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International Journal of Molecular... Oct 2023The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound... (Review)
Review
The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound assessment in patients with symptoms of thyroid dysfunction or neck mass. TNs are classified as benign tumours (non-malignant hyperplasia), benign neoplasms (e.g., adenoma, a non-invasive follicular tumour with papillary nuclear features) or malignant carcinomas (follicular cell-derived or C-cell derived). The differential diagnosis is based on fine-needle aspiration biopsies and cytological assessment (which is burdened with the bias of subjectivity). Raman spectroscopy (RS) is a laser-based, semiquantitative technique which shows for oscillations of many chemical groups in one label-free measurement. RS, through the assessment of chemical content, gives insight into tissue state which, in turn, allows for the differentiation of disease on the basis of spectral characteristics. The purpose of this study was to report if RS could be useful in the differential diagnosis of TN. The Web of Science, PubMed, and Scopus were searched from the beginning of the databases up to the end of June 2023. Two investigators independently screened key data using the terms "Raman spectroscopy" and "thyroid". From the 4046 records found initially, we identified 19 studies addressing the differential diagnosis of TNs applying the RS technique. The lasers used included 532, 633, 785, 830, and 1064 nm lines. The thyroid RS investigations were performed at the cellular and/or tissue level, as well as in serum samples. The accuracy of papillary thyroid carcinoma detection is approx. 90%. Furthermore, medullary, and follicular thyroid carcinoma can be detected with up to 100% accuracy. These results might be biased with low numbers of cases in some research and overfitting of models as well as the reference method. The main biochemical changes one can observe in malignancies are as follows: increase of protein, amino acids (like phenylalanine, tyrosine, and tryptophan), and nucleic acid content in comparison with non-malignant TNs. Herein, we present a review of the literature on the application of RS in the differential diagnosis of TNs. This technique seems to have powerful application potential in thyroid tumour diagnosis.
Topics: Male; Female; Humans; Thyroid Nodule; Spectrum Analysis, Raman; Thyroid Neoplasms; Adenocarcinoma, Follicular
PubMed: 37894812
DOI: 10.3390/ijms242015131 -
Thyroid : Official Journal of the... Nov 2022Medullary thyroid cancer (MTC) is a neuroendocrine tumor arising from parafollicular C-cells of the thyroid gland that, in rare cases, can cause a paraneoplastic... (Review)
Review
Medullary thyroid cancer (MTC) is a neuroendocrine tumor arising from parafollicular C-cells of the thyroid gland that, in rare cases, can cause a paraneoplastic ectopic Cushing's syndrome (ECS). The development of Cushing's syndrome (CS) in MTC patients is generally associated with advanced disease and poor prognosis. We described a case of severe CS due to MTC in a young male. We performed a systematic review to identify cases of ECS due to MTC. We searched PubMed, Scopus, and Web of Science for publications between database inception and February 2022 and we collected the patient characteristics, disease presentation, employed treatment strategies, and disease outcomes. In addition to our patient, we identified 96 cases of ECS due to MTC reported in literature. Mean age at diagnosis was 44.4 years (range 10-84), and there was a male predominance (male:female [M:F] = 1.8:1). Most patients (51%) presented with metastatic disease at diagnosis and showed severe hypercortisolism. Seventeen patients developed distant metastasis and hypercortisolism during follow-up. Interestingly, in 48% of patients, the diagnosis of CS followed the diagnosis of MTC with a median time of 48 months but, among patients in whom the diagnosis was concomitant (38%), symptoms due to hypercortisolism were frequently the reason for seeking medical advice. Pathology results showed evidence of adrenocorticotropic hormone (ACTH) or corticotropin releasing hormone (CRH) positive cells in 76% of patients in whom they were tested. The management of hypercortisolism was challenging in most patients with 48% requiring, eventually, definitive treatment with bilateral adrenalectomy (BLA). Recently, some limited evidence has emerged regarding tyrosine kinase inhibitors (TKIs) treatment for hypercortisolism in patients with ECS due to MTC. Despite limited information on survival, prognosis was generally poor and the main causes of death were either complications of CS or disease progression. Despite its rarity, MTC should be considered in the differential diagnosis of ECS. Management of hypercortisolism is a key factor to improve the patient's symptoms but it is often challenging and BLA is frequently required. Further studies are needed for investigating the role of TKIs in patients with MTC with ECS.
