Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent linkage of the gene for multiple endocrine neoplasia type 2A and 2B to the centromeric region of chromosome 10 has provided new insight into the causes of medullary thyroid carcinoma and has provided tools to diagnose gene carriers status for this syndrome with greater than 90% certainty. This review focuses on how these advances influence the clinical management of both sporadic and hereditary medullary thyroid carcinoma and discusses how tests based on the genetic linkage studies will aid in the early diagnosis and treatment of this syndrome. In addition, the authors have focused on several controversial management questions regarding the type and extent of surgery for this thyroid tumor, the management of the patient with metastatic disease, and the approach to management of other manifestations of multiple endocrine neoplasia types 2A and 2B. This review attempts to provide a balanced overview of these complex issues.
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PMID:Changing concepts in the management of hereditary and sporadic medullary thyroid carcinoma. 197 73

Eight Sipple's syndrome patients from four families have been reviewed. One family had the largest number of members with pheochromocytoma and/or medullary thyroid carcinoma. A total of 82 cases (47 females and 35 males) collected from the Japanese literature during the period 1960-1989, are also reviewed. The ages ranged from 22 to 73 (median 41) years, 13%, being over the age of 60 years (elderly patients). Pheochromocytoma occurred bilaterally in 72% of cases. With Sipple's syndrome, a relatively high urinary excretion of the epinephrine fraction and a high content of epinephrine in the tumor tissues were thought to be characteristic. Seventy-three patients underwent adrenalectomy with a successful outcome for 62 (85%). There needs to be careful periodic follow-up after unilateral adrenalectomy. Medullary thyroid carcinoma (MTC) also occurred bilaterally and was multicentric in 66% of cases, and was often found to be metastasized to the cervical lymph nodes at the time of surgery (35%). Parathyroid disease was found in 22% of cases: parathyroid adenoma in nine, hyperplasia in 10. Fourteen patients (17%) died of surgical complications, hypertensive crisis caused by excessive catecholamine release and/or widespread MTC metastases.
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PMID:Analysis of eight Sipple's syndrome patients and review of eighty-two cases from the Japanese literature. 198 Sep 32

In the last 15 years, 29 subjects (13 males, 16 females) aged 8-69 years, belonging to 3 kindreds with multiple endocrine neoplasia type 2 (MEN-2) were studied with rapid i.v. calcium gluconate infusions (2 mg Ca++/kg in 1 minute) in order to detect the presence of medullary thyroid cancer (MTC). Serum samples were obtained at 0, 2, 5, 7 and 10 minutes. Calcitonin was measured by radioimmunoassay using a commercial kit. On the basis of the results obtained in a control group of 28 healthy volunteers, hypercalcitoninemia (HCT) was defined as basal and stimulated values above 100 and 200 pg/ml, respectively, in either sex. In 2 patients with nodular goiter, HCT correctly predicted the malignant nature of the lesions. Out of 22 clinically normal subjects, 3 had HCT: one refused consent for surgery, but in the remaining 2 MTC was found, without extraglandular extension. Seven patients with surgically proven MTC have been followed; 4 have shown HCT: 3 women refused permission for exploratory surgery, and a 46 year old male with enlarged lymph nodes in the neck was found to have metastatic papillary thyroid cancer. Both calcitonin and thyroglobulin were immunohistochemically discovered in metastases and the original thyroid tumor (differentiated thyroid cancer, intermediate type). There were 2 false negative tests in patients with metastatic disease. This type of biochemical screening in members of MEN-2 kindreds allows early detection of MTC and its prevention through thyroidectomy in a preneoplastic stage (C-cell hyperplasia).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Multiple endocrine type 2 neoplasia in 3 families]. 198 20

