Diffuse thyroid uptake in chronic thyroiditis can be attributed to increased FDG uptake in activated lymphoid tissue [34]. 3B —37-year-old man with papillary thyroid carcinoma who underwent FDG PET/CT study after thyroidectomy and radioiodine ablation. The significance of incidental diffuse and focal thyroid FDG uptake is discussed. Fine-needle aspiration cytology of lesions confirmed diagnosis. Fig. In a systematic review performed by Shie et al. Fig. Treglia et al. Incidental FDG uptake within the thyroid gland has been reported in 1–4% of patients undergoing FDG PET or PET/CT for other reasons and can be characterized as focal or diffuse uptake [29, 30]. D, Anterior maximum intensity projection (A), axial contrast-enhanced CT (left, B–D), and fused PET/CT (right, B–D) images show FDG-avid metastatic lesions (arrows, B–D) in right lung (B), right acetabulum (C), and T10 vertebra (D). Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). Evaluation of Tumor Microvascular Response to Brivanib by Dynamic Contrast-Enhanced 7-T MRI in an Orthotopic Xenograft Model of Hepatocellular Carcinoma, Review. It is therefore often the first diagnostic choice for evaluating thyroid nodules [22]. A, FDG PET/CT anterior (left, A) and posterior (right, A) views, anterior maximum intensity projection (B), axial PET (C), and fused axial PET/CT (D) images show hypermetabolic lobulated 8-mm pulmonary nodule (arrows, B–D) typical for metastasis. Acta Med Austriaca. Dong et al. Fig. Karantanis et al. PET with 124I can provide specific dosimetric information, allows quantification of the volume of the thyroid tumor, and can be used as a surrogate marker before therapeutic intervention with 131I. Uptake of 123I in thyroid was 8.1% at 4 hours and 9.6% at 25 hours (normal range, 12–34% at 24 hours). ATC occurs in older age groups and is marked by rapid growth and extensive local invasion. [78] report that patients with SUV greater than 18 on FDG PET/CT had significantly worse 6-month survival rates than did those with SUV less than 18 (20% vs 80%), as did patients with FDG uptake volume greater than 300 mL compared with patients with FDG uptake volume less than 300 mL (10% vs 90%). Ultrasound combined with CT had higher sensitivity than did CT alone for detecting nodal metastases in levels II–V (95.9% vs 81.7%; n = 53; p = 0.025); however, CT had greater sensitivity than ultrasound for level VI nodal metastasis (66.7% vs 53.2%; p = 0.04) [27] because of the limitations of ultrasound in evaluating this compartment with the thyroid gland in place. However, especially in … She had rapid progression of disease, ending in death 3 months after study. medullary thyroid cancer) or tumors called pheochromocytomas, it is important to tell ... Computed tomography (CT) scan ... Positron emission tomography (PET) scan A PET scan8 can be very useful if your thyroid cancer is one that doesn’t take up radioactive iodine. C, Anterior maximum intensity projection (A), axial contrast-enhanced CT (left, B–D), and fused PET/CT (right, B–D) images show FDG-avid metastatic lesions (arrows, B–D) in right lung (B), right acetabulum (C), and T10 vertebra (D). When MTCs [medullary thyroid cancers] are not highly FDG [fluorodeoxyglucose] avid, and because they are neuroendocrine tumors with somatostatin receptors, you can do a gallium dotatate PET/CT as a more useful nuclear medicine imaging, and that can be helpful, particularly in finding tiny bone metastases. Treglia et al. Furthermore, because dedifferentiated thyroid carcinoma cells can have a reduced capacity to produce and secrete thyroglobulin, a low thyroglobulin level is not necessarily an indication of a small tumor burden in patients with a negative 131I scan and a measurable thyroglobulin level. Several studies have found a definite correlation between the thyroglobulin levels and the diagnostic accuracy of PET in these patients. 7A —52-year-old woman with thyroid mass confirmed as medullary carcinoma by fine-needle aspiration who underwent FDG PET/CT staging. She underwent total thyroidectomy, radioiodine ablation, neck dissection, and local radiotherapy for recurrence. Address correspondence to R. M. Subramaniam (, PET/CT in the Management of Thyroid Cancers, Original Article. About 50% of patients with ATC have a history of multi-nodular goiter, and about 20% have a history of DTC. MTC occurs in sporadic or hereditary form, the latter being part of type 2 multiple endocrine neoplasia (MEN2) syndromes. [33] found that 1.8% (46/2594) of patients with diffuse thyroid uptake on FDG PET/CT had chronic lymphocytic thyroiditis on the basis of thyroid function tests or ultrasound. 