Topics: Humans; Male; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Cushing Syndrome; Carcinoma, Neuroendocrine; Thyroid Neoplasms; Adrenocorticotropic Hormone; ACTH Syndrome, Ectopic
PubMed: 35833793
DOI: 10.1089/thy.2021.0696 -
Endocrine-related Cancer Feb 2016In differentiated thyroid carcinoma refractory to radioactive iodine (CDT-RTI), chemotherapy has been considered for decades to be the only systemic therapy with... (Review)
Review
In differentiated thyroid carcinoma refractory to radioactive iodine (CDT-RTI), chemotherapy has been considered for decades to be the only systemic therapy with palliative purpose. Phase II studies assessing the efficacy of different chemotherapy outlines have been published. Nevertheless, phase III studies in these tumours have not been performed. Our objective is to evaluate the effectiveness of chemotherapy in patients with CDT-RTI by a systematic review of published studies. Systematic research of the literature in Medline and Embase databases (among others) was carried out. The full texts of selected references were analysed by two independent reviewers and then assessed for risk of bias in each study. We also extracted data using specifically designed questionnaires. Later, a qualitative synthesis of results was performed and pooled data were calculated. We found that 16 studies with 473 patients published in the last 40 years were included out of 509 identified references in databases. Thirteen studies (176 patients) included data on response to treatment and histology. Four studies included 70 patients only with well-differentiated non-medullary tumours. Response rate (RR) was 22.1% (0-57%) for 13 studies, 25% for the 176 patients and 27.1% for the 70 patients, with 2.5, 3.4 and 2.8% complete responses respectively. Survival times could not be assessed or pooled due to the lack of data and heterogeneity of the studies, and was determined to have a high risk of bias. Although it has not been possible to find solid evidence about the efficacy of chemotherapy, the results shown indicate that it may have some effectiveness, although this should be proven with well-designed studies using modern drugs.
Topics: Adenocarcinoma; Antineoplastic Agents; Disease Progression; Humans; Severity of Illness Index; Thyroid Neoplasms; Treatment Outcome
PubMed: 27064164
DOI: 10.1530/ERC-15-0194 -
The Journal of Clinical Endocrinology... Sep 2015Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS... (Review)
Review
CONTEXT
Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS localization.
EVIDENCE ACQUISITION
Systematic review of medical literature for ECS case series providing individual patient data on at least one conventional imaging technique (computed tomography [CT]/magnetic resonance imaging) and one of the following: 111In-pentetreotide (OCT), 131I/123I-metaiodobenzylguanidine, 18Ffluoro-2-deoxyglucose-positron emission tomography (FDG-PET), 18F-fluorodopa-PET (F-DOPA-PET), 68Ga- DOTATATE-PET/CT or 68Ga-DOTATOC-PET/CT scan (68Gallium-SSTR-PET/CT).
EVIDENCE SUMMARY
The analysis comprised 231 patients (females, 50.2%; age, 42.617 y). Overall, 52.4%(121/231) had "overt" ECS,18.6% had "occult" ECS, and 29% had "covert" ECS. Tumors were located in the lung (55.3%), mediastinum-thymus (7.9%), pancreas (8.5%), adrenal glands (6.4%), gastrointestinal tract (5.4%), thyroid (3.7%), and other sites (12.8%), and primary tumors were mostly bronchial neuroendocrine tumors (NETs) (54.8%), pancreatic NETs (8%), mediastinum-thymus NETs (6.9%), gastrointestinal NETs (5.3%), pheochromocytoma (6.4%), neuroblastoma (3.2%), and medullary thyroid carcinoma (3.2%). Tumors were localized byCTin66.2%(137/207), magnetic resonance imaging in 51.5% (53/103), OCT in 48.9% (84/172), FDG-PET in 51.7% (46/89), F-DOPAPET in 57.1% (12/21), 131/123I-metaiodobenzylguanidine in 30.8% (4/13), and 68Gallium-SSTRPET/CT in 81.8% (18/22) of cases. Molecular imaging discovered 79.1% (53/67) of tumors unidentified by conventional radiology, with OCT the most commonly used, revealing the tumor in 64%, followed by FDG-PET in 59.4%. F-DOPA-PET was used in only seven covert cases (sensitivity, 85.7%). Notably, 68Gallium-SSTR-PET/CT had 100% sensitivity among covert cases.
CONCLUSIONS
Nuclear medicine improves the sensitivity of conventional radiology when tumor site identification is problematic. OCT offers a good availability/reliability ratio, and FDG-PET was proven useful. 68Gallium-SSTR-PET/CT use was infrequent, despite offering the highest sensitivity.
Topics: Cushing Syndrome; Diagnostic Imaging; Humans; Nuclear Medicine; Reproducibility of Results
PubMed: 26158607
DOI: 10.1210/JC.2015-1589 -
BMC Cancer May 2021It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid...
Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.
BACKGROUND
It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.
METHODS
For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.
RESULTS
Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported.
CONCLUSION
Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.
TRIAL REGISTRATION
PROSPERO registration number: CRD42019125245 .
Topics: Carcinoma, Neuroendocrine; Hematologic Diseases; Humans; Iodine Radioisotopes; Octreotide; Organometallic Compounds; Radiation Injuries; Radiation Tolerance; Radiopharmaceuticals; Renal Insufficiency; Thyroid Neoplasms; Treatment Outcome; Yttrium Radioisotopes
PubMed: 34016077
DOI: 10.1186/s12885-021-08257-x -
The Cochrane Database of Systematic... Mar 2020Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC (basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable.
