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J L Wémeau

Publications and source records attributed to J L Wémeau.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

Adenoma↗
PubMed2005

[Severe Graves' acropachy and dermopathy. Three case reports].

INTRODUCTION: Traditionally described, severe Graves' acropachy and tibial myxoedema are now only encountered in certain severe forms of Graves' disease, where they can be difficult to diagnose and hence delay the initiation of treatment. OBSERVATIONS: Three patients presented with severe ophthalmopathy, pretibial myxoedema and acropachy of different clinical forms. DISCUSSION: In supplement to the usual biopsies and X-rays, bone scintigraphy provides early diagnosis of acropachy. The severity of the immune disease, the episodes of hypothyroidism and cigarette smoking are the 3 main factors contributing to these extra-thyroid manifestations of Graves' disease. There is currently no treatment that can permanently resolve the functional and aesthetic problems of dermopathy and acropachy.

Adult↗
PubMed2005

[Monogenic severe insulin resistance syndromes].

PURPOSE: To make a point about monogenic insulin resistance syndromes. CURRENT KNOWLEDGE AND KEY POINTS: Extreme insulin resistance syndromes are rare entities. The clinical and biological presentation is similar to that one of metabolic syndrome. Polycystic ovaries syndrome, non-alcoholic liver steatosis, acanthosis nigricans and overall, lipo-atrophic syndrome must be sought. Genetically determined forms are mainly linked to mutations of the insulin receptor gene and to lipoatrophic syndrome-linked mutations. The three syndromes related to mutations of the insulin receptor gene are Type A syndrome, first described by Kahn in young women, whereas leprechaunism and Rabson-Mendenhall syndromes are of neonatal onset. Main insulin resistance syndromes associated with lipo-atrophy are 1) Berardinelli-Seip or congenital generalized lipo-atrophic syndrome linked to mutations of seipin or AGPAT2 gene, 2) Dunnigan or partial familial lipoatrophic syndrome linked to mutations of lamin A/C, or sometimes PPAR gamma gene, and 3) acro-mandibular dysplasia and Köbberling syndrome. FUTURE PROSPECTS AND PROJECTS: In conclusion, an early onset of insulin resistance, especially in association with lipodystrophy must suggest a monogenic insulin resistance syndrome. Outstanding advances in insulin resistance pheno- and genotype identification, despite incomplete yet, offers a better understanding of insulin resistance, atherosclerosis and ageing mechanisms, that should lead to therapeutic improvement.

Diagnosis, Differential↗
PubMed2004

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Delayed-Action Preparations↗
PubMed2004

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Adolescent↗
PubMed2002

[Thyroid nodule, cancer and pregnancy].

Pregnancy is a favorable condition for thyroid nodule formation and growth since iodine balance may be negative in addition to increasing production of hormones with thyroid stimulatory activity. Thyroid nodules may be discovered in pregnant women on routine examination: what is the risk for a nodule to be malignant, how should it be investigated? In case thyroid cancer is suspected, is there an impact of pregnancy on the tumor outcome and what treatments are available? Infrequently, diagnoses of toxic autonomous nodules or medullary carcinomas may be supported by elevated serum calcitonin or suppressed TSH value. Ultrasonography scanning and fine-needle aspiration biopsy (FNAB) best help to monitor thyroid nodules and guide their management. Toxic autonomous nodules can be either surgically resected in the second trimester of pregnancy or treated by percutaneous alcohol injection. When cytology findings are benign or indecisive, solid nodules require follow-up by neck palpation, in association to repeat ultrasonographic study and nodule aspiration as necessary. In this setting, thyroxine administered in small doses or iodine supply merit consideration. If FNAB samples are suggestive of suspicious or malignant lesions, thyroidectomy can be performed through the second trimester or delayed after delivery, depending on the pregnancy term. Observations of pregnant women with a rapid growing differentiated thyroid cancer have been reported. However, in matched studies comparing pregnant and nonpregnant women recurrence risk and cancer mortality are not significantly different.

Biomarkers↗
PubMed2001

[Pendred's syndrome. Current features].

Introduction Pendred's syndrome is a recessive autosomal disease, traditionally defined as the association of deaf-mutism, goiter and dysfunctional iodide organization revealed by the perchlorate discharge test. It represents 4 to 10% of the causes of congenital hypoacusis. Although described more than a 100 years ago, the association of thyroid and cochleo-vestibular damage remained unclear for many years. Genetic abnormalities Progress in molecular biology has revealed that the disease is related to alterations in the PDS gene situated on chromosome 7. The PDS gene is responsible for the production of pendrine, protein involved in anion (l-, Cl-) transportation, notably in the apical pole of the thyreocyte and the cochlear duct, where the endolympha is produced. Practical implications The truncation of pendrine related to the genetic alterations be responsible for the morpho-functional alterations in the cochlear apparatus and the thyroid. In this perspective, Pendred's syndrome would appear as a genetic disorder in anion transportation.

