Publications by authors named "Anne Charrié"

20 Publications

  • Page 1 of 1

Subclinical Hypothyroidism: is it Really Subclinical with Aging?

Aging Dis 2019 Jun 1;10(3):520-529. Epub 2019 Jun 1.

1Service de Gériatrie, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 1.6, p<0.01) than in the SCH population (2.3 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% 25.0%, p<0.01) but not ≥60y (34.4% 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction.
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http://dx.doi.org/10.14336/AD.2018.0817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538219PMC
June 2019

A challenging case: highly variable TSH in a mother and her two children.

Clin Chem Lab Med 2019 05;57(6):e114-e117

Laboratoire de Biochimie et biologie moléculaire, Centre de Biologie Sud Centre Hospitalier Lyon Sud, 69495 Pierre Bénite Cedex, France.

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http://dx.doi.org/10.1515/cclm-2018-0871DOI Listing
May 2019

Variability among TSH Measurements Can Be Reduced by Combining a Glycoengineered Calibrator to Epitope-Defined Immunoassays.

Eur Thyroid J 2017 Feb 22;6(1):3-11. Epub 2016 Dec 22.

Siamed'Xpress, Hôtel Technologique Morandat, Gardanne, France.

Objectives: Measuring protein markers with variable glycosylation, such as thyroid-stimulating hormone (TSH), with high accuracy is not an easy task. Despite highly sensitive third-generation tests, discrepancies among TSH assays still remain unsolved and are the focus of important standardization efforts. Earlier work from our group showed that a lack of similarity in epitope expression between standards and samples may account for discordant hormone measurements. In this study, we aimed at producing a glycoengineered TSH with serum-type glycosylation and compared its immunological behavior to that of the international standards.

Study Design: Recombinant glycoengineered TSH (rgTSH) was produced in glycoengineered Chinese hamster ovary cells to express a highly sialylated TSH and tested in newly designed assays. Two groups of assays targeting defined epitopes were constructed and TSH levels were estimated in a panel of 84 clinical samples (2.1-22.4 mIU/l) based on the use of the current 3rd IS 81/565, the 1st IRP 94/674 and rgTSH calibrations.

Results: Calibration based on rgTSH was found to significantly reduce the percentage difference means of assays compared to the pituitary standard. We also found that a switch from a mIU/l (3rd IS 81/565) to ng/l (rgTSH) basis can be established within the normal as well as in the mid to upper normal range of TSH levels. Of interest, TSH assays targeting the main immunogenic region displayed variable TSH values, indicating that, in this region, epitopes should be defined for assays to deliver similar values.

Conclusions: A glycoengineered TSH with serum-type glycosylation proved to be a new calibrator efficient in harmonizing TSH values.
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http://dx.doi.org/10.1159/000449463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465719PMC
February 2017

[Hypothyroidism Associated to TSH Hormone-Receptor Autoantibodies with Blocking Activity Assessed In Vitro].

Acta Med Port 2015 Sep-Oct;28(5):663-6. Epub 2015 Oct 30.

Serviço de Endocrinologia Pediátrica. Hospital Dona Estefânia. Centro Hospitalar de Lisboa Central. Lisboa. Portugal.

Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient's serum; it was estimated a 'moderate' blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis.
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February 2018

Liver and spleen elastography using supersonic shear imaging for the non-invasive diagnosis of cirrhosis severity and oesophageal varices.

Dig Liver Dis 2015 Aug 20;47(8):695-701. Epub 2015 Apr 20.

INSERM U1053, Université Bordeaux, Bordeaux, France; Centre d'investigation de la fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.

Background: Elastography is a promising non-invasive approach for assessing liver fibrosis. We assessed diagnostic performances of liver and spleen stiffness using supersonic shear imaging for diagnosing cirrhosis severity and oesophageal varices.

Methods: 401 consecutive cirrhotic patients were prospectively enrolled from November 2012 to March 2014. All patients underwent liver and spleen stiffness measurement with supersonic shear imaging and Fibroscan.

Results: Failures of measurement were 6.2% and 29.2% for liver and spleen stiffness (supersonic shear imaging), and 18.4% for liver stiffness (Fibroscan). Liver and spleen stiffness were correlated with severity of cirrhosis, with values increasing according to Child-Pugh subclasses and presence of complications. With a negative predictive value ≥90%, liver stiffness cut-offs for high-risk oesophageal varices, history of ascites, Child-Pugh B/C, variceal bleeding and clinical decompensation were 12.8, 19, 21.4, 30.5, and 39.4 kPa, respectively. Areas under the curve of spleen and liver stiffness (supersonic shear imaging), and liver stiffness (Fibroscan) were 0.80, 0.77 and 0.73 respectively for detection of oesophageal varices.

