The EANM guideline on radioiodine therapy of benign thyroid disease.

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

Thyroid functional and molecular imaging.

Radioiodine uptake (RAIU) test with iodine-123 (Na[123I]I) or iodine-131 (Na[131I]I) enables accurate evaluation and quantification of iodine uptake and kinetics within thyroid cells. Thyroid Scintigraphy (TS) employing Na[123I]I or 99mTc-pertechnetate (Na[99mTc]TcO4) provides information regarding the function and topographical distribution of thyroid cells activity, including detection and localization of ectopic thyroid tissue. Destructive thyrotoxicosis is characterized by low RAIU with scintigraphically reduced radiotracer activity in the thyroid tissue, while productive thyrotoxicosis (i.e. hyperthyroidism "stricto sensu") is characterized by high RAIU with scintigraphically diffuse (i.e. Graves' Disease, GD and diffuse thyroid autonomy) or focal (i.e. autonomously functioning thyroid nodules, AFTN) overactivity. Accordingly, RAIU and/or TS are widely used to differentiate different causes of thyrotoxicosis. In addition, several radiopharmaceuticals are also available to help differentiate benign from malignant thyroid nodules and inform clinical decision-making: scintigraphic identification of AFTNs obviate fine-needle aspiration (FNA) biopsy, and [99mTc]Tc-hexakis-(2­methoxy-2-isobutyl isonitrile ([99mTc]Tc-MIBI) and/or 18F-fluoro-d-glucose ([18F]FDG) may complement the work-up of cytologically indeterminate "cold" nodules for reducing the need for diagnostic lobectomies/thyroidectomies. Finally, RAIU studies are also useful for calculating the administered therapeutic activity of Na[131I]I to treat hyperthyroidism and euthyroid multinodular goiter. All considered, thyroid molecular imaging allows functional characterization of different thyroid diseases, even before clinical symptoms become manifest, and remains integral to the management of such conditions. Our present paper summarizes basic concepts, clinical applications, and potential developments of thyroid molecular imaging in patients affected by thyrotoxicosis and thyroid nodules.

Management of Differentiated Thyroid Cancer: The Standard of Care.

In the past decade, the management of differentiated thyroid cancer (DTC) underwent a paradigm shift toward the use of risk stratification with the goal of maximizing the benefit and minimizing the morbidity of radioiodine (131I) therapy. 131I therapy is guided by information derived from surgical histopathology, molecular markers, postoperative diagnostic radioiodine scintigraphy, and thyroglobulin levels. 131I is used for diagnostic imaging and therapy of DTC based on physiologic sodium-iodine symporter expression in normal and neoplastic thyroid tissue. We summarize the essential information at the core of multidisciplinary DTC management, which emphasizes individualization of 131I therapy according to the patient's risk for tumor recurrence.

A Clinical Challenge: Endocrine and Imaging Investigations of Adrenal Masses.

Incidentalomas are reported in 3%-4% of patients who undergo abdominal anatomic imaging, making adrenal mass evaluation a common occurrence. An adrenal mass can be caused by a variety of pathologies, such as benign cortical and medullary tumors, malignant tumors (primary or secondary), cysts, hyperplasia, hemorrhage, or more rarely infection/inflammation processes. Functioning tumors usually have increased hormonal production but they are less common. Regardless of their functional status, some tumors have the potential to behave aggressively. Anatomic and functional imaging together with biologic evaluation play a vital role in adrenal pathology subtyping. Most patients are initially evaluated by CT or MRI, which allows for tumor characterization (to a certain extent) and can rule out malignant behavior based on the absence of tumor growth during longitudinal follow-up. In the remaining patients for whom CT or MRI fail to characterize the pathogenesis of adrenal tumors, the use of specialized molecular imaging techniques should be performed after hormonal screening. This review emphasizes well-established and emerging nuclear medicine imaging modalities and describes their use across various clinical scenarios.

Primary Hyperparathyroidism: Defining the Appropriate Preoperative Imaging Algorithm.

Primary hyperparathyroidism is a common and potentially debilitating endocrine disorder for which surgery is the only curative treatment. Preoperative imaging is always recommended, even in cases of conventional bilateral neck exploration, with a recognized role for 99mTc-sestamibi scintigraphy in depicting ectopic parathyroid lesions. Scintigraphy can also play a major role in guiding a targeted, minimally invasive parathyroidectomy. However, the ability to recognize multiple-gland disease (MGD) varies greatly depending on the imaging protocol used. Preoperative diagnosis of MGD is important to reduce the risks of conversion to bilateral surgery or failure. In this article we discuss imaging strategies before first surgery as well as in the case of repeat surgery for persistent or recurrent primary hyperparathyroidism. We describe a preferred algorithm and alternative options. Dual-tracer 99mTc-sestamibi/123I subtraction scanning plus neck ultrasound is the preferred first-line option. This approach should improve MGD detection and patient selection for minimally invasive parathyroidectomy. Second-line imaging procedures in case of negative or discordant first-line imaging results are presented. High detection rates can be obtained with 18F-fluorocholine PET/CT or with 4-dimensional CT. The risk of false-positive results should be kept in mind, however. Adding a contrast-enhanced arterial-phase CT acquisition to conventional 18F-fluorocholine PET/CT can be a way to improve accuracy. We also briefly discuss other localization procedures, including 11C-methionine PET/CT, MRI, ultrasound-guided fine-needle aspiration, and selective venous sampling for parathyroid hormone measurement.

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients.

