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Objective:To investigate the efficacy and prognosis of different surgical approaches in sporadic medullary thyroid carcinoma.Methods:A retrospective analysis was conducted on 101 patients with sporadic medullary thyroid carcinoma (MTC) who underwent surgical treatment at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, from Feb. 2009 to Nov. 2023. The patients included 36 males and 75 females, with a male-to-female ratio of 1:2.1. The median age of the patients was 47 years old, with an age range of 21 to 72 years old. The study divided participants into two groups based on their surgical methods: an observation group (78 cases) and a control group (23 cases). The observation group received surgical methods in accordance with expert consensus, while the control group did not. The study compared the efficacy and prognosis of the two groups.Results:Statistical differences were found between the two groups in terms of stage II and III in TNM staging, intraoperative frozen pathological findings, number of lymph node resections in the central group, number of lymph node metastases in the central group, number of lymph node resections in the lateral cervical region, postoperative follow-up time, and five-year postoperative serum procalcitonin (Ctn) levels ( P<0.05) .Both groups of patients obtained a significant decrease in Ctn after surgical treatment. In the observation group, Ctn was at the remission level in 57 cases (73.1%), at the stable level in 13 cases (16.7%), and at the progression level in 8 cases (10.2%), while in the control group, Ctn was at the remission level in 20 cases (86.9%), at the progression level in 3 cases (13.1%), and there were no patients at the stable level after the operation.One patient (1.3 per cent) in the observation group had a recurrence after surgery; Two patients (8.7 per cent) in the control group had a recurrence. Conclusions:Standardised and thorough surgery can maximise the clearance of metastatic lymph nodes, effectively reduce the recurrence rate, achieve better efficacy, and improve the long-term prognosis of patients without increasing the risk of surgery and postoperative complications.
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ABSTRACT Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, it can also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT) and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastases of MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.
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Objective: To investigate the feasibility and value of histogram analysis based on two-dimensional gray-scale ultrasonography in the differential diagnosis of medullary thyroid carcinoma (MTC) and thyroid adenoma (TA). Methods: The preoperative ultrasound images of 86 newly diagnosed MTC patients and 100 TA patients treated in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2015 to October 2021 were collected. Histograms were performed based on the regions of interest (ROIs) delineated manually by two radiologists, thereafter, mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th) were generated. The histogram parameters between the MTC group and the TA group were compared, and the independent predictors were screened by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to compare the individual diagnostic efficacy and joint diagnostic efficacy of independent predictors. Results: Multivariate regression analysis showed that mean, skewness, kurtosis and 50th percentile were independent factors. The skewness and kurtosis in the MTC group were significantly higher than those in the TA group, and the mean and 50th percentile were significantly lower than those in the TA group. The area under the individual ROC curve of mean, skewness, kurtosis and 50th percentile is 0.654-0.778. The area under the combined ROC curve is 0.826. Conclusion: Histogram analysis based on two-dimensional gray-scale ultrasonography is a promising tool to distinguish MTC from TA, in which the joint diagnosis value of mean, skewness, kurtosis and 50th percentile is the highest.
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Humanos , Curva ROC , Diagnóstico Diferencial , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing year by year showing younger trend. The pathological types of thyroid cancer are papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are the two common types of thyroid cancer. Since MTC and PTC have different biological origins, invasiveness and prognosis. Therefore, the occurrence of both medullary carcinoma and papillary carcinoma is very rare and rarely reported in China and abroad and the treatment is challenging. In this paper, we review the pathogenesis, ancillary tests, diagnosis and treatment of this disease, with the aim of providing reference for clinical treatment of patients with medullary thyroid carcinoma complicated by papillary carcinoma.
