Parathyroid adenoma identified on office ultrasound
Posteriorly descended left superior parathyroid adenoma on ultrasound
The abnormal inferior parathyroid gland is generally easier to image with ultrasound since it is more superficial (ventral) in location, frequently up against the posterior/lateral surface of the inferior pole of the thyroid or just caudal to the inferior pole of the thyroid. Ectopic locations for the inferior parathyroid gland that can be seen with ultrasound are either intrathyroidal or intrathymic in the lower paratracheal neck. Intrathyroidal parathyroid glands are associated with the inferior parathyroid glands more than 90 % of the time and can be suspected in the setting of primary hyperparathyroidism [27, 28]. In many cases the abnormal intrathyroidal inferior parathyroid gland is actually just subcapsular within the inferior pole of the thyroid. This location can be suspected with ultrasound evaluation. If ultrasound-guided fine needle aspiration (FNA) of a truly intrathyroidal parathyroid is done for an apparent suspicious thyroid nodule, the cytopathologist will typically interpret the FNA as a follicular neoplasm, because of the lack of colloid in the specimen and uniform cytologic appearance of the cells. Knowing this fact should alert the surgeon to the possibility of an intrathyroidal parathyroid adenoma. The diagnosis can then be established with repeat ultrasound-guided FNA for parathyroid hormone (PTH) . Two or three aspirates are dispersed into 1 ml of normal saline and submitted to the lab for PTH. A level identified to be more than two times the blood level is considered abnormal. Frequently the PTH level is many times the blood level. The FNA can be submitted for cytologic analysis with PTH staining to establish the diagnosis of an intrathyroidal parathyroid, but this is less reliable than FNA for a PTH level . If aspiration of an intrathyroidal or extrathyroidal cystic nodule returns clear fluid, then a parathyroid cyst should be suspected . The diagnosis can be confirmed by submitting this aspirate for PTH level determination.
When an intrathyroidal parathyroid adenoma can be established preoperatively, then the surgical approach can be modified to a thyroidotomy with excision of the parathyroid adenoma or partial thyroidectomy of the inferior pole of the thyroid . In a patient with a relative lengthy neck, the ectopic intrathymic parathyroid adenoma can be identified with ultrasound low in the neck in a paratracheal location. The distance from the tip of lower pole of the thyroid can be measured for reference and surgical guidance. Small adenomas in this location, however, can be confused with paratracheal lymphadenopathy. The diagnosis may also be clarified with ultrasound-guided FNA for PTH. Finally, ectopic inferior or superior parathyroid adenomas posterior to the carotid artery and within the carotid sheath can sometimes be imaged with ultrasound and thus direct surgical dissection.
If the central neck compartment does not contain a clearly imaged abnormal parathyroid gland, then the ultrasonographer needs to include the medial upper neck as part of the assessment for hyperparathyroidism. Either the inferior or superior parathyroid gland can have arrested embryologic descent and ultimately become abnormal. The upper neck frequently contains lymphadenopathy. These lymph nodes, however, are typically located just medial or lateral to the internal jugular vein in the upper neck and inferior to the submandibular salivary gland as level 2 lymph nodes. Benign lymph nodes can be distinguished by a focal hyperechoic area or stripe indicating the fatty hilum of the lymph node. An undescended parathyroid adenoma will lack the hyperechoic focus and be located typically medial to carotid artery. A common location is near the level of the bifurcation of the carotid artery . A hypoechoic nodule imaged medial to the carotid artery close to the carotid bifurcation should be considered suspicious for an undescended parathyroid adenoma (see Fig. 25.3). The diagnosis can readily be confirmed with ultrasound-guided FNA for PTH like the evaluation for an intrathyroidal parathyroid adenoma. Gaining this information during the initial assessment of the neck for hyperparathyroidism, ultimately saves a long and frustrating central neck operation trying to locate a missing parathyroid gland and may limit collateral trauma to recurrent laryngeal nerves.
