Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., ¹³¹I, ¹²³I, ¹²⁴I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [¹⁸F]F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [¹⁸F]F-dihydroxyphenylalanine (6-[¹⁸F]FDOPA) PET/CT and/or [¹⁸F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.

Thyroid dysfunctions are among the most common endocrine disorders and accurate biochemical testing is needed to confirm or rule out a diagnosis. Notably, true hyperthyroidism and hypothyroidism in the setting of a normal thyroid-stimulating hormone level are highly unlikely, making the assessment of free thyroxine (FT4) inappropriate in most new cases. However, FT4 measurement is integral in both the diagnosis and management of relevant central dysfunctions (central hypothyroidism and central hyperthyroidism) as well as for monitoring therapy in hyperthyroid patients treated with anti-thyroid drugs or radioiodine. In such settings, accurate FT4 quantification is required. Global standardization will improve the comparability of the results across laboratories and allow the development of common clinical decision limits in evidence-based guidelines. The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests has undertaken FT4 immunoassay method comparison and recalibration studies and developed a reference measurement procedure that is currently being validated. However, technical and implementation challenges, including the establishment of different clinical decision limits for distinct patient groups, still remain. Accordingly, different assays and reference values cannot be interchanged. Two-way communication between the laboratory and clinical specialists is pivotal to properly select a reliable FT4 assay, establish reference intervals, investigate discordant results, and monitor the analytical and clinical performance of the method over time.

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring “diagnostic surgery” to provide a definitive diagnosis. ^99mTc-methoxy-isobutyl-isonitrile ([^99mTc]Tc-MIBI) and [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.