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PubMed2004

RET proto-oncogene mutations are restricted to codon 634 and 618 in Korean families with multiple endocrine neoplasia 2A.

Identification of the germline mutation in the RET proto-oncogene is important for the diagnosis of hereditary medullary thyroid carcinoma (MTC). Hereditary forms account for approximately 25%-30% of all cases of MTC. The objective of this study was to evaluate the prevalence of the RET mutation and the genotype-phenotype relation in Korean patients with MTC. Genomic DNAs were obtained from 33 patients with MTC (M:F = 10:23, 39.8 +/- 12.0 years) who underwent total thyroidectomy between 1997 and 2003 at the Samsung Medical Center. Exons 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were amplified with specific primers using polymerase chain reaction (PCR). Sequence analysis was performed on the polymerase chain reaction (PCR) product using an automatic sequence analyzer. Nine of the 33 patients (M:F = 3:6, 33.3 +/- 10.0 years) were identified as having RET mutations. Six patients had multiple endocrine neoplasia (MEN) 2A and one had familial medullary thyroid carcinoma (FMTC). The remaining two patients were thought to have sporadic MTC. Five of the patients with MEN 2A had RET mutations in codon 634 of exon 11 (3 patients, C634Y; 2 patients, C634R) and the other patient with MEN 2A had a RET mutation in codon 618 of exon 10 (C618R). The patient with FMTC had a mutation in codon 634 (C634W). The two patients with sporadic MTC had RET mutations in codon 634 (1 patient, C634Y; 1 patient, C634S). We were not able to identify any genotype-phenotype relations because of the limited number of patients. Twenty-seven percent (9/33) of the patients with MTC in this study had RET mutations. Taking other studies into account, 77% (10/13) of Korean families with MEN 2A, including 7 other families in three reports from Korea, had RET mutations in codon 634 (5 families, C634Y; 4 families, C634R; 1 family, C634W), and 23% (3/13) had RET mutations in codon 618 (2 families, C618R; 1 family, C618S). RET proto-oncogene mutations were restricted to codon 634 and 618 in Korean families with MEN 2A.

Adult↗
PubMed2005

Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders.

To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

Adult↗
PubMed2005

Ectopic adrenocorticotropic hormone-syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature.

Cushing's syndrome (CS) in medullary thyroid carcinoma (MTC) is rare. Only 50 cases have been reported. We report 10 cases of MTC with ectopic adrenocorticotropic hormone (ACTH)-dependent syndrome (EAS), analyzed retrospectively. Among 1640 patients with MTC, 13 developed EAS (0.7%). In 10 patients CS could unequivoqually be related to MTC (0.6%). CS was always clinically obvious. It revealed MTC in 3 cases and followed diagnosis by an average of 34.5 months in the others. Metastases were often present at diagnosis. Immunohistochemistry with ACTH antibodies was positive in one case. Diagnosis of ectopic CS was established according to clinical and biologic features, and absence of corticotropic adenoma as well as parallel evolution between tumor and CS. Therapy was medical and surgical: anticortisolic drugs alone or in association with somatostatin analogue, somatostatin analogue alone, and bilateral adrenalectomy. Eight patients died within 2 to 30 months, 4 of hypercortisolism complications (3 peritonitis and 1 hypokalaemia), 4 of MTC progression. EAS is a rare complication of MTC. The prognosis is poor because of frequency of metastasis at diagnosis. Persistent hypercortisolism can, by itself, lead to death, and has to be treated specifically.

Adrenocorticotropic Hormone↗
PubMed2006

Analysis of inherited genetic variants in ret proto-oncogene of Brazilian patients with apparently sporadic medullary thyroid carcinoma.

