Clinical Radiology xxx (2015) e1ee8
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Clinical significance of patterns of incidental thyroid uptake at 18F-FDG PET/CT K. Agrawal a, *, J. Weaver b, R. Ngu c, H. Krishnamurthy Mohan a, d a
Dept of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK School of medicine, King’s College London, London, UK c Department of Dental Maxillofacial Radiology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK d Clinical PET Centre, St Thomas’ Hospital, London, UK b
art icl e i nformat ion Article history: Received 4 August 2014 Received in revised form 22 December 2014 Accepted 29 December 2014
Incidental uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological 18F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be “nuisance lesions” by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of 18FFDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid 18F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave’s disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal 18F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction The prevalence of thyroid nodules in the general population is reported to be between 8% and 65%.1 2-[18F]-fluoro2-deoxy-D-glucose (18F-FDG) is a glucose analogue. The mechanism of 18F-FDG positron-emission tomography/ computed tomography (PET/CT) in the detection of tumours * Guarantor and correspondent: K. Agrawal, Department of Nuclear Medicine, Guy’s Hospital, Great Maze Pond, London SE19RT, UK. Tel.: þ44 020 71884106. E-mail address: [email protected] (K. Agrawal).
is based on the higher glycolytic metabolism of malignant tissue and the higher expression of membrane glucose transporter (GLUT) proteins.2 Due to the combined metabolic and anatomical information from PET/CT, it is currently widely used for cancer staging, restaging, detection of recurrent disease, and optimization of therapy in wide variety of malignancies. However, due to the nonspecific nature of 18F-FDG uptake, many benign pathological entities also show abnormal tracer uptake.3 In a study, approximately 12% of cancer patients undergoing 18F-FDG PET/CT had unexpected abnormal 18F-FDG uptake concerning for a second malignancy, of which 47% were due to
http://dx.doi.org/10.1016/j.crad.2014.12.020 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
18
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benign disease.4 Various patterns of incidental uptake within the thyroid on routine 18F-FDG PET/CT have been observed.5 Although in most of these patients underlying benign thyroid disease is identified, clinically significant pathological conditions have also been discovered in a small but significant number. Therefore, it is important for clinicians to understand the significance of the incidental uptake in these patients, to direct appropriate management whilst avoiding unnecessary investigations. This review describes the various patterns of 18F-FDG uptake observed within the thyroid gland and discusses their clinical significance and possible impact on patient management.
Normal variant The thyroid gland can be seen faintly on 18F-FDG PET/CT studies in patients without thyroid disease.6,7 The mechanism of tracer uptake in the normal thyroid, although not clear, most likely reflects low-grade glycolytic metabolism within thyroid epithelial cells (Fig 1).
Homogeneous diffuse thyroid uptake This probably is the most common variant of incidental uptake within the thyroid seen in clinical practice and has been reported in approximately 0.1e4.5% (mean 1.9%) of 18 F-FDG PET studies.8 A homogeneous diffuse pattern of thyroid uptake at 18F-FDG PET could be due to normal variation, chronic thyroiditis, hypothyroidism on hormonal replacement, and Graves’ disease.
Chronic thyroiditis and hypothyroidism The majority of studies in the literature support that chronic thyroiditis and hypothyroidism are frequent causes of diffuse thyroid uptake at 18F-FDG PET (Fig 2).9e11 Karantanis et al.9 demonstrated that 63 of 133 patients (47.4%) with diffuse thyroid uptake on 18F-FDG PET had a clinical diagnosis of hypothyroidism or autoimmune thyroiditis.9 They also noted that there is no significant correlation between maximum standardized uptake value (SUVmax) and thyroidstimulating hormone (TSH) or thyroid peroxidase (TPO) antibody levels in the serum. They recommended that even low-grade uptake in the thyroid should not be ignored as this may be associated with overt or subclinical hypothyroidism. The mechanism of uptake in the thyroid in these patients is not clear. One explanation could be the uptake of 18F-FDG within an activated lymphocyte infiltrate within the thyroid gland.
