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C Gicquel

Publications and source records attributed to C Gicquel.

10 recordsLinked to original sources
PubMed1995

Cushing's syndrome in medullary thyroid carcinoma.

Ectopic ACTH secretion is a rare cause of hypercortisolism. Induced metabolic disturbances are often serious, and the management of such patients may be difficult. We report here our experience with four medullary thyroid carcinoma (MTC) patients with distant metastases in whom an ectopic ACTH syndrome occurred. The clinical presentation was significant by the severity and the rapidity of the hypercortisolism. Diagnosis and follow-up were realized by measurements of plasma cortisol, urinary free cortisol, urinary 17-hydroxycorticosteroid, plasma ACTH, plasma LPH, serum calcitonin and carcino-embryonic antigen. Initial treatment with adrenalytic medical therapy failed to control the disease. Only bilateral adrenalectomy cured the excessive cortisol production, and for a long time despite tumor progression. In conclusion, bilateral adrenalectomy should be considered in MTC patients with Cushing's syndrome even at the stage of distant spread. In fact, with regard to the slow growth rate of most MTC's, they may survive for years.

Adrenalectomy↗
PubMed1995

Oncogenic mutations of alpha-Gi2 protein are not determinant for human adrenocortical tumourigenesis.

Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first described in growth hormone-producing pituitary tumours. They resulted in constitutive activation of the alpha s-subunit by decreasing intrinsic GTPase activity. A similar mutation, affecting codon Arg179 (exon 5) in the alpha-subunit of the Gi2 protein, the adenylyl cyclase-inhibiting protein, has been described by a single group in ovarian and adrenocortical tumours. We evaluated the frequency of activating mutations in the alpha-subunit of the Gi2 protein in 18 human adrenocortical tumours. We screened exons 5 (codon Arg179) and 6 (codon gln205) for mutations by denaturing gradient gel electrophoresis analysis of leucocyte and tumoural DNA. No abnormal migration pattern was found in either exon. The absence of mutation in exon 5, which includes the Arg179 codon, was confirmed in all tumoural DNA by direct sequencing. In conclusion, we did not find any oncogenic mutations in the GTPase domain of the alpha-subunit of the Gi2 protein in adrenocortical tumours. Thus, the previously oncogenic gip2 mutations do not appear to be determinant for adrenocortical tumourigenesis.

Adolescent↗
PubMed1992

Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases.

Twenty patients, 16 males and 4 females, aged 11-76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11, 10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuro-Peptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanillic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant metastase in 10. Iodine-131 MIBG therapy was performed in 11, among whom 9 were evaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3-60). Response to therapy was poor and warrants further cooperative trials.

3-Iodobenzylguanidine↗
PubMed1992

Molecular diagnosis of Turner's syndrome.

Turner's syndrome is a common disorder which occurs in around 1/3000 live births in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could help to reduce the number of time consuming karyotype analyses needed. The M27 beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects detects heterozygosity with multiallelic polymorphism. In Southern blotting, a single X chromosome yields a single hybridisation band. In this study, genomic DNA was extracted from leucocytes of 49 patients with Turner's syndrome (karyotypes: 45,XO, n = 29; 45,XO/46,XX, n = 4; 46,Xi(Xq), n = 1; 45,XO/46,Xi(Xq), n = 4; 45,XO/46,Xr(X), n = 4; 45,XO/46,XY, n = 4; 46,XXp-, n = 3), digested with EcoRI or HindIII, and analysed by Southern blotting. The molecular data for each patient were compared with DNA controls (homozygous 46,XX, heterozygous 46,XX and 46,XY DNA). A single band of reduced intensity compared to homozygous 46,XX control DNA was seen in 41 cases. Two hybridisation bands of different intensities were seen in four patients, in one of whom mosaicism was suspected on the basis of molecular analysis, despite a 45,XO karyotype. In four cases, Turner's syndrome failed to be detected: one 45,XO/46,XX mosaicism with only 4% of 45,XO cells and three distal Xp deletions. DNA analysis appears to be a useful and rapid tool in screening for Turner's syndrome and could be an alternative to cytogenetic analysis in diagnosing the disorder when severe growth retardation or delayed puberty are not accompanied by a Turner phenotype.

