Biomedical subjects

Olivier Chabre

Publications and source records attributed to Olivier Chabre.

12 recordsLinked to original sources

PubMed2006

Diagnosis of Cushing's syndrome: A retrospective evaluation of clinical practice.

BACKGROUND: The aim of this study was to evaluate the efficiency of the clinical diagnosis of Cushing's syndrome (CS). METHODS: A retrospective study was conducted of 72 consecutive patients with CS who, from 1995 to 2002, had been referred to the endocrinology department of a University Hospital by either endocrinologists or non-endocrinologists. Symptoms, signs, and biochemical screening tests used for confirmation of the diagnosis were recorded. Symptoms that led patients to a consultation were defined as reasons for consultation and were distinguished from other symptoms identified only by the referring physician. RESULTS: Fifty-one patients requested a consultation for reasons related to CS, predominantly weight gain (44%) and muscle weakness (21%). In contrast, 21 patients did not request a consultation for symptoms related to CS. Assessment of physical signs demonstrated that the clinical presentation of patients was similar in both groups. However, endocrinologists referred significantly more patients who had not expressed symptoms related to CS than non-endocrinologists (38% vs. 17%, p<0.05). Appropriate screening tests (overnight 1-mg dexamethasone suppression test and/or urinary free cortisol) were used in all patients referred by endocrinologists and in 45% of patients referred by non-endocrinologists. CONCLUSION: Our data show that many patients with CS do not spontaneously request a consultation for symptoms related to their condition. These patients are mostly identified by endocrinologists, who seem to have a better knowledge of physical signs and screening tests. Because endocrinologists are highly dependent upon non-endocrinologists for the recruitment of their patients, an improvement in the educational program is needed at the non-endocrinologist level. Our results may be of help in drafting the lines of this improvement by stressing the importance of the most specific physical signs and the most relevant screening tests for CS.

Journal Article↗

PubMed2006

Very early prophylactic thyroid surgery for infants with a mutation of the RET proto-oncogene at codon 634: evaluation of the implementation of international guidelines for MEN type 2 in a single centre.

OBJECTIVE: Genetic diagnosis available since 1993 established germinal mutations of the RET proto-oncogene at codon 634 as the main cause of inherited medullary thyroid carcinoma (MTC). International guidelines established in 1999 recommend that children with such mutations undergo a total thyroidectomy before age 5, with unspecified cervical neck dissection. Since 1993, only 41 of 275 thyroidectomies reported in RET 634 children were performed before age 5 (15%). The aim of this study was to evaluate the implementation of these guidelines in a single centre. DESIGN AND PATIENTS: Genetic diagnosis was proposed to the parents of all eight children born after 1992 from two RET 634 families. Total thyroidectomy was proposed before age 5 if the child carried a mutation. RESULTS: Genetic diagnosis was performed in all the children (aged 1-3) and thyroidectomy in the five who carried a mutation (aged 2-5). Cervical lymph node dissection varied from lymphadenectomy of central and lateral compartments in the eldest child to pickings in the youngest. There was no permanent hypoparathyroidism or recurrent nerve paralysis. C-cell hyperplasia, medullary thyroid carcinoma and lymph node metastasis were present in 5/5, 3/5 and 0/5, respectively. Undetectable pentagastrin-stimulated CT levels were achieved and maintained postoperatively in all five children (average follow-up 3.6 years). CONCLUSIONS: MEN 2 guidelines on thyroidectomy can be efficiently and safely implemented by a multidisciplinary team operating in a single centre. The lack of guidelines on cervical neck dissection remains a problem; this could be solved by determining an age under which this procedure would be deemed unnecessary.

Biomarkers, Tumor↗

PubMed2006

Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1.

BACKGROUND: The frequency of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1 (MEN1) remains unknown. AIM: To evaluate prospectively with endoscopic ultrasonography (EUS) the frequency of nonfunctioning (asymptomatic) pancreaticoduodenal tumors. PATIENTS AND METHODS: MEN1 patients without functioning pancreatic involvement underwent systematic pancreaticoduodenal EUS in nine GTE (Groupe des Tumeurs Endocrines) centers. Demographic and clinical factors predictive of pancreatic involvement were sought, and standardized biochemical measurements obtained. RESULTS: Between November 1997 and July 2004, 51 patients (median age: 39 [range: 16-71] yr) were studied. MEN1 had been diagnosed 3 [0-20] yr earlier, notably by genetic screening for 26 (51%) with asymptomatic disease. Twenty-five patients had minor biochemical anomalies (<2 x normal (N)) and serum somatostatin was 10.8 N in 1; EUS detected pancreatic lesions in 28 patients (54.9%; 95% CI: 41.3-68.7%). A median of three [1-9] tumors with a median diameter of 6 [2-60] mm was found per patient; for 19 (37.3%) patients a tumor measured > or =10 mm and > or = 20 mm in 7 (13.7%) patients. Only one duodenal lesion was found and three patients had peripancreatic adenopathies. Pancreatic tumors were not associated with any of the studied parameters, notably age, family history, biochemical anomalies. Sixteen of twenty-six patients underwent EUS monitoring over 50 [12-70] months; six (37.5%) had more and/or larger pancreatic lesions. CONCLUSION: The frequency of nonfunctioning pancreatic endocrine tumors is higher (54.9%) than previously thought. The size and number of these tumors can increase over time. Pancreatic EUS should be performed once MEN1 is diagnosed to monitor disease progression.

