Biomedical subjects

Brigitte Delemer

Publications and source records attributed to Brigitte Delemer.

10 recordsLinked to original sources

PubMed2006

Digestive calcitonin-secreting tumors of the foregut: comparison with non-calcitonin-secreting tumors.

OBJECTIVES: Digestive calcitonin-secreting endocrine tumors are very rare lesions of the foregut. This study was undertaken to compare the characteristics and the prognosis of these tumors and those of non-calcitonin-secreting endocrine tumors. METHODS: All patients with a digestive endocrine tumor of the foregut followed up in Reims University Hospital and whose serum calcitonin levels were determined between 1988 and 2004 were included. Clinical and tumor characteristics of calcitonin-positive and calcitonin-negative patients were compared. RESULTS: Thirty-two patients were included. Among the five (15.6%) with high calcitonin levels (median: 340 pg/ml, range: 42-7460 pg/ml), only one tumor was functioning (diarrhea). Significant differences between patients with positive and negative calcitonin levels were, respectively: liver metastases [5 (100%) versus 11 (40.7%); P=0.04], type according to the World Health Organization 2000 histological classification [notably 4 (80%) versus 3 (12.5%) poorly differentiated endocrine carcinomas; P=0.02] and Ki67 proliferation index [median: 25% (range: 20-30%) versus 7% (0-80%); P=0.03]. The only calcitonin-positive well-differentiated endocrine carcinoma had a high proliferation index (30%). Survival also differed significantly (P=0.001), as all calcitonin-positive patients died, with a median survival of 22.6 months (range: 1.2-27.2 months), versus five (18.5%) calcitonin-negative patients. Median follow-up period for the latter was 42.3 months (range: 3.4-208 months). CONCLUSIONS: The secretion of calcitonin appears predictive of a poor prognosis. Digestive endocrine calcitonin-secreting tumors correspond histopathologically to poorly differentiated or well-differentiated carcinomas with high proliferation indexes.

Adolescent↗

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↗

PubMed2006

Interferon-alpha-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves' disease.

Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.

Adult↗

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

Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients.

PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR). METHODS AND MATERIALS: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin. RESULTS: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, except for pituitary deficiency, were reported, with a probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8 years, respectively. Nonfunctioning status was the sole unfavorable factor (p = 0.0016). CONCLUSIONS: Surgery plus FSR is safe and effective. FSR focused to the target volume seems more suitable than standard radiotherapy, and standard fractionation reduces the risk of optic neuropathy sometimes observed after single-dose radiosurgery. Therefore, FSR allows us to consider combined transrhinoseptal surgery and early radiotherapy, with a curative goal without patient selection.

Adenoma↗

PubMed2005

Risk factors and long-term course of thyroid dysfunction during antiviral treatments in 221 patients with chronic hepatitis C.

AIM: To identify the predictive factors of dysthyroidism during treatment for chronic viral hepatitis C and to evaluate the long-term outcome of these patients. METHODS: Patients treated for chronic viral hepatitis C between 1990 and 2001 were analyzed retrospectively. Patients with dysthyroidism before treatment and patients positive for hepatitis B surface antigen or human immunodeficiency virus antibodies were excluded. Dysthyroidism was defined by an abnormal serum TSH level on two separate occasions. RESULTS: 221 consecutive patients were included. Among them, a hundred were treated twice by interferon alpha, 21 had 3 treatments and 3 had 4 treatments. Fifteen of these patients (7%) had dysthyroidism during antiviral therapy. There was no significant difference in the frequency of dysthyroidism during the first and the second treatment [respectively 4,1% (N = 9) and 6% (N = 6)]. Female gender and the presence of antimicrosome or antithyroperoxydase (anti-TPO) antibodies before antiviral treatment were predictive factors of dysthyroidism. Treatment by interferon and ribavirin did not increase the risk of dysthyroidism compared to monotherapy with interferon. Pegylated interferon (N = 49) was not a risk factor compared to standard interferon. Thirteen patients had hypothyroidism (2 of them as a result of biphasic thyroiditis) and 2 had hyperthyroidism. The antiviral treatment was continued in 11 patients. Seven out of 13 patients with hypothyroidism required an indefinite treatment (follow-up: 15 to 90 months). CONCLUSIONS: In our series, 7% of patients with chronic viral hepatitis C had a dysthyroidism during antiviral therapy. Predictive factors were female gender and positive antimicrosome or anti-TPO antibodies before treatment. Absence of dysthyroidism during a first antiviral treatment did not preclude from the risk of dysthyroidism during a second treatment.

Adult↗

PubMed2004

Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry.