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Purpose To explore the value of insulinoma associated protein 1(INSM1)in the pathological diagnosis and differential diagnosis of medullary thyroid carcinoma(MTC).Methods Twenty-eight cases of MTC were collected as the ex-perimental group and 25 cases of thyroid tumors(6 cases of transparent trabecular tumors,16 cases of poorly differentiated cancer,2 cases of spindle cell papillary carcinoma,and 1 case of thyroid paraganglioma)that needed to be differentiated from MTC in the same period were collected as the control group.The expression of INSM1 was detected using immunohistochemical EnVision method,and the sensitivity and specificity of INSM1 in MTC were analyzed,and compared with traditional MTC markers(Syn,CgA,CT,and CEA).Results The positive rate of IN-SM1 in the MTC group was96.4%(27/28),significantly high-er than the control group of 4.0%(1/25)(P<0.05).INSM1 had a sensitivity of 96.4%in MTC,significantly higher than CgA(71.4%)(P<0.05),and was positively expressed in CT negative MTC cases.The specificity of INSM1 in MTC was 96.0%,significantly higher than that of CEA(72.0%)(P<0.05).Conclusion INSM1 has high sensitivity and specificity in MTC,with a nuclear positive staining pattern,clear back-ground,and easy identification.It is superior to the traditional biomarkers and has high diagnostic value in MTC.
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Objective:To investigate the correlation of preoperative platelet distribution width (PDW) with clinical features and prognosis of patients with medullary thyroid carcinoma (MTC) .Methods:The clinical data of 160 MTC patients admitted to Zhejiang Cancer Hospital in Department of Head and Neck Surgery from Jun. 2007 to Sep. 2021 were retrospectively collected. There were 74 males and 86 females, aging 8-77 years (mean 48.73±13.76). The median was used to determine the cut-off value of PDW and divided into low PDW group and high PDW group. The correlation between preoperative PDW and clinicopathological features of MTC patients was analyzed by Chi-square test and Spearman correlation test. The relationship of preoperative PDW with overall survival (OS) and disease free survival (DFS) of patients were analyzed by Kaplan-meier and Log-rank test. Univariate and multivariate Cox regression analyses were used to analyze the risk factors for DFS in MTC patients.Results:The preoperative PDW level was closely correlated with the tumor size ( χ2=4.46, P=0.035), TNM stage ( χ2=5.02, P=0.025), bilateral lesions ( χ2=4.94, P=0.026) ,multiple lesions ( χ2=5.19, P=0.023), capsular invasion ( χ2=5.75, P=0.017), extrandular invasion ( χ2=4.27, P=0.039), and vascular tumor thrombus ( χ2=4.48, P=0.034) in MTC patients ( P<0.05). Spearman correlation test showed that preoperative PDW level was negatively correlated with clinical stage ( r=-0.166, P=0.036), lymph node metastasis ( r=-0.187, P=0.018), multiple lesions ( r=-0.176, P=0.026) and vascular tumor thrombus ( r=-0.220, P=0.005) in MTC patients ( P<0.05). Survival analysis showed that reduced PDW predicted worse DFS for MTC ( χ2=9.989, P=0.002). Multivariate Cox regression analysis showed that low PDW ( OR=0.847, 95% CI:0.724-0.992, P=0.040) and lymph node metastasis ( OR=4.913, 95% CI:2.415-9.995, P<0.001) were independent risk factors for DFS in MTC patients. Conclusion:Preoperative decreased PDW is a high risk factor for poor prognosis of MTC and can be used as an indicator to predict recurrence in MTC patients.
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Medullary thyroid carcinoma is a rare malignancy. We report a case of Medullary thyroid carcinoma in a 56-year-old male patient. Patient presented with lower limb paresis and severe hypokalemia. Cushing’s syndrome is a rare complication of Medullary thyroid carcinoma [MTC] and is due to ectopic Adrenocorticotropic [ACTH] secretion by tumor cells. Cushing’s syndrome presents a challenging diagnostic and management issue in patients with MTC. Entire clinical history, laboratory investigations, microscopic pictures are discussed in detail.
