Incremental Diagnostic Value of Preoperative ^99mTc-MIBI SPECT in Patients with a Parathyroid Adenoma

MATERIALS AND METHODS

The study cohort consisted of 52 consecutive patients with primary hyperparathyroidism (38 women, 14 men; mean age, 63.5 y; range, 32–84 y) who had parathyroid surgery to treat primary hyperparathyroidism. Serum calcium levels were taken before surgery and at 8 and 24 h after surgery (Table 1). Serum parathyroid hormone (PTH) levels were available for all patients before surgery. Gland weight was recorded after surgery, and each patient had a histopathologic examination of the removed glands for comparison with the scintigraphic results.

RESULTS

Among the 52 patients, planar scintigraphy using delayed imaging and dual-isotope technique correctly identified 41 adenomas (79%). SPECT correctly identified those adenomas, providing additional 3D information for the surgeon. Additionally, 9 more adenomas were identified on SPECT, for a sensitivity of 96% (Table 2). SPECT was superior to planar imaging in 6 patients with multinodular goiters (MNGs) and in 3 patients with ectopic adenomas. Figure 1 illustrates a patient with an adenoma lying posterior to the right lower thyroid pole, and Figure 2 shows a patient with a small adenoma just behind a large MNG. Altogether, ectopic adenomas were identified in 6 patients (11%) and MNGs were present in 16 patients (31%). Interestingly, gland size did not affect significantly the detectability of the SPECT studies compared with planar imaging, although the smallest adenoma (170 mg) was missed by planar imaging. ^99mTc-MIBI retention was noted in only 31 adenomas (60%), whereas the remaining adenomas demonstrated a rapid washout. The average uptake ratios of parathyroid counts to the left lobe, right lobe, and maximum thyroid activity were 1.20 ± 0.42, 1.29 ± 0.45, and 0.84 ± 0.35, respectively. Statistical analysis showed that the uptake ratio of parathyroid to maximum thyroid activity was significantly correlated with PTH levels before surgery (r = 0.408; P = 0.04). Otherwise, no significant correlation was found between parathyroid activity ratios and any of the blood chemistry or clinical variables. The average adenoma weight was 1.14 g (range, 0.17–4.0 g). There was no correlation between gland size and parathyroid uptake. Only 4 of 52 patients had transient symptoms of hypocalcemia after surgery. As expected, clinical symptoms after surgery showed significant inverse association with calcium levels after surgery (r = −0.4; P = 0.03). No laryngeal nerve injuries were encountered.

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FIGURE 1.

A 63-y-old woman with primary hyperparathyroidism. (A) Early ^99mTc-MIBI planar image (left) shows relatively uniform activity in thyroid gland and uniform washout on delayed image (middle). Pertechnetate scan (right) is congruent with early ^99mTc-MIBI scan. (B) Coronal (left), sagittal (middle left), and transaxial (middle right) representative SPECT slices and 3D volume-rendered image (right) show posterior location of adenoma (arrowhead) just behind lower pole of right thyroid lobe (double arrowheads).

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FIGURE 2.

A 75-y-old man with primary hyperparathyroidism. (A) Early ^99mTc-MIBI planar image (left) shows large MNG with irregular increased activity in left lobe. Delayed image (right) shows nonuniform washout. (B) 3D-volume rendered images show small adenoma attached to posterior aspect of right lower lobe (arrowhead).

DISCUSSION

Experienced endocrine surgeons can cure primary hyperparathyroidism with bilateral neck exploration in most patients (up to 95% of cases) without the aid of any preoperative imaging (13,14). However, morbidity and the rate of failed surgery can be high in less experienced hands (15,16). Considering that a solitary parathyroid adenoma is the most frequent cause of primary hyperparathyroidism (in 80%–85%), bilateral neck exploration is considered overtreatment in most cases: It increases the risk of recurrent laryngeal nerve injuries and the likelihood of hypoparathyroidism. In addition, a wide exploration distorts the normal anatomy of the neck, causing a high rate of complications at repeated exploration. In fact, bilateral neck exploration has been advocated only when parathyroid hyperplasia or double adenomas are suspected.

The intraoperative γ-probe technique can reduce surgical trauma and is considered most useful in patients with ectopic adenomas (13) and in patients with a normal thyroid gland (17). The prevalence of ectopic adenomas was reported to be as high as 20% (18), and this condition represents one of the most frequent causes of surgical failure. The γ-probe enables the surgeon to focus the search and provides instant feedback about the progress of the operation (19).