There is doubt about concentrations of circulating calcitonin gene-related peptide (CGRP) and the value of plasma CGRP measurements in the detection and follow-up of medullary thyroid carcinoma (MTC). Thus, we developed an immunochemiluminometric sandwich assay for CGRP using antibodies purified from a polyclonal antiserum against human CGRP. The assay was sensitive (limit of detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly specific [no cross-reaction with human calcitonin (CT)]. Normal plasma CGRP values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61% having detectable levels. Values in samples from patients with MTC were elevated: unoperated patients (n = 10), 4.7-137 pmol/L (median, 7.1); and operated patients with gross persistent or recurrent tumor (n = 14), 4.7-171 pmol/L (median, 23.2). In contrast, CGRP values were normal in 78% of nine postoperative patients with elevated CT, but no detectable tumor (range, less than 0.4 to 6.3 pmol/L; median, 1.6). CGRP levels increased after pentagastrin injection in MTC patients, but less than did CT values. Cultured MTC cells in vitro secreted large amounts of CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial cells secreted lesser amounts. We conclude that CGRP circulates in normal plasma, but at very low levels. Plasma CGRP concentrations are frequently high in patients with MTC, but primarily in those with gross tumor or metastases. Plasma CT assay is the preferable test for MTC, but CGRP assay deserves prospective study for a possible role in predicting gross metastasis.
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PMID:Determination of plasma calcitonin gene-related peptide concentrations by a new immunochemiluminometric assay in normal persons and patients with medullary thyroid carcinoma and other neuroendocrine tumors. 199 3

The authors investigated the humoral and tissue expression of six antigens associated with medullary thyroid cancer (MTC): calcitonin (CT), calcitonin gene-related peptide (CGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), somatostatin (SRIF), and thyroglobulin (TG). The antigens were studied in the neoplastic C cells using immunohistochemistry with specific antisera and in the plasma using specific radioimmunoassay. Eighteen patients (8 male and 10 female patients, aged 12-72 years) were studied. Mean follow-up was 70.7 months (range, 2-179 months). Nine patients (50%) died of their disease after a mean follow-up of 47.2 months (range, 2-116 months). By immunostaining, primary tumors expressed CT and CEA in all cases and NSE was positive in 90%, CGRP in 66%, SRIF in 63%, and TG in 58%. Metastatic tissues were positive in all cases of CT staining, 92.8% of CEA, 71.4% of NSE, 73.3% of CGRP, 38.5% of SRIF, and only 13.3% of TG staining. In positive cases the percentage of positive cells and the degree of staining were variable among the different antigens. The expression of an antigen in the neoplastic cells was associated with the hypersecretion of the corresponding antigen in the circulation in the case of CT and CEA. The levels of these antigens were elevated in all patients with metastases and could accurately predict the appearance of new metastases or indicate the effective treatment of previous metastases by surgery. In the case of NSE, CGRP, and SRIF, few patients had increased plasma concentrations of the antigens and these usually occurred during very advanced phases of the disease. Detectable levels of serum TG were never observed. When the outcome of the disease was compared with the expression of CT, CEA, NSE, CGRP, and TG, no correlation could be found. On the contrary, SRIF expression in the primary tumor could differentiate two groups of patients with different survival rates. SRIF-positive patients had survival rates of 100% and 50% at five and seven years, respectively, whereas SRIF-negative patients had survival rates of 40% at five years and 25% at seven years.
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PMID:Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. 199 39

The management of 12 patients with medullary thyroid carcinoma is reviewed. All patients underwent total thyroidectomy. Local nodal and extracapsular spread was aggressively resected, followed by radiotherapy. No patient died from uncontrolled local disease. Prolonged survival after radical treatment is demonstrated even in the presence of distant metastases.
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PMID:Experience in the surgical management of medullary thyroid carcinoma. 199 60