Graves’ disease It has been reported that increased 18F-FDG uptake in the thyroid in patients with Graves’ disease may be due to combination of increased blood flow and enhanced glucose utilization.12 Literature evaluation suggests approximately 30% of patients with Graves’ disease show increased 18F-FDG uptake in the thyroid.13 It has been observed that the intensity of 18FFDG uptake in the thyroid increases with increasing antithyroid antibodies. This was also seen to be associated with a shorter radioiodine half-life in Graves’ disease, which may have implications on radio-iodine therapy in these patients. Diffuse increased 18F-FDG uptake within the thyroid and
Figure 1 18F-FDG PET/CT study: axial CT (a), axial PET (b), axial fused PET/CT (c), coronal CT (d), coronal PET (e) and coronal fused PET/CT (f) images at the level of the thyroid showing normal uptake in the thyroid (arrow), which is very low grade and uniform. Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
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K. Agrawal et al. / Clinical Radiology xxx (2015) e1ee8
e3
Figure 2 A 39-year-old woman with non-Hodgkin’s lymphoma was referred for 18F-FDG PET/CT for staging. Intense uptake of tracer was noted in the right axillary lymph nodes with low-grade uptake in mediastinal nodes. In addition, (a) maximum intensity projection, (b) coronal PET, (c) axial PET, (d) coronal CT, (e) axial CT, (f) coronal fused PET/CT, and (g) axial fused PET/CT images showed diffuse homogeneous uptake of tracer in the thyroid gland (arrow), which on thyroid function tests and antibody profiling confirmed Hashimoto’s thyroiditis.
symmetrically increased uptake in the skeletal muscles and thymus has been described as a clue for the diagnosis of underlying Graves’ disease.11
Follow-up In general, incidental low-grade homogeneous diffuse increased thyroid 18F-FDG uptake rarely indicates thyroid cancer and is usually seen in patients with chronic thyroiditis, Grave’s disease, and hypothyroidism. Thyroid function tests and antibody profiling should be advised in these patients. There are no current data warranting further imaging with ultrasound or fine-needle aspiration cytology (FNAC) in these patients.
Heterogeneous diffuse uptake in the thyroid Although theoretically heterogeneous uptake can be seen in the multinodular goitre, Kurata et al.14 showed that
some heterogeneous diffuse uptake or focal on diffuse uptake was related to papillary carcinoma associated with Hashimoto’s thyroiditis (Fig 3). Lymphomatous involvement of the thyroid could give similar appearances (Fig 4).15 The present authors have observed a similar pattern in a patient with primary lung cancer with secondary thyroid metastases (Fig 5).
Focal uptake The prevalence of focal uptake within the thyroid varies from 0.1% to 4.8% (mean 2%). This could represent benign disease (Fig 6), although underlying malignancy has been increasingly associated with this pattern of uptake with a reported risk of malignancy being 34.8%.8 Primary thyroid cancer (Figs 7e8) or secondary metastatic deposits from other primary sites have been identified in this group of patients.
Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
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Figure 3 A 54 year-old woman with diffuse large B-cell lymphoma was referred for 18F-FDG PET/CT to evaluate treatment response. (a) Axial PET, (b) axial CT, (c) axial fused PET/CT; (d) coronal PET, (e) coronal CT, (f) coronal fused PET/CT, (g) sagittal PET, (h) sagittal CT, and (i) sagittal fused PET/CT images showed heterogeneous increased tracer uptake within the thyroid gland with a focal area of intense uptake in the right thyroid lobe upper pole (SUVmax 29.4). FNAC of the right thyroid upper pole nodule was suspicious for PTC, and the patient underwent thyroidectomy, which confirmed a PTC on a background of Hashimoto’s thyroiditis.