Undescended left inferior parathyroid adenoma on ultrasound
Another ultrasound-guided technique used to establish the presence of an undescended parathyroid is to obtain internal jugular venous blood samples from both veins to test for PTH [34, 35]. The side with an undescended parathyroid adenoma should have a level at least twice the peripheral baseline PTH.
Ultrasound has limitations in the central neck for identifying abnormal parathyroid glands. Parathyroid hyperplasia or small adenomas are more difficult to visualize. In addition, the deeper the parathyroid gland and the thicker the neck, the more difficult imaging becomes. Thyroid goiter or nodules make imaging posterior to the thyroid difficult. Exophytic nodules off the posterior aspect of the thyroid can be misinterpreted as a parathyroid adenoma. Hashimoto’s thyroiditis or Graves’ disease goiters are associated with imaged lymph nodes that can be confused with parathyroid adenomas. Calcifications within the thyroid or a thyroid nodule, cartilage or air within the edge of the trachea or larynx, and the sternoclavicular bone preclude imaging parathyroid glands located posterior to these structures. As a general rule, if an abnormal parathyroid gland cannot be seen with ultrasound, it is presumptive evidence that the abnormal parathyroid gland is more likely to be a superior parathyroid adenoma, because of the natural difficulty in imaging these glands with ultrasound. When an ectopic parathyroid adenoma can be seen with ultrasound, the surgical approach is much simpler than in the preimaging era when a standard bilateral cervical exploration was planned to locate the parathyroid adenoma in a patient with primary hyperparathyroidism. As reported by other investigators, it is the author’s preference to forego any other imaging technique for locating abnormal parathyroid glands once the offending parathyroid is precisely identified with ultrasound .
Another very useful localization study is the parathyroid nuclear medicine scan . Technetium sestamibi will be concentrated in any anatomic structure with increased mitochondria, which includes the thyroid gland and abnormal parathyroid glands. The parathyroid adenoma will hold on to the technetium sestamibi longer than the thyroid gland. This fact allows comparing the initial post-injection parathyroid scan with subsequent images taken 2–3 h later to undercover the location of the parathyroid adenoma. Another useful technique for parathyroid scanning is to obtain subtraction imaging. The patient is initially given technetium pertechnitate, which gets picked up by the thyroid gland and not abnormal parathyroid glands. This is followed by an injection of perchlorate, which washes the technetium pertechnitate out of the thyroid gland. Finally, an injection of technetium sestamibi is given. The patient must remain still between images taken after the two technetium injections. The computer can then subtract the first image from the second image to locate the abnormal parathyroid gland. Delayed imaging can be obtained with this technique as well. More precise localization is achieved by adding fused CT scan imaging or SPECT (single photon emission computed tomography) imaging . This gives a three dimensional localization to planar discordant imaging . Besides locating the abnormal gland, parathyroid scanning can alert the surgeon to the presence of an ectopic location.
One study on the technique concluded that combined SPECT/CT scanning produced more reliable localization of ectopic parathyroid adenomas . This is particularly useful for identifying the mediastinal parathyroid adenoma (see Fig. 25.4). Such knowledge can direct further diagnostic investigation of a suspected mediastinal parathyroid adenoma and obviate the need for a central neck parathyroid exploration. Undescended parathyroid adenomas are a little more difficult to discern, because of adjacent uptake of technetium sestamibi by salivary glands. Parathyroid sestamibi scans are successful in localizing approximately 70–80 % of parathyroid adenomas. Difficulties in localization of the abnormal parathyroid gland particularly arise with small adenomas and parathyroid hyperplasia . A study of 185 patients operated on for hyperparathyroidism, of which 19 % had ectopic parathyroid glands, found a significant positive correlation between adenoma weight and positive imaging studies. An ectopic parathyroid location, however, did not correlate with a negative imaging study .
