Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

18F-FDG PET/CT concurrent with first radioiodine post-therapeutic scan in high risk differentiated thyroid cancer: a useful tool or just an expensive diversion?

BACKGROUND: Aim of the present study was to evaluate the clinical impact of fluorine-18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) concurrent with post-therapeutic whole-body radioiodine scan (TxWBS) after first radioiodine (RAI) treatment in patients with high-risk differentiated thyroid carcinoma (DTC). METHODS: This was a retrospective, single-center study including 39 patients with DTC (22 females, 17 males, median age 54; IQR: 35-60 years, 87% papillary thyroid cancer, 13% follicular thyroid cancer). All patients underwent 18F-FDG-PET/CT and RAI treatment, both performed off L-T4 about 3 months after total thyroidectomy. TxWBS was obtained 3 days afterwards using planar technique and SPECT/CT of neck and thorax regions. Semiquantitative analysis was performed on positive 18F-FDG-PET/CT scans to assess SUVmax, SUVratio, MTV and TLG values in target lesions (hottest 18F-FDG-positive lesion present in each patient). Receiver operating characteristics (ROC) curve analysis was obtained to establish a cut-off point for SUVmax able to predict the presence of RAI nonavid lesions. Univariate and multivariate analyses were executed to find out predictive factors for abnormal 18F-FDG-PET/CT imaging. RESULTS: In 11 (28%) patients 18F-FDG-PET/CT and TxWBS were both negative and in 9 (23%) both positive, showing loco-regional or distant metastases. In 14 patients (36%) 18F-FDG-PET/CT showed more lesions than TxWBS, while in 5 (13%) patients more lesions were present at TxWBS than 18F-FDG-PET/CT. Overall, 23 patients (59%) showed 18F-FDG avid lesions and 18F-FDG-PET/TC changed the management in 14 (36%), including the choice to perform RAI therapy with higher activities than expected, lymph-node dissection for loco-regional metastases, direct therapy for solitary bone metastases. Through ROC curve analysis, a value superior to 7.25 of SUVmax was able to predict the presence of RAI non-avid lesion at TxWBS. Serum stimulated thyroglobulin and extranodal invasion resulted to be risk factors for abnormal 18F-FDG-PET/CT imaging. However, only extranodal invasion turned out to be an independent risk factor for abnormal 18F-FDG-PET/CT. CONCLUSIONS: The present study demonstrated the clinical value of RAI-concurrent 18F-FDG-PET/CT in patients with high-risk DTC. However, some questions remain open, including the pretherapeutic thyroglobulin level to use as indication to 18F-FDG-PET/CT and the predictive value of 18F-FDG-PET/CT semiquantitative parameters.

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131.

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes' radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.

Side effects of theragnostic agents currently employed in clinical practice.

Nuclear medicine plays an increasingly important role in several neoplasms management through a theragnostic approach by which targeted molecular imaging and radiotherapy are obtained with the use of radionuclide pairs with similar characteristics. In some cases, nuclear theragnostic use a pair of agents with identical chemical and biological characteristics while in others are employed theragnostic molecules which are not chemically or biologically identical but show similar biodistribution (so-called "twins in spirit" radiopharmaceuticals). This strategy was developed for the first time over 75 years ago, when iodine-131 was used for diagnostic imaging, confirmation of target expression and radionuclide therapy of thyroid cancer. Other theragnostic approaches were subsequently introduced with significant clinical results and some of them are currently considered standard treatment for different cancers. However, as any other therapy, also nuclear theragnostic treatment carries the potential risk of early deterministic and late stochastic off-target adverse effects, generally minimal and easily managed. This article reviews the reported side effects and risks of the main radiopharmaceuticals used for nuclear theragnostic in oncology for the treatment of thyroid cancer, neuroendocrine neoplasms, adrenergic tumors, metastatic prostate cancer, and liver tumors. Selecting appropriate patients using a multidisciplinary approach, meticulous pretreatment planning and knowledge of methods permit to decrease the incidence of these potential side effects.

Radiation dose in nuclear medicine: the hybrid imaging.