Parathyroid adenomas typically have a very high metabolic rate for their size and show high avidity for labeled MIBI. The presence of mitochondria-rich oxyphil cells and increased vascularity presumably accounts for ^99mTc-MIBI trapping (20,21). However, a small number of oxyphil cells in some adenomas may account for rapid washout of ^99mTc-MIBI from the adenoma. Thus, delayed imaging may be nondiagnostic when similar washout rates between thyroid and parathyroid tissue are observed. In our study, only 60% of adenomas showed retention of activity on delayed images. We found that early SPECT was most useful for localizing parathyroid adenomas and is superior to delayed dual-phase imaging. Delayed SPECT is not recommended because it may cause unnecessary delay in surgery and may yield false-negative results due to rapid washout. Planar ^99mTc-MIBI parathyroid imaging is associated with a large number of equivocal or false-negative studies (10,22). In our study, only 79% of the adenomas were identified by planar imaging. Another major limitation is related to the presence of concomitant thyroid nodules that often are ^99mTc-MIBI avid and, therefore, can mimic a parathyroid lesion, causing false-positive scintigraphic results, particularly using the dual-phase ^99mTc-MIBI technique (23). Several authors found different effects of thyroid abnormalities on the sensitivity of the scan (23–25). For this reason, some physicians discourage the use of preoperative ^99mTc-MIBI scintigraphy and the γ-probe technique in patients with hyperparathyroidism who have a concomitant MNG (17). However, although an MNG lowered the sensitivity of planar imaging in our patients, it did not affect the high sensitivity of SPECT, despite the high proportion of patients (31%) with MNGs. This discrepancy is explained by the fact that most adenomas were posterior to the thyroid gland (12/16 patients; 75%) and, therefore, were difficult to identify on planar imaging. Two other adenomas were ectopic, 1 of which had a false-negative SPECT result. The weight of the adenoma had no significant effect on the higher sensitivity of SPECT. Although oblique views have been advocated for parathyroid adenomas superimposed on the thyroid (behind the thyroid lobe), this technique is not useful for an intrathyroid parathyroid adenoma and should be replaced by SPECT. Norman et al. claims that surgeons should be extremely cautious in deciding intraoperatively that a positive MIBI scan is a false-positive scan (19). Our experience is in accordance with this conclusion that when properly applied, conducted, and interpreted, there is no such thing as a false-positive MIBI scan.

The literature contains both supportive and conflicting claims for the use of SPECT in parathyroid adenomas. Chen et al. (12) claims that SPECT does not provide additional information, whereas others assert that tomographic ^99mTc-MIBI scintigraphy allows topographic localization without improving the detection rate (20). Neumann et al. (26), who used double-phase SPECT MIBI in patients with hyperparathyroidism, defined a positive study as a focal increased activity showing preferential retention of activity over time and, not surprisingly, found a low sensitivity of 55% for localization of adenomas before surgery. In contrast, Moka et al. (27) found a sensitivity of 95% by the use of a SPECT technique compared with 87% sensitivity of planar imaging, even though tomographic imaging was performed 120 min after injection (when many adenomas are already washed out). However, the exact topographic quadrant position was achieved in only 88%.

Our data support the use of preoperative SPECT before the initial operation, not only to select patients who are candidates for minimally invasive radioguided surgery (17) but also to provide accurate 3D information on deeply seated or ectopic adenomas. The aim is to avoid, or at least to reduce, the frequency of surgical failures. The use of quantification analysis in our study showed that high PTH levels before surgery predicted significantly higher uptake of ^99mTc-MIBI in the adenoma. This relationship between the intensity of tumor uptake and the hormonal function suggests that patients with higher presurgical PTH levels may benefit more from radioguided surgery. Takebayashi et al. (28) used semiquantitative analysis with planar imaging (including only 9 parathyroid adenomas) and found a higher ratio of parathyroid-to-thyroid counts in larger glands.

CONCLUSION

Our data indicate that preoperative SPECT in patients with primary hyperparathyroidism is highly important for accurate localization of parathyroid adenomas and for the selection of patients who are candidates for minimally invasive radioguided surgery, including patients with a nodular goiter. Planar imaging has a much lower sensitivity compared with SPECT. The washout kinetics of ^99mTc-MIBI are unreliable in the dual-phase technique. SPECT is mandatory for 3D evaluation of parathyroid adenomas, and it should be the primary preoperative imaging method.