IJNM, 21(3): 50-55, 2006 Original Article Thyroid Ectopia in Hyperthyroidism Aban M. Samuel Nuclear Medicine, Mandakini Nuclear Imaging Centre, Mumbai Aims: Analyse the frequency and sites of ectopic thyroid tissue detected during scintimaging of the hyperthyroid gland. Materials and methods: 190 consecutive scintimages of hyperthyroid glands were analysed. Dynamic flow and perfusion studies, Technetium-99m pertechnetate (Tc-99m04 - ) thyroid uptake and static images were obtained in the anterior RAO and LAO views along with a marker view to establish landmarks at the sternal notch and any palpable nodules. Results: Hyperthyroid glands showed Tc-99m04 - uptake values ranging from 3% to over 30%. 87% of the glands were diffuse goiters while the remaining were due to Plummers disease or autonomous hot nodules. The size of the glands showed a mild to moderate enlargement with the longest length of the lobes being 5-7 cms. Ectopic tissue in the form of pyramidal lobe, thyroglossal tract, lingual, sublingual or substernal sites were noted. 44% of patients with elevated thyroid uptakes and a diffuse enlargement of the gland showed the presence of ectopic thyroid tissues. Of these, single ectopic sites was present in 78% of cases while the remaining showed dual and one case triple site of ectopia. There was no correlation of the presence of ectopia with size of gland enlargement, %thyroid uptake, clinical severity of the hyperthyroidism or the presence of antimicrosomal or antithyroglobulin antibodies. No thyroid stimulating immunoglobulin assays were done in our patients, however reports strongly suggest the association of detection of ectopic tissue with the presence of thyroid stimulating immunoglobulins in Graves disease and hyperthyroidism. Conclusions: It is therefore proposed that in the case of unavailability of assays for thyroid stimulating thyroid antibodies in Graves disease the detection of ectopic tissue can be used as a marker for Graves disease. Key words: Thyroid scintimaging, hyperthyroidism, ectopic thyroid tissue. Acknowledgements: The author wishes to thank Dr. A. L. Parihar for permitting access to the data from Mandakini Nuclear imaging center. Also thanks goes to the dedicated technicians and the administrative staff of the centre. Introduction Correspondence to: A. M. Samuel Nuclear Medicine Consultant Mandakini Imaging Center, Mumbai-400 077 Phone: 2506 6589, 2506 6590 Email:ams1940@hotmail.com Thyroid scintigrams performed in hyperthyroid patients have often shown the appearance of thyroid gland vestiges, namely a pyramidal lobe or a thyroglossal duct. The detection of these vestiges in patients with hyperthyroidism is indicative of autoimmune hyperthyroidism. In Graves disease, stimulating thyrotropin (TSH) receptor antibodies cause a significantly more frequent appearance of vestiges of the thyroglossal tract. (1). 50
Indian Journal of Nuclear Medicine, Vol. 21, No. 3, September, 2006 In contrast, disseminated autonomously functioning thyroid nodules rarely show a pyramidal lobe. The frequency of pyramidal lobe visualization in patients with Graves disease differs significantly from patients with multifocal or disseminated autonomously functioning nodules. In euthyroid patients, the detection of thyroid vestiges may be a reflection of iodine deficiency with or without latent primary hypothyroidism. I-123 is better in delineating thyroid vestiges than Tc-99m pertechnetate (Tc-99mO 4- ). In this study these vestiges were detected during thyroid scintigraphy using Tc-99m04 - in hyperthyroid patients and the data was analysed to assess the frequency and distribution of ectopia associated with hyperthyroidism accompanying Graves disease. Material and methods 190 consecutive scans of hyperthyroid patients were reviewed. Routine planar thyroid scintigraphy was performed on a single head Elscint SPX4 gamma camera using LEAP collimator. Dynamic study was first acquired at 1 second a frame for 120 seconds. Delayed static images were obtained 20 minutes later in the anterior and right and left anterior oblique views. Thyroid uptake values were obtained with the software provided by the manufacturer using the data from the dynamic acquisition and the syringe counts before and after injection. Uptake values were expressed as % thyroid uptake of the injected dose. Normal values in our patients ranged from 0.2-3 % of the injected dose of Tc- 99m04 -. Values above 3% were considered as hyperthyroid. (2,3) Gland size was measured along its longest distance in cms. Gland size 3-5cms was considered as mild enlargement, 5-7 cms as moderate and more than 7cms as large gland. Ectopic thyroid tissue was identified as pyramidal tissue arising from the right, left lobes or the isthmus of the thyroid gland. Thyroglossal tract and tissue seen in the midline at the level of the cricoid and the sublingual or lingual above the hyoid cartilage. Results Tables 1 to 6 show the analysis of the data: 1. The majority of the patients had a moderate diffuse enlargement of the gland. A lesser number were toxic multinodular or autonomous hot nodules. 