Hybrid imaging procedures such as single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT) showed a rapid diffusion in recent years because of their high sensitivity, specificity, and accuracy, due to a more accurate localization and definition of scintigraphic findings. However, hybrid systems inevitably lead to an increase in patient radiation exposure because of the added CT component. Effective doses due to the radiopharmaceuticals can be estimated by multiplying the administered activities by the effective dose coefficients, while for the CT component the dose-length product can be multiplied by a conversion coefficient k. However, the effective dose value is subject to a high degree of uncertainty and must be interpreted as a broad, generic estimate of biologic risk. Although the effective dose can be used to estimate and compare the risk of radiation exposure across multiple imaging techniques, clinicians should be aware that it represents a generic evaluation of the risk derived from a given procedure to a generic model of the human body. It cannot be applied to a single individual and should not be used for epidemiologic studies or the estimation of population risks due to the inherent uncertainties and oversimplifications involved. Practical ways to reduce radiation dose to patients eligible for hybrid imaging involve adjustments to both the planning phase and throughout the execution of the study. These methods include individual justification of radiation exposure, radiopharmaceutical choice, adherence to diagnostic reference levels (DLR), patient hydration and bladder voiding, adoption of new technical devices (sensitive detectors or collimators) with new reconstruction algorithms, and implementation of appropriate CT protocols and exposure parameters.

Accumulation of 131I in Esophageal Diverticulum Diagnosed by SPECT/CT.

A 72-year-old man underwent total thyroidectomy and radioiodine remnant ablation for papillary thyroid cancer in 2016. The posttherapy whole-body scan showed uptake in the neck, classified as residual thyroid tissue. Two years later, the patient came to our observation to perform a second radioiodine therapy for high levels of thyroglobulin. The planar posttherapy scan showed a focal radioiodine area in the neck. SPECT/CT diagnosed a voluminous esophageal diverticulum located in the upper third of the esophagus. A CT performed to discover the source of thyroglobulin excluded locoregional or distant metastases and confirmed the presence of a Zenker diverticulum.

Imaging in endocrinology: 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in differentiated thyroid carcinoma: clinical indications and controversies in diagnosis and follow-up.

In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG-PET/CT plays in clinical practice is that it can be used to obtain prognostic information in patients with increasing thyroglobulin (Tg) levels and negative (131)I whole-body scan post-thyroidectomy and radioiodine (RAI) ablation. FDG-PET/CT may also have a potential role in the initial staging and follow-up of high-risk patients with aggressive histological subtypes, in the identification of patients who are at the highest risk of disease-specific mortality, in the management of patients with RAI-refractory disease, in clinical trials of novel targeted therapies in patients with advanced metastatic disease, and in the evaluation of thyroid nodules with indeterminate fine-needle aspiration for cytology. However, several controversies remain to be resolved, namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT, whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas. The aim of the present article is to provide an overview of the data about the molecular basis for, clinical indications of, and controversies related to the use of FDG-PET/CT in patients with DTC.

Papillary thyroid microcarcinoma: proposal of treatment based on histological prognostic factors evaluation.

BACKGROUND: Papillary thyroid cancer accounts for approximately 80% of thyroid tumors and its incidence has increased over the past decades. Papillary thyroid microcarcinomas (PMCs), defined by the World Health Organization as less than 1.0 cm in size, are identified with greater frequency. The majority of patients with PMCs follows a benign clinical course, however a subgroup of these carcinomas is as aggressive as bigger tumors. Risk factors related with poor outcome have not been defined and the optimal treatment has not been proved. The authors investigated histologic prognostic factors predicting high risk patients considered for more aggressive treatment and propose reviewed therapeutic guidelines based on analysis of histopathologic features which determined the recurrence rate. STUDY DESIGN: One hundred forty nine patients with PMC who underwent surgery were retrospectively analyzed. Clinical and histopathologic parameters potentially predicting patient outcome and recurrent disease were statistically investigated, after a minimum follow-up of 5 years. RESULTS: After a median follow-up of 5.4 years 28 of 149 patients experienced recurrent disease. All of them were reoperated on and newly treated with radioiodine administration. The multivariate statistical analysis identified extrathyroidal invasion (Odds Ratio, OR, 58.54; P=0.013), the solid pattern (OR,25.77; P>0.001), the tumor multifocality (OR, 15.80; P= 0.005), and the absence of tumor capsule (OR, 9.74; P=0.015) as significant and indipendent risk factors for the appearance of PMCs recurrences. Of note, none of the PMC "incidentally" discovered at histopathological examination alone experienced recurrent disease during follow-up. CONCLUSIONS: Although most PMC have favourable long-term prognosis, some patients (19% in our series) presented aggressive clinical course strongly correlated with some histopathologic features (extrathyroidal invasion, tumor multifocality, solid pattern and absence of capsule) who need to be investigated and for whom a radical therapeutic approach is recommended based on total thyroidectomy and regional lymphadenectomy followed by radioiodine administration.

Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging.

OBJECTIVE: The aim of this study was to investigate the appropriate time for performing an iodine-131 post-therapy whole-body scan (TxWBS) through a qualitative and semiquantitative analysis of early and late scans. MATERIALS AND METHODS: This study evaluated pairs of scans of 134 patients who underwent TxWBS on the third and seventh day. The scans were analyzed to evaluate sites, intensity of uptake, concordance or discordance between the scans, relationship with risk factors, and serum thyroglobulin (Tg) levels. To evaluate early and late radioiodine kinetics in thyroid remnants and metastases, 65/134 pairs of scans (48.5%) were subjected to a semiquantitative analysis. RESULTS: The early and late scans furnished concordant images in 108/134 patients (80.5%). In 10/134 patients (7.5%), early scans provided more information compared with late scans, showing lymph node and distant metastases in seven and three patients, respectively. In 16/134 patients (12%), late scans provided more data compared with early scans, with thyroid remnants and lymph node and distant metastases demonstrated in four, seven, and five patients, respectively. Negative early/positive late TxWBS results in patients were found to be significantly correlated (P=0.007) with elevated serum levels of Tg and a high-risk for recurrence (P=0.003). CONCLUSION: This study suggests that in about 20% of patients early or late TxWBS can miss the visualization of thyroid remnants or lymph node or distant metastases, which can be achieved performing both studies. High-risk patients with elevated serum Tg levels should be considered for a late TxWBS, which can demonstrate a possible metastatic involvement that was not diagnosed or that was downstaged by early TxWBS.

The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview.

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis.

Diagnostic performance of (99m)Tc-MIBI scan in predicting the malignancy of thyroid nodules: a meta-analysis.

Several studies have investigated the diagnostic performance of (99m)Tc-MIBI scan in the evaluation of thyroid nodules suspicious for malignancy with conflicting results. The aim of our study is to meta-analyze published data on this topic. A comprehensive literature search of studies published through December 2012 regarding the diagnostic performance of (99m)Tc-MIBI scan in the evaluation of thyroid nodules suspicious for malignancy was carried out. Pooled sensitivity and specificity of (99m)Tc-MIBI scan on a per lesion-based analysis and the area under the ROC curve were calculated. Pathological reports of thyroid nodules were considered as reference standard. Twenty-one studies were included in the meta-analysis. Pooled sensitivity and specificity of (99m)Tc-MIBI scan in detecting malignant thyroid nodules were 85.1 % [95 % confidence interval (95 % CI): 81.1-88.5 %] and 45.7 % (95 % CI: 42.7-48.7 %), respectively, on a per lesion-based analysis, irrespective of eventual results of previous technetium pertechnetate ((99m)TcO4) or iodine-123 ((123)I) scan. The area under the ROC curve was 0.78. A sub-analysis restricted to data on hypofunctioning nodules on (99m)TcO4 or (123)I scans was performed: pooled sensitivity and specificity of (99m)Tc-MIBI scan in these nodules were 82.1 % (95 % CI: 77.2-86.3 %) and 62.8 % (95 % CI: 58.9-66.7 %), respectively, on a per lesion-based analysis. The area under the ROC curve was 0.81. (99m)Tc-MIBI scan is a sensitive diagnostic tool in predicting the malignancy of thyroid nodules. Therefore, this imaging method could be helpful in patients with thyroid nodules in which malignancy is suspected on the basis of conventional diagnostic techniques. Higher specificity can be reached when hypofunctioning thyroid nodules are considered.

