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Thyroid. 2016 Aug;26(8):1101-9. doi: 10.1089/thy.2016.0135. Epub 2016 Jul 8.

(99m)Tc-Methoxy-Isobutyl-Isonitrile Scintigraphy Is a Useful Tool for Assessing the Risk of Malignancy in Thyroid Nodules with Indeterminate Fine-Needle Cytology.

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1 Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Nuclear Medicine Unit, University of Messina , Messina, Italy .
2 Nuclear Medicine and PET/CT Centre, Oncology Institute of Southern Switzerland , Bellinzona, Switzerland .
3 Department of Economical, Business, and Environmental Sciences, and Quantitative Methods, University of Messina , Messina, Italy .
4 Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Messina , Messina, Italy .



Thyroid nodular disease is a very common clinical problem. The diagnostic algorithm includes laboratory tests, thyroid ultrasound (US), thyroid scintigraphy, and, if necessary, US-guided fine-needle aspiration cytology. However, cytology results are reported as indeterminate in a not negligible number of patients. This is a central problem in the workup of patients, since about 55-85% of those undergoing surgery do not have thyroid cancer at final histology diagnosis. The aim of this study was to evaluate prospectively the role of (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) thyroid scintigraphy in differentiating malignant from benign thyroid nodules with indeterminate cytology using quantitative analysis.


One hundred five patients affected by nodular thyroid goiter and with a euthyroid or hypothyroid functional status were prospectively evaluated. All patients had a suspicious nodule ≥15 mm in maximal diameter on US. All nodules were "cold" on (99m)Tc-pertechnetate scintigraphy and had a cytological diagnosis of class III or IV according to the Bethesda system. Planar images of the thyroid were acquired 10 and 60 minutes after (99m)Tc-MIBI administration. All cold nodules were MIBI-positive. Using quantitative analysis, the MIBI washout index (WOind) was calculated as a percentage reduction value of mean MIBI nodular uptake between early (+10 minutes) and late (+60 minutes) scans.


Subdividing the patients into positive and negative for malignancy (either including or excluding patients with Hürthle cell adenoma) and performing receiver operating characterist curve analysis, the optimal WOind cutoff in differentiating malignant from benign follicular lesions was set at -19%. The overall sensitivity and specificity of (99m)Tc-MIBI quantitative analysis in identifying patients with malignant lesions was 100% and 90.9%, respectively. However, after excluding patients with Hürthle cell adenomas from the negative patient group, the overall sensitivity and specificity both reached 100%.


The use of MIBI scintigraphy using quantitative analysis in the workup of cold nodules with indeterminate cytology is suggested in order to stratify patient risk for a malignant lesion better, thus reducing the number of patients referred to surgery. Surgical treatment should be planned in those patients with a WOind up to -19%.

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