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Objective:To investigate the risk factors of cervical lymph node metastasis (LNM) and survival analysis in patients with medullary thyroid carcinoma (MTC) .Methods:93 patients with MTC admitted to the Department of General Surgery and Department of Otorhinolaryngology, First Medical Center of PLA General Hospital from Sep. 2008 to Aug. 2020 were analyzed retrospectively, including 45 males and 48 females, with an average age of 47 years old. SPSS 26.0 statistical software was used for data processing of the initial surgical year and procedures, tumor pathological stages, preoperative calcitonin (Ctn) level, preoperative carcinoembryonic antigen (CEA) level, LNM status, recurrence free survival (RFS) , etc. The risk factors of LNM and prognosis of MTC patients were analyzed by COX univariate and multivariate regression. Kaplan Meier method was used to estimate the survival rates of independent risk factors affecting prognosis and draw their survival curves.Results:The median follow-up time of 93 patients was 53 months, ranging from 2 to 192 months. The 1-year, 3-year, 5-year and 10-year survival rates were 97.8%, 96.6%, 94.6% and 88.9% respectively. Multivariate COX regression analysis showed that Initial surgical procedures ( P=0.018) and preoperative Ctn level ( P=0.012) were independent risk factors of central cervical LNM. Preoperative Ctn level ( P=0.028) and Capsule invasion ( P=0.024) were the independent risk factors of lateral cervical LNM. Preoperative Ctn level≥180.30 pg/ml and ≥234.15pg/ml indicated central and lateral cervical LNM respectively (all P<0.001) . Distant metastasis was an independent risk factor of RFS ( P=0.037) of MTC. Conclusions:Standardized surgical procedures are recommended for initial treatment of MTC, which can reduce the possibility of residual occult metastasis and the risk of reoperation. Distant metastasis affects prognosis of MTC.
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【Objective】 To investigate the clinical features and gene analysis of one pedigree with multiple endocrine neoplasia type 2A （MEN2A） so as to clarify the diagnosis and classification of the disease， guide treatment and prevention， and improve prognosis. 【Methods】 The clinical data of a 36-member MEN2A family， including 6 probands， with medullary thyroid carcinoma， were investigated， and the peripheral blood genomic DNA of 28 family members （blood sample of one proband was not collected） was extracted. PCR amplification was performed on exons 8， 10， 11， 13， 14， 15 and 16 of the RET gene， and the products were directly sequenced. 【Results】 Review of the medical history showed that two probands with medullary thyroid carcinoma were accompanied with hyperparathyroidism， and one family member had pheochromocytoma. The RET gene mutation test confirmed that 13 family members， consisting of 5 probands and 8 family members， had the RET proto-oncogene exon 10 missense mutation. The heterozygous missense had mutation c.1852T>A， leading to the conversion of cysteine （TGC） at position 618 to serine （AGC） （Cys618Ser）. All subjects carrying RET gene Cys618Ser mutation had abnormal thyroid ultrasound change， accompanied with elevated calcitonin levels. Subjects carrying wild type of RET gene had normal calcitonin levels. The family was finally diagnosed with MEN2A by RET gene detection. 【Conclusion】 RET gene detection plays key role in the diagnosis and treatment of patients with MEN2A family and has guiding value in the follow-up and prognosis of asymptomatic carriers. There is a positive correlation between calcitonin level and the RET protooncogene mutation Cys618Ser. Patients suspected of MEN2A should be screened in time.