Carrier Proteins↗
PubMed2001

[Apoptosis and the thyroid: the Fas pathway].

THE APOPTOTIC FAS/FAS-L PATHWAY: Represents a major apoptotic pathway and involves the specific interaction between a membrane receptor, Fas, harbored by the target cell and a membrane ligand, Fas-L, harbored by the cytotoxic cell. FAS AND NORMAL THYROID GLAND: Normal thyrocytes express Fas receptor but not its ligand. The control of thyroid gland volume results from an equilibrium between the trophic action of TSH and thyrocyte apoptosis, which is limited to some extent by resistance to Fas activation by producing an inhibitor of the apoptotic signal transduction. FAS AND HASHIMOTO'S THYROIDITIS: Aberrant expression of Fas-L by thyrocytes induces their fratricide apoptosis. Thyroid-infiltrating lymphocytes are resistant to apoptosis by overexpressing the antiapoptotic protein Bcl2. FAS AND GRAVES' DISEASE: Autoantibody-dependant stimulation of the thyrotropin receptor favors goiter formation by reducing thyrocyte apoptosis. It induces repression of Fas expression and production of a soluble Fas, whose serum levels are correlated with clinical course. FAS AND THYROID CANCER: Tumoral cells are resistant to apoptosis by inhibiting the apoptotic signal transduction and exert Fas counter-attack by inducing apoptosis of antitumoral lymphocytes.

Apoptosis↗
PubMed2001

Pseudohypoparathyroidism Ia and hypercalcitoninemia.

Pseudohypoparathyroidism Ia (PHP Ia) is characterized by resistance to PTH and many other stimuli because of deficiency of stimulatory G protein alpha-subunit. To determine the incidence, natural history, and mechanism of C cell dysfunction in PHP, calcitonin assays were performed in six patients with PHP Ia and four with pseudopseudohypoparathyroidism from three unrelated families. Controls included healthy subjects and patients with PHP Ib or hypoparathyroidism. The mean basal level of calcitonin was higher in PHP Ia patients than in controls (95.3 +/- 112.7 vs. 3.7 +/- 2.4 pg/mL; P = 0.005; n < 10). In PHP Ia patients, calcitonin levels rose over the normal range (30 pg/mL) after pentagastrin infusion in five patients and remained normal in one. Familial medullary thyroid carcinoma was clinically, biologically, and ultrasonographically ruled out over a mean follow-up exceeding 3 yr. Genomic screening for RET protooncogene mutations failed to reveal any anomaly. The calcitonin infusion test, which induced a significant increase in plasma cAMP in controls 30 and 60 min after infusion, failed to produce this response in PHP Ia patients, suggesting that the action of calcitonin was specifically impaired. PHP Ia may therefore be an independent etiology of hypercalcitoninemia and hyperresponsiveness to pentagastrin infusion.

Adult↗
PubMed2001

Chromogranin A assay and (131)I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma.

UNLABELLED: We assessed the performance of a new serum chromogranin A (CgA) assay in combination with the results of (131)I-metaiodobenzylguanidine (MIBG) scintigraphy for diagnosis and follow-up in 89 patients with clinical findings suggestive of pheochromocytoma. METHODS: The study population consisted of 41 patients with proven pheochromocytoma and 48 patients with refuted pheochromocytoma. Eighty-seven scintigraphy examinations were performed, 52 in patients with proven pheochromocytoma (39 before surgery and 13 after surgery) and 35 in patients with refuted pheochromocytoma. RESULTS: The sensitivity of the CgA level was 90.2%, and the specificity was 99.0% and 92.3% in the control and refuted pheochromocytoma groups, respectively. A significant relationship was seen between serum levels of CgA and tumor mass (r = 0.70; P < 10(-5)). The postoperative CgA level was an early and accurate predictor of curative surgery or relapse. The concordance between CgA levels and scintigraphic data was 90.8%. CONCLUSION: Serum CgA level is an effective marker of pheochromocytoma. Increased levels strongly correlate with tumor mass; therefore, small tumors may go undetected. The concordance between CgA level and the results of (131)I-MIBG scintigraphy is high. A CgA level in the reference range is highly predictive of normal scintigraphy findings.

3-Iodobenzylguanidine↗
PubMed2001

[Identification of eight new mutations in the c-erbAB gene of patients with resistance to thyroid hormone].

Resistance to thyroid hormone (RTH) is a rare genetic disorder, usually associated with different mutations in the c-erbAB gene that encodes the beta type receptor of thyroid hormone (TRB). It is characterized by elevated serum thyroid hormone and inappropriate TSH secretion. The numerous mutations so far detected are clustered in three hot spot areas in the ligand binding domain of TRB. In the context of a national survey we have detected 16 different mutations in the c-erbAB gene, in 22 families presenting with RTH. Eight of these mutations had not been described previously. Two are located in an area not known to harbor naturally occurring mutations. This observation could lead to define a fourth cluster of mutations in the c-erbAB gene.

