Search

Introduction: Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131). Areas covered: Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023. Expert opinion: In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs. [ABSTRACT FROM AUTHOR]

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 mIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22 +/-0.27 mg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 mIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism(SCH) on CV risk, CVD, andmortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)–ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN–ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN–ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN–ALK), particularly in those with STRN–ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN–ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. Methods: This is a retrospective, single-center observational study conducted over 16 years (2001–2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy. Results: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases. Conclusions: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin. [ABSTRACT FROM AUTHOR]