Multi-tracer imaging of thyroid nodules: is there a role in the preoperative assessment of nodular goiter?

Abstract

For the preoperative assessment of thyroid nodules, ultrasonography (US) and scintigraphy using technetium99 m pertechnetate or iodine-123 are the routine imaging methods in most thyroid centres. As a function of exogenous dietary iodine intake, the probability of malignancy ranges from 8% to 20% for a hypoechoic nodule and from 5% to 15% for a hypofunctional nodule. This means that in an iodine-sufficient area, the likelihood that a hypoechoic, hypofunctional nodule will be malignant is higher than in an iodine-deficient area. Furthermore, with an increase in iodine supplementation, there is a shift from follicular to papillary thyroid carcinoma [1]. In the case of hypoechogenicity and/or hypofunction of the nodule an ultrasonography-guided fine-needle aspiration biopsy (ugFNAB) should be performed for further evaluation of possible malignancy. This approach is sufficient to diagnose papillary thyroid carcinoma with an accuracy of more than 90% [2, 3]. However, the problem of differentiating follicular adenoma from follicular thyroid carcinoma remains when using US, 99mTc pertechnetate scintigraphy and ugFNAB preoperatively. Against this background, additional radionuclides and tracers have been used in recent years to improve the preoperative evaluation of hypoechoic and/or hypofunctional thyroid nodules. Years ago thallium-201 scintigraphy, performed as a single imaging modality or using the subtraction technique, was thought to provide the answer to this problem. However, with an increasing number of studies it became clear that also 201Tl is not able to differentiate benign from malignant follicular neoplasia [4, 5]. Following the introduction of the 99mTc-labelled cationic complexes sestamibi (MIBI) and tetrofosmin, the ability of these tracers to answer a number of questions within oncology was evaluated. Both MIBI and tetrofosmin have their place in the post-therapeutic work-up of differentiated thyroid carcinoma (DTC) [6, 7]. However, it remains unclear whether there is really a role for cationic complexes in the preoperative assessment of thyroid nodules. In a paper on this issue by Mezosi et al., the authors described the role of 99mTc -MIBI scintigraphy in the differential diagnosis of cold thyroid nodules [8]. A total of 52 patients with hypofunctional thyroid nodules on 99mTc pertechnetate scintigraphy were investigated using single planar imaging 20–40 min after intravenous injection of 400 MBq 99mTc-MIBI. Histology revealed thyroid carcinoma in 15 cases (9 papillary, 3 follicular, 2 medullary, 1 anaplastic) and benign thyroid disease in 44 patients (19 adenoma, 24 nodular goitre, 1 Hashimoto’s disease). For the evaluation of MIBI scintigraphy a visual score from 0 (no MIBI uptake) to 3 (increased MIBI uptake compared with surrounding thyroid tissue) was used. All of the 12 patients with differentiated thyroid cancer (DTC) demonstrated equal (2) or increased (3) MIBI uptake as compared with surrounding thyroid tissue. However, 15 out of 19 (79%) and 13 out of 24 (54%) patients with adenoma and nodular goitre respectively also had a score of 2 or 3. If one looks only at MIBI hot nodules, 10 out of 12 (83%) patients with DTC and 12 out of 19 patients with adenoma (63%) demonstrated the pattern of score 3, whereas none of the patients with nodular goitre did so. This means that MIBI is able to differentiate in most cases between nodular goitre on the one hand and adenoma and differentiated carcinoma on the other. Nevertheless, the clinically relevant goal of finding a tracer that is able to differentiate between follicular adenoma and differentiated follicular carcinoma is not fulfilled by MIBI. In a similar study performed by our group in 1996, 62 patients with hypofunctional thyroid nodules on 99mTc pertechnetate scintigraphy underwent MIBI scintigraphy 30 and 120 min after intravenous injection of 370 MBq 99mTc MIBI [9]. MIBI uptake in the nodule 30 min after injection (early image) was described as lower than (A), equal to (B) or superior to (C) that in the surrounding thyroid tissue. Histology of the 62 investigated patients revealed DTC in 11, anaplastic thyroid cancer in one, adenoma in 27, degenerative nodular goitre in 22 and Hashimoto’s disease in one. All of the 11 patients with DTC demonstrated equal or increased MIBI uptake (B and C). However, increased MIBI uptake was seen in only 5 of 11 DTCs (45%). MIBI uptake patterns B and C were seen in 23 out of 27 patients with thyroid adenoma (85%). In 63% of patients with thyroid adenoma (17 out of 27), MIBI uptake in the nodule was superior to that in the surrounding tissue (C).