Adolescent↗
PubMed2001

[Normal values of plasma methoxyamines in the setting of renal insufficiency and peri-operative stress. Consequences for the etiological diagnosis of hypertension].

INTRODUCTION: HPLC plasma methoxyamines measurements are the updated technique for the diagnosis of adrenergic hypersecretion. Their reliability meets that of urinary measurements. Significance of increased values is not yet fully established for the etiological diagnosis of hypertension in some situations, especially in case of renal insufficiency and in the peri-operative period. The aim of this study is to define the "normal" range of the values of plasma methoxyamines in both of those conditions. PATIENTS AND METHODS: in a General and Endocrine Surgical Unit, 3 homogeneous group of 20 patients each have been studied: group 1, control (patients awaiting thyroidectomy); group 2, patients on maintenance hemodialysis submitted for hyperparathyroidism; group 3, patients submitted to digestive surgery. Measurements were done pre-operatively in group 1, pre and post-operatively in group 2, and post-operatively in group 3. RESULTS: in comparison to the control (11.8 nmol/l), we observed in group 2 a 18 fold increase preoperatively, and a 29 fold increase at post-operative day 1. In group 3, we observed a 2.3, 2.7 and 2 fold increase at post-operative days 1,2 and 3 respectively. All those results were statistically significant. CONCLUSION: Results of measurements of plama methoxyamines should always be matched to the serum creatinine levels. They are meaningful for the diagnosis of endocrine origin of hypertension only late after the early post-operative period.

Chromatography, High Pressure Liquid↗
PubMed2001

[New perspective in the medical management of primary hyperparathyroidism].

Most of the medical proposed for patients with primary hyperparathyroidism are inefficient or dangerous, with the exception of oestrogens and physiological doses of vitamin D in selected cases. PTH analogs, calcimimetic drugs and anti-PTH immunization now provide attractive management perspectives.

Humans↗
PubMed2000

Concordance of eight kits for antithyroid peroxidase autoantibodies determination.

Numerous methods are proposed to quantify antithyroid peroxidase autoantibodies. No standardization exists but most assays use the standard MRC 66/387 with a calibration factor. Costs of the tests vary between the different kits. We evaluated the concordance of eight peroxidase autoantibodies assay kits in two centres, using a panel of sera from 269 subjects: controls (n=100), patients with autoimmune thyroid disease (n=77; Graves' disease, Hashimoto's thyroiditis), patients with non-autoimmune thyroid disease (n=69; nodular goiter, differentiated thyroid carcinoma) and individual sera with thyroglobulin antibodies only (n=23). The concordance between the eight methods was high, ranging from 88.3% to 98.8% with the total panel of sera. The majority of assays demonstrated high diagnostic performance. We encountered some false-positive results at borderline positive levels, and the nonrecognition of some sera by competitive assays.

Autoantibodies↗
PubMed2000

[Suppressive hormone therapy for thyroid nodules. Prospective evaluation. Preliminary results].

The benefit of thyroid hormone for patients with thyroid nodule is still controversial. Suppressive therapy is not useful to distinguish benign or malignant tumors, since some malignant nodules become smaller and most benign nodules do not shrink with thyroid hormone therapy. A prospective evaluation was conducted by the french Groupe de Recherche sur la Thyroïde on 123 patients with solitary nodules : ultrasonographic volume of the nodules regressed from 2.76 to 2.39 ml with suppressive doses of levothyroxine for 18 months, while a progression from 3.6 to 4.1 ml was seen for patients with placebo. The benefit of the suppressive therapy was also obvious on the micronodular dystrophy detected by ultrasonography. No side effects were seen in treated patients. These preliminary results argue for the benefit of suppressive therapy, as suggested by meta-analysis of the published randomized trials.

Humans↗
PubMed2000

Resistance to thyroid hormone in a family with no TRbeta gene anomaly: pathogenic hypotheses.

UNLABELLED: Syndromes of resistance to thyroid hormone (RTH) are almost always linked to a defective triiodothyronine-receptor B gene (TRB). Only six families with RTH exhibiting a normal TRB gene have been reported so far. We report another and discuss possible mechanisms. PATIENTS AND METHODS: We studied a kindred expressing a typical RTH phenotype. DNA was amplified and the TRB gene was sequenced. Linkage analysis assessed linkage between the TRB gene and RTH phenotype. RESULTS: Direct sequencing of the TRB gene failed to identify any anomaly in the coding exons. Linkage analysis demonstrated that the RTH phenotype was not linked to the TRB gene in this family. CONCLUSION: TRB1 and TRB2 genes were not defective in this family. Multiple mechanisms might account for this situation at the pre-receptor, receptor and post-receptor levels. The most likely hypothesis is the involvement of an abnormal nuclear cofactor serving a specific function in the regulation of thyroid hormone action.

Adult↗