Integrated Diagnostics and Theranostics of Thyroid Diseases

This open access book provides basic concepts on Integrated Diagnostics and Theranostics with special emphasis on different human thyroid diseases. Thyroid diseases are increasingly detected (incidentally in many cases) but are clinically negligible in a significant proportion of patients. Accordingly, it is urgent to move from the simple disease detection to a reliable disease characterization in order to concentrate efforts on patients in need of tailored disease management. The current scenario of in vitro and in vivo diagnostics, is fastly moving toward the Integrated Diagnostics (i.e. convergence of imaging, pathology and laboratory tests with advanced information technology). Furthermore, the integration of different information will aid clinicians to properly select treatments and stratify patients’ prognosis over time. Theranostics is a perfect paradigm of such integrated approach and radioiodine, indicated for benign and malignant thyroid disease management, was the first and is still the mostly used theranostic agent in medicine. Featuring basics concepts and clinical cases discussions the Atlas will be an invaluable tool for clinicians, laboratory specialists, imaging physicians and biomedical technologists involved in diagnosis and therapy of thyroid diseases. Preface Acknowledgments Contents 1: Integrated Diagnostics: The Future of Diagnostic Medicine? 1.1 Introduction 1.2 Diagnosis and Diagnostics 1.3 Integrated Diagnostics 1.4 Conclusions References 2: Artificial Intelligence and Machine Learning in Integrated Diagnostic 2.1 Background 2.2 Artificial Intelligence and Machine Learning 2.3 AI in Integrated Diagnostic: Challenges and Future Prospects 2.4 Conclusions References 3: Biochemical Diagnosis of Thyroid Dysfunctions 3.1 Introduction 3.2 Physiological Basis of Thyroid Function Laboratory Assessment 3.3 Thyroid Function Tests 3.3.1 Performance Characteristics of Thyroid Function Assays 3.3.2 Thyroid-Stimulating Hormone 3.3.2.1 Normal Range 3.3.2.2 Circadian Variability 3.3.2.3 Individual Variation 3.3.3 Free Thyroid Hormones 3.4 Diagnosis of Thyroid Dysfunctions 3.4.1 Subclinical Thyroid Dysfunctions 3.4.2 Overt Thyroid Dysfunctions 3.4.2.1 Hyperthyroidism 3.4.2.2 Hypothyroidism 3.5 Management of Inconsistent Results 3.5.1 Analytical Interferences in Immunoassays 3.5.2 Nonthyroidal Illness 3.6 Conclusion References 4: Integrated Thyroid Imaging: Ultrasound and Scintigraphy 4.1 Basics of Thyroid Imaging 4.1.1 Sonography 4.1.1.1 B-Mode Sonography (Gray-Scale Ultrasound) 4.1.1.2 Cine-Mode and Tomographic Ultrasound 4.1.1.3 Color Doppler Ultrasound (CDUS) and Contrast-Enhanced Ultrasound (CEUS) 4.1.1.4 Ultrasound Elastography 4.1.2 Radionuclide Imaging 4.1.2.1 99mTc-Pertechnetate/123Iodine 4.1.2.2 99mTc-Methoxy-Isobutyl-Isonitrile (MIBI) Imaging 4.1.3 Hybrid Imaging 4.1.3.1 Hybrid Imaging with 99mTc-Pertechnetate and 123I-NaI 4.1.3.2 Hybrid Imaging with 18F-FDG-PET 4.2 Integrated Imaging of Thyroid Disorders 4.2.1 Diffuse Thyroid Diseases 4.2.1.1 Diffuse Incidental Thyroid 18F-FDG-Uptake 4.2.1.2 Nodular Thyroid Diseases Autonomously Functioning Thyroid Nodules 4.2.2 Imaging in the Risk Assessment of Thyroid Nodules 4.2.2.1 Ultrasound Risk Stratification Systems (B-Mode Ultrasound, UE, CEUS) 4.2.2.2 Value of 99mTc-Pertechnetate/ 123I−Scintigraphy 4.2.2.3 Value of MIBI Imaging 4.2.2.4 Incidental Focal Uptake on 18F-FDG Imaging 4.2.2.5 Thyroid Nodules with Indeterminate Cytology 4.2.3 Medication-Induced Thyroid Dysfunction 4.2.4 Aberrant Localization of Thyroid Tissue and Congenital Hypothyroidism 4.2.5 Tracers Beyond 18F-FDG—Present and Future Directions References 5: Non-invasive Imaging Biomarkers of Thyroid Nodules with Indeterminate Cytology 