Surgical results
In both patients, surgery was uneventful. The parathyroid adenomas were identified visually in the APW within the expected position (Figure 2). In the first patient (#1), the adenoma presented as a cystic tumour of about 35 mm in diameter; in the second patient (#2), the adenoma was solid with a diameter of about 15 mm (Figure 3). After removal of the adenomas (weight: 4,400 (#1) and 985 mg (#2), respectively), PTH decreased within 10 minutes into the normal range: 89.3 (#1) and 59.2 pmol/L (#2) before excision versus 5.7 (#1) and 2.5 pmol/L (#2) ten minutes after resection.
Serum calcium and PTH were in the normal range three months after surgery in both patients. No permanent recurrent nerve palsy was observed. Patient #2 showed a marked clinical improvement within a few days after surgery.
Histological examination revealed classical parathyroid adenoma, in the first patient (#1) with cystic degeneration.
Radioactivity measurements
The ex vivo count rate over the removed parathyroid adenomas 120 minutes after MIBI-injection were 196 cps in the cystic adenoma (#1) and 855 cps in the solid adenoma (#2). Compared to these ex vivo activities, all other counted activities were calculated as relative radioactivity (RRA) compared to the ex vivo count rates.
The relative radioactivities 60, 90 and 120 minutes after MIBI administration differed in all the tested regions (Figure 4).
Before removal of the parathyroid adenomas, the relative radioactivities over the APW were above 1.5 in both patients. No differences in counted radioactivity were found over the APW within the tested area of about 30 mm in diameter. However, the direction of the collimated gamma probe had a marked effect on the measured count rates, which were highest when the probe was angled towards the heart. For measurement of the RRA over the APW region, the gamma probe was therefore always pointed in a straight posterior direction. After excision of the parathyroid adenoma, the relative radioactivities in the APW decreased to 1.16 (#1) and 0.89 (#2), respectively, while relative radioactivities over the left ventricle, about 2.5–3 cm distant from the tested APW region, ranged between 2.0 and 5.0.
In contrast to the APW and the left heart, the relative radioactivities over the left neck and the right lung were always clearly below 1.0. Over time, one patient (#1) had slightly increasing relative radioactivities over the abdomen, which probably was due to tracer accumulation in the urinary bladder as this patient was not catheterized (Figure 4).
Discussion
In this exploratory study, we examined the feasibility of RGS in two patients with APW parathyroid adenoma using a transsternal approach. As expected from the physiological tracer distribution, very high relative radioactivities were found over the heart on all measurements whereas the relative radioactivities over the lung and the neck were clearly below 1.0. Within the APW, no differences in count rates were detected within an area of 30 mm in diameter, approximately twice the diameter of the probe face. In this area, the relative radioactivities before removal of the parathyroid adenomas were always clearly above 1.0. Concerning intraoperative localization (guidance) of the adenoma, however, RGS had to be assessed as not very helpful. Removal of the parathyroid adenoma led to a slight reduction of radioactivity within this area in both patients. The relative radioactivities, however, were still around 1.0, and higher when compared to the relative radioactivities over the neck and the lung.
Background activity as the key for RGS
During the last two decades, preoperative multimodality imaging, minimal invasive parathyroidectomy, intraoperative PTH measurement, and RGS have had a profound effect on parathyroid surgery and become routine at many endocrine surgical centres[15, 18, 19]. RGS using 99mTc-MIBI has been proposed to be particularly useful in patients with ectopic parathyroid adenomas[2, 5, 12, 20, 22, 23]. Numerous application protocols regarding RGS have been reported, with injected radioactivity ranging from 37 to 740 MBq 99mTc-MIBI. Concerning the time interval between application and scanning, protocols are rather similar with tracer injection around the start of surgery, which usually results in an interval of about 30 to 90 minutes[1–4, 22]. Administration of 370 MBq is probably most common[2, 4]. This protocol seems to be the best compromise regarding detection accuracy and radiation protection of the personnel.
99mTc-MIBI was originally developed for myocardial scintigraphy[24]. The lipophilic tracer is taken up and bound to the mitochondria of viable myocardium as well as other hypermetabolic mitochondria-rich tissues. Thus it is more avidly taken up by parathyroid adenomas and hyperplastic parathyroid tissue than by normal parathyroid glands[9, 11]. Uptake of 99mTc-MIBI is, however, not specific to parathyroid tissue. Consequently, for detection of abnormal hyperfunctioning parathyroid tissue, different uptake kinetics between adenoma or hyperplastic glands and the surrounding tissue are required. Most of the protocols in the neck are using a 20% cut-off. Based on that criterion, surgery is considered successful when radioactivity of the removed specimen is more than 20% higher than that of the surrounding (thyroid) tissue[4, 13, 14].
RGS for localization of APW adenoma
This study shows that RGS for localization of APW parathyroid adenoma is limited by high myocardial background activity. Due to the short distance between the heart and the APW region, the RRA within the APW region remained relatively high even after removal of the parathyroid adenoma. The count rates substantially depended on probe direction. Therefore, in our experience, RGS is not very helpful concerning intraoperative localization of APW parathyroid adenomas when performing surgery via a transsternal approach.
Some surgeons, however, prefer left thoracotomy for removing APW parathyroid adenoma[19, 25–28], which might lead to an improved discrimination due to a different position of the gamma probe. Furthermore, during the last decade, an increasing number of reports regarding minimal-invasive surgery of mediastinal parathyroid adenoma have been published[29, 30]. Even though most of these adenomas were localized in the upper and anterior mediastinum, the feasibility of minimal-invasive surgery in APW parathyroid adenoma using a robot-assisted approach has been demonstrated[31, 32]. None of these robot-assisted operations, however, focused on RGS. Important enough, RGS for APW parathyroid adenoma surgery would probably require special equipment since the usual commercial gamma probes are not designed for this approach. Thus, the feasibility of RGS in APW parathyroid adenoma using robot-assisted surgery remains to be demonstrated.
Testing of cure
After removal of the parathyroid adenomas, a clear RRA reduction within the APW region was found. In addition, the activity over the removed adenomas was much higher when compared to other reference areas (neck, lung). On the other hand, however, the RRA over the APW was still around 1.0 after removal of the adenomas.
Regardless the extent of RRA decrease, decreasing activity does not give evidence of biochemical cure at all since other hyperfunctioning glands (e.g. in the neck) cannot be excluded. Since intraoperative PTH measurement showed normalization within 10 minutes in both patients, no further surgery or exploration was necessary in the two patients.
