ORIGINAL 

Annals of Nuclear Medicine Vol. 3, No. 1, 31-36, 1989 

Thyroid carcinoma in solitary hot thyroid lesions on Tc-99m sodium pertechnetate scans 

Katsuji IKEKUBO,* Megumu HINO,* Hidetomi ITO,* Masami OTANI,* Haruji YAMAGUCHI,* Yasuhiko SAIKI,* Kazuyo UI,* Yoko HABUCHI,* Takashi ISHIHARA** and Toru MORI*** 

*Department of Nuclear Medicine, **Department of Internal Medicine, Kobe City General Hospital, Kobe 650, Japan ***Department of Internal Medicine, Kyoto University School of Medicine, Kyoto 606, Japan 

Sixteen patients with nonsuppressible solitary hot thyroid lesions (SHTL) identified on T3 suppression images using Tc-99m sodium pertechnetate were studied over a period of 5 years. Of the 16 patients, 7 (44%) had papillary adenocarcinoma (PAC) and 9 (56%) had follicular adenoma (FA). Of the 7 patients with PAC, 3 were toxic and 4 nontoxic. Of the 9 patients with FA, 2 were toxic and 7 nontoxic. The Tl-201 chloride thyroid scans were useful in locating SHTL and revealing extranodular thyroid tissue. The echography was sensitive to visualization of the nodule structures. However, there were no significant differences between the clinical findings, radionuclide images, and echograms between for PAC and FA. All patients with PAC were treated by partial thyroidectomy and there were neither regional nor distant metastasis in any of them. In conclusion, our study provided the following extremely interesting result: SHTL in the present series have a higher incidence of malignancy than previously reported autonomously functioning thyroid lesions (AFTL). Histological examination is necessary for the diagnosis and management of SHTL and surgical treatment should be considered. 
Key words: Solitary hot thyroid lesions, Tc-99m sodium pertechnetate, Papillary adenocarcinoma, Histological examination 

INTRODUCTION 

THYROID SCINTIGRAPHY is an excellent method of evaluating regional functions of thyroid tissue. We1 have routinely undertaken thyroid scans with Tc-99m sodium pertechnetate (Tc-99m) and Tl-201 chloride (Tl-201) for the evaluation of thyroid nodules. 
 From 1981 to 1987 we performed 3486 Tc-99m thyroid scans and found 22 patients with hot or warm nodules. Sixteen patients (0.46%) had undergone histologically examination of their solitary hot thyroid lesions (SHTL) which were nonsuppressible according to T3 suppression images. For the diagnosis and management of these patients with SHTL, we performed scintigraphic and echographic evaluations and analyses of clinical and pathological findings. 

 Received May 25, 1988; revision accounted August 11, 1988.
 For reprints contact: Katsuji Ikekubo, Department of Nuclear Medicine. Kobe City General Hospital, 4-6, Nakamachi, Minatojima, Chuo-ku, Kobe, 650, JAPAN. 

 The following is a detailed report of our surprising results: the incidence of carcinoma (44%) in hot nodules was considerably higher than reported in previous studies2-11 on AFTL or hot nodules on radioiodine scans. 