Fifteen patients with medullary carcinoma of the thyroid (MCT), who had persistently elevated levels of serum calcitonin (CT) and carcinoembryonic antigen (CEA) after total thyroidectomy, were studied in order to localize the sites of the recurrent disease. Routine diagnostic examinations, including ultrasonography (US) and computed axial tomography (CAT), were carried out in all the cases. Scintigraphy with radio-iodinated metaiodobenzylguanidine ((131I)-MIBG) was performed in 13 cases; selective venous catheterization (SVC) to reveal a gradient of CT levels was performed in 12 cases. Ten patients underwent both (131I)-MIBG scintigraphy and SVC. US and CAT revealed the sites of recurrent tumor in only 4 out of the total 15 patients. SVC in basal conditions showed the presence of small metastases in 2 cases, and after intravenous stimulus with pentagastrin in 4 others. The MIBG scan showed metastatic foci of sporadic MCT in 2 patients, residual medullary thyroid tissue in 4 others, and a pheochromocytoma in a previously undiagnosed patient with Sipple's syndrome. More particularly, MIBG scan and SVC showed the localization of residual or metastatic tumor in 10 cases. In all 10 cases, results of the MIBG scan and SVC were confirmed as true positive by subsequent surgery and histopathologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:(131I)meta-iodobenzylguanidine scintigraphy and selective venous catheterization after thyroidectomy for medullary thyroid carcinoma. 204 83

Calcitonin determination is of central importance in the diagnosis and follow-up of medullary thyroid carcinoma. Stimulation tests must be applied, particularly for early recognition of familial medullary thyroid carcinomas and for early diagnosis of relapses/metastases, since the basal calcitonin levels are still within the normal range initially. The pentagastrin stimulation test has proven to be the most effective one, though it is associated with considerable adverse effects. TRH is also able to stimulate calcitonin secretion in medullary thyroid carcinoma. The present study examines the value of TRH stimulation compared with pentagastrin stimulation in patients with occult or manifest metastases of medullary thyroid carcinoma. Both patients with occult metastases displayed a marked calcitonin increase after pentagastrin stimulation, but not after TRH stimulation. While calcitonin increased after pentagastrin in the two patients with manifest metastases, TRH produced a clear rise in only one of them and even caused the serum calcitonin concentration to drop continuously in the other one. Thus, TRH cannot be regarded as a reliable calcitonin stimulant in medullary thyroid carcinoma.
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PMID:Is thyrotropin-releasing hormone as reliable a calcitonin stimulant as pentagastrin in medullary thyroid carcinoma? 211 16

99mTc(V)-DMSA scintigraphy is a non-invasive diagnostic tool for diagnostic differentiation and localisation of medullary carcinoma of the thyroid. For primary tumours its sensitivity is 77%. This diagnostic means is not only helpful for the diagnosis of primary tumours, but is especially informative for recidives and metastases of the medullary carcinoma of the thyroid. Its sensitivity for recidives and metastases is 66%. The sensitivity obtained in our study, which included four patients, corresponded to that reported in the literature.
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PMID:[Medullary carcinoma of the thyroid and 99mTc(V)-DMSA scintigraphy. Clinical results with a new radiopharmaceutical]. 217 51

We investigated the copy number and possible rearrangement of the four protooncogenes, c-myc, N-myc, N-ras, and c-erb-B, in DNA from seven untreated primary cancers or metastases of medullary thyroid carcinoma and an established human medullary thyroid carcinoma cell line, TT, using the Southern blotting technique. The purpose of this study was two-fold: 1) to examine whether protooncogene perturbations in medullary thyroid carcinoma could be considered as a prognostic marker; and 2) to determine whether the protooncogenes could have a possible role in medullary thyroid tumorigenesis. Neither amplification nor rearrangement of the protooncogenes was detectable in the DNA from any tumor samples or in the cell line. Our results suggest that DNA-evident amplification and rearrangement of the c-myc, N-myc, N-ras, and c-erb-B oncogenes may not be mechanisms through which these oncogenes become activated in this malignancy.
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PMID:C-myc, N-myc, N-ras, and c-erb-B: lack of amplification or rearrangement in human medullary thyroid carcinoma and a derivative cell line. 218 86


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