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Introducción: El carcinoma medular de tiroides, representa aproximadamente entre el 5 - 10 por ciento de todos los carcinomas tiroideos, aparece con más frecuencia entre los 25 y 60 años y en el sexo femenino. Se distinguen dos tipos: el esporádico (no hereditario) y el familiar (hereditario). La localización más frecuente es la unión del tercio superior de lóbulo tiroideo con el tercio medio, que es la zona de mayor concentración de células C. Objetivo: Presentar el caso de paciente masculino operado de carcinoma medular de tiroides, tipo esporádico, en la provincia de Cienfuegos. Caso clínico: Paciente masculino de 60 años de edad, piel blanca, que acudió a la consulta; refiere aumento de volumen del cuello acompañado de disfonía y disfagia a los alimentos sólidos. Al examen físico se constató la presencia del nódulo tiroideo. Se le realizó ultrasonido que corrobora la presencia de un nódulo en el lóbulo derecho del tiroides. La biopsia por aspiración con aguja fina informó el nódulo como sospechoso de malignidad. Se le realizó tiroidectomía total, informándose por la biopsia por parafina de la pieza como un carcinoma medular del tiroides. En la actualidad lleva 6 meses de operado con evolución favorable. Conclusiones: El carcinoma medular de tiroides constituye una entidad rara y agresiva más frecuente en los pacientes mayores de 45 años, cuyo tratamiento de elección es la cirugía(AU)
Introduction: Medullary thyroid carcinoma accounts for approximately 5-10 percent of all thyroid carcinomas. It appears more frequently at ages 25-60 years and in females. Two types are distinguished: sporadic (nonhereditary) and familial (hereditary). The most common location is the union of the upper third of the thyroid lobe to the middle third, the area with the highest concentration of C cells. Objective: To present the case of a male patient operated on for medullary thyroid carcinoma, of sporadic type, in the Cienfuegos Province. Clinical case: A 60-year-old male patient of white skin attended consultation. He reported an increase in neck volume accompanied by dysphonia and dysphagia for solid food. The physical examination revealed the presence of the thyroid nodule. Ultrasound was performed, which confirmed the presence of a nodule in the right lobe of the thyroid. Fine needle aspiration biopsy reported the nodule as suspicious for malignancy. A total thyroidectomy was performed, after which, paraffin biopsy of the specimen permitted to report a medullary carcinoma of the thyroid. At present, he has been operating for six months, with favorable evolution. Conclusions: Medullary thyroid carcinoma is a rare and aggressive entity, more frequent in patients over 45 years of age, whose treatment of choice is surgery(AU)
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Humanos , Masculino , Pessoa de Meia-Idade , Tireoidectomia/métodos , Neoplasias da Glândula Tireoide/etiologia , Carcinoma Medular/epidemiologia , Biópsia por Agulha Fina , Seleção de Sítio de Tratamento de Resíduos , Relatório de PesquisaRESUMO
Objective:To investigate the pathogenesis of Cushing′s syndrome induced by medullary thyroid carcinoma.Methods:Started from April 2011 to present, three medullary thyroid carcinoma patients with Cushing′s syndrome were enrolled in this study. All patients were 40 to 50 years old, one female and two males. The blood pressure, blood glucose, thyroid function and antibodies, calcitonin, and carcinoembryonic antigen(CEA)were detected. The qualitative and localized diagnosis of Cushing′s syndrome was performed by high- and low-dose dexamethasone suppression tests as well as imaging examinations. The biopsies of all patients were taken to test the immunostaining of calcitonin, adrenocorticotropin(ACTH), and corticotropin-releasing hormone(CRH).Results:According to the clinical manifestation and function tests, three patients were diagnosed as medullary thyroid carcinoma accompanied by ACTH-dependent Cushing′s syndrome. All patients showed positive immunohistochemical staining of calcitonin and CRH, with negative immunostaining of ACTH in one and positive immunostaining of ACTH in two patients. Therefore, the diagnosis of ectopic CRH syndrome caused by medullary thyroid carcinoma was definite.Conclusions:Medullary thyroid carcinoma is a rare cause of Cushing′s syndrome. Tumor cells secrete ACTH and CRH, which in turn cause hypercorticoremia. Ectopic CRH syndrome is very rare. Early diagnosis can be made by immunohistochemical staining of biopsy tissues to guide early targeted treatment and improve the prognosis.