Mutations in different exons of ret proto-oncogene are responsible for the development of medullary thyroid carcinoma (MTC). The mutations can occur as sporadic or as part of multiple endocrine neoplasia (MEN) type 2 hereditary syndromes. Here we report the first focused study of sporadic MTC in Brazilian patients regarding clinical and molecular analysis of ret proto-oncogene. Our study seeks to estimate the risk of hereditary MTC cases among apparently sporadic cases in a Brazilian population and describe ret genetic variants in their germinative lineage. Germinative sequence variants were screened by DNA sequencing and denaturing gradient gel electrophoresis (DGGE) analysis of exons 10, 11, 13, 14, 15, and 16 of 24 Brazilian patients with apparently sporadic MTC. We identified 1 inherited case of 24 (4%) patients with apparently sporadic MTC. Polymorphisms for the ret proto-oncogene coding region were identified in codon 769 of exon 13 (LeuCTT--> LeuCTG) at a frequency of 13% (3/24) and in codon 904 of exon 15 (SerTCC--> SerTCG) at a frequency of 16.6% (4/24). The observed frequency (4%) of inherited disease among apparent sporadic MTC strengthens routine application of ret proto-oncogene germinative DNA screening in all cases of apparently sporadic MTC ascertained at Brazilian cancer hospitals.

Adult↗
PubMed1994

Polysialic acid of the neural cell adhesion molecule in the human thyroid: a marker for medullary thyroid carcinoma and primary C-cell hyperplasia. An immunohistochemical study on 79 thyroid lesions.

We recently reported that the gold-labeled monoclonal antibody MAb 735, reactive with a long-chain form of alpha-2,8-linked polysialic acid (polySia) found on the neural cell adhesion molecule (NCAM), is useful to immunohistochemically distinguish small-cell lung carcinomas from neuroendocrine carcinomas with higher grade of differentiation (carcinoids) and other types of lung carcinomas (Am J Pathol 1991;139:297). In this study, we tested the occurrence of polySia in various types of malignant thyroid tumors and C-cell hyperplasia to determine whether polySia is a useful adjunct for the differential diagnosis of medullary thyroid carcinoma (MTC) and other thyroid neoplasms and to distinguish primary from secondary (reactive) C-cell hyperplasia (CCH). We examined formaldehyde-fixed and paraffin-embedded sections of 79 thyroid lesions, consisting of 33 MTC (14 familial and 19 sporadic tumors), 13 follicular, 11 papillary, 16 anaplastic carcinomas, and four glands with primary and two with secondary CCH. We applied a direct and an indirect immunogold-silver technique for polySia, CT, and CEA detection, respectively. All 33 MTC showed a strong cell-surface-associated immunoreactivity for polySia, which was sensitive to endoneuraminidase digestion. The polySia immunoreactivity of nerves served as an internal control in all specimens. Immunoreactivity for CT and CEA was present in all MTC with the exception of one recurrent tumor with features of an anaplastic MTC type. All other thyroid neoplasms were nonreactive for polySia, CT, and CEA. Primary CCH associated with MTC showed a strong polySia immunostaining, which was less intense in primary CCH not combined with MTC. In normal-appearing C cells and in secondary CCH, staining for polySia was absent in the majority of cases. We conclude that polySia of NCAM is a valuable marker to distinguish medullary carcinomas from other types of thyroid carcinomas. Furthermore, it allows for the discrimination of primary from secondary C-cell hyperplasia and may be helpful to better define the normal range of C cells in unaffected members of a family with a history of multiple endocrine neoplasia (MEN)-II.

Adolescent↗
PubMed1985

Resistance to metocurine-induced neuromuscular blockade in patients receiving phenytoin.

Recent reports have described resistance to pancuronium-induced neuromuscular blockade in patients chronically receiving anticonvulsants. This study examines the pharmacokinetics and pharmacodynamics of metocurine (MTC) in 12 patients undergoing craniotomy--six on chronic phenytoin therapy and six comparable controls. Each patient received MTC 0.2 mg/kg during the induction of general anesthesia. Quantification of plasma MTC concentration was performed by radioimmunoassay, while the response to MTC was evaluated by evoked compound electromyography (ECEMG). Patients in the phenytoin group were resistant to this dosage of MTC, as demonstrated by their response (83 +/- 16% compared with 98 +/- 2% depression of ECEMG in control patients, P less than 0.05) and by recovery index, defined as the time required for recovery from 25 to 75% of the control ECEMG (53 +/- 22 min compared with 125 +/- 54 min in control patients, P less than 0.01). Similarly, the total duration of neuromuscular blockade, measured to recovery to 90% of control ECEMG, was significantly shorter in the phenytoin group (122 +/- 25 min compared with 269 +/- 64 min in the control group, P less than 0.01). Plasma concentration-time curves were fit to biexponential equations for both groups. These were used to generate two-compartment models. Neither the model parameters nor the plasma concentrations of MTC at any time in the study were significantly different for the two groups. The pharmacodynamic analysis, however, showed that patients on phenytoin require a higher plasma concentration of MTC (0.415 +/- 0.095 microgram/ml compared with 0.249 +/- 0.066 microgram/ml in control patients at 50% ECEMG, P less than 0.01) to effect a given level of neuromuscular blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Prognostic variables and calcitonin in medullary thyroid cancer.