Mediastinal parathyroid adenoma on technetium sestamibi scan
A newer useful imaging study for localizing parathyroid adenomas is 4D CT scan imaging . The 4th dimension added to CT scanning is time. Rapid CT scanning is obtained to compare baseline images of the neck and chest with arterial phase images and venous phase images. The parathyroid adenoma has a rich blood supply that creates a localized arterial blush and venous retention that allows separating parathyroid adenomas from lymphadenopathy. If the parathyroid adenoma is immediately adjacent to the thyroid gland then it is more difficult to separate out the abnormal parathyroid gland from the vascular thyroid gland. However, the 4D CT scanning is very useful when the parathyroid adenoma is anatomically separated from the thyroid gland. The CT imaging aids the surgeon in the precise location of the abnormal parathyroid gland and is particularly useful in identifying an ectopic location for a parathyroid adenoma, especially when other imaging modalities are negative (see Fig. 25.5) .
Undescended right superior parathyroid adenoma on 4D CT scan
The best algorithm for parathyroid imaging is evolving. Ultrasound imaging has no ionizing radiation and can be very accurate in the hands of an experienced and dedicated parathyroid Radiologist. The advent of accurate office imaging of the neck with surgeon performed ultrasound makes this the first approach of choice for many endocrine surgeons, the author included. Additional information concerning thyroid pathology is obtained that can direct further evaluation with ultrasound-guided FNA and ultimately preoperative planning. It can be useful to reimage the patient with ultrasound on the operating table to affirm the abnormal parathyroid localization prior to starting the operation. A clearly positive ultrasound exam may be all that is necessary before proceeding with a minimally invasive parathyroidectomy operation. Parathyroid scanning with technetium sestamibi is typically the most useful imaging study following ultrasound. If both ultrasound and nuclear medicine scanning are negative, then 4D CT scanning can be obtained . The role for 4D CT scanning is evolving into a primary modality of parathyroid imaging at some institutions, displacing nuclear medicine studies .
The present day imaging techniques for hyperparathyroidism have the distinct advantage of localizing an ectopic parathyroid gland preoperatively. This ultimately can save a lot of operative time and frustration looking for a missing parathyroid gland. It can then direct a minimally invasive operative approach even for an ectopic parathyroid adenoma when combined with intraoperative parathyroid hormone monitoring . The failed operative exploration calls into play the next level of imaging studies, which involve invasive radiologic techniques: arteriography and venous sampling.
Invasive Vascular Imaging
Angiography done with conventional techniques demonstrates a blush of enhancement after contrast injection. This would necessitate selective arterial injections in bilateral internal thoracic, common carotid, inferior thyroid, and superior thyroid arteries . Digital subtraction angiography has been found superior to conventional arteriography by some institutions . Immediately following the arteriographic contrast injection, the arterial vessel is injected with a hypocalcemic stimulating agent (sodium citrate) and then venous blood samples obtained from a catheter in the superior vena cava looking for at least a 1.4 times step-up in the PTH level as a confirmation of the localization . The National Institute of Health has found this localizing technique their invasive imaging procedure of choice with 92 % positive predictive feedback for the combined digital subtraction angiography and arterial stimulation venous sampling. The arterial stimulation venous sampling was less helpful than the digital subtraction angiography . Invasive arterial imaging in the head and neck region, however, carries the rare risk of inducing embolism and stroke that must be discussed with the patient before proceeding with this imaging modality.
Selective venous sampling for PTH is another useful invasive imaging technique that does not carry the risk of arterial embolization. The primary head and neck venous drainage is mapped out and multilevel venous samples drawn for PTH bilaterally down into the superior vena cava. Selective venous drainage tributaries are also sampled for PTH. Each sample level must be carefully marked on the venous contrast image, and the final PTH levels used to reconstruct the anatomy for PTH, pinpointing a significant step-up point in the PTH of at least twice the baseline elevated PTH . Commonly the step-up PTH is much higher than twice normal (see Fig. 25.6). The technique is very time consuming and requires an experienced interventional radiologist to conduct the study, which may involve as many as 50 selective venous blood samples. Venous drainage PTH levels do not give the same precise localization image of an identified contrast blush within an adenoma as with angiography, but can be very helpful to direct the operative approach to the ectopic parathyroid adenoma or subsequent arteriographic imaging [50, 52]. In general, a missing abnormal parathyroid gland requires two confirming localization imaging studies to direct reoperation with confidence of finding the abnormal parathyroid gland. A positive parathyroid sestamibi scan and a positive 4D CT scan may be all that is necessary to localize a mediastinal ectopic parathyroid adenoma. Frequently, however, one of these imaging studies is negative and invasive imaging studies may be required to further confirm the localization of an ectopic parathyroid adenoma. This is particularly true for ectopic parathyroids within the mediastinum. In some cases a positive invasive imaging study prompts reassessment of the interpretation of images obtained with noninvasive imaging to reestablish the localization of the ectopic parathyroid adenoma.