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Multiple endocrine neoplasia-IIb (MEN-IIb) is a rare hereditary autosomal dominant syndrome caused by mutations in the RET proto-oncogene. It's characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), mucosal neuromas, and Marfanoid habitus. Because of the rarity of MEN-IIb and finiteness of clinical cognition, the majority of the patients suffer a delayed diagnosis. A MEN-IIb patient with the lingual mucosal neuromas since childhood was admitted in the Third Xiangya Hospital of Central South University in November, 2018. He had surgical history of mitral valve prolapse and spinal deformity. He was diagnosed with MTC and PHEO at the age of 22 and 28, respectively, and received surgical treatments. Sequencing of RET gene revealed a de novo heterozygous p.M918T mutation in the patient. Being aware of the unique clinical phenotype and screening of RET gene mutation may lead to the early diagnosis and better long-term outcome for MEN-IIb.
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Criança , Humanos , Masculino , Neoplasias das Glândulas Suprarrenais , Genes , Neoplasia Endócrina Múltipla , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2b/genética , Mutação , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genéticaRESUMO
Medullary thyroid carcinoma (MTC) constitutes around 5% of all thyroid cancers with a worse prognosis. It accounts for 13% ofthyroid cancer-related deaths. A 23-year-old male presented with a 4-year history of progressively increasing thyroid swellingwith similar family history. On examination, butterfly-shaped firm swelling of size 7 × 3 cm in the right and 7 × 4 cm in the leftseen on the anterior aspect of neck with regular margins and nodular surface moving with deglutition extending from the thyroidcartilage to clavicle head and laterally beyond the sternocleidomastoid into the posterior triangle muscle. Pemberton’s signwas negative. Computed tomography neck showed enlarged both thyroid lobes with areas of cystic degeneration and 15 mmretrosternal extension of the left lobe of thyroid with bilateral IB, II, and V lymphadenopathy. Serum calcitonin level was 4435 pg/ml.Fine-needle aspiration cytology favored features of MTC. Total thyroidectomy with central compartment neck dissection wasdone. Intraoperative frozen sections of bilateral level III were found to be tumor free, so proceeded with thyroid excision andcentral compartment neck dissection. Histopathology revealed MTC with bilateral multifocal capsular and lymphovascularinvasion and metastatic foci in the right central compartment lymph node. Hence, early diagnosis in family members offers ahigher likelihood of cure and long-term survival.
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Existe mucha controversia sobre los beneficios de la medición de la calcitonina sérica (CT) durante la evaluación inicial de pacientes con nódulos tiroideos. El objetivo del estudio fue evaluar la identificación temprana del carcinoma medular de tiroides (CMT) a través de la medición rutinaria de CT sérica en una cohorte de Buenos Aires, Argentina. Se estudiaron consecutivamente a los pacientes con enfermedad nodular de la tiroides (n=1017). La CT se midió por quimioluminiscencia (valor normal: hasta 18 pg/ml en hombres y 12 pg/ml en mujeres). En dos pacientes, la hipercalcitoninemia se confirmó en mediciones repetidas. La aspiración con aguja fina con medición de CT en el líquido obtenido identificó la presencia del CMT. El estudio genético fue positivo en uno (mutación exón 14, Val804Met, CMT familiar). El otro presentó un polimorfismo (heterocigoto exón 13 L769L - heterocigoto exón 15 S904S). En ambos casos, la CT se normalizó 3 meses después de la cirugía y se mantuvo en valores normales después de 6 años de seguimiento. La medición rutinaria de la CT en nódulos tiroideos fue útil para detectar dos casos de CMT, uno de ellos esporádico y el otro familiar en la cohorte seguida. La prevalencia de CMT fue de 0.2%.
