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Simple Summary To capitalize on the revolutionary anticancer efficacy of immune checkpoint inhibitors (ICPi) in an expanding list of tumors, including hematological malignancies, it is mandatory to mitigate the immune-related (ir) adverse events, among which prevail the ir thyroid disorders. Currently, most available data on ir thyroid disorders are derived from solid tumors. Our review provides a comprehensive and updated overview of ir thyroid disorders, dissecting several intriguing issues, namely: (i) the elusive biological background, (ii) the epidemiological profile, (iii) the clinical spectrum, (iv) the diagnostic and therapeutic algorithms, (v) the predictive value of antithyroid antibodies for the development of ir thyroid disorders, and (vi) the prognostic significance. To contribute to the decision-making, this review provides an on-hand presentation of the latest reviews, meta-analyses, and pharmacovigilance studies addressing ir thyroid disorders, as well as of the most widely applied treatment guidelines. The current challenges and future perspectives, as regards a tailored approach to ir thyroid disorders, are critically discussed. Abstract Background: Until more data are available to shed light on the thyroid disorders related to immune checkpoint inhibitors (ICPi) implemented for the treatment of hematological malignancies, the decision-making is guided by pertinent data derived mostly from solid tumors. Methods: The present review provides a comprehensive and updated overview of the thyroid disorders related to ICPi, namely to inhibitors of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death (PD) 1 (PD-1), and the ligand of the latter (PD-L1). Results: With the increasing recognition of ir thyroid disorders, many outstanding issues have emerged. Ir thyroid disorders are reminiscent of, but not identical to, thyroid autoimmunity. Interclass and intraclass ICPi differences regarding thyroid immunotoxicity await interpretation. The available data concerning the predictive value of thyroid autoantibodies for the development of ir thyroid disorders are inconclusive. Mounting data indicate an association of ir thyroid disorders with ICPi efficacy, but a causative link is still lacking. The path forward is a tailored approach, entailing: (i) the validation of tumor-specific, patient-specific, and ICPi-specific predictive factors; (ii) appropriate patient selection; (iii) the uncoupling of antitumor immunity from immunotoxicity; (iv) a multidisciplinary initiative; and (v) global registry strategies. Conclusions: Untangling and harnessing the interrelationship of immuno-oncology with endocrinology underlying the ir thyroid disorders will yield the optimal patient care.

Simple Summary Leveraging lessons learned from the coronavirus disease 2019 (COVID-19) pandemic, resilient health systems focus on the preservation of the continuum of care of chronic diseases, especially of cancer, beyond addressing emergency health requirements. Obesity has a detrimental impact on COVID-19 and affects the epidemic of thyroid cancer (TC). TC, especially differentiated TC (DTC), is a notable paradigm of obesity-related cancers. Thus, obesity–COVID-19–(D)TC interplay can be a constant threat to public health. The present review dissects the COVID-19–(D)TC association in the setting of obesity and beyond, highlighting: (i) the interrelationship between immunity, inflammation, obesity, oxidative stress, and cancer underlying this association; (ii) the challenging management of (D)TC in the COVID-19 era; (iii) the impact of COVID-19 on (D)TC and vice versa; and (iv) the oncogenic potential of SARS-CoV-2. Future perspectives for understanding and harnessing the COVID-19–(D)TC association to inform decision-making are underlined. Abstract Background: Conceived of as the “silver lining” of the dark cloud of the coronavirus disease 2019 (COVID-19) pandemic, lessons taught by this catastrophe should be leveraged by medical authorities and policy makers to optimize health care globally. A major lesson is that resilient health systems should absorb sudden shocks incited by overwhelming health emergencies without compromising the continuum of care of chronic diseases, especially of cancer. Methods: The present review dissects the association between COVID-19 and thyroid cancer (TC), especially with differentiated TC (DTC), focusing on available data, knowledge gaps, current challenges, and future perspectives. Results: Obesity has been incriminated in terms of both COVID-19 severity and a rising incidence of TC, especially of DTC. The current conceptualization of the pathophysiological landscape of COVID-19–(D)TC association implicates an interplay between obesity, inflammation, immunity, and oxidative stress. Whether COVID-19 could aggravate the health burden posed by (D)TC or vice versa has yet to be clarified. Improved understanding and harnessing of the pathophysiological landscape of the COVID-19–(D)TC association will empower a mechanism-guided, safe, evidence-based, and risk-stratified management of (D)TC in the COVID-19 era and beyond. Conclusion: A multidisciplinary patient-centered decision-making will ensure high-quality (D)TC care for patients, with or without COVID-19.