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Endocrine-related Cancer Jul 2019Thyrotoxicosis with concomitant thyroid cancer is rare and poorly recognized, which may result in delayed diagnosis, inappropriate treatment and even poor prognosis. To...
Thyrotoxicosis with concomitant thyroid cancer is rare and poorly recognized, which may result in delayed diagnosis, inappropriate treatment and even poor prognosis. To provide a comprehensive guidance for clinicians, the etiology, pathogenesis, diagnosis and treatment of this challenging setting were systematically reviewed. According to literatures available, the etiologies of thyrotoxicosis with concomitant thyroid cancer were categorized into Graves' disease with concurrent differentiated thyroid cancer (DTC) or medullary thyroid cancer, Marine-Lenhart Syndrome with coexisting DTC, Plummer's disease with concomitant DTC, amiodarone-induced thyrotoxicosis with concomitant DTC, central hyperthyroidism with coexisting DTC, hyperfunctioning metastases of DTC and others. The underlying causal mechanisms linking thyrotoxicosis and thyroid cancer were elucidated. Medical history, biochemical assessments, radioiodine uptake, anatomic and metabolic imaging and ultrasonography-guided fine-needle aspiration combined with pathological examinations were found to be critical for precise diagnosis. Surgery remains a mainstay in both tumor elimination and control of thyrotoxicosis, while anti-thyroid drugs, beta-blockers, 131I, glucocorticoids, plasmapheresis, somatostatin analogs, dopamine agonists, radiation therapy, chemotherapy and tyrosine kinase inhibitors should also be appropriately utilized as needed.
Topics: Combined Modality Therapy; Diagnosis, Differential; Disease Management; Humans; Hyperthyroidism; Thyroid Neoplasms; Thyroidectomy; Thyrotoxicosis
PubMed: 31026810
DOI: 10.1530/ERC-19-0129 -
Anticancer Research Aug 2016Medullary thyroid cancer (MTC) is a rare but aggressive thyroid malignancy. The gold-standard biomarker for its diagnosis and follow-up is calcitonin (CT); however, it... (Review)
Review
Medullary thyroid cancer (MTC) is a rare but aggressive thyroid malignancy. The gold-standard biomarker for its diagnosis and follow-up is calcitonin (CT); however, it has a variable half-life dependent on its circadian variability. It has been suggested that a more stable hormone, procalcitonin (PCT), may overcome these problems and its introduction to routine practice may give more accurate results in the diagnosis and follow-up of MTC. We systematically reviewed Pubmed, Scopus, Biosis Previews and Embase databases up to March 2016. A total of 15 out of 184 articles were retrieved and analyzed. Of these 15 studies, 3 were case reports. In these 15 studies, the values of CT and PCT were assessed in both patients with MTC and patients that were either healthy volunteers or with benign/malignant thyroid nodular disease or with bacterial infection. Our search suggests that PCT seems to be a useful biomarker for the diagnosis and follow-up of MTC when used in conjunction with CT, particularly in a small proportion of tumors that are CT-negative or secrete low levels of CT. So far, there has not been enough data to suggest a specific threshold for normal PCT. However, most studies indicate a value of 0.1 ng/ml as an acceptable cut-off in everyday clinical practice. At present, CT should continue to be the primary biomarker in MTC with the addition of PCT in some patient groups. Nevertheless, larger patient series need to be conducted in order to provide safer and more accurate results.
Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Neuroendocrine; Circadian Clocks; Humans; Thyroid Neoplasms
PubMed: 27466480
DOI: No ID Found -
Diagnostic Cytopathology Jan 2016The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC).... (Review)
Review
BACKGROUND
The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates.
RESEARCH DESIGN AND METHODS
A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015.
RESULTS
Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report.
CONCLUSIONS
The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.
Topics: Biomarkers, Tumor; Biopsy, Fine-Needle; Calcitonin; Carcinoma, Neuroendocrine; Diagnosis, Differential; Gene Expression; Humans; Lymph Nodes; Practice Guidelines as Topic; Sensitivity and Specificity; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 26481456
DOI: 10.1002/dc.23375 -
Reviews in Endocrine & Metabolic... Aug 2023Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally accepted for several reasons, including the lack of recommendations for managing indeterminate Ctn values (ICV); such as 10-to-100 pg/mL. This study aimed to gather data on 1) the frequency of ICV among patients undergoing Ctn test and 2) the MTC rate among patients with ICV.