2. The incidence of solitary cold nodules in our data was 8%. 3. The uptake value varied from 3 to more than 30%. There was no correlation of the uptake values with the size of the gland. 4. Triple ectopia 1 case. 5. Total cases with ectopia were 73 that is 44% of diffuse hyperthyroid goiters had evidence of thyroid ectopia. 6. No ectopia was present in the cases of multinodular toxic goiters or those with autonomous hot nodules. In our data 4 cases of ectopia with a normal gland and normal thyroid uptake of Tc04 was detected in 100 cases analysed. Table 1: Distribution of patients with hyperthyroidism undergoing Tc-99m04 - Thyroid scanning Incidence of hyperthyroidism Total cases % of cases Total cases scanned 190 100 Diffuse hyperthyroid 166 87 Plummers disease 16 8.4 Autonomous hot nodule 8 4.2 Table 2: Scan findings in Hyperthyroidism Enlargement of the gland Number of cases Percentage of cases Mild 57 34 Moderate 95 57 Large 6 3.6 51
Aban M. Samuel et al Table 3: Scan findings Distribution of tracer Number of patients Percentage % Diffuse tracer distribution 158 90 Cold nodules 13 8 Hot nodules 3 2 Table 4: Uptake values of Tc-99m04 - pertechnatate Uptake of Tco4 at 20 minutes postinjection Number of cases Percentage% 3-5% 34 20.5 5-15 89 53 15-30 26 16 >30 18 11 Table 5: Sites of single ectopia Sites of ectopia Number thyroglossal 20 sublingual 6 substernal 4 pyramidal right 8 left 16 isthmus 3 Total cases 57 Table 6: Sites of dual ectopia Sites of ectopia Number of cases Thyroglossal and pyramidal 6 Thyroglosssal and substernal 4 Pyramidal and sublingual 3 Pyramidal and substernal 5 52
Indian Journal of Nuclear Medicine, Vol. 21, No. 3, September, 2006 Figure 1: A pyramidal lobe and a substernal concentration below the right lobe of the thyroid. Both these tissues are visualized in the dynamic images along with the thyroid gland. Figure 2: Patient with hyperthyroidism showing a long thyroglassal tract becoming into a pyramidal lobe and a faint lingual thyroid. 53
Aban M. Samuel et al Discussion Ectopic thyroid tissue is the result of abnormal migration of the gland as it travels from the floor of the primitive foregut to its destined pretracheal position. The prevalence of ectopic thyroid tissue ranges between 7%-10%. Patients with ectopic thyroid tissue are usually euthyroid, but can present with signs and symptoms of upper aerodigestive tract obstruction. In one case report ectopic mediastinal thyroid tissue was removed surgically because of substernal chest pain. It recurred 9 years later when the patient developed Graves disease. The authors proposed that the recurrence of the ectopic thyroid tissue was due to the influence of thyroid stimulating immunoglobulin (4,5) Radionuclide thyroid imaging in patients with hyperthyroidism showed 84% were found to have diffuse toxic hyperplasia (Graves disease), while 12% had autonomously functioning nodules (Plummer s disease), 3% had Graves disease developing in a multinodular gland, and in the remaining 1%, either a clear diagnosis could not be established or the thyrotoxicosis was due to thyroiditis or the Jod-Basedow phenomenon. (4) It was found that a thyroid scan seldom provides additional diagnostic information in patients with Graves disease when a diffuse goitre is present. However, if patients are to be treated with radioiodine (I-131), thyroid imaging with tracer quantitation can replace a 24-h I-131 uptake measurement, this having the advantages that the patients are required to attend only once, and that the gland size can be measured. In addition, visual confirmation of tracer uptake by the thyroid is obtained and patients with thyroiditis will not receive inappropriate therapy. When single or multiple thyroid nodules are palpated, a thyroid scan is crucial in establishing an accurate diagnosis, as it is not otherwise possible to differentiate between Plummer s disease and Graves disease developing in a multinodular gland. Indeed, (32%) with single autonomously functioning nodules, the initial clinical assessment had been incorrect.(6) In our study which was done on patients reporting with hyperthyroidism for the reasons stated above we found 90% were diffuse goiters while the remaining were toxic multinodular or autonomous hot nodules. 