The role of positron emission tomography and positron emission tomography/computed tomography in thyroid tumours: an overview.

Positron emission tomography (PET) and PET/computed tomography (PET/CT) with different tracers have been increasingly used in patients with thyroid tumours. The aim of this article is to perform an overview based on literature data about the usefulness of PET imaging in this setting. The role of Fluorine-18-Fluorodeoxyglucose (FDG) PET and PET/CT in differentiated thyroid carcinoma (DTC) is well established, particularly in patients presenting with elevated serum thyroglobulin levels and negative radioiodine whole-body scan. Iodine-124 PET and PET/CT may serve a role in staging DTC and obtaining lesional dosimetry for a better and more rationale planning of treatment with Iodine-131. FDG-PET and PET/CT are useful in the post-thyroidectomy staging of high-risk patients with less differentiated histological subtypes. PET and PET/CT with different tracers seem to be useful methods in localizing the source of elevated calcitonin levels in patients with recurrent medullary thyroid carcinoma. Incorporation of FDG-PET or PET/CT into the initial workup of patients with indeterminate thyroid nodules at fine needle aspiration biopsy deserves further investigation. FDG-PET report should suggest further evaluation when focal thyroid incidentalomas are described because these findings are associated with a significant risk of cancer.

Aggressive papillary thyroid microcarcinoma: prognostic factors and therapeutic strategy.

BACKGROUND AND AIM: Papillary thyroid carcinomas smaller than 1 cm are classified as papillary microcarcinomas (PMCs). Papillary microcarcinomas are usually considered low-risk tumors; however in some cases, PMCs behave aggressively and metastasize early, giving rise to clinically metastatic disease. Debate exists in the literature about prognostic factors and therapeutic management to PMC. We report here the long-term experience of our referral center for malignant thyroid disease. METHODS: We retrospectively analyzed 149 consecutive patients with PMC who underwent surgery at our institution between 2000 and 2005; 49 of them (33% of cases) were treated also with radioiodine therapy. Clinical and histopathological parameters potentially predicting patient outcome and recurrent disease were statistically investigated, after a minimum follow-up of 5 years. RESULTS: After a median follow-up of 5.4 years (range, 5-11 years), 28 (19%) of 149 patients experienced recurrent disease. All of them were reoperated on and newly treated with radioiodine administration. Of these 28 patients, 27 are living without disease, whereas 1 patient died due to metastatic thyroid cancer to lungs. The multivariate statistical analysis identified extrathyroid invasion (odds ratio [OR], 58.54; P=0.013), the solid pattern (OR, 25.77; P<0.001), the tumor multifocality (OR, 15.80; P=0.005), and the absence of tumor capsule (OR, 9.74; P=0.015) as significant and independent risk factors for the appearance of PMC recurrences. Of note, in most patients who experienced recurrent disease, the PMC had been diagnosed preoperatively and often for the presence of cervical clinically evident lymphadenopathy. On the other hand, none of the PMC "incidentally" discovered at histopathological examination alone experienced recurrent disease during follow-up. CONCLUSIONS: Although most PMCs have an indolent course, there is a fraction (19% in our series) of patients with PMC and aggressive behavior strongly correlated with some histopathological features (extrathyroid invasion, solid pattern, tumor multifocality, and absence of a capsule) who need to be individualized and for whom a radical therapeutic approach is recommended based on total thyroidectomy and lymphadenectomy followed by radioiodine administration.

Percutaneous ultrasound-guided laser ablation is effective for treating selected nodal metastases in papillary thyroid cancer.