There is much controversy about the benefits of the use of serum calcitonin (CT) in the initial evaluation of patients with thyroid nodules. The objective of the study was to early identify medullary thyroid carcinoma (MTC) through the routine measurement of CT in thyroid nodular pathology in a large cohort of patients from Buenos Aires, Argentina. Consecutive patients with nodular thyroid disease (n=1017) were studied. CT was measured by chemiluminescence, normal value: up to 18 pg/ml in men and 12 pg/ml in women. In two patients, hypercalcitoninemia was confirmed in repeated measurements. Fine needle aspiration with CT measurement in the needle wash fluid identified MTC in nodules with citology abnormalities. The genetic study was positive in one patient (mutation exon 14, Val804Met, MTC familiar). The other presented a polymorphism (exon 13 L769L heterozygous - exon 15 S904S heterozygous). In both cases, CT was normalized 3 months after surgery and remained normal after 6 years of follow-up. The routine measurement of CT in thyroid nodular pathology was useful to detect two cases of MTC, one of them sporadic and the other familiar in this cohort. The prevalence of MTC was 0.2%.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Calcitonina/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Carcinoma Neuroendócrino/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Imuno-Histoquímica , Biomarcadores/sangue , Estudos de Coortes , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/sangue , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/sangue , Biópsia por Agulha Fina , Diagnóstico Precoce , LuminescênciaRESUMO
Objective To analyze the clinical features of medullary thyroid carcinoma(MTC) and the risk factors of cervical lymph node metastasis.Methods A retrospective analysis of 84 cases of thyroid surgery in the First Affiliated Hospital of Zhengzhou University from Jan.2012 to Jun.2018 and confirmed by routine pathology as MTC patients was performed.Chi-square test and logistic regression were used to analyze patients' age,gender,clinical features such as tumor diameter,number of lesions,and invasion of the capsule and risk factors associated with cervical lymph node metastasis.Results Statistical analysis found that the incidence of lymph node metastasis significantly increased in patients with central region ≥ 1 cm (x2=4.196,P=0.041),multiple lesions (x2=5.946,P=0.015),and thyroid capsule invasion (x2=15.277,P＜0.001) and the difference was statistically significant.The incidence of cervical lymph node metastasis was significantly higher in patients with the tumor diameter ≥ 1 cm(x2=5.269,P=0.022),multiple lesions(x2=4.550,P=0.033),and thyroid capsule invasion(x2=19.253,P＜0.001) and the difference was statistically significant.Logistic regression analysis showed that thyroid capsule invasion was an independent risk factor for central lymph node metastasis (OR=7.551,P=0.001) and cervical lymph node metastasis (OR=8.067,P＜0.001).Of the 84 patients who received calcitonin before surgery,56 patients had preoperative calcitonin＞200 pg/ml,and the cervical lymph node metastasis rate was 55.4％ (31/56).28 patients had preoperative calcitonin＜200 pg/ml,and the cervical lymph node metastasis rate was 28.6％ (8/28).The former increased and the difference was statistically significant.Of the 18 patients who underwent preoperative detection of carcinoembryonic antigen (CEA),8 patients had CEA＞30 ng/ml,cervical lymph node metastasis was 75％ (6/8);10 patients had CEA＜30 ng/ml,and the cervical lymph node metastasis was 60％(6/10).Conclusions Higher cervical lymph node metastasis is a clinical feature of MTC.For patients with thyroid capsule invasion,the risk of cervical lymph node metastasis is significantly increased,and prophylactic cervical lymph node dissection is required.Preoperative detection of calcitonin and CEA can be used to diagnose MTC and predict lymph node metastasis.The cervical lymph node dissection can be considered with reference to the concentration.
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Despite its low incidence,medullary thyroid carcinoma(MTC)is featured by its fast progression and poor prognosis.Early diagnosis and treatment is therefore particularly important.As a convenient and non-invasive diagnostic tool,ultrasound plays a key role in the diagnosis and follow-up of MTC.In recent years,the application of conventional ultrasound,ultrasonic elastography,and ultrasound-guided fine needle aspiration biopsy has dramatically improved the diagnostic accuracy of MTC.