6D —74-year-old woman with Hürthle cell carcinoma who presented with increasing thyroglobulin levels and negative 131I whole-body scan after thyroidectomy. The advantages of MRI over CT include excellent tissue contrast and lack of radiation exposure. 10A —65-year-old woman with metastatic anaplastic thyroid carcinoma who underwent FDG PET/CT study after chemoradiation. Metastasis localization is also improved with use of 124I-PET/CT compared with conventional imaging. Fig. She underwent total thyroidectomy, radioiodine ablation, neck dissection, and local radiotherapy for recurrence. However, the previously mentioned retrospective study by Treglia et al. Fig. In these patients, the diagnosis of medullary thyroid cancer is usually discovered by the symptom of a lump in the neck. 1A —23-year-old woman with melanoma of right shoulder who underwent restaging FDG PET/CT study after resection and adjuvant chemotherapy. F-DOPA and somatostatin analogs labeled with 68Ga may be valuable in the evaluation of MTC in the future. Mass was found adherent to local structures. Lee et al. The American Thyroid Association recommends FDG PET and PET/CT for the evaluation of distant metastatic disease, especially bone lesions. The biochemical marker doubling time was also found to affect the detection rates, with shorter doubling times correlating with higher detection rates. Medullary Thyroid Cancer (MTC) accounts for 1%– 2% of thyroid cancers in the United States. 7C —52-year-old woman with thyroid mass confirmed as medullary carcinoma by fine-needle aspiration who underwent FDG PET/CT staging. C, Anterior maximum intensity projection (A), axial PET (B), and axial fused PET/CT (C) images show diffusely increased FDG uptake (maximum standardized uptake value, 5.58) in thyroid gland (arrows), which was incidentally noticed. Most well-differentiated thyroid carcinomas are relatively slow growing and can be FDG negative [43]. 9A —65-year-old man with anaplastic thyroid cancer. A, Anterior maximum intensity projections of head and neck (top, A) and body (bottom, A) in two acquisitions, axial PET (B), and fused PET/CT (C) images of brain (left, B and C) and chest (right, B and C) show intensely FDG-avid metastatic lesions (arrows, B and C) in left parietal bone and mediastinal node. Features are consistent with subacute thyroiditis. [87] reported a patient-based analysis (n = 26) of F-DOPA PET showing a sensitivity of 81%, which is considerably higher than the sensitivity of FDG PET/CT in MTC [87]. The evolving value of non-FDG radiotracers, including 124I, 18F-dihydroxyphenylalanine, and 68Ga somatostatin analogs, is summarized. 7A —52-year-old woman with thyroid mass confirmed as medullary carcinoma by fine-needle aspiration who underwent FDG PET/CT staging. His thyroglobulin level at time of study was 478.4 ng/mL. 2B —57-year-old man with bronchioalveolar carcinoma. In a similar meta-analysis of 12 studies and literature review, Miller et al. Gallium-68-labeled somatostatin analogs have been developed for PET of somatostatin receptors in neuroendocrine tumors. Similarly, detection rates were 69% and 45% when carcinoembryonic antigen levels were greater than 5 ng/mL and less than or equal to 5 ng/mL, respectively. Fig. In combination with thyroglobulin, FDG PET/CT provides important prognostic information (Fig. However, a recent study by Giovanella et al. 8A —58-year-old woman with metastatic medullary carcinoma of thyroid who underwent FDG PET/CT after thyroidectomy, radioiodine ablation, multiple neck dissections, and chemoradiation with elevated biochemical markers. Adrenal FDG uptake resolved after thyroidectomy and debulking surgery. The relatively low detection rate of disease in patients with low calcitonin levels is likely a result of a smaller tumor mass or microscopic disease [72]. Vural et al. After study, patient underwent chemoradiation. PET/CT has proven useful for the detection of recurrent or metastatic disease, as well as provision of prognostic information in patients with DTC and elevated thyroglobulin levels with negative iodine scintigraphy. Address correspondence to R. M. Subramaniam (, PET/CT in the Management of Thyroid Cancers, Original Article. No significant difference in detection rate was found when the calcitonin levels were below 500 pg/mL or 500–1000 pg/mL [71]. 