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Vincent Rohmer

Publications and source records attributed to Vincent Rohmer.

14 recordsLinked to original sources
PubMed2006

Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group.

PURPOSE: No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (131I) -labeled bivalent hapten is evaluated. PATIENTS AND METHODS: Twenty-nine patients with advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA) -indium BsMAb, followed 4 days later by a 131I-labeled bivalent hapten. Overall survival (OS) was compared with 39 contemporaneous untreated MTC patients with comparable prognostic indicators. RESULTS: OS was significantly longer in high-risk, treated patients (Ct DT < 2 years) than in high-risk, untreated patients (median OS, 110 v 61 months; P < .030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in CtDT, experienced significantly longer survival than nonresponders (median OS, 159 v 109 months; P < .035) and untreated patients (median OS, 159 v 61 months; P < .010). Treated patients with bone/bone-marrow disease had a longer survival than patients without such involvement (10-year OS, 83% v 14%; P < .023). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. CONCLUSION: pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

Antibodies, Monoclonal↗
PubMed2005

Genetic testing in pheochromocytoma or functional paraganglioma.

PURPOSE: To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl). PATIENTS AND METHODS: We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria. RESULTS: We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. CONCLUSION: Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.

Adolescent↗
PubMed2005

Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.

CONTEXT: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. OBJECTIVE: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. DESIGN, SETTING, AND PARTICIPANTS: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. MAIN OUTCOME MEASURES: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology, and disease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. RESULTS: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SDHD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43 SDHB and 19 SDHD mutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated age-related penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). CONCLUSIONS: For clinical follow-up, features of SDHB mutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.

Adolescent↗
PubMed2005

Prognostic value of an increase in the serum thyroglobulin level at the time of the first ablative radioiodine treatment in patients with differentiated thyroid cancer.

PURPOSE: The aim of this study was to assess the prognostic factors for treatment efficacy, and in particular the increase in serum thyroglobulin (Tg) level at the time of the first ablative radioiodine treatment, in patients with differentiated thyroid carcinoma (DTC). METHODS: A retrospective chart review was performed on 407 patients treated for DTC by total thyroidectomy and (131)I ablation between 1995 and 2002, and examined 5-12 months later with diagnostic (131)I whole-body scan and serum Tg measurement after thyroid hormone treatment withdrawal. At the time of the ablative radioiodine treatment, serum Tg level was determined just before (131)I administration (TgD0) and 5 days later (TgD5); Tg variation was expressed as the ratio TgD5/TgD0. At the first post-ablation follow-up examination, unsuccessful ablation was defined by a Tg level > or =2 ng/ml and/or abnormal (131)I uptake. RESULTS: Ablation was unsuccessful in 51 patients. Univariate analysis showed high TgD0 level, low TgD5/TgD0 ratio extrathyroidal invasion, (131)I uptake in the neck (excluding the thyroid bed) during the ablative treatment and distant metastases to be significantly associated with unsuccessful ablation. On logistic multivariate analysis, TgD0 level <5 ng/ml and TgD5/TgD0 ratio > or =20 were independently associated with successful ablation. A receiver operating characteristic curve analysis determined that a TgD5/TgD0 ratio greater than 20 had a 97% positive predictive value for successful ablation. When both TgD0 and TgD5/TgD0 ratio were considered, that is, TgD0 <5 ng/ml or TgD0 > or =5 ng/ml but TgD5/TgD0 ratio >20, ablation was unsuccessful in only 12/301 patients. CONCLUSION: Our data show that the TgD5/TgD0 ratio may be used as a new prognostic indicator of (131)I treatment efficacy in patients with DTC.

Adolescent↗
PubMed2005

[Thyroid dysfunction and pregnancy].

The pregnancy is a state of thyroid hyperstimulation, therefore of changes of thyroid hormone values. Results of thyroid hormone measurement have to be analysed in the context of gestation age. Hyperthyroidism, mostly represented by Graves' disease, requires a multidisciplinary management, owing to possible maternal, foetal and neonatal complications. Treatment with antithyroid drugs, is a compromise between the risk of uncontrolled maternal hyperthyroidism and the risk of iatrogenic foetal hypothyroidism. Evaluation of foetal thyroid function considers the titre of thyrotropin receptor antibodies in the mother's blood, the dose of antithyroid drugs to maintain euthyroidism in the mother, and the signs of foetal hyperthyroidism on ultrasound. Maternal hypothyroidism is associated with foetal and maternal morbidity. Untreated or inappropriately treated, it is associated with poorer performances of offspring in intelligence tests. Thyroid autoimmunity is associated with hypofertility, particularly with spontaneous abortion. Screening for thyroid dysfunction during pregnancy, although not systematic, should have broad indications.