OBJECTIVES
The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add-on test for detection of MTC in people with thyroid nodules.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018.
SELECTION CRITERIA
We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed).
DATA COLLECTION AND ANALYSIS
Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS-2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible.
MAIN RESULTS
In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%. An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow-up in calcitonin-negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment. At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%). Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) .
AUTHORS' CONCLUSIONS
Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.
Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Diagnosis, Differential; Humans; Randomized Controlled Trials as Topic; Thyroid Neoplasms; Thyroid Nodule
PubMed: 32176812
DOI: 10.1002/14651858.CD010159.pub2 -
Cancers Apr 2021A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile... (Review)
Review
Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87-3.12 and OR: 3.41, 95% CI: 1.46-7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47-1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35-1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66-6.48) followed by TKIs (OR:1.51, 95% CI: 0.59-3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64-4.64) and TKIs (OR:1.64, 95% CI: 0.35-7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87-5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.
PubMed: 33946147
DOI: 10.3390/cancers13092159 -
Hormones (Athens, Greece) Oct 2017Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours (NETs). On the other hand, only a few studies have evaluated the detection rate (DR) of this imaging method in recurrent medullary thyroid carcinoma (MTC). We aimed to perform a systematic review and a meta-analysis of the DR of somatostatin receptor PET or PET/CT in patients with recurrent MTC to add evidence-based data to this setting.
METHODS
A comprehensive computer literature search of studies published in PubMed/MEDLINE and the Cochrane Library Database through May 2017 and regarding somatostatin receptor PET or PET/CT in patients with recurrent MTC was carried out. DR was determined on a per patient-basis. A sub-analysis considering serum calcitonin (Ctn) values was also performed.
RESULTS
Nine studies on the diagnostic performance of somatostatin receptor PET or PET/CT in detecting recurrent MTC were discussed in the systematic review. The meta-analysis of these selected studies provided the following DR on a per patient-based analysis: 63.5% [95% confidence interval (95%CI): 49-77]. Heterogeneity among the selected studies was found. DR of somatostatin receptor PET or PET/CT increased in patients with higher serum Ctn levels (83% for Ctn >500 ng/L).
CONCLUSIONS
In patients with recurrent MTC, somatostatin receptor PET or PET/CT demonstrated a non-optimal DR which increased in patients with higher serum Ctn values. The diagnostic performance of somatostatin receptor PET or PET/CT in recurrent MTC is lower compared to that of the same imaging method in the majority of NETs.
Topics: Carcinoma, Neuroendocrine; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Receptors, Somatostatin; Thyroid Neoplasms
PubMed: 29518756
DOI: 10.14310/horm.2002.1756 -
Clinical Endocrinology Dec 2019The significant variation in the clinical behaviour of sporadic medullary thyroid carcinoma (sMTC) causes uncertainty when planning the management of these patients....
BACKGROUND
The significant variation in the clinical behaviour of sporadic medullary thyroid carcinoma (sMTC) causes uncertainty when planning the management of these patients. Several tumour genetic and epigenetic markers have been described, but their clinical usefulness remains unclear. The aim of this review was to evaluate the evidence for the use of molecular genetic and epigenetic profiles in the risk stratification and management of sMTC.
METHODS
MEDLINE and Embase databases were searched using the MeSH terms "medullary carcinoma", "epigenetics", "molecular genetics", "microRNAs"; and free text terms "medullary carcinoma", "sporadic medullary thyroid cancer", "sMTC", "RET", "RAS" and "miR". Articles containing less than ten subjects, not focussing on sMTC, or not reporting clinical outcomes were excluded. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale.
RESULTS
Twenty-three studies met the inclusion criteria, and key findings were summarized in themes according to the genetic and epigenetic markers studied. There is good evidence that somatic RET mutations predict higher rates of lymph node metastasis and persistent disease, and worse survival. There are also several good quality studies demonstrating associations between certain epigenetic markers such as tumour miR-183 and miR-375 expression and higher rates of lymph node and distant metastasis, and worse survival.
CONCLUSIONS
There is a growing body of evidence that tumour genetic and epigenetic profiles can be used to risk stratify patients with sMTC. Further research should focus on the clinical applicability of these findings by investigating the possibility of tailoring management to an individual's tumour mutation profile.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Female; Humans; Lymphatic Metastasis; Male; MicroRNAs; Mutation; Proto-Oncogene Mas; Thyroid Neoplasms
PubMed: 31301229
DOI: 10.1111/cen.14060 -
Head & Neck Aug 2019The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs).
METHODS
We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib-related AEs were calculated using random-effect model.
RESULTS
Eight trials with 101 metastatic MTCs were included for meta-analyses. The overall PR and SD were 21% (95% CI = 9-33) and 58% (95% CI = 41-75), respectively. Hand-foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs.
CONCLUSION
Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.
Topics: Antineoplastic Agents; Carcinoma, Neuroendocrine; Humans; Sorafenib; Thyroid Neoplasms
PubMed: 31162772
DOI: 10.1002/hed.25832