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Humanos , Biópsia por Agulha Fina , Técnicas de Imagem por Elasticidade , Neoplasias da Glândula Tireoide , Diagnóstico por Imagem , UltrassonografiaRESUMO
Objective To explore whether MiR-129-5p participates in radiosensitivity of medullary thyroid cell MZ-CRC-1 by inhibiting the gene expression of high mobility group protein B1 ( HMGB1) . Methods The radioresistant cell line MZ-CRC-1/R was established from MZ-CRC-1. Cell survival fraction was analyzed by colony formation assay. The expressions of miR-129-5p in MZ-CRC-1 and MZ-CRC-1/R cells were detected by qRT-PCR. Cell viability was determined by MTT assay. Cell apoptosis was measured by flow cytometry. Dual-luciferase reporter assay was performed to confirm the relationship between miR-129-5p and HMGB1. Besides, the protein expressions of HMGB1 and p-AKt were evaluated by western blot. Results Compared with that of MZ-CRC-1 cells, the survival fraction of MZ-CRC-1/R cells was significantly increased (t=3. 038, 4. 330, 4. 885, 4. 568, P<0. 05), the cell viability of MZ-CRC-1/R cells was also increased ( t=3. 637, 7. 734, 11. 896, 14. 522, P<0. 05) , and the expression of miR-129-5p(0.26±0.03) was significantly decreased in MZ-CRC-1/R cells(1.00±0.06) (t=19. 107, P<0. 05) . Compared with miR-NC-inhibitor group, cell viability was promoted and cell apoptosis was blocked in the miR-129-5p-inhibitor group ( t=5. 156, 6. 005, 9. 649, 8. 659, P<0. 05) . Moreover, miR-129-5p mimic suppressed cell viability and enhanced cell apoptosis after irradiation ( t=3. 118, 5. 034, 6. 005, 7. 488, 6. 362, P<0. 05) . Overexpression of miR-129-5p inhibited the protein expressions of HMGB1 and p-AKt (t=9. 325, 10. 614, P<0. 05). In addition, HMGB1 depletion rescued cell apoptosis that was reduced by miR-129-5p inhibitor in MZ-CRC-1 cells ( t=6. 700, P<0. 05) , while HMGB1 overexpression attenuated the effect of miR-129-5p upregulation on MZ-CRC-1/R cells ( t=7. 073,P<0. 05) . Conclusions miR-129-5p increased the radiosensitivity of medullary thyroid-like cell MZ-CRC-1 by inhibiting HMGB1.
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Prognosis of medullary thyroid carcinoma(MTC)is worse,and occurrence of early metastasis is easy. Hereditary and sporadic MTC have different clinical characteristics and prognosis. The diagnostic value of ultrasound,CT,MRI and bone scintigraphy is special. Calcitonin(Ctn)is found to have diagnostic specificity,while carcinoembryonic antigen(CEA)is useful for evaluating disease progression. Whether hereditary or sporadic MTC,surgeons should pay attention to the subsequent genetic detection. Different surgical strategies are required for hereditary and sporadic MTC. Active surgery is necessary for patients with regional recurrence and nodal metastasis. Advanced progressive MTC could be treated by palliative surgery,external radiotherapy or systemic treatment with the tyrosine kinase inhibitor. Measurement of doubling times of serum Ctn and CEA can evaluate recurrence and metastasis after surgery.
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ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Mutação em Linhagem Germinativa/genética , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Proteínas Proto-Oncogênicas c-ret/genética , Triagem de Portadores Genéticos/métodos , Fatores de Tempo , Brasil , Neoplasias da Glândula Tireoide/patologia , Imuno-Histoquímica , Transfecção/métodos , Rearranjo Gênico/genética , Reprodutibilidade dos Testes , Fatores de Risco , Fatores Etários , Carcinoma Neuroendócrino/patologia , Medição de Risco , Detecção Precoce de Câncer , Estudos de Associação GenéticaRESUMO
Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.
Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.