Antithyroid Agents↗
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↗
PubMed2004

Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors.

Thyroid oncocytic adenomas are a class of tumors characterized by the presence of abundant mitochondria. We performed a differential display RT-PCR analysis on two oncocytic adenomas and their paired controls. We then carried out a microarray analysis using the 460 selected, differentially expressed clones on four other oncocytomas and their paired controls. Thirty genes, 12 encoded by mitochondrial DNA and 18 nuclear-encoded, were overexpressed by a factor of at least 2 in the tumors compared with the controls. Seven of the 18 nuclear-encoded genes are involved in protein metabolism: DKFZP434I116, B3GTL, SNX19, RP42, SENP1, UBE2D3, and the CTSB gene, which is known to be particularly deregulated in most thyroid tumors. Other genes are implicated in signal transduction (ITGAV) or tumorigenesis (AF1q). Immunohistochemistry allowed us to confirm overexpression of the ITGAV and CTSB genes at the protein level and showed a marked relocation of the CTSB protein. We confirmed the overexpression of the AF1q oncogene in 56% of 18 oncocytic tumors by quantitative RT-PCR analysis, which attested to the heterogeneity of these tumors. Our results show an increased expression of genes involved in protein metabolism in oncocytoma, the significance of which requires investigation.

Adenine Nucleotide Translocator 2↗
PubMed2004

Transcriptional profiling reveals coordinated up-regulation of oxidative metabolism genes in thyroid oncocytic tumors.

Oncocytomas are large cell tumors characterized by an abnormal proliferation of mitochondria. To investigate this phenomenon in thyroid oncocytomas, we determined gene expression profiles of 87 samples using microarrays of 6720 PCR products from cDNA clones. Samples included 29 thyroid oncocytomas and six papillary carcinomas, the remainder representing other thyroid pathologies or mitochondria-rich tumor samples, normal thyroid samples, and two thyroid cell lines. Hierarchical clustering and supervised analysis identified two specific oncocytic clusters and 163 distinctly regulated genes between oncocytoma and normal thyroid. Differential expression of five selected genes (APOD, BCL-2, COX, CTSB, and MAP2) was confirmed by immunohistochemistry. The two specific oncocytic clusters were rich in mitochondrial genes and revealed coordinated expression of nuclear and mitochondrial respiratory chain genes. We also observed the up-regulation of genes involved in mitochondrial biogenesis, such as nuclear respiratory factor 1 and the endothelial nitric oxide synthase. Several oxidative metabolism genes were overexpressed in oncocytomas, including those from the tricarboxylic acid cycle (MDH1) and cytosolic glycolysis (GAPD, ENO1, and GPI). On the contrary, the lactate dehydrogenase A gene, involved in anaerobic metabolism, was down-regulated. Our results suggest that, unlike a large number of solid tumors, thyroid oncocytomas produce energy through an aerobic pathway.

Adenoma, Oxyphilic↗
PubMed2004

Decreased expression of thyrotropin receptor gene suggests a high-risk subgroup for oncocytic adenoma.

OBJECTIVE: The malignancy of thyroid oncocytic tumours, or oncocytomas, is higher than that of follicular tumours. The aim of this study was to investigate the role of thyroid-specific genes in oncocytic tumours and papillary carcinomas. DESIGN AND METHODS: We compared 29 oncocytic tumours with 12 papillary carcinomas. Real-time quantitative PCR was used to measure the expression of thyroid-specific differentiation markers (thyrotrophin-stimulation hormone receptor (TSHR), thyroglobulin (TG) and Na(+)/I(-) symporter (NIS)), transcription factors (thyroid transcription factor-1 (TTF-1) and paired box gene-8 (PAX8)) and nuclear receptors (peroxisome proliferator-activated receptor (PPARgamma1) and thyroid hormone receptor (TRbeta1)) involved in thyroid carcinogenesis. RESULTS: TSHR, TTF-1 and TRbeta1 levels were significantly lower in oncocytic tumours than in papillary carcinomas, as a result of specific biological changes in oncocytic tumours. However, PAX8 and PPARgamma1 did not seem to be involved in the process. Applying the criterion of the underexpression of the thyroid-specific differentiation markers, TSHR, TG and NIS, we classified the oncocytic tumours and papillary carcinomas into three groups. In the first, all three markers were underexpressed; in the second, TSHR was normal while TG and NIS were underexpressed; and in the third, only NIS was underexpressed. The expression patterns revealed that 13 of the 24 oncocytic adenomas underexpressing TSHR in our study, as did four of the five oncocytic carcinomas. CONCLUSION: Cases of oncocytic adenoma associated with low levels of TSHR could be putative oncocytic carcinomas and should therefore receive adequate follow-up [corrected].

