Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients.

Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine

State of the art and future directions in the systemic treatment of medullary thyroid cancer

PURPOSE OF REVIEW: Systemic treatment is the only therapeutic option for patients with progressive, metastatic medullary thyroid cancer (MTC). Since the discovery of the rearranged during transfection (RET) proto-oncogene (100% hereditary, 60-90% sporadic MTC), research has focused on finding effective systemic therapies to target this mutation. This review surveys recent findings. RECENT FINDINGS: Multikinase inhibitors are systemic agents targeting angiogenesis, inhibiting growth of tumor cells and cells in the tumor environment and healthy endothelium. In the phase III EXAM and ZETA trials, cabozantinib and vandetanib showed progression-free survival benefit, without evidence of prolonged overall survival. Selpercatinib and pralsetinib are kinase inhibitors with high specificity for RET; phase I and II studies showed overall response rates of 73% and 71% in first line, and 69% and 60% in second line treatment, respectively. Although resistance mechanisms to mutation-driven therapy will be a challenge in the future, phase III studies are ongoing and neo-adjuvant therapy with selpercatinib is being studied. SUMMARY: The development of selective RET-inhibitors has expanded the therapeutic arsenal to control tumor growth in progressive MTC, with fewer adverse effects than multikinase inhibitors. Future studies should confirm their effectiveness, study neo-adjuvant strategies, and tackle resistance to these inhibitors, ultimately to improve patient outcomes

Recent results of basic and clinical research in MEN1:opportunities to improve early detection and treatment

Due to the variable expression of multiple endocrine neoplasia type 1 (MEN1), it is difficult to predict the course of the disease. However, knowledge about the normal function of the MEN1 gene product, together with the effects of cellular derangement by subsequent genetic events, has increased considerably. At first, the possible existence of a genotype-phenotype correlation is discussed. Thus, mild-and late-onset phenotypes may be distinguished from more malignant phenotypes depending on the character of the primary MEN1 disease gene mutation. Subsequently, tumor-promoting factors such as gender, additional genetic mutations and ecogenetic factors may contribute to the course of the disease. New developments in management are based on the knowledge and experience of the multidisciplinary teams involved. Finally, the metabolic effects of MEN1 mutations in aged patients are discussed. Early identification of predisposition to the disease, together with knowledge about the natural history of specific mutations, risks of additional mutations and periodic clinical monitoring, allow early treatment and may improve life expectancy and quality of life

The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs

Cardiovascular effects of overt and subclinical hyperthyroidism:focus on differentiated thyroid cancer

Thyroid hormone stimulates cardiac inotropy and chronotropy via direct genomic and non-genomic mechanisms. Hyperthyroidism magnifies these effects, resulting in an increase in heart rate, ejection fraction and blood volume. Hyperthyroidism also affects thrombogenesis and this may be linked to a probable tendency towards thrombosis in patients with hyperthyroidism. Patients with hyperthyroidism are therefore at higher risk for atrial fibrillation, heart failure and cardiovascular mortality. Similarly, TSH suppressive therapy for differentiated thyroid cancer is associated with increased cardiovascular risk. In this review, we present the latest insights on the cardiac effects of thyroid suppression therapy for the treatment of thyroid cancer. Finally, we will show new clinical data on how to implement this knowledge into the clinical practice of preventive medicine

The Diagnostic Value of 18F-FDG PET/CT Scan in Characterizing Adrenal Tumors

CONTEXT: Imaging plays an important role in the characterization of adrenal tumors, but findings might be inconclusive. The clinical question is whether 18F fluodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is of diagnostic value in this setting.OBJECTIVE: This meta-analysis was aimed at the diagnostic value of 18F-FDG PET/CT in differentiating benign from malignant adrenal tumors discovered either as adrenal incidentaloma or during staging or follow-up of oncologic patients.DATA SOURCES: PubMed, EMBASE, Web of Science, and Cochrane Library were searched to select articles between 2000 and 2021.STUDY SELECTION: We included studies describing the diagnostic value of 18F-FDG PET/CT in adult patients with an adrenal tumor. Exclusion criteria were 10 or fewer participants, insufficient data on histopathology, clinical follow-up, or PET results. After screening of title and abstract by 2 independent reviewers, 79 studies were retrieved, of which 17 studies met the selection criteria.DATA EXTRACTION: Data extraction using a protocol and quality assessment according to QUADAS-2 was performed independently by at least 2 authors.DATA SYNTHESIS: A bivariate random-effects model was applied using R (version 3.6.2.). Pooled sensitivity and specificity of 18F-FDG PET/CT for identifying malignant adrenal tumors was 87.3% (95% CI, 82.5%-90.9%) and 84.7% (95% CI, 79.3%-88.9%), respectively. The pooled diagnostic odds ratio was 9.20 (95% CI, 5.27-16.08; P &lt; .01). Major sources of heterogeneity (I2, 57.1% [95% CI, 27.5%-74.6%]) were in population characteristics, reference standard, and interpretation criteria of imaging results.CONCLUSIONS: 18F-FDG PET/CT had good diagnostic accuracy for characterization of adrenal tumors. The literature, however, is limited, in particular regarding adrenal incidentalomas. Large prospective studies in well-defined patient populations with application of validated cutoff values are needed.</p

Surgical Complications and Referral Patterns in 567 Patients with Differentiated Thyroid Cancer in the Northern Region of the Netherlands:A Population-Based Study Towards Clinical Management Implementation

Background In the Netherlands, differentiated thyroid cancer (DTC) is treated surgically in three different hospital types, including university, teaching, and non- teaching peripheral hospitals. This study evaluates postoperative complications and referral patterns in patients with DTC in the northern region of the Netherlands to gain an understanding on how to improve management implementation. Methods Data from 567 patients diagnosed between 1989 and 2009 were obtained from the Netherlands Cancer Registry and were supplemented with information from hospital digital information systems and patient records from 15 hospitals: 1 university, 3 teaching, and 11 peripheral hospitals. Surgically treated patients with a histologically proven DTC derived from the original pathology reports were included. Results Surgical treatment could be performed in a single procedure in 234 patients (41.3%), but several surgeries were needed in the remaining 333 patients (58.7%). Recurrent laryngeal nerve (RLN) palsy occurred after all types of thyroid surgical procedures, but mostly after initial (hemi)thyroidectomy and reoperations. RLN was temporary in 3.2% of the nerves at risk and persistent in 1.8%. Temporary hypocalcemia developed in 13.7% of patients, and persistent hypocalcemia occurred in 4.8%. Patients were mainly referred to the university hospital from a non-teaching (40.7%, 48/118) or teaching hospital (11.1%, 16/144); however, 80% of patients were not referred. Conclusions The complication rate and number of multiple surgeries support the efforts in optimizing clinical management in thyroid cancer. Careful considerations prior to initial surgical treatment by early discussion in telemedicine-based regional tumor boards could possibly prevent reoperations and potentially diminish complications