Primary thyroid cancer
Metastases
Classical papillary thyroid cancer (PTC) and follicular variant of PTC are the most prevalent primary thyroid cancer type in these patients.8
Despite the rich thyroid vasculature, it is rarely the site of metastatic disease.16 Metastasis to the thyroid is clinically established in only
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Clinical significance of patterns of incidental thyroid uptake at 18F-FDG PET/CT K. Agrawal a, *, J. Weaver b, R. Ngu c, H. Krishnamurthy Mohan a, d a
Dept of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK School of medicine, King’s College London, London, UK c Department of Dental Maxillofacial Radiology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK d Clinical PET Centre, St Thomas’ Hospital, London, UK b
art icl e i nformat ion Article history: Received 4 August 2014 Received in revised form 22 December 2014 Accepted 29 December 2014
Incidental uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological 18F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be “nuisance lesions” by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of 18FFDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid 18F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave’s disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal 18F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction The prevalence of thyroid nodules in the general population is reported to be between 8% and 65%.1 2-[18F]-fluoro2-deoxy-D-glucose (18F-FDG) is a glucose analogue. The mechanism of 18F-FDG positron-emission tomography/ computed tomography (PET/CT) in the detection of tumours * Guarantor and correspondent: K. Agrawal, Department of Nuclear Medicine, Guy’s Hospital, Great Maze Pond, London SE19RT, UK. Tel.: þ44 020 71884106. E-mail address: [email protected] (K. Agrawal).
is based on the higher glycolytic metabolism of malignant tissue and the higher expression of membrane glucose transporter (GLUT) proteins.2 Due to the combined metabolic and anatomical information from PET/CT, it is currently widely used for cancer staging, restaging, detection of recurrent disease, and optimization of therapy in wide variety of malignancies. However, due to the nonspecific nature of 18F-FDG uptake, many benign pathological entities also show abnormal tracer uptake.3 In a study, approximately 12% of cancer patients undergoing 18F-FDG PET/CT had unexpected abnormal 18F-FDG uptake concerning for a second malignancy, of which 47% were due to
http://dx.doi.org/10.1016/j.crad.2014.12.020 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
18
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benign disease.4 Various patterns of incidental uptake within the thyroid on routine 18F-FDG PET/CT have been observed.5 Although in most of these patients underlying benign thyroid disease is identified, clinically significant pathological conditions have also been discovered in a small but significant number. Therefore, it is important for clinicians to understand the significance of the incidental uptake in these patients, to direct appropriate management whilst avoiding unnecessary investigations. This review describes the various patterns of 18F-FDG uptake observed within the thyroid gland and discusses their clinical significance and possible impact on patient management.
Normal variant The thyroid gland can be seen faintly on 18F-FDG PET/CT studies in patients without thyroid disease.6,7 The mechanism of tracer uptake in the normal thyroid, although not clear, most likely reflects low-grade glycolytic metabolism within thyroid epithelial cells (Fig 1).
Homogeneous diffuse thyroid uptake This probably is the most common variant of incidental uptake within the thyroid seen in clinical practice and has been reported in approximately 0.1e4.5% (mean 1.9%) of 18 F-FDG PET studies.8 A homogeneous diffuse pattern of thyroid uptake at 18F-FDG PET could be due to normal variation, chronic thyroiditis, hypothyroidism on hormonal replacement, and Graves’ disease.
Chronic thyroiditis and hypothyroidism The majority of studies in the literature support that chronic thyroiditis and hypothyroidism are frequent causes of diffuse thyroid uptake at 18F-FDG PET (Fig 2).9e11 Karantanis et al.9 demonstrated that 63 of 133 patients (47.4%) with diffuse thyroid uptake on 18F-FDG PET had a clinical diagnosis of hypothyroidism or autoimmune thyroiditis.9 They also noted that there is no significant correlation between maximum standardized uptake value (SUVmax) and thyroidstimulating hormone (TSH) or thyroid peroxidase (TPO) antibody levels in the serum. They recommended that even low-grade uptake in the thyroid should not be ignored as this may be associated with overt or subclinical hypothyroidism. The mechanism of uptake in the thyroid in these patients is not clear. One explanation could be the uptake of 18F-FDG within an activated lymphocyte infiltrate within the thyroid gland.