Adolescent↗

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

Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model.

Aberrant expression of ectopic G protein-coupled receptors (GPCRs) in adrenal cortex tissue has been observed in several cases of ACTH-independent macronodular adrenal hyperplasias and adenomas associated with Cushing's syndrome. Although there is clear clinical evidence for the implication of these ectopic receptors in abnormal regulation of cortisol production, whether this aberrant GPCR expression is the cause or the consequence of the development of an adrenal hyperplasia is still an open question. To answer it, we genetically engineered primary bovine adrenocortical cells to have them express the gastric inhibitory polypeptide receptor. After transplantation of these modified cells under the renal capsule of adrenalectomized immunodeficient mice, tissues formed had their functional and histological characteristics analyzed. We observed the formation of an enlarged and hyperproliferative adenomatous adrenocortical tissue that secreted cortisol in a gastric inhibitory polypeptide-dependent manner and induced a mild Cushing's syndrome with hyperglycemia. Moreover, we show that tumor development was ACTH independent. Thus, a single genetic event, inappropriate expression of a nonmutated GPCR gene, is sufficient to initiate the complete phenotypic alterations that ultimately lead to the formation of a benign adrenocortical tumor.

Adenoma↗

PubMed2005

Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and Cushing's syndrome features.

CONTEXT: Aberrant expression of LH/human chorionic gonadotropin (hCG) receptor has been suggested in several cases of bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The cortisol production is then directly controlled by endogenous secretion of LH/hCG. However, the direct involvement of this aberrant LH/hCG receptor expression in the development of the hyperplasia has not been demonstrated. Moreover in most cases, whenever investigated, the aberrant expression of LH/hCG receptor has been associated with the ectopic expression of other G protein-coupled receptors such as gastric inhibitory polypeptide, serotonin, or vasopressin receptors. OBJECTIVE: The aim of this study was to explore the action of LH/hCG receptor on the development of adrenal hyperplasia. RESULTS: The ectopic expression of this single nonmutated gene transduced into bovine adrenocortical cells was sufficient to induce not only the aberrant cortisol secretion but also hyperproliferation and benign transformation. The cells were transplanted beneath the kidney capsule of adrenalectomized immunodeficient mice. Only the cells expressing the LH/hCG receptor gene formed an enlarged tissue with a high proliferation rate. The tissue expressing LH/hCG receptor was responsible for elevated plasma cortisol and decreased plasma ACTH levels in transplanted mice. These animals displayed physiological changes similar to those of patients with Cushing's syndrome, including muscle atrophy, thin skin, spleen atrophy, and hyperglycemia. CONCLUSIONS: These results demonstrate that a single genetic event such as the inappropriate expression of the nonmutated LH/hCG receptor gene is sufficient to initiate the phenotypic changes that cause the development of a benign adrenocortical tumor.

Adrenal Cortex↗

PubMed2004

Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic Acid microarrays identifies several candidate genes as markers of malignancy.

The aim of this study was to identify predictor sets of genes whose over- or underexpression in human sporadic adrenocortical tumors would help to identify malignant vs. benign tumors and to predict postsurgical metastatic recurrence. For this, we analyzed the expression of 230 candidate genes using cDNA microarrays in a series of 57 well-characterized human sporadic adrenocortical tumors (33 adenomas and 24 carcinomas). We identified two clusters of genes (the IGF-II cluster containing eight genes, including IGF-II, and the steroidogenesis cluster containing six genes encoding steroidogenic enzymes plus eight other genes) whose combined levels of expression appeared to be good predictors of malignancy. This predictive value was as strong as that of the pathological score of Weiss. The analysis of the population of carcinomas (13 tumors) for genes whose expression would be strongly different between recurring and nonrecurring tumors allowed identification of 14 genes meeting these criteria. Among these genes, there are probably new markers of tumor evolution that will deserve additional validation on a larger scale. Taken together, these results show that the parallel analysis of the expression levels of a selected group of genes on microgram quantities of tumor RNA (a quantity that can be obtained from fine needle aspirations) appears as a complementary method to histopathology for the diagnosis and prognosis of evolution of adrenocortical carcinomas.