Blotting, Southern↗
PubMed1992

Monoclonality of corticotroph macroadenomas in Cushing's disease.

The pathophysiological mechanism of pituitary ACTH oversecretion in Cushing's disease remains unclear. The question of whether a collection of corticotroph cells is a primary pituitary event or is driven by increased production of hypothalamic corticotropin releasing factor is still debated. Establishing whether or not there is a clonal nature of such pituitary lesions has important conceptual and practical implications. Clonal composition of corticotroph cell adenomas was determined by X chromosome inactivation analysis using a DNA probe, M27 beta, which detects a multiallelic polymorphism in 90% of females. A first digestion by PstI reveals the polymorphism. A second digestion by MspI or its methylation sensitive isoschizomer HpaII, distinguishes the active from the inactive copy. DNA was extracted from 11 corticotroph macroadenomas responsible for Cushing's disease or Nelson's syndrome. Eight of the 11 female patients were heterozygous for the locus and included in the study. Blood leukocytes were available for 5 females and were used as controls. All 8 tumors demonstrated a monoclonal pattern while the 5 leukocyte DNA were polyclonal. Ours results show that a somatic modification plays an important role in the pathogenesis of corticotroph macroadenomas allowing monoclonal expansion of a genetically aberrant cell.

Adenoma↗
PubMed1991

5-Fluorouracil, doxorubicin, and cisplatin as treatment for adrenal cortical carcinoma.

Fourteen patients with progressive metastatic adrenal cortical carcinoma were treated with a combination of 5-fluorouracil (5-FU), doxorubicin, and cisplatin (FAP). All had a large tumor burden. Six patients had a hormone-producing tumor; mitotane treatment was given to five of them during chemotherapy for its possible antihormonal effects. Treatment could be evaluated in 13 patients. The overall response rate was 23% (95% confidence interval [CI], 5% to 54%). A complete remission, which lasted for 42 months, was achieved in one patient. Partial remissions, which lasted for 6 and 11 months, were achieved in two patients. Cardiotoxicity appeared in three patients, myelotoxicity in four, and nephrotoxicity in one. This confirms that this regimen is an active combination for the treatment of metastatic adrenal cortical carcinoma.

Adolescent↗
PubMed1990

Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas.

Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors.

Adrenal Gland Neoplasms↗
PubMed1989

[Riedel's thyroiditis. 3 cases].

Three cases of Riedel's thyroiditis are reported. The clinical presentation varied, with thyroid nodule in 2 cases (associated with cervical lymph node enlargement in 1 case) and compressive goitre with mediastinal involvement in the third case. The histological diagnosis of Riedel's thyroiditis is difficult and was made retrospectively in these 3 patients; it is based on the absence of malignant cells and the presence of fibrosis, inflammatory infiltrates and, inconstantly, vascular lesions of the occlusive phlebitis type.

Adrenal Cortex Hormones↗
PubMed1988

[H-NMR spectroscopy of plasma cannot be used for cancer screening].

Water-suppressed proton nuclear magnetic resonance spectra were generated from plasma taken from 25 apparently healthy individuals, 103 patients with malignancies and 32 patients with benign thyroid tumors. Narrow linewidths from the lipoprotein methylene and methyl resonances were observed in only 61% of the patients with malignant tumors and in contrast to the results of Fossel et al., there was a considerable overlap of values between patients with and without malignant tumors. We studied the area of the CH2 and CH3 signals which was significantly increased in 83% of the patients with overt malignant disease. However this was also found in 20% of healthy subjects and in 47% of those with benign thyroid tumor. Lipoproteins (VLDL and chylomicrons) can reproduce these modifications. The present data suggest that considerable caution should be taken in interpreting water-suppressed proton NMR spectra for cancer detection.

False Positive Reactions↗