7B —52-year-old woman with thyroid mass confirmed as medullary carcinoma by fine-needle aspiration who underwent FDG PET/CT staging. Mass was found adherent to local structures. [58] states that 88% of patients (n = 102) with a positive FDG PET/CT scan had thyroglobulin levels greater than 5.5 ng/mL. Contrast-enhanced computed tomography and PET with [18 F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [18 F]FDOPA and [68 Ga]DOTATOC are the preferred tracers for medullary thyroid cancer. Fig. Use of this agent is based on the postulation that F-dopa is retained by MTC metastases owing to intracellular decarboxylation, a feature of the neuroendocrine origin of MTC [86]. Although this finding is not always present, this alternating pattern of 131I uptake to FDG uptake has been described as a “flip-flop” uptake pattern [51]. An 18-year-old Caucasian male presented to the UPMC Ear, Nose, and Throat Center with recent onset of painful ATC has very poor cure and long-term survival rates [8], with a median survival duration of 5 months and a 1-year survival rate of less than 20% [9]. In a similar meta-analysis of 12 studies and literature review, Miller et al. 4C —62-year-old man with metastatic follicular carcinoma of thyroid who underwent FDG PET/CT study after thyroidectomy, multiple radioiodine ablations, and chemoradiation. Multiple studies have shown a high sensitivity of FDG PET for Hürthle cell thyroid carcinoma relative to other imaging modalities. Plotkin et al. Uptake of 123I in thyroid was 8.1% at 4 hours and 9.6% at 25 hours (normal range, 12–34% at 24 hours). However, well-known disadvantages of ultrasound include operator dependence, limited localization of cervical metastatic lesions, especially in the central compartment when the thyroid gland remains in situ, and restricted evaluation of the posterior mediastinal and the retrosternal spaces [23]. Patient was found to have persistently elevated thyroglobulin level. Fine-needle aspiration cytology of lesion (arrows) showed papillary thyroid carcinoma. PET/CT has proven useful for the detection of recurrent or metastatic disease, as well as provision of prognostic information in patients with DTC and elevated thyroglobulin levels with negative iodine scintigraphy. Thyroid cancer is the most common endocrine cancer, accounting for approximately 1.0–1.5% of all new cancers diagnosed each year in the United States [1]. OBJECTIVE. The most common site for distant metastases is the lungs; less common are metastases to the bone marrow and brain. Maximum standardized uptake value (SUVmax) has also been shown to be a significant prognostic factor. She underwent total thyroidectomy, radioiodine ablation, neck dissection, and local radiotherapy for recurrence. However, a recent study by Giovanella et al. Medullary thyroid carcinoma (MTC) is a neuroendocrine tumour originating from the neural crest-derived parafollicular C cells of the thyroid gland and accounts for about 1 to 2% of thyroid malignancies [ 1, 2 ]. One of these patients underwent further surgery and the other three received high-dose radiation therapy. [85] compared 124I-PET/CT to more conventional imaging for detection of DTC recurrence (n = 19), finding that five patients showing uptake on 124I-PET/CT scans had lesions that were not visible on posttreatment 131I scans. Fig. Although its utility is limited in patients with MEN type IIA syndrome, FDG PET/CT is useful in patients with sporadic MTC or MEN type IIB syndrome, and elevated biochemical markers are associated with positive studies in patients with MTC. The objective of this review is to synthesize the value of FDG PET/CT and to summarize the evolving role of non-FDG PET/CT in the management of various thyroid cancers. 3A —37-year-old man with papillary thyroid carcinoma who underwent FDG PET/CT study after thyroidectomy and radioiodine ablation. B, Anterior maximum intensity projection (A), axial contrast-enhanced CT (left, B–D), and fused PET/CT (right, B–D) images show FDG-avid metastatic lesions (arrows, B–D) in right lung (B), right acetabulum (C), and T10 vertebra (D). A, Anterior maximum intensity projections of head and neck (top, A) and body (bottom, A), axial PET (left, B) and fused PET/CT (right, B), and coronal PET (left, C) and fused PET/CT (right, C) images show large necrotic mass (arrows) in lower anterior neck with intense peripheral FDG uptake (maximum standardized uptake value, 11.4) and FDG-avid right axillary lymphadenopathy. ATC lesions have high FDG avidity, and PET/CT has been found useful in the clinical management of patients with ATC. Mass was found adherent to local structures. FDG PET/CT is useful at initial staging and in the early evaluation of