Endocrine Journal 2013, 60 (8), 985-990
Original
Factors associated with fluorine-18-fluorodeoxyglucose uptake in benign thyroid nodules Kenji Ohba1), 2), Shigekazu Sasaki1), Yutaka Oki1), Sadahiko Nishizawa3), Akio Matsushita1), Atsuto Yoshino2), Takafumi Suda1) and Hirotoshi Nakamura1), 4) 1)
Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan Department of Emergency Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan 3) Hamamatsu Medical Imaging Center, Hamamatsu Medical Photonics Foundation, Hamamatsu 434-0041, Japan 4) Department of Internal Medicine, Kuma Hospital, Kobe 650-0011, Japan 2)
Abstract. Thyroid nodules that exhibit focal uptake of fluorine-18 (18F)-fluorodeoxyglucose (FDG) are relatively frequent. Although the clinical features and associated mechanisms of FDG-avid lesions in both thyroid cancer and cytologically indeterminate nodules have been extensively studied, not much information is available on benign nodules. Therefore, in this retrospective study, the clinical, serological, and sonographic features of 15 benign FDG-avid nodules were compared with those of 17 non-avid lesions. Univariate analysis indicated that the FDG-positive and -negative nodules were similar with regard to age, gender, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, tumor size, 4 B-mode sonographic findings (i.e., shape, margin, texture, and echo level), and/or elasticity. The presence of intranodular blood flow and the absence of a cystic component were associated with a greater possibility of positive FDG uptake. Multivariate analysis showed that vascularity was the only independent factor predicting FDG uptake. Across a wide range of tumor types, the extent of FDG uptake is positively correlated with tumor perfusion; this observation is consistent with the results of this study, which shows that FDG uptake in benign thyroid nodules is associated with increased vascularity. Key words: 18F-FDG, PET, Ultrasound, Benign thyroid nodule, Intranodular vascularity
IN CURRENT clinical practices, fluorine-18 (18F)-fluorodeoxyglucose (FDG) is the most widely used positron emission tomography (PET) tracer. Because 18FFDG-PET is now commonly used for evaluation, the number of thyroid disorders detected using this imaging modality is increasing. Based on the accumulation pattern of the thyroid disorder, FDG uptake is classified as focal or diffuse. Focal FDG uptake is relatively frequent, occurring in approximately 1% patients that are referred for a PET examination [1]. Systematic reviews of thyroid lesions with focal FDG uptake have reported 33.2% –34.8%, 62.1% –62.7%, and 2.5% – 4.7% for malignant, benign, and indeterminate lesions, respectively [2 – 4]. Although the clinical features and associated mechanisms for thyroid cancer [5 – 9] and thyroid nodules with indeterminate cytology [10 – 13] Submitted Apr. 12, 2013; Accepted May 8, 2013 as EJ13-0155 Released online in J-STAGE as advance publication May 24, 2013
Correspondence to: Kenji Ohba, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. E-mail:
[email protected] ©The Japan Endocrine Society
have been extensively studied, not much information is available about such findings for benign lesions [14]. Here, clinical, serological, and sonographic features of benign thyroid nodules with FDG uptake were retrospectively reviewed and compared with those without FDG uptake.
Patients and Methods Patients From May 2007 to May 2012, 37 patients underwent ultrasound (US) and other evaluations at the Division of Endocrinology and Metabolism, Hamamatsu University School of Medicine, for suspected nodules identified through whole-body cancer screening or staging using 18F-FDG-PET/computed tomography (CT) or combined 18F-FDG–PET and CT. Forty-eight consecutive thyroid lesions were evaluated, among them, 29 nodules with FDG uptake were aspirated using US-guided fine needle aspiration biopsy (FNAB); the results showed that 10 were malignant, 4 indeter-
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minate, and 15 had benign cytology. Regarding the remaining 19 nodules showing non-avid FDG uptake, 2 nodules were excluded because they were located in a lobe with an FDG-avid lesion. Among the 17 nodules with non-avid FDG uptake, based on the FNAB in 11 nodules and the lack of suspicious sonographic findings of malignancy, such as micro-calcifications and/or intranodular hypervascularity [15] in 6 nodules, a diagnosis of benign lesions was made. Finally, the clinical, serological, and sonographic features of the 15 benign nodules with FDG uptake were retrospectively reviewed and compared with the 17 benign nodules without FDG uptake. The institutional review board approved this study, and neither informed consent nor patient approval was required for retrospective review of images and records (No. 24-126). Methods Combined 18F-FDG-PET and whole-body CT were performed at Hamamatsu Medical Imaging Center. 18 F-FDG-PET/CT was performed at Seirei Hamamatsu Hospital and Hamamatsu University School of Medicine. The protocol for 18F-FDG-PET has been described previously [16]. Focal uptake was visually categorized as positive by radiologists if the uptake was determined to be higher than that of the normal thyroid background. The standardized uptake value (SUV) was calculated as follows: SUV = FDG region / (FDG dose / WT), where the FDG region is the decay-corrected regional FDG concentration in Bq/mL, the FDG dose is the injected FDG in Bq, and WT is the body weight in grams. Maximum SUV (SUVmax) was defined as the SUV derived from the single voxel showing the highest uptake within a defined region of interest. The serum thyroid stimulating hormone (TSH) concentrations were measured with the Elecsys platform (Roche Diagnostics K.K., Tokyo, Japan) and anti-thyroglobulin antibodies (TgAb) were measured with a commercial radioimmunoassay kit (Cosmic Co., Tokyo, Japan). Reference ranges used were as follows: TSH 0.5-5.0 μIU/mL and TgAb 20% cystic content were scored as C [20]. US-guided FNAB was performed using a 22-G needle and a 10-mL syringe and 2 passes were made per nodule. Pathologists examined samples obtained using FNAB. Statistical analysis Data were expressed as either as mean ± standard deviation (SD), numbers, or percentages. Differences between FDG-uptake-positive and FDG-uptakenegative groups were evaluated using unpaired t-test for continuous variables and Fisher’s exact test or Mann–Whitney test for categorical variables. For FDG uptake, logistic regression analyses were performed to detect predictors with odds ratio before (univariate) and after (multivariate) adjustment with variables. All variables with a p-value
