Clinical Usefulness of Tc-99m-MIBI for Thyroid Nodule Imaging.
Matthias Schmidt
Department of Nuclear Medicine, University of Cologne,
Kerpener Str. 62, 50937 Koln, Germany
e-mail: Matthias.Schmidt@uni-koeln.deThe rationale for the use of Tc-99m-MIBI for evaluation of cold or suspicious thyroid nodules lies in the clinical usefulness of Tc-99m-MIBI to exclude thyroid malignancy in thyroid nodules because of its excellent negative predictive value.
According to German guidelines, thyroid nodules ≥1 cm are evaluated by thyroid scintigraphy and FNAB is recommended for further evaluation of cold thyroid nodules [73–75]. European and American guidelines are even more focused on the diagnostic evaluation by FNAB. However, guidelines are not consistent concerning the recommendation which nodules should be biopsied [9, 9a, 10, 10a, 12, 76, 79]. The European thyroid association recommends fine-needle aspiration of every thyroid nodule >1 cm and of every smaller suspicious nodule in ultrasound, and reserves thyroid scintigraphy for patients with low TSH or multinodular goiter. The American thyroid association [10] recommends FNAB of nodules >1–1.5 cm and reserves thyroid scintigraphy for patients with low TSH too. Other guidelines advocate the selection of nodules for biopsy on the basis of additional suspicious sonographic criteria [12]. In addition to these recommendations, one has to bear in mind that inconclusive results of FNAB occur in 3–33% and require repeat FNAB [14– 16]. More recent literature expands the recommendation of fine-needle biopsy on nodules <1 cm [31]. In a country with long-standing iodine deficiency, FNAB to such an extent as recommended by guidelines would be impossible and not reasonable: under the hypothesis that all patients with such nodules would undergo FNAB and that sensitivity and specificity of cytology were 85%, the positive predictive value of a pathologic cytologic finding will reach 1.5% only according to the Bayestheorem. This is clinically unacceptable and points towards the limited practicability of guidelines [4]. These conclusions are supported by an earlier publication of Raber et al.: under routine conditions of a teaching hospital in Austria, 2,071 cold thyroid nodules were diagnosed and evaluated by 49 doctors and 33 pathologists between 1975 and 1995. Only 47.3% of the fine-needle biopsies resulted in a conclusive diagnosis. The positive predictive value of a suspicious fine-needle biopsy for thyroid cancer was 35% only. A normal cytological result missed thyroid cancer in 15% [32]. Other support of the limited value of FNAB came from a literature review of Tee et al.: the authors analyzed the available literature and identified 12 studies with altogether 54,415 patients from 1966 until 2005 and concluded that FNAB missed one third of thyroid carcinomas [33]. As a consequence, preselection of thyroid nodules for FNAB is required to increase the pretest probability to at least 5–10%. A combination of sonographic criteria and scintigraphy, even in patients with normal TSH levels, is suited to select thyroid nodules for FNAB. In this scenario, Tc-99m-MIBI has gained increasing interest in the past years.
Tc-99m-MIBI has been used as a tumor imaging agent including the detection and localization of thyroid carcinomas for many years (e.g., papillary, follicular, Hurthle cell or medullary thyroid carcinomas, lymphoma) [34–36]. The clinical value of Tc-99m-MIBI as a tumor imaging agent lies in the fact that increased uptake in cold/hypofunctioning thyroid nodules (Mismatch between pertechnetate and Tc-99m-MIBI scan) increases the likelihood of malignancy while low uptake (Match between pertechnetate and Tc-99m-MIBI scan) excludes thyroid malignancies with a very high negative predictive value of >97% [8]. Hurtado-Lopez summarized nine publications with 448 patients and reported on a negative predictive value of 100%. Further literature research identified additional publications [19, 24] with few falsenegative results, that is, MIBI-negative in patients with differentiated thyroid cancer after operation. Our own data [27] included only one false-negative patient, in whom a papillary microcarcinoma was missed. Even in the light of the few false-negative patients in whom Tc-99m-MIBI was negative despite a thyroid carcinoma was identified after operation, the high negative-predictive value (>97%) of a negative Tc-99m-MIBI scan is clinically important and is an additional parameter to justify a conservative and nonsurgical management. In addition and in contrast, the positive predictive value of about 20% [27] of a pathological Tc-99m-MIBI scan for identification of a patient with a differentiated thyroid carcinoma is clinically helpful and relevant because it raises the likelihood of thyroid carcinoma to a level that surgery can be justified in analogy to the cytological diagnosis of follicular proliferation, having about the same positive predictive value for thyroid carcinoma as a positive Tc-99m-MIBI scan. However, the positive predictive value is dependent on the prevalence of thyroid malignancies of the patient population studied [37].
In conclusion, based on the available literature and our own institutional experience, Tc-99m-MIBI is a valuable method for further evaluation of (on pertechnetate scintigraphy) cold thyroid nodules, especially if the nodule is not easily amenable to fine needle aspiration biopsy (= FNAB) and/or FNAB is equivocal. There are at least 12 publications from 1993 to 2009 with more than 600 patients demonstrating the clinical usefulness for evaluation of thyroid nodules against the histopathological “golden standard” justifying the above-mentioned indications [8, 27]. The main finding is that a negative Tc-99m-MIBI excludes a malignant thyroid tumor. Apart from the evaluation of cold thyroid nodules, this technique is of special interest in nodules which are not easy to reach by FNAB and in multinodular goiter if patients do not want multiple or serial FNAB. It is the author´s opinion that the results of the publications and the many years of experience from different groups justify the use of Tc-99m-MIBI for thyroid imaging though to the author’s knowledge no commercially available Tc-99m-MIBI kit has official approval for this indication at the time of writing this chapter. Figure 7.2 provides an algorithm on how to include Tc-99m-MIBI scintigraphy in the evaluation of cold thyroid nodules [81]. SPECT gave incremental diagnostic information in about 34% of examinations.
Fig. 7.2 Algorithm for management of cold/hypofunctioning thyroid nodule (reproduction with permission from Lehmanns Media [81])