8 % of patients had a cold nodule which is higher than that reported. In another report gamma camera pertechnetate and radioiodine thyroid scans were reviewed to determine the incidence of recognition of a pyramidal lobe. Ten to 17% of normals and of patients with various thyroid disease states had a pyramidal lobe on their scans. However, in patients with diffuse toxic goiter, 43% had a pyramidal lobe on the thyroid images. There appears to be a correlation between elevated thyroid function studies (likely in thyroid mass) and the incidence of a pyramidal lobe on thyroid scans in diffuse toxic goiter. (7) In yet another report there were 12 instances of pyramidal lobes in the hyperthyroid men (12 of 26 = 46%) and 24 cases in women (24 of 74 = 32%). The site of origin of the pyramidal lobe was from the left in 17, from right in 16, and from the midline in 3 cases. During the period of review of all thyroid images, only one other case of a pyramidal lobe was found (a case of multinodular goiter).(8). In a case report of a 49-year-old man with a clinical diagnosis of Graves diseases. Tc-99m04 - scan revealed a diffuse toxic goiter and radiotracer concentration in the thyroglossal duct. He was given 10 mci of I-131 orally as treatment of thyrotoxicosis. Repeat scanning of the anterior neck 2 days later revealed concentration of radioiodine in the diffusely enlarged gland and the thyroglossal duct as found on the Tc-99m pertechnetate scan, thus confirming the presence of functioning thyroid tissue in the thyroglossal duct. (9). In our study we have observed that thyroid ectopia in diffuse toxic Graves disease had an incidence of 44%. No ectopia was associated with other forms of hyperthyroidism. This suggests that the presence of thyroid stimulating antibodies not only stimulate the thyroid gland per se but also the vestiges. This phenomenon is peculiar to Graves disease and could be a hallmark of Graves pathogenesis and the presence of thyroid stimulating immunoglobulins. In Graves disease, stimulating TSH receptor antibodies cause a significantly more frequent appearance of vestiges of the thyroglossal tract. (1). Reports in literature have all described the presence of the pyramidal lobe accompanying the hyperthyroid state of Graves disease. In our observations there was a significant number of cases who showed not only pyramidal lobe but thyroglossal tract, lingual, sublingual and substernal uptake of Tc-99m04 - in these vestiges also. In fact two and in one patient three sites of ectopia was seen. There was no correlation of the site and number of the ectopia with the thyroid uptake values, the clinical severity of the disease the size of the goiter or the presence of antimicrosomal and /or anti thyroglobulin antibodies. We have not evaluated thyroid stimulating immunoglobulins (TSI) in our patients. However survey of literature has established a strong association of TSI with the stimulation of thyroid vestiges. (1,4,5) It is felt that the detection of ectopic tissue in hyperthyroid patients could be used as a surrogate marker for Graves disease in the absence of available tests for measuring TSI. References 1. Wahl R, Muh U, Kallee E.: Hyperthyroidism with or without pyramidal lobe Graves disease or disseminated autonomously functioning thyroid tissue?. Clin Nucl Med. 1997 Jul;22(7):451-8. 54
Indian Journal of Nuclear Medicine, Vol. 21, No. 3, September, 2006 2. Celso Darío Ramos Denise Engelbrecht Zantut Wittmann Elba Cristina Sá de Camargo Etchebehere Marcos Antonio Tambascia Cleide Aparecida Moreira Silva Edwaldo Eduardo Camargo Thyroid uptake and scintigraphy using 99m Tc pertechnetate: standardization in normal individuals Sao Paulo Med. J. vol.120 no.2 São Paulo Mar. 2002 3. Egberto Gaspar de Moura: What need is there for standardization of thyroid uptake or scintigraphy using 99m Tc pertechnetate in thyroid disease diagnosis?. Sao Paulo Med. J. vol.120 no.2 São Paulo Mar. 2002 4. Basaria S, Cooper DS Graves disease and recurrent ectopic thyroid tissue. Thyroid. 1999 12:1261-4. 5. Braga-Basaria M, Liu A, Nicol TL, Basaria S.: Images in thyroidology. Graves disease unmasking ectopic thyroid tissue. Thyroid. 2004 ;14:83-4 6 Fogelman I, Cooke SG, Maisey MN. The role of thyroid scanning in hyperthyroidism.eur J Nucl Med. 1986;11:397-400. 7. Levy HA, Sziklas JJ, Rosenberg RJ, Spencer RP.: Incidence of a pyramidal lobe on thyroid scans Clin Nucl Med. 1982 7:560-1. 8. Spencer RP, Scholl RJ, Erbay N. Tc-99m pertechnetate thyroid images in hyperthyroidism. Size, distribution, and presence of a pyramidal lobe. Clin Nucl Med. 1997 8:519-22. 9 Rao PN, Pandit N, Kumar R, Upadhya IV, Vidya Sagar MS: Ectopic functioning thyroid tissue in the thyroglossal duct detected by radionuclide imaging. Clin Nucl Med. 2005 30:630-631. 55