METHODS
This review was conducted according to the Meta-analyses Of Observational Studies in Epidemiology guidelines. PubMed and Cochrane databases were searched, with no language restrictions. The final search was completed on January 2023. Then, quality assessment and proportion meta-analyses were performed.
RESULTS
The online search retrieved 233 articles and 15 were included for quantitative analysis. The risk of bias was low. The number of patients undergone Ctn testing was 29,533. The pooled percentage of those with ICV was 1.7% (95% confidence interval [CI]:1.2-2.3). The pooled proportion of MTC incidence among patients with ICV was 9.6% (95% CI:5-14.1). Heterogeneity was explained by the covariates of Ctn assay sensitivity and the resection rate. The subgroup with Ctn 10-20 pg/mL showed a significantly lower MTC rate than the subgroup with Ctn 20-100 pg/mL.
CONCLUSIONS
The percentage of ICV among patients with thyroid nodules who underwent Ctn testing is negligible. The rate of MTC in patients with ICV cannot be overlooked. Among the ICV intervals, the risk of MTC increases significantly when Ctn is above 20 pg/mL.
Topics: Humans; Thyroid Nodule; Calcitonin; Prevalence; Thyroid Neoplasms
PubMed: 37254023
DOI: 10.1007/s11154-023-09811-7 -
Recent Patents on Anti-cancer Drug... 2016Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC.
OBJECTIVE
The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC.
METHODS
A systematic review was performed using Pubmed and Google patents databases.
RESULTS
We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field.
CONCLUSION
Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Drug Design; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Proto-Oncogene Mas; Thyroid Neoplasms
PubMed: 27306881
DOI: 10.2174/1574892811666160614115356 -
American Journal of Otolaryngology 2022Medullary thyroid carcinoma (MTC) is a rare and aggressive form of thyroid neoplasia that requires multidisciplinary collaboration for effective management. We...
PURPOSE
Medullary thyroid carcinoma (MTC) is a rare and aggressive form of thyroid neoplasia that requires multidisciplinary collaboration for effective management. We systematically appraise the quality of clinical practice guidelines (CPG) for the diagnosis and treatment of MTC using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.
MATERIALS AND METHODS
A systematic literature search was performed to identify CPGs pertaining to the diagnosis and treatment of MTC. Data were abstracted from guidelines meeting inclusion criteria and appraised by four independent reviewers in the six domains of quality defined by the AGREE II. Intraclass correlation coefficients (ICC) were calculated across domains to qualify interrater reliability.
RESULTS
Fourteen guidelines met inclusion criteria. No guideline achieved a score of >60 % in five or more AGREE II quality domains, which is required to gain designation as 'high' quality. One "average quality" guideline authored by the British Thyroid Association achieved a score of >60 % in three quality domains. The remaining thirteen (92.9 %) CPGs demonstrated low quality content, with deficits most pronounced in domains 3, 5, and 6, suggesting a lack of rigorously developed, clinically applicable, and transparent information.
CONCLUSIONS
As the diagnosis and treatment of MTC continues to evolve, the development of high-quality guidelines becomes increasingly important; few existing meet appropriate standards.
Topics: Humans; Carcinoma, Neuroendocrine; Reproducibility of Results; Thyroid Neoplasms
PubMed: 36037729
DOI: 10.1016/j.amjoto.2022.103606 -
The British Journal of Radiology Aug 2023Although it is generally accepted that medullary thyroid cancer (MTC) cells do not take up iodine, there are reports indicating that this can occur. Additionally, the...
OBJECTIVES
Although it is generally accepted that medullary thyroid cancer (MTC) cells do not take up iodine, there are reports indicating that this can occur. Additionally, the potential for radioactive iodine (RAI) to reduce the risk of recurrence within the thyroid bed following thyroid remnant ablation in MTC is uncertain. A systematic review was therefore undertaken.