Conclusion: Liver stiffness using supersonic shear imaging is a relevant diagnostic tool for assessing cirrhosis severity and its complications. Spleen stiffness shows promising results for the detection of oesophageal varices but is not yet sufficiently robust for clinical practice owing to high failure rates.
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http://dx.doi.org/10.1016/j.dld.2015.04.008DOI Listing
August 2015

Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism.

Eur J Endocrinol 2014 Oct;171(4):451-60

Hospices Civils de LyonLyon, FranceFédération d'EndocrinologieService d'Endocrinologie PédiatriqueService de Médecine NucléaireService de Gynécologie-ObstétriqueService de NéonatalogieService de BiochimieGroupement Hospitalier Est, F-69003 Lyon, FranceService de BiochimieService d'EndocrinologieCentre Hospitalier Lyon Sud, 69310 Lyon, FranceFaculté de Médecine Lyon-EstUniversité Lyon 1, Lyon, FranceFaculté de PharmacieLyon, FranceFaculté de Médecine et de Maïeutique Lyon Sud - Charles MérieuxLyon, FranceCARMEN INSERM U1060Lyon, FranceINSERM U1052Lyon, FranceService de Biostatistiques162 Avenue Lacassagne, 69003 Lyon, France Hospices Civils de LyonLyon, FranceFédération d'EndocrinologieService d'Endocrinologie PédiatriqueService de Médecine NucléaireService de Gynécologie-ObstétriqueService de NéonatalogieService de BiochimieGroupement Hospitalier Est, F-69003 Lyon, FranceService de BiochimieService d'EndocrinologieCentre Hospitalier Lyon Sud, 69310 Lyon, FranceFaculté de Médecine Lyon-EstUniversité Lyon 1, Lyon, FranceFaculté de PharmacieLyon, FranceFaculté de Médecine et de Maïeutique Lyon Sud - Charles MérieuxLyon, FranceCARMEN INSERM U1060Lyon, FranceINSERM U1052Lyon, FranceService de Biostatistiques162 Avenue Lacassagne, 69003 Lyon, France Hospices Civils de LyonLyon, FranceFédération d'EndocrinologieService d'Endocrinologie PédiatriqueService de Médecine NucléaireService de Gynécologie-ObstétriqueService de NéonatalogieService de BiochimieGroupement Hospitalier Est, F-69003 Lyon, FranceService de BiochimieService d'EndocrinologieCentre Hospitalier Lyon Sud, 69310 Lyon, FranceFaculté de Médecine Lyon-EstUniversité Lyon 1, Lyon, FranceFaculté de PharmacieLyon, FranceFaculté de Médecine et de Maïeutique Lyon Sud - Charles MérieuxLyon, FranceCARMEN INSERM U1060Lyon, FranceINSERM U1052Lyon, FranceService de Biostatistiques162 Avenue Lacassagne, 69003 Lyon, France Hospices Civils de LyonLyon, FranceFédération d'Endocr

Context: Hyperthyroidism occurs in 1% of neonates born to mothers with active or past Graves' disease (GD). Current guidelines for the management of GD during pregnancy were based on studies conducted with first-generation thyroid-binding inhibitory immunoglobulin (TBII) assays.

Objective: This retrospective study was conducted in order to specify the second-generation TBII threshold predictive of fetal and neonatal hyperthyroidism, and to identify other factors that may be helpful in predicting neonatal hyperthyroidism.

Methods: We included 47 neonates born in the Lyon area to 42 mothers harboring measurable levels of TBII during pregnancy. TBII measurements were carried out in all mothers; bioassays were carried out in 20 cases.

Results: Nine neonates were born with hyperthyroidism, including five with severe hyperthyroidism requiring treatment. Three neonates were born with hypothyroidism. All hyperthyroid neonates were born to mothers with TBII levels >5 IU/l in the second trimester (sensitivity, 100% and specificity, 43%). No mother with TSH receptor-stimulating antibodies (TSAb measured by bioassay) below 400% gave birth to a hyperthyroid neonate. Among mothers of hyperthyroid neonates, who required antithyroid drugs during pregnancy, none could stop treatment before delivery. Analysis of TBII evolution showed six unexpected cases of increasing TBII values during pregnancy.

Conclusion: Maternal TBII value over 5 IU/l indicates a risk of neonatal hyperthyroidism. Among these mothers, a TSAb measurement contributes to identify more specifically those who require a close fetal thyroid ultrasound follow-up. These results should be confirmed in a larger series.
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http://dx.doi.org/10.1530/EJE-14-0254DOI Listing
October 2014

New-generation thyroglobulin assay: performance and implications for follow-up of differentiated thyroid carcinoma.