MATERIALS AND METHODS 

Twenty two patients had hot or warm nodules corresponding to palpable nodules on Tc-99m thyroid scans. One of them had toxic multinodular goiter and the other 21 patients had single nodules. For the 16 patients with solitary nodules, we performed clinical evaluations with radionuclide thyroid scans, ultrasonography (US) and blood chemistry, and histological examination of nodules. 
 Tc-99m thyroid uptake and images with Tc-99m or Tl-201 were obtained with an Ohio Nuclear Sigma 410 gamma camera equipped with a converging collimator. Thyroid scan and uptake were performed 30 minutes after an intravenous administration of 2 mCi of Tc-99m sodium pertechnetate (Tc-99m) as previously reported.12 Briefly, patients were laid in a supine position. A gamma camera was set at 10 cm from the anterior surface of the neck. The counts were accumulated in DEC PDP 11/34 for 2 minutes and the uptake rate was calculated by the previously described formula.12 Tc-99m thyroid uptake in normal subjects was determined to be in the range of 0.4-2.5%. The suppression images and uptake rates were obtained after administration of L-T3 (75 ug a day for 7 days). In cases in which the uptake was reduced to less than 50 percent of the initial value and less than 1% after T3, the suppression test results were interpreted as positive. Tl-201 chloride (Tl-201) imaging was performed 20 minutes after an intravenous administration of 2 mCi of the tracer. 
 The US was performed with a high resolution realtime linear scanner, Yokogawa RT 2800, with a 7.5 megahertz transducer. 
 Serum thyroid hormones and TSH were measured with commercially available radioassay kits. Serum thyroglobulin (Tg) was measured with a doubleantibody RIA kit (Eiken Co. Tokyo). As positive Anti-Tg autoantibodies cause incorrect assay results in the Tg assay, anti-Tg antibodies were determined initially and antibody-positive serum was rejected for measurement of Tg. The TSH receptor antibody (TRAb) was measured with a TRAb kit (R.S.R. Ltd., U.K.). 
 Histological diagnosis of the nodules was based on microscopic findings for the tissue obtained by needle biopsy using a Vim-Silverman needle or operation. 
 In the present study a hyperactive focal area with complete suppression of extranodular tissue was depicted as a "hot" nodule and a "warm" nodule indicated a relatively more hyperactive area with persistent extra nodular thyroid tissue activity. 
 The patients were diagnosed as toxic or nontoxic on the basis of the usual clinical and laboratory criteria for hyperthyroidism. In some cases, a TRH test was performed to determine the thyroid status. 

RESULTS 

Clinical data for 16 patients with SHTL are shown in Table 1. Of the 16 patients, 9 had follicular adenoma (FA) and 7 had papillary adenocarcinoma (PAC). 
 All 9 patients with FA were female whose average age was 51 years. The size of the nodules ranged from 0.5 cm to 4.5 cm, with an average of 2.5 cm in diameter. Of the 7 patients with PAC, 5 were female and 2 were male. Their mean age was 51 years. The size of the nodules ranged from 1.6 cm to 5.0 cm with a mean of 3.5 cm. 
 Two patients with FA and 3 with PAC showed mild hyperthyroidism. None of the hyperthyroid patients showed TSH response to TRH. TRAb was not detected in any of the 16 patients. Serum Tg concentrations were increased in 14 of 15 patients. 
 None of the 16 patients had either exophthalmos or cardiac complications. 
 The results of thyroid uptake and T3 suppression tests with Tc-99m and the radionuclide scintigraphy and echography findings are shown in Table 2. The thyroid uptake in patients with FA ranged from 0.2 to 7.9% (mean+-SD: 1.9+-2.5%) and from 0.4 to 7.5% (mean+-SD: 2.6+-2.8%) for patients with PAC. The mean thyroid uptake was 2.0% in toxic patients and 2.3% in nontoxic patients. 
 Out of 9 FA patients, 7 tested negatively for T3 suppression while 4 of the 7 PAC patients had negative suppression test results. 
 In all 16 patients warm or hot nodules were revealed on Tc-99m thyroid scans. The I-123 thyroid scans were also performed on 3 patients (Pt. 6, 9, 16). These images showed warm lesions similar to those on the Tc-99m scans. 
 Twelve patients showed focal accumulation of Tl-201 corresponding to a hot or warm nodule on a Tc-99m scan. One patient (Pt. 15) showed a large defect on the Tl-201 image that was identified by US as being a large cyst. 
 The US revealed that 9 out of 16 nodules developed into a cystic formation. 
 Of 9 patients with FA, 3 underwent surgical removal of the nodule, while the remaining 6 patients continued to be under observation. All patients with PAC were treated by partial thyroidectomy and neither regional nor distant metastases were detected in the PAC patients. All 5 toxic patients became euthyroid after undergoing partial thyroidectomies. 
 Serum Tg was measured about one month after the partial thyroidectomies performed on the 7 patients with PAC and 1 patient with FA. A marked reduction of serum Tg was observed in all cases. 
 The various cases are shown in Figs. 1-4. 
 Figure 1 shows Tc-99m and Tl-201 images in a FA patient (patient 1). The Tl-201 scan demonstrated not only an abnormal accumulation of the tracer corresponding to the hot nodule on the Tc-99m scan, but also a substernal extending tumor and both normal lobes that were nonvisualized on the Tc-99m scan. Surgical removal of the tumors was performed. There was no histological difference between the hot nodule and the substernal extending tumor. 
 Figure 2 shows Tc-99m and Tl-201 images in a PAC patient (patient 13). The Tc-99m scan shows a large hot left nodule with nonvisualization of the right lobe. The Tl-201 scan shows increased radioactivity in the left lobe and visualizes a small right lobe. 
 Figure 3 shows Tc-99m thyroid images before and after T3 administration and ultrasonogram in a FA patient (patient 6). The warm left nodule was not suppressed after T3. Ultrasonograms indicate a nodule with a cyst. 
 Figure 4 shows also T3 suppression images in a PAC patient (patient 16). The warm left nodule is not suppressed by T3. The ultrasonogram shows a large solid nodule. 