Persistent primary hyperparathyroidism after failed parathyroid exploration
Operative Approach to Ectopic Parathyroid Adenomas
There are three anatomic levels of operative approach to the ectopic abnormal parathyroid:
Upper neck cranial to the thyroid notch that contains an undescended parathyroid gland.
Central neck from the thyroid notch to visible superior mediastinum that can be assessed with the standard collar incision for parathyroid exploration.
Mediastinum caudal to the usual visualized level from a standard cervical exploration.
It is helpful to address the operative approach to each of these levels separately, following the embryologic descent of the parathyroid glands.
Undescended Ectopic Parathyroid
Either the inferior parathyroid gland (3rd pharyngeal pouch) or the superior parathyroid gland (4th pharyngeal pouch) can be responsible for an undescended ectopic parathyroid . A 31-year study of 1750 patients with renal hyperparathyroidism revealed a 0.91 % incidence (16 patients) of undescended parathyroid. The ratio of undescended inferior to superior parathyroid glands was 3 to 1 . The location in the upper neck is slightly different for each of these glands. Since the inferior parathyroid gland descends with the thymus gland, the undescended complex has been termed the “parathymus.”  The presence of thymus tissue in the upper neck associated with an ectopic parathyroid gland is the anatomic clue that this represents an ectopic inferior parathyroid gland. The inferior parathyroid can rarely be totally undescended and be as high in the neck as near the angle of the jaw at the level of the hyoid bone. In this location imaging studies will confuse it with submandibular lymph nodes on ultrasound and submandibular salivary glands on parathyroid sestamibi scans. More commonly, the undescended inferior parathyroid gland is found adjacent to the carotid artery at the level of the bifurcation . It is typically anterior/medial to the carotid artery and in this location can be distinguished on the initial neck ultrasound examination from lymph nodes that are typically lateral to the internal jugular vein or medial to the internal jugular vein, but lateral to the carotid artery (see Figs. 25.3 and 25.7). A hypoechoic nodular structure on ultrasound medial to the carotid artery in the setting of primary hyperparathyroidism should be considered an undescended parathyroid adenoma until proven otherwise. It is rare, however possible, to have an ectopic parathyroid adenoma lateral to the carotid artery [55, 56].
Undescended left inferior parathyroid adenoma
The superior parathyroid gland when undescended can be typically found medial/posterior to the common carotid artery just below the bifurcation . In this position it can sometimes be imaged with ultrasound. The undescended superior parathyroid gland can also be found posterior to the upper larynx/pharynx and in this position the adenoma requires 4D CT scan imaging for an accurate localization (see Fig. 25.5). If the superior parathyroid primordium fails to separate from the remaining endoderm of the 4th pharyngeal pouch, it may migrate to a retropharyngeal location with the pyriform sinus primordium . This can lead to an undescended parathyroid adenoma within the pyriform sinus that can be visualized on a laryngoscopic examination as a unilateral superficial bulging of the pyriform sinus. In this rare case, the parathyroidectomy approach can be conducted via laryngoscopy, ideally using endoscopic CO2 laser resection . A very rare location for an undescended parathyroid is within the vagus nerve or even hypoglossal nerve [60, 61]. Tissue between the 3rd and 4th pharyngeal pouches contributes to these nerves and can therefore have elements of parathyroid tissue within the nerve that may ultimately develop into a parathyroid adenoma. Vocal cord paralysis has been reported as a presenting sign of intravagal ectopic parathyroid adenoma .