Adenocarcinoma, Follicular↗
PubMed2003

When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations?

BACKGROUND: Once familial medullary thyroid carcinoma gene carrier status is established, thyroidectomy must be performed in infancy for mutations in exon 10, but in familial medullary thyroid carcinoma with non-cysteine RET mutations, which is characterized by a late onset of C-cell disease, the appropriate timing of thyroidectomy is unclear. METHODS: We analyzed the cases of 76 patients who underwent thyroidectomy (mean age, 35.2 years); 66 patients underwent concomitant lymphadenectomy. RESULTS: Before the operation, 35 patients had abnormal basal calcitonin levels. Nine and 30 patients had negative or positive pentagastrin test results, respectively. We found normal thyroid in 4% of the patients, C-cell hyperplasia in 29% of the patients, medullary thyroid carcinoma in 67% of the patients (microscopic in 82.4%), and nodal metastases in 19.6% of the patients. The aggressiveness of the disease varied significantly between those patients with preoperative positive pentagastrin test results and those patients with high basal calcitonin levels, with a surgical cure rate of 60% and 34.3%, respectively. All patient who did not achieve cure had high basal preoperative calcitonin levels, which were related to macroscopic medullary thyroid carcinoma and nodal metastases in 5 of 9 patients. CONCLUSION: Thyroidectomy should not be delayed until basal calcitonin level becomes abnormal, at which time advanced disease may be present. As soon as the pentagastrin stimulation test becomes abnormal, operation should be undertaken on early staged disease to achieve cure for the patient. When performed while pentagastrin stimulation test is still negative, thyroidectomy may be truly prophylactic and should be recommended at 5 to 6 years.

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↗
PubMed2000

Cushing's Syndrome Caused by a Well-Differentiated Ileal Neuroendocrine Carcinoma.

We report a very rare case of Cushing's syndrome caused by an ileal adrenocorticotrophin-secreting well-differentiated endocrine carcinoma with liver metastases. A 62-yr-old woman presented with clinical and biological signs suggestive of paraneoplastic Cushing's syndrome Radiological investigations, including magnetic resonance imaging of the pituitary gland, chest and abdominal computerized tomography scan, smalI bowel barium study and pancreatic endoscopic scan, 111 -pentetreotide scintigraphy (octreoscan), esogastroduodenoscopy, and colonoscopy did not detect the source of the ectopic adrenocorticotropic hormone (ACTH) secretior but showed a few liver nodules. Because a 10 mo-long ketoconazole treatment was not effective, a bilateral adrenalectomy was performed in order to control the Cushing's syndrome, and a liver nodule biopsy diagnosed a metastatic neuroendocrine tumor. Subsequently, a second laparotomy disclosed a 1.8 cm ileal neuroendocrine tumor, cosecreting ACTH and serotonin on immunohistochemistry with many liver metastases. ACTH and secretion by intestinal neuroendocrine tumors is rare, and the secretion is a most always clinicailly silent. Cushing's syndrome caused by an intestinal low grade neuroendocrine tumor is even rarer, with only two previous cases reported in the literature. Our observation underlines the difficulty of localizing the source of ectopic ACTI-I secretion in paraneoplastic Cushing's syndrome.

Journal Article↗
PubMedDate not supplied

Abnormal stimulation of the thyrotrophin receptor during gestation.

Pregnancy induces physiological alterations in thyroid function which may make difficult the interpretation of results of thyroid hormone measurement. A state of hyperstimulation of the thyroid gland is common in early pregnancy. In a few cases, thyroid hormone values will deviate from the normal range, which corresponds to the gestational transient thyrotoxicosis. This syndrome is closely associated with hyperemesis gravidarum. The relationship between the two syndromes, demonstrated by epidemiological studies, has been illustrated by an exceptional case of familial recurrent gestational thyrotoxicosis presenting as hyperemesis gravidarum due to hypersensitivity of the thyrotrophin receptor to hCG. However, the exact mechanisms of hyperemesis gravidarum have not yet been identified. Gestational transient thyrotoxicosis has to be distinguished from Graves' disease, because the latter is associated with potential maternal and fetal complications when thyrotoxicosis is not controlled, whereas the former has usually a favourable outcome. The existence of other cases of thyroid hypersensitivity or hCG endowed with abnormal thyrotrophic activity is suspected. They may be identified only by assessment of the thyroid function in cases of hyperemesis gravidarum. The identification of these cases would be helpful to understand the mechanisms of specificity of glycoprotein hormone receptors.

Amino Acid Sequence↗