Ann Endocrinol (Paris) 2014 Sep 26;75(4):227-31. Epub 2014 Aug 26.

Service fédéré de biochimie et biologie moléculaire, centre hospitalier Lyon Sud, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; CarMeN-Inserm U1060, université Claude-Bernard Lyon 1, 69921 Oullins, France; Faculté de médecine et de maïeutique Lyon Sud-Charles Mérieux, 69921 Oullins, France.

Objectives: Differentiated thyroid cancer (DTC) requires long-term follow-up by serum thyroglobulin assay and cervical ultrasound, due to the risk of recurrence. Guidelines recommend basal assay under hormone therapy at 3 months, repeated at 6-12 months post-surgery, with or without associated isotopic ablation, after stimulation by recombinant human TSH to improve assay sensitivity. It was hypothesized that a new-generation assay kit with lower limits of detection and quantification would improve the sensitivity of the basal assay, enhance detection of premature recurrence and decrease the rate of false-negatives, thereby avoiding the need for the complementary stimulation test.

Material And Methods: A validation study of the second-generation thyroglobulin serum assay was performed in the laboratory of the Lyon Sud Hospital Centre (Lyon, France), with comparison to stimulation test results. Low-concentration serum pools were constituted, including patients followed for stage I to III DTC for whom basal and post-stimulation samples were available in the serum bank.

Results: The new assay proved robust and reliable, with good correlation with the technique presently used in the Lyon hospitals. None of the 54 patients showed false-negative results, which was the objective of our choice of threshold, and 5 were false-positive, for thyroglobulin thresholds of 0.1μg/L at baseline and 1.0μg/L post-stimulation. Positive and negative predictive values were 100% and 87.8% respectively.

Conclusion: These results allow an improvement in the follow-up algorithm for DTC, replacing the stimulation test by the new-generation thyroglobulin assay in post-therapeutic assessment.
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http://dx.doi.org/10.1016/j.ando.2014.06.003DOI Listing
September 2014

Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men.

Physiol Behav 2014 Mar 25;127:37-44. Epub 2014 Jan 25.

Centre de Recherche en Nutrition Humaine Rhône-Alpes, Centre Hospitalier Lyon Sud, 69310 Pierre Bénite, France; Centre Européen pour la Nutrition & la Santé (CENS), Lyon, France.

The effects of frequent eating on health and particularly on appetite and metabolism are unclear. We have previously shown that frequent eating decreased appetite and energy intake at the subsequent meal in lean men. In the present study, we tested the same pattern in obese subjects. Seventeen obese men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180min (F4), followed by an ad libitum buffet (T240) in an experimental restaurant. Subjects rated their appetite throughout the sessions. (ii) two sessions consisting of the same breakfasts F1 and F4 in a Clinical Centre, followed by a standardized meal. Blood sampling was performed to study ghrelin, glucagon-like peptide-1 (GLP-1), and metabolic kinetics. Indirect calorimetry measurements were performed. After F4, at T240min, ghrelin concentration (P=0.03) and hunger ratings (P<0.001) were lower while GLP-1 concentration (P=0.006) and satiety ratings (P=0.02) were higher. In F4, subjects consumed at the buffet, less food in grams (P=0.04) and less energy from low energy dense foods (P=0.01), but total energy intakes were not different between conditions. In F4, the area under the curve was lower for insulin (P=0.02) and non-esterified fatty acids (NEFA) (P=0.03). Diet induced thermogenesis was reduced in F4 (P=0.03) between T0 and T240. Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run.
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http://dx.doi.org/10.1016/j.physbeh.2014.01.004DOI Listing
March 2014

Fast test: clinical practice and interpretation.

Ann Endocrinol (Paris) 2013 Jul 19;74(3):174-84. Epub 2013 Jun 19.

Unité mixte de recherche 7004, centre national de la recherche scientifique, institut de physique biologique, faculté de médecine, université Louis-Pasteur, 67000 Strasbourg, France.

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http://dx.doi.org/10.1016/j.ando.2013.05.003DOI Listing
July 2013

An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.

Physiol Behav 2013 Feb 17;110-111:169-78. Epub 2013 Jan 17.

Centre de Recherche de l'Institut Paul Bocuse, Château du Vivier, 69130 Ecully, France.

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.
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http://dx.doi.org/10.1016/j.physbeh.2013.01.009DOI Listing
February 2013

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

Clin Endocrinol (Oxf) 2013 Mar;78(3):358-64

Hospices Civils de Lyon et Université Lyon 1, Centre de Médecine Nucléaire, Centre d'Investigation Clinique et Fédération d'Endocrinologie, Groupement Hospitalier Est, Centre de Recherche en Neurosciences, Lyon, France.