DISCUSSION 

The thyroid imaging with Tc-99m is considered to be simple, easily performed, and a useful routine diagnostic tool for the evaluation of the regional functions of thyroid nodules. It has been reported that hot nodules are almost always benign and that malignant AFTL are exceedingly uncommon. The most interesting piece of evidence in the present study is that the incidence of carcinoma in SHTL was considerably higher at 7/16 (44%) than in previous reports2-11 concerning carcinoma in AFTL. 
 From discrepancies between Tc-99m and radioiodine images which have been reported,13-16 one can see that the SHTL in the present study are not identical to AFTL which were confirmed by radioiodine scan. Although we did not have an opportunity to perform radioiodine scans on all of the carcinoma patients, three cases that also had warm lesions on radioiodine scans and five toxic cases that became euthyroid after surgical removal of the nodules were considered to be AFTL. That is, 4 of 7 PAC patients were considered to have AFTL. We don't know the exact reason for the high incidence of carcinoma in our small series studied by Tc-99m scans. An earlier article15 reported that the sensitivity of Tc-99m in detecting lesions was higher than that of I-123 scanning, and in the majority of cases the discrepancy was due to the fact that hot or warm lesions shown on the Tc-99m scan were cold or nonvisualized on the I-123 scan. Our study suggests that more hot lesions in carcinoma were detected on Tc-99m scans than on I-123 scans. 
 Another interesting finding is that neither regional nor distant metastases were found in the 7 carcinomas. It is conceivable that the cancer in SHTL in our study grows slowly. These thyroid tumors are considered to have the capacity to trap Tc-99m pertechnetate, independent of pituitary stimulation. The T3 suppression image is useful in differentiating the tumors from TSH depending hyperplastic nodules. 
 Although the Tc-99m uptake of the nodules was not suppressed, some of those tested positively for T3 suppression. As a significantly decreased uptake in extranodular tissue after T3 in a small warm nodule might result in positive T3 suppression, it is useful to compare the Tc-99m uptake of nodules before and after T3 when evaluating the function of the nodules. 
 Since Tl-201 images are also very useful in visualizing both the tumor itself and the remaining thyroid tissue, TSH stimulation is not always necessary to confirm TSH dependent thyroid tissue. In case 1, a Tl-201 image visualized both hot and nonvisualized tumor lesions on the Tc-99m scan. 
 It is certain that the US is a very important procedure for examination of the structure of a nodule but we could not differentiate carcinoma from benign tumors with a scan, US or any other clinical findings; therefore, it is very important to perform a histological examination. 
 Our results indicate that histological or cellular examination by needle or fine needle aspiration biopsy together with Tc-99m and Tl-201 scans is necessary for the diagnosis and management of SHTL. 

ACKNOWLEDGEMENT 

The Authors wish to thank Ms. J.A. Colburn for her help in the preparation of the manuscript. This work is supported in part by a grant from the Grant-in-Aid for Medical Research of Kobe City General Hospital. 

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