treatment response and follow-up. Fine-needle aspiration cytology of lesions confirmed diagnosis. Patient had multiple FDG-avid lesions, with highest maximum standardized uptake value of 7.41. Bogsrud et al. [89] concluded that F-DOPA PET/CT was superior on both per-patient and per-lesion analyses. B, Anterior maximum intensity projection (A), axial PET (B), and axial fused PET/CT (C) images show diffusely increased FDG uptake (maximum standardized uptake value, 5.58) in thyroid gland (arrows), which was incidentally noticed. [65] reported a sensitivity of 95.8% and a specificity of 95% for FDG PET/CT in Hürthle cell thyroid carcinoma (n = 44). Role of [(18)F]FDG-PET/CT in the detection of occult recurrent medullary thyroid cancer. As DTC cells dedifferentiate, their radioiodine uptake generally decreases and their glucose metabolism generally increases [49, 50]. F-DOPA PET is also being investigated for metabolic imaging of MTC. Mass was found adherent to local structures. Fig. Fig. Therefore, before obtaining a CT scan in patients with thyroid cancer, a discussion among the treating team, which includes both surgeons and endocrinologists, should be performed to determine the benefit-to-risk ratio. CONCLUSION. The most common types include papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), Hürthle cell thyroid carcinoma, medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). In group 2, 68Ga PET/CT sensitivities were 56%, 57% and 9% for detecting neck lymph nodes, lung and liver metastases and 100% for bone metastases, superior than bone scan (44%). CT has a sensitivity of 80–90.6% for detecting cervical metastases, although it may fail to detect diffuse interstitial lung metastases that may be visualized on radioiodine scintigraphy [26]. [27] evaluated the diagnostic accuracies of ultrasound, CT, and the combination of the two in primary tumor and cervical lymph-node metastases in PTC by comparing their results to pathologic specimens (n = 299). A, Anterior maximum intensity projection (A), axial PET (top, B and C) and fused PET/CT (bottom, B and C) images show intensely FDG-avid residual thyroid lesion (arrows, B), which was found to extend retrosternally, and FDG-avid pulmonary metastasis (arrows, C). Although FDG PET does not provide information beyond that yielded by ultrasound for local preoperative assessment of thyroid cancer [28], several studies have reported that it has a high sensitivity (up to 85%) and specificity (up to 95%) for distant metastases in patients with DTC [45, 46]. Hürthle cell thyroid carcinoma is an aggressive histologic subtype of thyroid cancer, with a high risk of metastasis and a worse prognosis when compared with DTC [62]. B, FDG PET/CT anterior (left, A) and posterior (right, A) views, anterior maximum intensity projection (B), axial PET (C), and fused axial PET/CT (D) images show hypermetabolic lobulated 8-mm pulmonary nodule (arrows, B–D) typical for metastasis. Of these patients, four (80.0%) were confirmed to have recurrence using either histologic or other radiologic means. Combined PET-CT is shown to be more accurate than PET alone in the detection and anatomic localization, leading to improved diagnostic accuracy in most cancers, including suspected recurrent or metastatic well-differentiated thyroid cancer. The biochemical marker doubling time was also found to affect the detection rates, with shorter doubling times correlating with higher detection rates. These studies show higher diagnostic accuracy of PET/CT with high thyroglobulin levels. PTC and FTC are classified as differentiated thyroid cancers (DTCs) [2], whereas ATC is also referred to as undifferentiated thyroid cancer [3]. His thyroglobulin level at time of study was 478.4 ng/mL. Fluorine-18 FDG PET/CT is valuable in the management of many human solid tumors [10–19]. Each of these histologically classified diseases is biologically and clinically distinct. 7B —52-year-old woman with thyroid mass confirmed as medullary carcinoma by fine-needle aspiration who underwent FDG PET/CT staging. [59] have observed higher PET positivity in patients older than 40 years compared with younger patients (70% vs 53%). However, FDG PET/CT plays a valuable role (Figs. The most common site for distant metastases is the lungs; less common are metastases to the bone marrow and brain. Antibody testing showed significantly elevated anti– thyroid peroxidase antibody level of 1633 ng/mL and antithyroglobulin level of 1740 ng/mL. Risk factors associated with the development of thyroid cancer include exposure to radiation to the head and neck region, especially in childhood, exposure to radioactive fallout due to nuclear power plant accidents or nuclear weapons testing, family history of thyroid malignancy, and a diet low in iodine. Both SUVmax and FDG uptake volume were found to be of prognostic value for survival of patients with ATC. [37] performed a meta-analysis of 34 studies evaluating incidental focal thyroid uptake detected by FDG PET/CT (n = 215,057) and found a pooled malignancy risk of 36.2% (95% CI, 33.8–38.6%). 