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Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.

Thyroid cancers (TC) have increasingly been detected following advances in diagnostic methods. Risk stratification guided by refined information becomes a crucial step toward the goal of personalized medicine. The diagnosis of TC mainly relies on imaging analysis, but visual examination may not reveal much information and not enable comprehensive analysis. Artificial intelligence (AI) is a technology used to extract and quantify key image information by simulating complex human functions. This latent, precise information contributes to stratify TC on the distinct risk and drives tailored management to transit from the surface (population-based) to a point (individual-based). In this review, we started with several challenges regarding personalized care in TC, for example, inconsistent rating ability of ultrasound physicians, uncertainty in cytopathological diagnosis, difficulty in discriminating follicular neoplasms, and inaccurate prognostication. We then analyzed and summarized the advances of AI to extract and analyze morphological, textural, and molecular features to reveal the ground truth of TC. Consequently, their combination with AI technology will make individual medical strategies possible.

Many thyroid cancer patients have suffered from treatment delays caused by the coronavirus disease 2019 pandemic. Although there have been many reviews, recommendations, or clinical experiences, clinical evidence that evaluates patient disease status is lacking. The aim of our research was to evaluate thyroid cancer behaviour in the post-COVID-19 era. Patients and Methods: A retrospective study was conducted and thyroid cancer patient data from February 1, 2017 to September 15, 2020 were pooled for analysis. The demographic, ultrasound and pathological data of the pre-and post-COVID-19 groups were compared. Lymph node metastases, tumour size, extrathyroidal extension, and multifocality were compared year-by-year to evaluate annual changes in patient characteristics. Regression analyses were adopted to reveal cancer behaviour along with the admission date interval and to reveal risk factors for lymph node metastasis. Patient ultrasound data were compared before and after the lockdown to assess tumour progression. The outcomes of delays in treatment ≤180 days were then studied. Results: The post-lockdown patients were more likely to have multiple lesions (31.2% vs 36.5%, p = 0.040), extrathyroidal extension (65.5% vs 72.2%, p = 0.011) and lymph node metastases (37.7% vs 45.0%, p = 0.007), while tumour size remained stable (1.01cm vs.1.02cm, p = 0.758). The lymph node metastasis rate increased by year (p < 0.001). The tumour size correlated negatively with the post-lockdown admission date (p = 0.002). No significant difference in tumour size, multifocality or lymph node metastasis on ultrasound was revealed between the pre-and post-lockdown group. No significant difference in tumour size, multifocality, extrathyroidal extension or lymph node metastasis was revealed among patients with a delayed treatment time ≤180 days. Conclusion:Patients with a COVID-19-induced treatment delay had more aggressive cancer behaviour. Rebound medical visits and annually increasing aggressiveness may be potential reasons for this observation, as individual patient tumour did not progress during the delay.

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Despite the fact that levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues, some strategies have been developed. Novel formulations (liquid solutions and soft-gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft-gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.

Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the medications, food and beverages that interact with levothyroxine and to assess their effects, mechanisms and treatments. Methods: A systematic review on interfering substances that interact with levothyroxine was performed. Web of Science, Embase, PubMed, the Cochrane library, grey literature from other sources and the lists of references were searched for human studies comparing the levothyroxine efficacy with and without interfering substances. The patient characteristics, drug classes, effects and mechanism were extracted. The NHLBI study quality assessment tools and the JBI critical appraisal checklist were used to assess the quality of included studies. Results: A total of 107 articles with 128 studies were included. Drugs interactions were revealed in calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants and other drugs. Some food and beverage could also induce malabsorption. Proposed mechanisms included direct complexing, alkalization, alteration of serum thyroxine-binding globulin levels and acceleration of levothyroxine catabolism via deiodination. Dose adjustment, administration separation and discontinuation of interfering substances can eliminate the interactions. Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. The qualities of most included studies were moderate. Conclusion: Lots of medications and food can impair the bioavailability of levothyroxine. Clinicians, patients and pharmaceutical companies should be aware of the possible interactions. Further well-designed studies are needed to provide more solid evidence on treatment and mechanisms.