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1.
Eur J Endocrinol ; 173(6): 819-26, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26392472

ABSTRACT

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.


Subject(s)
Adrenal Gland Neoplasms/genetics , Bronchial Neoplasms/genetics , Multiple Endocrine Neoplasia Type 1/genetics , Neuroendocrine Tumors/genetics , Pancreatic Neoplasms/genetics , Parathyroid Neoplasms/genetics , Pituitary Neoplasms/genetics , Thymus Neoplasms/genetics , Adolescent , Adrenal Gland Neoplasms/epidemiology , Adult , Age Distribution , Bronchial Neoplasms/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neuroendocrine Tumors/epidemiology , Pancreatic Neoplasms/epidemiology , Parathyroid Neoplasms/epidemiology , Pedigree , Pituitary Neoplasms/epidemiology , Thymus Neoplasms/epidemiology , Young Adult
2.
Horm Metab Res ; 44(5): 334-8, 2012 May.
Article in English | MEDLINE | ID: mdl-22517554

ABSTRACT

Thirty per cent of the paragangliomas and pheochromocytomas reported are hereditary. Mutations in SDHB, SDHC, SDHD, and more recently SDHAF2 and TMEM127 genes have been described in these hereditary tumors. We looked for mutations in these 5 genes in a series of 269 patients with paragangliomas and/or pheochromocytomas. The SDHB, SDHC, and SDHD genes were analyzed in a series of 269 unrelated index patients with paragangliomas and/or pheochromocytomas using dHPLC screening of point mutations followed by direct sequencing and Multiplex PCR Liquid Chromatography to detect large rearrangements confirmed by quantitative PCR. In a second phase, we adapted Multiplex PCR Liquid Chromatography to the SDHAF2 and TMEM127 genes. This method and direct sequencing were applied to 230 patients without the SDHB, C, D mutations. Of the 269 patients, 44 carried a mutation (16.3%). Thirty-seven different mutations were identified: 18 in SDHB (including 2 large deletions), 8 in SDHD, 6 in SDHC, 5 in TMEM127, and no mutations in SDHAF2. Thirteen mutations have not been published so far. An exhaustive study of the different genes is needed to make possible a familial genetic diagnosis in paraganglioma and pheochromocytoma hereditary syndromes. Although mutations in SDHC and TMEM127 are less frequent than mutations in SDHB and SDHD, they also have less evident clinical feature indicators. Analyzing SDHAF2 must be restricted to familial extra-adrenal paragangliomas. Multiplex PCR Liquid Chromatography is a sensitive, fast, and inexpensive method for screening large rearrangements, which are infrequent in these syndromes.


Subject(s)
Adrenal Gland Neoplasms/genetics , Genetic Predisposition to Disease , Mutation , Paraganglioma/genetics , Pheochromocytoma/genetics , Adolescent , Adrenal Gland Neoplasms/congenital , Adrenal Gland Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Child , Female , Genetic Testing , Humans , Male , Membrane Proteins/genetics , Middle Aged , Paraganglioma/congenital , Paraganglioma/diagnosis , Pheochromocytoma/congenital , Pheochromocytoma/diagnosis , Succinate Dehydrogenase/genetics , Young Adult
3.
J Neuroradiol ; 30(4): 268-79, 2003 Sep.
Article in French | MEDLINE | ID: mdl-14566194

ABSTRACT

The authors report their 10 year experience on postsurgical MRI of the sphenoidal region. All patients underwent MRI examination 4 days after surgery, then between 2 and 3 months and one year or more after surgery. The reproducibility of pulse sequences is mandatory to make a diagnosis of recurrent adenoma as early as possible.


Subject(s)
Adenoma/surgery , Magnetic Resonance Imaging , Pituitary Neoplasms/surgery , Sphenoid Bone/surgery , Adenoma/pathology , Follow-Up Studies , Humans , Pituitary Neoplasms/pathology , Sphenoid Bone/pathology
4.
Ann Endocrinol (Paris) ; 64(3): 198-201, 2003 Jun.
Article in French | MEDLINE | ID: mdl-12910061