Graves’ disease It has been reported that increased 18F-FDG uptake in the thyroid in patients with Graves’ disease may be due to combination of increased blood flow and enhanced glucose utilization.12 Literature evaluation suggests approximately 30% of patients with Graves’ disease show increased 18F-FDG uptake in the thyroid.13 It has been observed that the intensity of 18FFDG uptake in the thyroid increases with increasing antithyroid antibodies. This was also seen to be associated with a shorter radioiodine half-life in Graves’ disease, which may have implications on radio-iodine therapy in these patients. Diffuse increased 18F-FDG uptake within the thyroid and
Figure 1 18F-FDG PET/CT study: axial CT (a), axial PET (b), axial fused PET/CT (c), coronal CT (d), coronal PET (e) and coronal fused PET/CT (f) images at the level of the thyroid showing normal uptake in the thyroid (arrow), which is very low grade and uniform. Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
18
F-FDG PET/CT, Clinical
K. Agrawal et al. / Clinical Radiology xxx (2015) e1ee8
e3
Figure 2 A 39-year-old woman with non-Hodgkin’s lymphoma was referred for 18F-FDG PET/CT for staging. Intense uptake of tracer was noted in the right axillary lymph nodes with low-grade uptake in mediastinal nodes. In addition, (a) maximum intensity projection, (b) coronal PET, (c) axial PET, (d) coronal CT, (e) axial CT, (f) coronal fused PET/CT, and (g) axial fused PET/CT images showed diffuse homogeneous uptake of tracer in the thyroid gland (arrow), which on thyroid function tests and antibody profiling confirmed Hashimoto’s thyroiditis.
symmetrically increased uptake in the skeletal muscles and thymus has been described as a clue for the diagnosis of underlying Graves’ disease.11
Follow-up In general, incidental low-grade homogeneous diffuse increased thyroid 18F-FDG uptake rarely indicates thyroid cancer and is usually seen in patients with chronic thyroiditis, Grave’s disease, and hypothyroidism. Thyroid function tests and antibody profiling should be advised in these patients. There are no current data warranting further imaging with ultrasound or fine-needle aspiration cytology (FNAC) in these patients.
Heterogeneous diffuse uptake in the thyroid Although theoretically heterogeneous uptake can be seen in the multinodular goitre, Kurata et al.14 showed that
some heterogeneous diffuse uptake or focal on diffuse uptake was related to papillary carcinoma associated with Hashimoto’s thyroiditis (Fig 3). Lymphomatous involvement of the thyroid could give similar appearances (Fig 4).15 The present authors have observed a similar pattern in a patient with primary lung cancer with secondary thyroid metastases (Fig 5).
Focal uptake The prevalence of focal uptake within the thyroid varies from 0.1% to 4.8% (mean 2%). This could represent benign disease (Fig 6), although underlying malignancy has been increasingly associated with this pattern of uptake with a reported risk of malignancy being 34.8%.8 Primary thyroid cancer (Figs 7e8) or secondary metastatic deposits from other primary sites have been identified in this group of patients.
Please cite this article in press as: Agrawal K, et al., Clinical significance of patterns of incidental thyroid uptake at Radiology (2015), http://dx.doi.org/10.1016/j.crad.2014.12.020
18
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Figure 3 A 54 year-old woman with diffuse large B-cell lymphoma was referred for 18F-FDG PET/CT to evaluate treatment response. (a) Axial PET, (b) axial CT, (c) axial fused PET/CT; (d) coronal PET, (e) coronal CT, (f) coronal fused PET/CT, (g) sagittal PET, (h) sagittal CT, and (i) sagittal fused PET/CT images showed heterogeneous increased tracer uptake within the thyroid gland with a focal area of intense uptake in the right thyroid lobe upper pole (SUVmax 29.4). FNAC of the right thyroid upper pole nodule was suspicious for PTC, and the patient underwent thyroidectomy, which confirmed a PTC on a background of Hashimoto’s thyroiditis.
Primary thyroid cancer
Metastases
Classical papillary thyroid cancer (PTC) and follicular variant of PTC are the most prevalent primary thyroid cancer type in these patients.8
Despite the rich thyroid vasculature, it is rarely the site of metastatic disease.16 Metastasis to the thyroid is clinically established in only