Adolescent↗

PubMed2004

Selective venous sampling in recurrent and persistent hyperparathyroidism: indication, technique, and results.

Between 1992 and 2002, 542 patients underwent a surgical treatment for hyperparathyroidism in our department. Twenty-three selective venous sampling procedures (SVS) were performed because of the failure of the other methods of diagnosis. These patients have recurrent or persistent hyperparathyroidism. Noninvasive methods of topographical diagnosis have failed or they have given contradictory results. In our experience, the surgeon needs a precise localization of the pathological glands in these difficult cases. In our series of SVS, specificity was 85.7% and sensitivity was 94.7%. Our results show that a high postoperative gradient of parathyroid hormone in the internal thoracic veins indicates an ectopic pathological gland in the thymus. A high gradient in a vertebral vein indicates a pathological superior parathyroid gland, usually in a retro-esophageal position.

Adult↗

PubMed2004

Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients.

OBJECTIVE: Phaeochromocytoma is a rare tumour of the chromaffin cells, the diagnosis of which is based on an assay of metanephrines and treatment is surgical excision of the tumour. It is usually discovered due to a rich and varied symptomatology or classic paroxysmal hypertension. The main purpose of this study was to specify the exact circumstances of discovery of the phaeochromocytomas operated on in our university hospital between 1990 and 2002. DESIGN AND METHODS: Forty-one consecutive and complete case reports of patients who had surgery for phaeochromocytoma were analysed retrospectively. This series includes 10 patients with a genetic disorder predisposing to phaeochromocytoma. RESULTS: The association of headaches and palpitations with sweating was found in only 24% of cases (10/41). Blood pressure anomalies led to the discovery of phaeochromocytoma in only 51% of cases (21/41) and 59% (24/41) of all the patients suffered from hypertension. In almost half the cases (20/41), the tumour was discovered by an imaging method (ultrasonography, CT scan or MRI) which had been performed for reasons unrelated to a blood pressure abnormality. CONCLUSIONS: Phaeochromocytoma, the symptoms of which are not very specific and during which hypertension is present in only half the patients, is a disease that remains rare. Its incidence could be increasing because of changes in the method of detection. Indeed, in our study, different imaging techniques led to its incidental discovery in half of the cases.

Adrenal Gland Neoplasms↗

PubMed2003

[Pancreatic tumors].

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Diagnosis, Differential↗

PubMed2003

Extracapsular hematoma of the parathyroid glands.

The objective of this study was to standardize surgical treatment of cervicothoracic hematoma due to parathyroid gland rupture. Only 19 such hematomas have been reported in the literature, and there is no consensus about the best time to operate or the surgical approach. We have now treated four new cases of extensive hematoma from the time of the initial bleeding except in the case of severe hemodynamic or respiratory troubles or nerve compression. Two of the patients were operated on after a minimal 3 months delay, with perfect results. The other two were operated on during the first month with great technical difficulty and incomplete results. In one case the gland was not excised, but parathyroid apoplexy afforded a spontaneous remission, although the hyperparathyroidism recurred 7 years later. We concluded that, first, if there are no severe compressive or hemodynamic symptoms, the surgical treatment must be performed more than 3 months after the bleeding, as the dissection then is as simple as any well ordered surgery. In case of an extensive hematoma accompanied by shock or compression, we propose simple emergency drainage, with reoperation 3 months later. Second, parathyroid apoplexy sometimes offers spontaneous remission of primary hyperparathyroidism, although late recurrence is always possible and surgical treatment then cannot be avoided.

Aged↗

PubMed2003

Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing's disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage.

Bilateral inferior petrosal sinus sampling (BIPSS) is the most reliable procedure for distinguishing Cushing's disease from ectopic ACTH secretion. However, it is less reliable at predicting the lateralization of the pituitary corticotroph microadenoma. We sought to determine whether this could be improved by taking into account the pattern of venous drainage and the precise location of the catheters. We retrospectively studied data from 86 patients who underwent BIPSS. Cushing's disease was predicted in 74 patients, of whom 69 underwent transsphenoidal surgery. Surgical cure was obtained in 65 patients, with identification of a corticotroph microadenoma in 58 cases. In 49 patients the location of the microadenoma predicted by the intersinus ACTH gradient could be compared with the pathologist's data. BIPSS accurately predicted the lateralization of the microadenoma in only 57% of these patients. Prediction was improved to 71% when both venograms and catheters were symmetric (35 patients). In this subgroup accuracy was 86% in patients with both catheters in the inferior petrosal sinuses compared with 50% in patients with both catheters in the cavernous sinuses (CS). Two transient sixth nerve palsies occurred during CS catheterization. Our data suggest that BIPSS results are much improved when venous drainage is symmetric. Catheterization of CS did not improve the results and was less safe.

Adenoma↗