ABSTRACT

We report a case of a renin secreting tumor, which is a very rare cause of secondary high blood pressure. A 22-year-old woman was hospitalised for exploration of high blood pressure (160/110 mmHg) with severe hypokaliemia (2,7 mmol/l) and secondary hyperaldosteronism. Physical examination was normal except the high blood pressure. Bioassays show increased kaliuresis (66 mmol/24h), plasma renin (89 pg/ml in clinostastism--108 pg/ml in orthostatism), pro-renin (1207 pg/ml in clinostastism--1412 pg/ml in orthostatism) and aldosterone (210 pg/ml in clinostastism--566 pg/ml in orthostatism). The rest of the endocrine tests were normal (cortisol and ACTH at 8:00 am, urinary free cortisol, overnight 1 mg dexamethasone suppression test). Doppler ultrasound method, performed by an experienced radiologist, did not show renal artery stenosis. Abdominal computerized tomography showed a nodular formation at the upper pole of the right kidney, isodense to renal medullary. The size tumor was 15 mm. The renal vein sampling shows high values of renin on both sides whereas, for the pro-renin, the values were higher on the tumor side. In spite of treatment with CEI (Converting Enzyme Inhibitors) and calcium antagonists, the blood pressure was not controlled. Hypokaliemia persisted (3 mmol/l) in spite of high daily potassium intake (64 mmol/l of potassium chloride). After tumor resection, reninoma was diagnosed by the pathology examination and blood pressure, plasma rennin, plasma aldosterone level returned to normal.


Subject(s)
Hypertension/etiology , Kidney Neoplasms/metabolism , Renin/metabolism , Adult , Aldosterone/blood , Enzyme Precursors/blood , Humans , Hypokalemia/etiology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/surgery , Renal Veins , Renin/blood , Tomography, X-Ray Computed
5.
Neurochirurgie ; 48(2-3 Pt 2): 173-85, 2002 May.
Article in French | MEDLINE | ID: mdl-12058124

ABSTRACT

Specific MR techniques are required for optimal detection of adenocorticotropic hormone secreting adenomas responsible for Cushing's disease. Adequate MR sequences, high resolution coronal T1 and T2 - weighted images, dynamic MR imaging, post-gadolinium delayed images, dose of gadolinium adjusted for each sequence can routinely demonstrate pituitary adenomas less than 3 mm in Cushing's disease.


Subject(s)
Adenoma/diagnosis , Cushing Syndrome/diagnosis , Magnetic Resonance Imaging/methods , Pituitary Neoplasms/diagnosis , Adenoma/complications , Adenoma/pathology , Adenoma/surgery , Adult , Contrast Media , Cushing Syndrome/etiology , Cushing Syndrome/pathology , Female , Follow-Up Studies , Gadolinium , Humans , Hypophysectomy , Male , Middle Aged , Nelson Syndrome/diagnosis , Nelson Syndrome/etiology , Nelson Syndrome/pathology , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Retrospective Studies
6.
J Clin Endocrinol Metab ; 85(11): 4254-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11095463

ABSTRACT

We analyzed the kinetics of CD4 cells, human immunodeficiency virus (HIV) viral load, and autoantibodies in acquired immune deficiency syndrome patients with Graves' disease (GD) after immune restoration on highly active antiretroviral therapy (HAART; retrospective study). Five patients (median age, 41 yr) were diagnosed with GD after 20 (range, 14-22) months on HAART on the basis of clinical and biological hyperthyroidism, diffuse hyperfixation of thyroid scan, and the presence of anti-TSH receptor (anti-TSHR) antibodies (Ab). GD was diagnosed several months after the plasma HIV ribonucleic acid load became undetectable, when the CD4+ cell count had risen from 14 (range, 0-62) to 340 (range, 163-460) x 10(6) cells/L. Antithyroid peroxidase (anti-TPO) and anti-TSHRAb appeared 14 (range, 9-18) and 14 (range, 11-20) months after starting HAART and 12 (range, 6-15) and 11 (range, 9-17) months after the increase in CD4+ cells. In 3 patients, TPOAb preceded TSHRAb by 3-10 months. No other autoantibodies were detected. Thyroid antibodies were absent in a group of 55 HIV-1-positive patients with comparable response to HAART and no symptoms of hyperthyroidism (cross-sectional study). Thyroid-specific autoimmunity can occur upon immune restoration with HAART. Our observations suggest a relationship between thymus-dependent immune reconstitution after immunosuppression and autoimmunity and may provide insight into the pathophysiology of GD.


Subject(s)
Autoantibodies/blood , Graves Disease/complications , Graves Disease/immunology , HIV Infections/complications , HIV Infections/immunology , Immunoglobulins, Thyroid-Stimulating/blood , Adult , Antiretroviral Therapy, Highly Active , Antiviral Agents/therapeutic use , CD4 Lymphocyte Count , Female , Graves Disease/blood , HIV Infections/drug therapy , HIV-1/isolation & purification , Humans , Iodide Peroxidase/immunology , Male , RNA, Viral/blood , Receptors, Thyrotropin/immunology , Thyrotropin/blood , Thyroxine/blood , Time Factors , Viral Load
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