The surgical approach to the typical undescended parathyroid gland requires precise localization with imaging studies, usually ultrasound and/or a 4D CT scan (see Figs. 25.4, 25.5, and 25.7). The localization is preferably confirmed with directed fine needle aspiration for PTH, usually done with ultrasound guidance . For the parathyroid glands not amenable to ultrasound-guided FNA, elevated internal jugular venous PTH samples will confirm the ectopic imaged location in the upper neck . A precise localization with a 4D CT scan can be enough to direct surgery in the classic clinical setting of primary hyperparathyroidism (see Figs. 25.5 and 25.8).
Undescended right superior parathyroidectomy
Depending on the patient’s anatomy and the location of the ectopic undescended parathyroid adenoma, surgery can be done under local anesthesia through a field block combined with intravenous sedation (Monitored Anesthesia Care). Otherwise, general anesthesia can be used with the optional use of intraoperative nerve monitoring for testing the vagus nerve during surgical exposure. If the undescended parathyroid adenoma can be imaged with ultrasound, then the ultrasound examination can be repeated in the operating room once the patient is positioned for surgery for planning the operative incision. If the parathyroid can’t be imaged with ultrasound, the relative location to the bifurcation of the carotid artery and hyoid bone can be noted for reference in planning the location of the incision. Generally a transverse incision is made in the upper medial neck on the side of the tumor following a natural skin line (see Figs. 25.4, 25.7, and 25.9). The incision is extended in the deeper anterior neck to mobilize the sternohyoid muscle medially and the sternocleidomastoid muscle laterally to expose the underlying carotid artery. An adjunct to guide dissection and identification of the abnormal parathyroid gland that the author has found useful is to inject the patient with technetium sestamibi approximately 2–3 h prior to the start of the surgery to allow use of a gamma probe to locate the abnormal parathyroid gland (see Fig. 25.10). This technique is useful even if the parathyroid sestamibi scan was negative preoperatively. A skin gamma radioactive count in counts/second (with or without a columnator, the author prefers without) is obtained before the incision and the gamma probe used to direct deeper dissection once the carotid artery area is exposed. The closer the dissection gets to the parathyroid adenoma the higher the radioactive counts become. Once the parathyroid adenoma has been excised, the ex-vivo radioactive counts can be taken to confirm that an offending parathyroid gland has been removed. The surgery is similarly combined with intraoperative PTH monitoring to insure that only one abnormal parathyroid gland exists . With this approach frozen section confirmation of a parathyroid adenoma is not usually necessary.
Undescended left inferior parathyroidectomy
Gamma probe localization of a left superior parathyroid adenoma
Central Neck Ectopic Parathyroid
The standard cervical collar incision close to the isthmus of the thyroid can generally be used to identify and excise an ectopic abnormal parathyroid gland between the thyroid notch of the larynx down to the upper superior mediastinum. A precise localization of the abnormal parathyroid gland preoperatively is extremely helpful in planning surgical dissection and allowing a minimally invasive parathyroidectomy approach. This may allow a laterally placed transverse incision to approach the central neck by medially displacing the lateral edge of the strap muscles along the medial edge of the sternocleidomastoid muscle . The author prefers to continue with the transverse central neck incision even in reoperative cases since this gives the greatest flexibility to dissect both sides of the central neck if operative findings dictate that approach, as when the intraoperative PTH levels do not drop sufficiently to indicate only unilateral disease. Use of the gamma probe following injection of the patient 2–3 h preoperatively with technetium sestamibi can be helpful in directing deeper dissection for a posteriorly displaced parathyroid adenoma. Prior to the central neck incision, four quadrant skin radioactive counts can be recorded form the general area of the normal anatomic location of the four parathyroid glands (right inferior and superior, left inferior and superior). These radioactive counts can be used as a reference to guide deeper dissection, since the radioactive counts will increase the closer the gamma probe gets to the abnormal parathyroid gland. Once the parathyroid gland is excised, ex-vivo radioactive counts over in-vivo radioactive counts of at least 20 % can be used to readily confirm that the abnormal parathyroid gland had been discovered and removed (see Fig. 25.10). This technique will be most helpful in an ectopic parathyroid adenoma localized on a parathyroid sestamibi scan. The author, however, has also found it useful even in patients with a negative preoperative localization study using technetium sestamibi (unpublished results). A significant drop of the intraoperative PTH levels can also be used to confirm uni-glandular parathyroid disease that allows for minimally invasive parathyroidectomy surgery . Intraoperative PTH monitoring is equally effective for surgical management of hyperfunctioning ectopic parathyroid glands. An evaluation of surgical results in 1195 patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism found 120 patients (10 %) had hyperfunctioning ectopic glands. There was an overall 93 % operative success for these patients using a combination of preoperative localization studies and intraoperative PTH monitoring .