6B —74-year-old woman with Hürthle cell carcinoma who presented with increasing thyroglobulin levels and negative 131I whole-body scan after thyroidectomy. After surgery, a substantial number of patients have residual or metastatic disease that is not radioiodine avid, and PET/CT has emerged as a powerful tool in the assessment of patients who have recurrent or metastatic tumor not demonstrable with other imaging modalities [47]. Features are consistent with subacute thyroiditis. Current Update on Medullary Thyroid Carcinoma, Review. Purpose. These analogs have a high affinity for somatostatin receptors, which are overexpressed in neuroendocrine tumor cells [94, 95]. CT and MRI are useful in the workup for locally advanced thyroid cancers to assess tumor extension into surrounding structures and cervical lymph node metastases, which can assist with surgical planning [25]. Diagnostic Test: 18F-fluorocholine PET/CT 18F-fluorocholine PET/CT imaging of the neck, mediastinum and whole body. F-DOPA was positive in all five patients with known lesions and in eight of 13 patients with negative or inconclusive results on conventional imaging. Interestingly, it was also observed in their study that the sensitivity of FDG PET/CT for MTC recurrence in patients with multiple endocrine neoplasia (MEN) type IIA syndrome was significantly lower (23%); for patients with MEN type IIA with calcitonin levels less than 2000 pg/mL, sensitivity fell to 0%. After study, patient underwent chemoradiation. Fig. However, CT scans have limitations in the setting of managing patients with thyroid cancer because the administration of iodinated contrast medium can delay the administration of postoperative radioactive iodine therapy. Chen et al. Patient underwent total thyroidectomy followed by radioiodine ablation and is on regular follow-up. To evaluate 68Ga-DOTATATE PET/CT for staging of patients with carcinoid, neuroendocrine tumors, medullary thyroid cancer and other cancers expressing somatostatin receptors. A, Anterior maximum intensity projection (A), axial PET (B), and axial fused PET/CT (C) images show diffusely increased FDG uptake (maximum standardized uptake value, 5.58) in thyroid gland (arrows), which was incidentally noticed. 8B —58-year-old woman with metastatic medullary carcinoma of thyroid who underwent FDG PET/CT after thyroidectomy, radioiodine ablation, multiple neck dissections, and chemoradiation with elevated biochemical markers. Patient had multiple FDG-avid lesions, with highest maximum standardized uptake value of 7.41. Thyroid cancer is the most common endocrine cancer. Furthermore, ATC lesions, whether primary or metastatic, consistently show high FDG uptake [77]. [64] found a sensitivity of 92% and specificity of 95% for FDG PET/CT in Hürthle cell thyroid carcinoma, whereas corresponding values for 131I-WBS were 65% and 94% and those for ultrasound were 37% and 94% (n = 327). Mass extends into upper mediastinum and displaces trachea and larynx to right. This test is also used to look … The diagnosis of medullary thyroid cancer is usually found in individuals without an inherited genetic cause of the cancer (about 75% of patients). A, In staging PET/CT study, anterior maximum intensity projection (A) and coronal (B) and axial (C) fused PET/CT images show incidental focal right thyroid FDG uptake (maximum standardized uptake value, 7.22). PET/CT informed planning of subsequent total thyroidectomy with central lymph-node dissection, and mediastinal or cervical lymph-node debulking was performed. Many studies evaluating the role of FDG PET/CT in evaluating recurrent or metastatic DTC have been published, and meta-analyses of such studies have been performed. 1) in the thyroid has been reported in 0.6–3.3% of patients undergoing FDG PET or PET/CT and commonly represents benign disease such as thyroiditis [31–33]. Fig. The American Thyroid Association recommends FDG PET and PET/CT for the evaluation of distant metastatic disease, especially bone lesions.

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