcium and PTH level.

Bibliography:

Abbas JS, Hashem SI, Faraj WG, Khalifeh MJ, Horani MH, Salti IS. The outcome of cervical exploration for asymptomatic and symptomatic patients with primary hyperparathyroidism. World J Surg 2006;30:69-75.

Berri RN, Lloyd LR. Detection of parathyroid adenoma in patients with primary hyperparathyroidism: The use of office-based ultrasound in preoperative localization. Am J Surg 2006;191:311-314.

Casara D, Rubello D, Cauzzo C, Pelizzo MR. 99m Tc-MIBI radio-guided minimally invasive parathyroidectomy: Experience with patients with normal thyroids and nodular goiters. Thyroid 2002;12:53-61.

Chen H, Mack E, Starling JR. A comprehensive evaluation of perioperative adjuncts during minimally invasive parathyroidectomy. Which is more Reliable? Ann Surg 2005;242:375-383.

Chen H, Pruhs Z, Starling J, Mack E. Intraoperative parathyroid hormone testing improves cure rates in patients undergoing minimally invasive parathyroidectomy. Surgery 2005;138:583-590.

Cohen MS, Finkelstein SE, Brunt LM, Haberfeld E, Kangrga I, Moley JF, Lairmore TC. Outpatient minimally invasive parathyroidectomy using local/regional anesthesia: A safe and effective operative approach for selected patients. Surgery 2005;138:681-689.

Dewan AK, Kapadia SB, Hollenbeak CS, Stack BC Jr. Is routine frozen section necessary for parathyroid surgery? Otolaryngol-Head Neck Surg 2005;133:857-862.

Eigelberger MS, Cheah WK, Ituarte PH, Streja L, Duh QY, Clark OH. The NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism, are they too limited? Ann Surg 2004;239:528-535.

Gilat H, Cohen M, Feinmesser R, Benzion J, Shvero J, Segal K, Ulanovsky D, Shpitzer T. Minimally invasive procedure for resection of a parathyroid adenoma: The role of preoperative high-resolution ultrasonography. J Clin Ultrasound 2005;33:283-287.

Gordon LL, Snyder WH, Wians F, Nwariaku F, Kim LT. The validity of quick intraoperative parathyroid assay: An evaluation in 72 patients based on gross morphologic criteria. Surgery 1999;126:1030-1035.

Grady JA, Bumpous JM, Fleming MM, Flynn MB, Turbiner E, Lentsch EJ, Ziegler CH. Advantages of a targeted approach in minimally invastive radioguided parathyroidectomy surgery for primary hyperparathyroidism. Laryngscope 2006;116:431-435.

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 2002;57:241-249.

Hanif F, Coffey JC, Romics L Jr, O’Sullivan K, Aftab F, Redmond HP. Rapid intraoperative parathyroid hormone assay—more than just a comfort measure. World J Surg 2006;30:156-161.

Henry JF, Raffaelli M, Iacobone M, Volot F. Video-assisted parathyroidectomy via lateral approach versus conventional surgery in the treatment of sporadic primary hyperparathyroidism: Results of a case-control study. Surg Endosc 2001;15:1116-1119.

Henry J-F, Sebag F, Tamagnini P, Forman C, Silaghi H. Endoscopic parathyroid surgery: Results of 365 consecutive procedures. World J Surg 2004;28:1219-1223.

Iacobone M, Scarpa M, Lumachi F, Favia G. Are frozen sections useful and cost-effective in the era of intraoperative qPTH assays? Surgery 2005;138:1159-1165.

Krausz Y, Bettman L, Guralnik L, Yosilevsky G, Keidar Z, Bar-Shalom R, Even-Sapir E, Chisin R, Israel O. Technetium-99m-MIBI SPECT/CT in primary hyperparathyroidism. World J Surg 2006;30:76-83.

Lee JA, Inabnett WB III. The surgeon’s armamentarium to the surgical treatment of primary hyperparathyroidism. J Surg Oncol 2005;89:130-135.

Lorberboym M, Ezri T, Schachter PP. Preoperative technetium Tc99m Sestamibi SPECT imaging in the management of primary hyperparathyroidism in patients with concomitant multinodular goiter. Arch Surg 2005;140:656-660.

Micoli P, Berti P, Materazzi G, Donatini G. Minially invasive video-assisted parathyroidectomy (MIVAP). EJSO 2003;29:188-190.

Mozzon M, Mortier P-E, Jacob PM, Soudan B, Boersma AA, Proye CA-G. Surgical management of primary hyperparathyroidism. The case for giving up quick intraoperative PTH assay in favor of routine PTH measurement the morning after. Ann Surg 204;240:949-954.

Mun H-C, Conigrave A, Wilkinson M, Delbridge L. Surgery for hyperparathyroidism: Does morphology or function matter most? Surgery 2005:138-1111-1120.

Naitoh T, Gagner M, Garcia-Ruiz A, Heniford BT. Endoscopic endocrine surgery in the neck. Surg Endosc 1998;12:202-205.

Niederle BE, Schmidt G, Organ CH, Niederle B. Albert J and his surgeon: A historical reevaluation of the first parathyroidectomy. J Am Coll Surg 2006;202:181-190.

Norman J, Chheda H. Minimally invasive parathyroidectomy facilitated by intraoperative nuclear mapping. Surgery 1997;122:998-1004.

Ollila DW, Caudle AS, Cance WG, Kim HJ, Cusack JC, Swasey JE, Calvo BF. Successful minimally invasive parathyroidectomy for primary hyperparathyroidism without using intraoperative parathyroid hormone assays. A J Surg 2006;191:52-56.

Rubello D, Giannini S, Martini C, Piotto A, Rampin L, Fanti S, Armigliat M, Nardi A, Carpi A, Mariani G, Gross MD, Pelizzo MR. www.sciencedirect.com.

Ruda JM, Stack BC Jr, Hollenbeak CS. The cost-effectiveness of additional preoperative ultrasonography or sestamibi-SPECT in patients with primary hyperparathyroidism and negative findings on sestamibi scans. Arch Otolaryngol Head Neck Surg 2006;132:46-53.

Siperstein A, Berber E, Mackey R, Alghoul M, Wagner K, Milas M. Prospective evaluation of sestamibi scan, ultrasonography, and rapid PTH to predict the success of limited expoloration for sporadic primary hyperparathyroidism. Surgery 2004;156:872-880.

Solorzano CC, Carneiro-Pla DM, Irvin GI III. Surgeon-performed ultrasonography as the initial and only localizing study in sporadic primary hyperparathyroidism. J Am Coll Surg 2006;202:18-24.

Tibbin S, Bondeson A, Ljungberg O. Unilateral parathyrodectomy in hyperparathyroidism due to single adenoma. Ann Surg 1982;195:245-251.

Ugur O, Kara PO, Bozkurt MF, Hamaloglu E, Tezel GG, Slanci BV, Karabulut E, Sayek I. In vivo characterization of parathyroid lesions by use of gamma probe: Comparison with ex vivo count method and frozen section results. Otol Head Neck Surg 2006;134:316-320.

Wang TS, Ostrower ST, Heller KS. Persistently elevated parathyroid hormone levels after parathyroid surgery. Surgery 2005;138:1130-1136.

Weber CJ, Ritchie JC. Retrospective analysis of sequential changes in serum intact parathyroid hormone levels during conventional parathyroid exploration. Surgery 1999;126:1139-1144.

Wild JL, Weigel T, Chen H. The need for intraoperative parathyroid hormone monitoring during radioguided parathyroidectomy by video-assisted thoracoscopy (VATS). Clin Nucl Med 2006;31:9-12.

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