CONTEXT: Mini-invasive procedures may be useful for control of local neck nodal metastases of papillary thyroid cancer (PTC) in high-risk patients. OBJECTIVE: Our objective was to assess the effectiveness and safety of ultrasound (US)-guided laser ablation (LA) for nonsurgical treatment of small-size neck metastases of PTC. DESIGN AND SETTING: We conducted a pilot study on a surgically controlled metastasis, followed by a prospective trial with a 12-month follow-up. PARTICIPANTS: Participants included five patients with previous total thyroidectomy and neck dissection for PTC, with eight new lymph node metastases in an area already treated with surgical dissection and lymph node volume less than 2 ml and absent radioiodine uptake. OUTCOME MEASURES: We evaluated thyroglobulin (Tg) and US changes of the lymph nodes 6 and 12 months after LA as well as tolerability and side effects of the procedure. RESULTS: A single LA treatment induced progressive volume reduction of the eight metastatic lymph nodes. Mean baseline volume decreased from 0.64 ± 0.58 to 0.07 ± 0.06 ml at 12-month control. Mean volume reduction was 64.4 ± 0.19% at 6 months (P < 0.02 vs. baseline) and 87.7 ± 0.11% at 12 months (P < 0.01 vs. baseline). No regrowth was registered. Mean serum Tg on LT4 decreased from 8.0 ± 3.2 ng/ml to 2.0 ± 2.5 ng/ml at 12-month control (P < 0.02 vs baseline). In three patients (60%) Tg levels were undetectable at 12-month control. Pain was tolerable in two cases and mild in three cases. Transient dysphonia in one patient was the only complication. After 1 yr, no cancer seeding was present. CONCLUSION: LA is a well-tolerated outpatient procedure that results in a rapid cytoreduction of cervical nodal metastases of PTC. Mini-invasive procedures may be used in lieu of surgery as an adjunctive therapy for small-burden local/regional disease recurrence. They are occasionally associated with an anatomical or biochemical cure, but long-term follow-up or controlled trials are needed.

Serum cytokeratin 19 fragments: a dedifferentiation marker in advanced thyroid cancer.

BACKGROUND: This study was undertaken to evaluate serum cytokeratin 19 fragment (Cyfra 21.1) expressions in patients with advanced thyroid carcinoma and to explore the relationship between serum Cyfra 21.1 and the degree of radioiodine ((131)I) avidity of thyroid carcinoma cells. METHODS: Enrolled were 76 consecutive patients with advanced thyroid carcinoma submitted to high-activity (131)I treatment. In each patient, serum thyroglobulin (Tg) and Cyfra 21.1 were measured before (131)I administration and compared with the posttreatment whole-body scan results. RESULTS: Thirty-one (41%) of 76 patients had iodine-avid and 45 (59%) had iodine-refractory diseases respectively. Significantly higher serum Cyfra 21.1, but not Tg, levels were found in patients with (131)I-refractory disease compared with patients with iodine-avid disease (P<0.01). CONCLUSIONS: This is the first report describing the potential role of serum Cyfra 21.1 as marker of dedifferentiation and resistance to (131)I therapy in patients with advanced thyroid carcinoma.

PET Imaging in Recurrent Medullary Thyroid Carcinoma.

Purpose. To perform an overview about the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using different radiopharmaceuticals in recurrent medullary thyroid carcinoma (MTC) based on biochemical findings (increased tumor marker levels after primary surgery). Methods. A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through February 2012 regarding PET or PET/CT in patients with recurrent MTC was performed. Results. Twenty-nine studies comprising 714 patients with suspected recurrent MTC were retrieved. Twenty-seven articles evaluated the role of fluorine-18-fluorodeoxyglucose (FDG) PET or PET/CT in recurrent MTC with conflicting results. Diagnostic accuracy of FDG-PET and PET/CT increased in MTC patients with higher calcitonin and carcinoembryonic antigen values, suggesting that these imaging methods could be very useful in patients with more advanced and aggressive disease. Eight articles evaluated the role of fluorine-18-dihydroxyphenylalanine (FDOPA) PET or PET/CT in recurrent MTC reporting promising results. Overall, FDOPA seems to be superior but complementary compared to FDG in detecting recurrent MTC. Few studies evaluating other PET tracers are also discussed. Conclusions. PET radiopharmaceuticals reflect different metabolic pathways in MTC. FDOPA seems to be the most useful PET tracer in detecting recurrent MTC based on rising levels of tumor markers. FDG may complement FDOPA in patients with more aggressive MTC.