UNLABELLED: Few studies have concerned the rare functioning endocrine pancreatic tumors associated with multiple endocrine neoplasia type 1 (MEN 1). When sporadic, these tumors have a poor prognosis. AIM: To analyze the frequency, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas and somatostatinomas recorded in the GTE (Groupe des Tumeurs Endocrines) registry. METHODS: Records of the patients whose GTE registry codes included glucagonoma, VIPoma or somatostatinoma were reviewed. The diagnosis was confirmed when there were clinical signs of a functioning tumor and/or when blood levels of the peptide were higher than twice the upper limit of normal. RESULTS: Among 580 patients with MEN 1, duodeno-pancreatic involvement was present in 307 (52.9%). Five (1.6%) had a glucagonoma, 3 (0.98%) a VIPoma and 2 (0.65%) a somatostatinoma. A clinical syndrome was present in 1 patient with glucagonoma, in the 3 with VIPomas and in 1 with somatostatinoma. Tumor size was greater than 3 cm more often for these rare tumours (67%) than in patients with other type of duodeno-pancreatic involvement (28%) (P=0.02) and visceral metastases were more frequent (40% vs 15%; P=0.056). Ten-year survival of patients with glucagonomas, VIPomas or somatostatinomas (53.8%; CI95%: 15.5-92.1) was poorer than that of patients with insulinomas (91.4%; CI95%: 83.399.5; P=0.01) or gastrinomas (81.7%; CI95%: 74.9-88.5; P=0.20) and close to that of patients with non-functioning tumors (62.2%, CI95%: 41.0-83.9; NS). CONCLUSION: Glucagonomas, VIPomas and somatostatinomas, especially the functioning type, are very rare in patients with MEN 1. Prognosis is poor, probably because of large tumor size and high rate of metastasis. Survival is similar to that in patients with non-functioning tumors.

Adolescent↗

PubMed2002

Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD.

We studied 11 new kindreds with primary pigmented nodular adrenocortical disease (PPNAD) or Carney complex (CNC) and found that 82% of the kindreds had PRKAR1A gene defects (including seven novel inactivating mutations), most of which led to nonsense mRNA and, thus, were not expressed in patients' cells. However, a previously undescribed base substitution in intron 6 (exon 6 IVS +1G-->T) led to exon 6 skipping and an expressed shorter PRKAR1A protein. The mutant protein was present in patients' leukocytes and tumors, and in vitro studies indicated that the mutant PRKAR1A activated cAMP-dependent protein kinase A (PKA) signaling at the nuclear level. This is the first demonstration of an inactivating PRKAR1A mutation being expressed at the protein level and leading to stimulation of the PKA pathway in CNC patients. Along with the lack of allelic loss at the PRKAR1A locus in most of the tumors from this kindred, these data suggest that alteration of PRKAR1A function (not only its complete loss) is sufficient for augmenting PKA activity leading to tumorigenesis in tissues affected by CNC.

Adenocarcinoma↗

PubMed2002

Study of diurnal fluctuations of plasma methoxyamines in healthy volunteers.

OBJECTIVE: We studied the diurnal fluctuations of plasma concentrations of methoxyamines (metanephrine and normetanephrine) and of their parent amines (epinephrine and norepinephrine) in normotensive subjects. DESIGN: Serial blood sampling at 09.00 h, 11.00 h, 12.00 h, 14.00 h, 16.00 h, 18.00 h and 20.00 h in 28 healthy volunteers at rest. Determination of plasma concentrations of free catecholamines and total methoxyamines (free and sulpho-conjugates) was carried out by high-performance liquid chromatography with electrochemical detection. RESULTS: Mean (+/- SD) plasma concentrations of total metanephrine (MN) and normetanephrine (NMN) were 4.31 +/- 1.73 nmol/l (range: 0.96-9.3 nmol/l) and 8.13 +/- 2.54 nmol/l (range: 3.14-17.0 nmol/l), respectively. The NMN/MN ratio ranged between 0.8 and 7.8 (mean +/- SD 2.1 +/- 1.0). Mean plasma concentrations of free epinephrine and norepinephrine were 0.21 +/- 0.12 nmol/l (range: 0.06-1.39 nmol/l) and 1.61 +/- 0.62 nmol/l (range: 0.47-4.01 nmol/l), respectively. Despite marked intraindividual fluctuations, mean methoxyamine and catecholamine levels remained constant over the entire duration of the experiment. CONCLUSIONS: The absence of fluctuations of plasma levels of total methoxyamines suggests that their measurement could be carried out at any time within the diurnal time frame. Further investigations, however, remain necessary to validate these findings in patients with hypertension and/or pheochromocytoma, and to explain the ever important intraindividual variation in plasma concentrations of methoxyamines and of their parent compounds.

Adult↗

PubMed1996

Bilateral Thyroid and Ultimobranchial Medullary Carcinoma.

The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.

Journal Article↗