METHODS
Studies of patients with MTC of any age or stage receiving RAI, either as adjuvant postoperative treatment or primary treatment for unresectable disease, or as treatment for recurrent or metastatic disease were eligible for inclusion. Randomised and non-randomised studies were identified by electronic searching of Medline and Embase databases. A risk of bias assessment (ROBINS-I) was carried out for each study. Outcome measures sought included overall survival, locoregional relapse-free survival, rates of locoregional recurrence, and changes in serum calcitonin. A protocol was registered with PROSPERO before the systematic review was undertaken.
RESULTS
There were no randomised studies. Ten non-randomised studies (525 patients) and ten case reports (21 patients) met the inclusion criteria, with all studies containing a high risk of bias. There were case reports reporting responses to RAI, both as adjuvant treatment and for recurrent/metastatic disease.
CONCLUSIONS
The proportion of metastatic or recurrent MTC which take up iodine remains unknown. A possible role of RAI ablation for patients with localised MTC and raised calcitonin post-thyroidectomy should be explored.
ADVANCES IN KNOWLEDGE
Although there is insufficient data to recommend changes to current treatment policies, this review suggests avenues for further research.
Topics: Humans; Thyroid Neoplasms; Carcinoma, Medullary; Iodine Radioisotopes; Calcitonin; Neoplasm Recurrence, Local; Thyroidectomy; Retrospective Studies
PubMed: 37335288
DOI: 10.1259/bjr.20220660 -
Biomedicines Mar 2023We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive... (Review)
Review
Efficacy and Safety of [Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.
BACKGROUND
We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC).
METHODS
Studies identified in PubMed from inception to 13 May 2021 must have assessed [Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest.
RESULTS
Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL ( = 7), bronchial NETs ( = 6; one also included NETs of unknown origin), and MTC ( = 3). Overall, [Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs.
CONCLUSIONS
[Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.
PubMed: 37189646
DOI: 10.3390/biomedicines11041024 -
European Thyroid Journal Apr 2021Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are...
INTRODUCTION
Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC.
METHODS
We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported.
RESULTS
Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates.
CONCLUSION
Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.
PubMed: 33981617
DOI: 10.1159/000509457 -
Nuclear Medicine Communications Dec 2023Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most... (Meta-Analysis)
Meta-Analysis
Sensitivities evaluation of five radiopharmaceuticals in four common medullary thyroid carcinoma metastatic sites on PET/CT: a network meta-analysis and systematic review.
OBJECTIVES
Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most effective method in recent years. However, the sensitivity of each radiopharmaceutical varies greatly in different metastatic sites. We aim to investigate and compare five novel and common PET or PET/CT radiopharmaceutical sensitivities at the four most frequent metastatic sites by network meta-analysis.
METHODS
We searched for studies evaluating PET/CT radiopharmaceutical sensitivities at different metastatic sites in PubMed, Web of Science, Embase, and Cochrane Library. The risk bias was analyzed, and publication bias was accessed by funnel plot asymmetry tests. We performed both global inconsistency and local inconsistency tests by evaluating the agreement between direct and indirect comparisons. Then, we made pairwise meta-analyses and network meta-analyses for each metastatic site. Finally, we performed the surface under the cumulative ranking curves (SUCRA) and calculated the SUCRA values to rank the probability of each radiopharmaceutical being the most sensitive method.
RESULTS
In our results, 243 patients from 9 clinical studies which accessed sensitivities of different radiopharmaceuticals in MTC metastatic sites were included. For lymph nodes and liver, TF2/ 68 Ga-SSM288 showed the highest SUCRA values (0.974 in lymph nodes, 0.979 in liver). The SUCRA values for 18 F-DOPA and 68 Ga-SSA for bone metastatic lesions were nearly identical (0.301 and 0.319, respectively) and were higher than the other three radiopharmaceuticals. For lung lesions, 11 C-methionine had the highest SUCRA value (0.412).
CONCLUSION
TF2/ 68 Ga-SSM288 had the best sensitivity in lymph nodes and liver lesions. 11 C-methionine was most sensitive in lung lesions. While 18 F-DOPA and 68 Ga-SSA had familiar sensitivities to be the best two radiopharmaceuticals.
Topics: Humans; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Network Meta-Analysis; Thyroid Neoplasms; Dihydroxyphenylalanine; Methionine
PubMed: 37769014
DOI: 10.1097/MNM.0000000000001773