Patients with nonlocalizing imaging studies preoperatively for primary hyperparathyroidism or an inadequate drop of the intraoperative PTH levels following excision of the preoperatively localized abnormal parathyroid gland pose a different problem to the endocrine surgeon. This frequently requires a 4 gland exploration looking for 1 or more abnormal parathyroid glands. Previous studies on reoperative surgery for persistent primary hyperparathyroidism prior to the advent of current parathyroid imaging techniques demonstrated that the majority of missed parathyroid adenomas were still in the central neck compartment and could be reached through the initial parathyroid exploration incision [50, 66, 67]. In the hands of an experienced endocrine surgeon this occurrence can be minimized by a systematic operative approach to uncover the abnormal ectopic parathyroid gland. The search for an ectopic parathyroid gland is aided by knowledge of whether the missing parathyroid gland is suspected to be an inferior or superior parathyroid gland. This is sometimes difficult to precisely determine intraoperatively. The presence of thymus gland with the parathyroid gland is a tip-off that the identified parathyroid gland, irrespective of the location, is an inferior parathyroid gland. Searching for symmetrical parathyroid locations is also helpful, but sometimes the missing parathyroid is not easy to locate.
The missing inferior parathyroid gland requires looking first in the thyrothymic ligament down to and including the cervical extension of the thymus gland all the way to as much of the superior mediastinal portion of the thymus gland that can be retracted into the neck . A negative localization then requires searching the deeper paratracheal and paraesophageal tissues from above the superior pole of the thyroid to the thoracic inlet. The weight of an enlarged inferior parathyroid gland can displace it posteriorly all along the path of embryologic descent. Sometimes, a more superiorly identified parathyroid gland reveals that the initial localized parathyroid gland lateral to the mid-thyroid was not in fact the superior parathyroid gland, but the inferior parathyroid gland. Intraoperative nerve monitoring using electrode imbedded endotracheal tubes can be very helpful in identifying the course of the recurrent laryngeal nerve for preservation while exposing the deeper paratracheal and paraesophageal tissues . A negative localization then requires searching the carotid sheath from the thoracic inlet to superior to the thyroid. The missing parathyroid gland can be posterior to the carotid artery .
With a continued negative exploration, a missing inferior parathyroid gland could possibly be an intrathyroidal parathyroid adenoma [27, 28]. In this case the preoperative ultrasound assessment of the thyroid is extremely helpful in determining whether thyroid lobectomy is indicated. A normal thyroid ultrasound precludes any need for thyroid lobectomy. It’s helpful to know the size and location of the ultrasound identified thyroid nodules to determine whether there is a possibility of an intrathyroidal parathyroid adenoma. Intraoperative ultrasound may be helpful at this point. Typically, the intrathyroidal parathyroid adenoma is subcapsular and can be readily unroofed. If a true intrathyroidal parathyroid adenoma is suspected representing a missing inferior parathyroid, usually a partial thyroidectomy of the lower half of the thyroid lobe is sufficient to exclude this possibility, but only if there are thyroid nodules suspicious for a missing adenoma . A clearly suspicious thyroid nodule for an intrathyroidal parathyroid adenoma can be approached through a thyroidotomy and enucleation of the nodule.