OBJECTIVES/HYPOTHESIS: Medullary thyroid cancer (MTC) is a nonepithelial, neuroendocrine tumor with a more aggressive clinical behavior than differentiated thyroid cancer. The purpose of the study was to review a single institution's experience with MCT since 1969. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective review of 30 patients treated for MTC at a tertiary care referral center between 1969 and 2000. There were 17 female and 13 male patients, median age at presentation was 38 years, and median follow-up for survivors was 12.4 years. RESULTS: Seventy percent of patients had sporadic MTC, 6.7% had familial MTC, 16.7% had multiple endocrine neoplasia syndrome type IIA, and 6.7% had multiple endocrine neoplasia syndrome type IIB. The cumulative overall survival rates at 5, 10, and 20 years were 97%, 88%, and 84%, respectively; disease-free survival rates were 97%, 74%, and 29%, respectively. Advanced tumor stage (P = .014) and multiple endocrine neoplasia syndrome type IIB predicted decreased disease-specific survival. Variables affecting disease-free survival were post-thyroidectomy calcitonin level (P = .001), vascular invasion (P = .005), perineural invasion (P = .010), extrathyroidal extension (P < .001), and the presence of nodal metastases (P = .001). Locoregional control rates were 83% at 5 years and 70% at 10 years. Vascular invasion (P = .004), extrathyroidal extension (P = .008), and post-thyroidectomy basal calcitonin level (P = .003) predicted locoregional failure. Many patients in the series experienced prolonged survival despite elevated calcitonin levels. CONCLUSION: Long-term disease-free survival is uncommon in MTC, but the study data indicate that the majority of patients with MTC live for prolonged periods, despite biochemical evidence of persistent disease. Adverse pathological features such as extrathyroidal extension and vascular and perineural invasion were predictors of disease recurrence. The use of serum markers in the follow-up of patients with MTC must be interpreted within the clinical context.

Adolescent↗
PubMed2003

C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients.

Routine calcitonin (CT) assay programs and genetic testing for RET proto-oncogene mutations have consistently modified the management and understanding of C-cell proliferative disorders. We report a series of 66 consecutive patients with C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) observed in our institution within an 8-year time period. All the patients had a preoperative basal CT assay and an RET proto-oncogene sequencing. Seventeen patients (F-M ratio: 8:9, mean age: 29.7 y) had a multiple endocrine neoplasia Type 2: 3 children <10 years of age had CCH only, and 14 patients had an MTC, with neoplastic CCH in 10/14 cases. Twenty-seven patients (F-M ratio: 18:9, mean age: 56.6 y) had a sporadic MTC, with physiological CCH in 8 and neoplastic CCH in 3 cases. Twenty-two men (mean age: 46.2 y) had CCH only (physiological CCH in 17 men and neoplastic CCH in 5). We conclude that (1) clinical and pathological characteristics (familial MTC, tumor multifocality, neoplastic CCH) usually associated with hereditary MTC may be misleading and that on the contrary, RET sequencing gives no false positive result; (2) sporadic neoplastic CCH accompanies (and probably precedes) a number of sporadic MTC; and (3) women presenting with a sporadic elevated basal CT have a 100% risk of having an MTC (15/15), but this risk is 3-fold less in men (31%), who will most often have CCH only (69%).

Adolescent↗
PubMed1992

Improved time-of-flight MR angiography of the brain with magnetization transfer contrast.