CONTEXT: Adrenal tumors in noncancer patients are common. OBJECTIVE: Evaluate performance of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) in distinguishing between benign and malignant adrenal tumors. DESIGN: Retrospective chart review 2010-2019. SETTING: Academic institution. PATIENTS: One hundred and seventeen noncancer patients, defined as having no history of cancer or with cancer in remission for ≥5 years, completed 18F-FDG-PET/CT to evaluate adrenal masses, with pathologic diagnoses or imaging follow-up (≥12 months). INTERVENTION: 18F-FDG-PET/CT of 117 indeterminate adrenal masses. MAIN OUTCOME MEASURES: Receiver operator characteristic curve of the ratios of adrenal lesion standardized uptake value (SUV)max to liver SUVmean and of adrenal lesion SUVmax to aortic arch blood pool SUVmean were constructed. RESULTS: Seventy benign and 47 malignant masses (35 adrenocortical carcinomas [ACCs], 12 adrenal metastases) were identified. Malignant masses had higher median liver SUV and blood pool SUV ratios than benign masses (6.2 and 7.4 vs 1.4 and 2.0, P < .001). Median liver and blood pool SUV ratios of ACC (6.1 and 7.3, respectively) and metastases (6.7 and 7.7, respectively) were higher than those of than adenomas (1.4 and 2.2, P < .05 for all comparisons). Optimal liver SUV ratio to discern between benign and malignant masses was 2.5, yielding 85% sensitivity, 90% specificity, and 7 false negative results (including 3 ACCs). Optimal blood pool SUV ratio was 3.4, yielding 83% sensitivity, 90% specificity, and 8 false negative results (including 4 ACCs). CONCLUSION: When used in conjunction with other clinical assessments, 18F-FDG-PET/CT can be a valuable tool in evaluating adrenal masses in noncancer patients.

Functional imaging in ectopic Cushing syndrome.

PURPOSE OF REVIEW: Ectopic adrenocorticotropic hormone (ACTH)-secreting tumors are commonly small, yet they often lead to fulminant forms of Cushing syndrome. High-resolution functional imaging modalities, such as [Ga]-DOTATATE, have been recently introduced in clinical practice for the identification of neuroendocrine tumors. In this review, we focus on the performance of [Ga]-DOTATATE as a tool for localizing primary and metastatic sources of ectopic Cushing syndrome (ECS). RECENT FINDINGS: Prompt surgical removal of ectopic ACTH-secreting tumors is the mainstay of therapy in patients with ECS. Detecting such tumors with conventional cross-sectional imaging is often unsuccessful, owing to their small size. [Ga]-DOTATATE has been approved in 2016 by the Federal Drug Administration for imaging well differentiated neuroendocrine tumors. Data regarding the performance of [Ga]-DOTATATE for detecting ectopic ACTH-secreting tumors remain limited, in part owing to the recent introduction of this imaging modality in clinical practice, and in part because of the low prevalence of ECS. Nevertheless, [Ga]-DOTATATE has been reported to be useful in identifying primary and metastatic ectopic ACTH-secreting lesions that were not apparent on other imaging studies, impacting the clinical care of many patients with ECS. SUMMARY: [Ga]-DOTATATE-based imaging, which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, has generally high, although variable resolution in detecting the source(s) of ECS.

EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy.

INTRODUCTION: Scintigraphic evaluation of the thyroid gland enables determination of the iodine-123 iodide or the 99mTc-pertechnetate uptake and distribution and remains the most accurate method for the diagnosis and quantification of thyroid autonomy and the detection of ectopic thyroid tissue. In addition, thyroid scintigraphy and radioiodine uptake test are useful to discriminate hyperthyroidism from destructive thyrotoxicosis and iodine-induced hyperthyroidism, respectively. METHODS: Several radiopharmaceuticals are available to help in differentiating benign from malignant cytologically indeterminate thyroid nodules and for supporting clinical decision-making. This joint practice guideline/procedure standard from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides recommendations based on the available evidence in the literature. CONCLUSION: The purpose of this practice guideline/procedure standard is to assist imaging specialists and clinicians in recommending, performing, and interpreting the results of thyroid scintigraphy (including positron emission tomography) with various radiopharmaceuticals and radioiodine uptake test in patients with different thyroid diseases.

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours.

OBJECTIVES: Localization of ectopic ACTH-secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68 Ga]-DOTATATE PET/CT ([68 Ga]-DOTA-(Tyr3 )-octreotate)] is an FDA-approved high-resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utility of [68 Ga]-DOTATATE in patients with ECS, however, are scarce. The objectives of this study were to determine the efficacy for ECS localization and the clinical benefit of [68 Ga]-DOTATATE imaging. METHOD: We conducted a retrospective review of all cases with ECS evaluated with [68 Ga]-DOTATATE from November 2016 through October 2018 at three referral centres. The clinical benefit of [68 Ga]-DOTATATE was based on detection of new tumours and resultant changes in management. RESULTS: Over the study period, 28 patients with ECS underwent [68 Ga]-DOTATATE: 17 for identification of the primary tumour and 11 during follow-up. [68 Ga]-DOTATATE identified the suspected primary ECS in 11/17 patients (65%). Of these, nine patients underwent surgery: eight with confirmed ECS (5 bronchial, 1 thymic, 1 pancreatic and 1 metastatic neuroendocrine tumour of unknown primary origin) and one patient with a false-positive scan (adrenal gland). Of the 11 patients with ECS who underwent [68 Ga]-DOTATATE evaluation during follow-up, the study led to changes in clinical management in 7/11 (64%) patients. CONCLUSIONS: [68 Ga]-DOTATATE is sensitive in detecting primary and metastatic ECS, often identifies occult tumours after conventional imaging, and impacts clinical care in the majority of patients.

Controversies, Consensus, and Collaboration in the Use of 131I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.

BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.