The missing superior parathyroid gland requires a complete mobilization of the superior pole of the thyroid lobe to insure that an ectopic parathyroid gland posterior to the tip of the superior pole of the thyroid or above the superior tip of the thyroid lobe is not overlooked. Sometimes a superior parathyroid gland in a normal location requires complete mobilization of the superior pole to uncover the location of the parathyroid gland. With negative exploration after mobilization of the superior pole of the thyroid, the deeper paratracheal and paraesophageal tissues must be dissected all the way down into the superior posterior mediastinum . The superior parathyroid adenoma can lie even posterior to the trachea or esophagus. This exposure is similar to looking for a missing inferior parathyroid adenoma.
A common ectopic displacement of a superior parathyroid adenoma is to the deep paratracheal and paraesophageal tissues posterior or caudal to the inferior pole of the thyroid and sometimes even down into the superior posterior mediastinum (see Fig. 25.11). The carotid sheath needs to be explored if dissection continues to be unsuccessful for localization of the missing superior parathyroid gland. A truly intrathyroidal superior parathyroid adenoma is very unusual, but possible. The same assessment of the thyroid with ultrasound is essential to revealing the location of a possible intrathyroidal superior parathyroid adenoma. In the author’s experience this rare occurrence is usually within the posterior mid-portion of the thyroid and can be approached sometimes through a thyroidotomy and enucleation of the nodule so as to avoid a thyroid lobectomy.
Paratracheal right superior parathyroid adenoma
Exploration for a missing ectopic parathyroid adenoma can be aided by gamma probe localization following the injection of technetium sestamibi prior to the operation. The author has found this very useful on a number of occasions. It does not require a positive preoperative sestamibi scan to be useful, since most parathyroid adenomas do take up technetium sestamibi. The intraoperative gamma probe is more sensitive than the parathyroid imaging study. The timing of the exploration after the injection is not critical. The author has found it useful even up to 6 h following the injection of technetium sestamibi. The reason for this is that gamma probe radioactive counts used to aid dissection are all relative to the location of where the counts are taken (skin versus parathyroid adenoma) at the time of surgical exploration. Radioactive counts are obtained from the skin level using the gamma probe and recorded in the four usual quadrants of the thyroid. Then with deeper central neck exploration the ectopic parathyroid adenoma can be suspected when increasing radioactive counts are detected above the skin level and gradually higher radioactive counts as the gamma probe gets closer to the parathyroid adenoma. The gamma probe is very specific in the directional indication of the location of an ectopic parathyroid adenoma, thus aiding the surgeon as to where to look for the missing ectopic parathyroid gland. Unfortunately, some parathyroid adenomas weakly concentrate technetium sestamibi, depending of the degree of increased mitochondria within the parathyroid adenoma and oxyphil versus chief cell component, so that gamma probe localization is not helpful. Small parathyroid adenomas also become more difficult to localize with the gamma probe. Even so, generally nothing is lost in trying to use gamma probe localization for difficult intraoperative parathyroid adenoma localization and identification.
If a thorough central neck exploration for a missing ectopic parathyroid adenoma is performed as described and remains negative, then the location is presumed to be undescended or mediastinal. The undescended location can be suspected by taking bilateral internal jugular venous blood samples for PTH and detecting a distinct lateralization (two to fourfold ioPTH gradient) . Lee et al. reported using this technique to successfully locate and remove undescended parathyroid adenomas in three patients . Sometimes all four parathyroid glands are identified. In this case supernumerary parathyroid glands can be suspected, assuming the correct clinical diagnosis of hyperparathyroidism has been firmly established. The most common location will be associated with the thymus gland and excision of cervical thymus and as much of the superior mediastinal thymus as can be retracted into the neck is indicated . With a negative exploration for the offending abnormal parathyroid gland, in depth imaging studies for an undescended or mediastinal ectopic parathyroid gland is indicated. The author prefers to wait for 3 months to allow complete healing of the initial cervical exploration, before undertaking extensive imaging studies for the missing ectopic parathyroid gland.