5.1 Introduction 5.2 Uniting Medical Imaging with Artificial Intelligence 5.2.1 Quantitative Imaging 5.2.2 Artificial Intelligence 5.3 Modalities 5.3.1 Ultrasonography 5.3.1.1 Conventional (B-Mode) Ultrasonography 5.3.1.2 TI-RADS 5.3.1.3 Elastosonography 5.3.2 Computed Tomography 5.3.3 Magnetic Resonance Imaging 5.3.3.1 Diffusion-Weighted Magnetic Resonance Imaging 5.3.3.2 Magnetic Resonance Spectroscopy 5.3.3.3 Multiparametric MRI 5.3.4 [99mTc]Tc-MIBI Scintigraphy 5.3.5 [18F]FDG PET/CT 5.3.6 Combined Approaches 5.4 Future Perspectives References 6: Diagnostics and Theranostics of Benign Thyroid Disorders 6.1 Introduction 6.2 Radiopharmaceuticals for Thyroid Imaging and Therapy 6.3 Graves’ Disease 6.4 Toxic Nodular Goiter and Toxic Multi-Nodular Goiter 6.5 Radioiodine Therapy for Hyperthyroidism 6.5.1 Radioiodine Therapy in Graves’ Disease 6.5.2 Radioiodine Therapy in Patients with Toxic Nodular and Toxic Multi-Nodular Goiter 6.6 Non-Toxic Goiter 6.7 Radioiodine Therapy of Non-TOXIC Goiter 6.8 Radioiodine Therapy in Pediatric Patients 6.9 Side Effects of Radioiodine Therapy References 7: Radioiodine Theranostics of Differentiated Thyroid Carcinoma 7.1 Introduction 7.2 Diagnosis 7.3 Surgical Treatment 7.4 Staging and Risk Stratification for Differentiated Thyroid Cancer 7.5 Post-operative Management 7.6 Post-operative 131I Therapy 7.7 Benefits of 131-I Therapy in Thyroid Cancer 7.8 Preparation for 131I Therapy 7.9 131I Therapy Administration 7.9.1 Diagnostic and Post-therapy 131-I Scans with Diagnostic Intent 7.9.2 Integration of Histopathology, Laboratory, and Scintigraphy Information 7.10 Determining the Prescribed Therapeutic 131I Activity 7.11 The Role of Dosimetry for Thyroid Cancer Treatment 7.12 Radioiodine Theranostics 7.13 Treatment of Advanced Disease 7.14 Future Perspectives References 8: Biomarkers and Molecular Imaging in Postoperative DTC Management 8.1 Introduction 8.2 Biomarkers: Tg and TgAb 8.2.1 Biomarkers Role in DTC Patients Treated by Total Thyroidectomy and 131I 8.2.2 Biomarkers Role in DTC Patients Treated by Total Thyroidectomy 8.2.3 Biomarkers Role in DTC Patients Treated by Lobectomy 8.2.4 Patients with Positive TgAb 8.3 Molecular Imaging 8.3.1 Whole-Body Scintigraphy and SPECT/CT 8.3.1.1 Postoperative Setting 8.3.1.2 Posttherapy Setting 8.3.1.3 Response Assessment, Disease Monitoring, and Long-Term Follow-Up 8.3.2 PET/CT Imaging 8.3.2.1 Postoperative Setting 8.3.2.2 Suspicious Relapse 8.3.2.3 Prognostic Role of PET Imaging 8.3.2.4 Assessment of Iodine Refractory Disease 8.3.2.5 124I 8.3.2.6 Other PET Tracers 8.4 Future Perspectives: Artificial Intelligence and Radiomics References 9: Definition of Radioactive Iodine Refractory Thyroid Cancer and Redifferentiation Strategies 9.1 Definition of Radioiodine Refractory Thyroid Cancer 9.1.1 Clinical Presentation 9.1.2 Radioactive Iodine Treatment 9.1.3 The Role of [18F]FDG PET/CT in the Definition of Rai Refractory DTC 9.2 Treatment and Management of RAI Refractory Thyroid Cancer 9.3 Redifferentiation Strategies 9.4 Conclusions References 10: Integrated Diagnostics and Theragnostics of Medullary Thyroid Carcinoma and Related Syndromes 10.1 Medullary Thyroid Carcinoma and Related Syndromes 10.1.1 Medullary Thyroid Carcinoma 10.1.2 Multiple Endocrine Neoplasia Type 2 10.2 Role of Imaging According to Different Clinical Situations 10.2.1 Prophylactic Thyroidectomy for MTC Does Not Require any Preoperative Imaging 10.2.2 Indications of Imaging for Persistent/Recurrent MTC 10.2.3 18F-FDOPA PET/CT Prior Initial Surgery 10.3 18F-FDG PET and Prognostication 10.4 Peptide Receptor Targeting and Theragnostic Approaches 10.5 Immuno-PET for CEA Targeting 10.6 Future Perspectives References Correction to: Integrated Thyroid Imaging: Ultrasound and Scintigraphy