The authors hypothesized that magnetization transfer contrast (MTC) could be used to improve flow contrast in time-of-flight (TOF) magnetic resonance (MR) angiography. Two- and three-dimensional flow-compensated gradient-echo images were obtained with and without MTC. MTC images were obtained by applying low-power radio-frequency (RF) radiation with a frequency offset from the bulk "free" water resonance frequency before the excitation RF pulse. The signal intensity of stationary tissue decreased as the power applied for the MTC pulse was increased. A smaller decrease occurred in venous signal intensity as measured in the superior sagittal sinus, and less change was seen in the arterial signal intensity as measured in the middle cerebral artery. Cerebrospinal fluid showed no MTC effect. The use of MTC improved small-vessel depiction on maximum-intensity projection images. The authors conclude that use of MTC can substantially enhance the quality of TOF MR angiography of the brain.

Adult↗
PubMed1984

Characteristics of the peritoneal mass transfer of parathormone in patients under continuous ambulatory peritoneal dialysis therapy.

Recent studies have shown that the mass transfer coefficients (MTC) for low- and middle-molecular-weight substances are maintained at medium terms in patients under continuous ambulatory peritoneal dialysis (CAPD) therapy. We have studied the MTC for parathormone (MW 5,500-6,000) in 29 patients under CAPD. 11 patients were assessed once, 9 patients were assessed twice, and 9 were assessed three times, with 6-month intervals between assessments; in 15 cases nitroprusside (4.5 mg/l) was added to the dialysate, and in 2 cases the assessment was carried out during an episode of peritonitis. A bicompartmental model with exponential ultrafiltration was used, and the generation rates were calculated by mass balance. The MTC was calculated by minimization of the quadratic error, following the procedure of Runge and Kutta. The mean MTC values were 21.2 +/- 5.9 for urea, 10.26 +/- 5.9 for creatinine 2.8 +/- 1.8 for inulin and 1.0 +/- 0.8 for parathormone (PTH), with significant correlation between the MTC values for PTH and inulin (r = 0.5, p less than 0.01). There is a direct correlation between MTCPTH and peritoneal PTH clearance, and an inverse one between MTCPTH and serum PTH, with r = 0.8 and 0.51, respectively. No correlation was found between the MTC for inulin or PTH and the duration of the CAPD therapy, nor with the number of episodes of peritonitis. No significant medium-term variations were detected in the MTC values for PTH and inulin. Both peritonitis and the intraperitoneal administration of nitroprusside induce significant increases in the MTCPTH.

Creatinine↗
PubMed2004

Medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is subdivided into sporadic (75 %) and hereditary (25 %) forms. Several germline mutations in the RET proto-oncogene are the source of distinct clinical phenotypes in hereditary MTC including familial MTC (FMTC) and multiple endocrine neoplasia 2A (MEN 2A) and 2B (MEN 2B). The higher the penetrance of the MEN 2 phenotype the earlier the progression of MTC which forms the basis for the currently recommended codon-related concept of prophylactic thyroidectomy. In patients with sporadic MTC, routine calcitonin (CT) measurement in nodular goiter patients has been shown to reduce the frequency of advanced tumor stages. Patients with CT levels over 100 pg/ml after pentagastrin stimulation are recommended for total thyroidectomy. In patients with unexpected sporadic MTC after histological examination, completion thyroidectomy is currently only recommended when CT levels remain elevated. The extent of lymph node dissection in patients with MTC is controversial. However, with respect to lymphonodal micrometastases, systematic compartment-oriented microdissection has been shown to reduce the frequency of lymphonodal recurrence. On the other hand, to avoid unnecessary lymph node dissection, a more individualized concept is required in the future. New chemotherapeutic agents (tyrosine kinase inhibitors), therapeutic nuclids (90Yttrium-labeled octreotide), and chemoembolization of liver metastases are currently the most promising therapeutical concepts in patients with distant metastases.

Calcitonin↗
PubMed2001

The interphase microtubule damage checkpoint defines an S-phase commitment point and does not require p21(waf-1).

Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of the cell cycle (G(1)MTC) for which little is known. The present study shows that the G(1)MTC is intact in activated T lymphocytes from mice with the p21(waf-1) gene deleted. However, p21(waf-1) gene deletion does affect the ratio of cells that arrest at the G(1)MTC and the spindle checkpoint after MTD. The G(1)MTC arrests T lymphocytes in G(1) prior to cdc2 up-regulation and prior to G(1) arrest by p21(waf-1). Once cells have progressed past the G(1)MTC, they are committed to chromosome replication and metaphase progression, even with extreme MTD. The G(1)MTC is also present in a human myeloid cell line deficient in p21(waf-1) gene expression. The p21-independent G(1)MTC may be important in cellular responses to MTD such as those induced by drugs used to treat cancer.

Animals↗
PubMed2003

Analysis of cancer/testis antigens in sporadic medullary thyroid carcinoma: expression and humoral response to NY-ESO-1.

Cancer/testis antigens (CTA) are tumor-associated antigens expressed during ontogenesis, in a number of solid tumors but not in normal tissues except testis. Most of these CTA are highly immunogenic, eliciting a humoral and cellular response in the patients with advanced cancer, and are useful for tumor-specific immunotherapy. Medullary thyroid carcinoma (MTC) is a neoplasm derived from the parafollicular cells of the thyroid and occurs in either a sporadic or a familial form. In the present study, we examined by RT-PCR the expression of a number of genes encoding CTA in 23 surgical samples of sporadic MTC. Among the 11 cDNA antigens examined, RAGE, MAGE-4, and GAGE 1-2, were not expressed in any of the tissues. SSX 2 was present only in one tissue, whereas BAGE, GAGE 1-6, MAGE-1, MAGE-2, MAGE-3, and SSX 1-5 were detected in two to five samples. NY-ESO-1 cDNA was the most frequent, being detected in 15 of 23 examined samples (65.2%). Six (26.1%) tissues did not express any CTA-specific mRNA, whereas 10 tumors expressed only one gene (43.5%), 3 (21.4%) expressed 2 genes, and 4 displayed a broad CTA gene expression. NY-ESO-1 expression in primary MTC tissues significantly correlated with tumor recurrence. The presence of specific anti-NY-ESO-1 antibodies was searched in the sera of MTC-affected patients examined by ELISA using recombinant NY-ESO-1 protein. A humoral response against this CTA was detected in 6 of 11 NY-ESO-1 expressing patients (54.5%), and in 1 of 6 patients with NY-ESO-1-negative tumor. No anti-NY-ESO-1 antibodies were detected in healthy subjects (n = 17). The presence of anti-NY-ESO-1 antibodies was searched also in the sera of MTC affected patients whose tissues were not available for CTA analysis. Anti-NY-ESO-1 antibodies were present in 15 of 42 sera (35.7%), demonstrating that MTC is a neoplasm frequently associated with humoral immune response to NY-ESO-1. Serological survey may be useful as a way to identify patients with humoral immune response to NY-ESO-1 that provide a new attractive target for vaccine-based immunotherapy of MTC.

Adult↗
PubMed2003

Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin-secreting parafollicular C cells of the thyroid occurring sporadically and as a component of the multiple endocrine neoplasia type 2/familial medullary thyroid carcinoma syndrome. The primary genetic cause of multiple endocrine neoplasia type 2 is germline mutation of the RET protooncogene. Somatic point mutations in RET also occur in sporadic MTC. Although RET mutation is likely sufficient to cause C-cell hyperplasia, the precursor lesion to MTC, tumor progression is thought to be due to clonal expansion caused by the accumulation of somatic events. Using the genome-scanning technique comparative genomic hybridization, we identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and amplifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4) and their ligands glial cell line-derived neurotrophic factor, neurturin, persephin, and artemin that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC.

Adolescent↗
PubMed2003

Calcitonin-specific transcription and splicing targets gene-directed enzyme prodrug therapy to medullary thyroid carcinoma cells.

Recurrent and metastatic medullary thyroid carcinoma (MTC) remains difficult to treat due to its limited responsiveness to chemotherapy, radiotherapy, and imaging. To investigate an alternative therapeutic approach, we examined the feasibility of targeting gene-directed enzyme/prodrug therapy delivered by adenoviral vectors to MTC. We previously described a modified human calcitonin (CT)/CT gene-related peptide promoter that produced increased expression while maintaining specificity for MTC cells. In this study, we introduced an additional level of specificity by using cell-specific splicing and examined whether the selectivity of the gene-directed enzyme/prodrug therapy for MTC was enhanced when both the promoter and splicing features were combined in a single transcription unit. Two replication-defective adenoviruses were constructed that expressed the Escherichia coli purine nucleoside phosphorylase (PNP) gene under the transcriptional control of a modified T2 promoter (Ad.T2-PNP) or the T2 promoter in combination with a CT minigene cassette in which the PNP gene was imbedded within the CT gene exon 4 (Ad.T2-CT/PNP). The specificity of PNP expression by Ad.T2-PNP, Ad.T2-CT/PNP, and control viruses in the MTC cell line, TT, and in a panel of non-MTC cell lines was evaluated. The highest level of PNP gene expression and the most effective cell killing in the presence of prodrug occurred in TT cells infected with Ad.T2-PNP, followed by Ad.T2-CT/PNP. Infection of most non-MTC cell lines, even with high multiplicities of Ad.T2-PNP, produced only low-level PNP expression that resulted in minimal cell killing in the presence of prodrug. High-level expression of PNP and effective cell killing was observed with both adenoviral gene constructs. The highest level of cell specificity was achieved with the combined use of promoter and splicing regulation in the Ad.T2-CT/PNP virus.

Adenoviridae↗
PubMed2003

Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.

UNLABELLED: A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01). IN CONCLUSION: 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.

Adult↗
PubMed2004

High frequency of bone/bone marrow involvement in advanced medullary thyroid cancer.

High hematological toxicity has been observed with anti-carcinoembryonic antigen radioimmunotherapy (RIT) in medullary thyroid carcinoma (MTC), suggesting metastatic bone involvement (BI). This retrospective study evaluated the rate of BI in MTC patients enrolled in two phase-I/II RIT trials using anti-carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid bispecific antibodies and [(131)I]di-diethylenetriamine pentaacetic acid hapten. Thirty-five patients underwent bone scintigraphy, bone magnetic resonance imaging (MRI), and post-RIT immunoscintigraphy (IS). IS performed in MTC patients was compared with IS conducted in 12 metastatic colorectal carcinoma (CRC) patients. Quantitative analysis of bone uptake was performed in three MTC and three CRC patients. In the MTC group, bone scintigraphy detected BI in 56.6% of patients, MRI in 75.8%, and IS in 88.6%. BI was confirmed by undirected (random) bone marrow biopsy, by bone surgery, or by two positive imaging methods in 74.3% of the patients. Sensitivity per patient of bone scintigraphy, MRI, and IS were 72.7, 100, and 100%, respectively. In contrast, IS visualized BI in only 33.3% of CRC patients; bone uptake was lower in CRC than in MTC patients. Bone MRI combined with post-RIT IS disclosed a much higher BI rate in advanced MTC than previously reported in the literature.

Adult↗
PubMed2005

Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level.

Prediction of remission in medullary thyroid carcinoma (MTC) depends on histopathological information often unavailable before surgery. Simply requiring a venous blood sample, preoperative basal calcitonin levels may be a better indicator of remission. In this institutional series of 224 consecutive patients with MTC and elevated preoperative basal calcitonin levels, postoperative calcitonin levels normalized in 28 (62%) of 45 patients with node-negative MTC and in 18 (10%) of 177 patients with node-positive MTC. On multivariate analysis, preoperative basal calcitonin levels greater than 500 pg/ml best predicted the failure to achieve biochemical remission, followed by nodal metastasis and reoperative status. Cumulative rates of biochemical remission fell continuously with rising serum basal calcitonin in node-negative patients. Node-positive patients did not achieve biochemical remission when their preoperative basal calcitonin levels exceeded 3000 pg/ml. Nodal metastasis started emerging at basal calcitonin levels of 10-40 pg/ml (normal range, <10 pg/ml). Distant metastasis and extrathyroidal growth began appearing in patients with node-positive MTC at basal calcitonin levels of 150-400 pg/ml. There were no differences between patients with sporadic and hereditary MTC after adjusting for multiple testing. Preoperative basal calcitonin levels may thus help individualize the extent of surgery and postoperative follow-up intervals for MTC.

Adolescent↗