Objective: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries.

Design: Multicentric prospective study.

Patients: A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery.

Measurement: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity.

Results: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold.

Conclusion: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test.
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http://dx.doi.org/10.1111/cen.12001DOI Listing
March 2013

Thyroxin overdose due to rheumatoid factor interferences in thyroid-stimulating hormone assays.

Clin Chem Lab Med 2011 May 9;49(5):873-5. Epub 2011 Feb 9.

Department of Nuclear Medicine, University Hospital and University Bordeaux, Pessac, France.

Background: Immunoassays are susceptible to interferences by anti-hormone antibodies, heterophilic antibodies or rheumatoid factor (RF).

Methods: We report a case of levothyroxin overdose because of gross overestimation of thyroid-stimulating hormone (TSH) by chemiluminescent and IRMA assays. Alternate assays were performed and heterophilic antibodies blocking tubes were used.

Results: Analytical investigations revealed: i) non-linear concentrations of TSH after serum dilutions, ii) decreased TSH concentrations after removal of heterophilic antibodies, iii) appropriately decreased TSH concentrations in alternate TSH assays and iv) identification of increased concentrations of RF.

Conclusions: The presence of RF may be responsible for false determination of TSH concentrations preventing monitoring of TSH.
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http://dx.doi.org/10.1515/CCLM.2011.144DOI Listing
May 2011

TSH Isoforms: About a Case of Hypothyroidism in a Down's Syndrome Young Adult.

J Thyroid Res 2010 Jul 14;2010:703978. Epub 2010 Jul 14.

Laboratoire du Service de Médecine Nucléaire, Centre Hospitalier de Chambéry, 73000 Chambéry, France.

Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case.
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http://dx.doi.org/10.4061/2010/703978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957696PMC
July 2010

Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: a simple definition of the threshold value, with emphasis on potential pitfalls of the method.

Clin Chem Lab Med 2010 Aug;48(8):1171-7

Hospices Civils de Lyon, Service Médecine Nucléaire, Groupement Hospitalier Est, Lyon, France.

Background: Thyroglobulin measurements in fine-needle aspirate (FNA-Tg) is an accurate method for the diagnosis of lymph node metastasis in differentiated thyroid carcinoma. The goal of this study is to determine the most appropriate diagnostic threshold value for FNA-Tg.

Methods: Ultrasound-guided fine-needle aspiration-cytology (FNA-C) and FNA-Tg were performed on suspicious lymph nodes in 114 consecutive patients with thyroid cancer prior to thyroidectomy (n=13) or during follow-up (n=93), and in 16 control subjects. Functional sensitivity of the thyroglobulin assay was 0.7 ng/mL. Sensitivity and specificity of FNA-Tg and FNA-C were determined for different cut-off values within a range of 0.69-1.34 nanogram/punction (ng/p) using receiver operating characteristic curve analysis.

Results: The FNA-Tg cut-off value of 0.93 ng/p offers the best diagnostic performances: 94.2% sensitivity, 97.8% specificity. FNA-C showed 100% specificity in diagnostic samples, but low sensitivity of 71% due primarily to inadequate samples. Combining FNA-C and FNA-Tg resulted in 98% sensitivity and 100% specificity.

Conclusions: A unique threshold of 0.93 ng/p gives high sensitivity and specificity, even in non-thyroidectomized patients. However, since false negative results may be observed in poorly differentiated thyroid cancer, FNA-C should remain combined to FNA-Tg.
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http://dx.doi.org/10.1515/CCLM.2010.220DOI Listing
August 2010

Calcium-sensing receptor autoantibodies in primary hyperparathyroidism.

Clin Chim Acta 2009 Aug 8;406(1-2):94-7. Epub 2009 Jun 8.

University of Lyon, F-69002 Lyon, France.

Background: Mutations in the extracellular calcium-sensing receptor (CaSR) gene are known to be implicated in some cases of primary hyperparathyroidism. However, not all patients display such mutations and so the mechanisms of primary hyperparathyroidism are still largely unknown. An autoimmune origin has been suggested, as autoantibodies against the CaSR have been detected in some patients. The aim of our study was to investigate the presence of CaSR autoantibodies in a large cohort of patients with primary hyperparathyroidism.

Methods: Seventy-five patients were tested for the presence of anti-parathyroid antibodies using an immunoblotting assay with the recombinant extracellular domain of the human CaSR and an immunofluorescence technique with parathyroid adenoma.

Results: Five of 75 (6.7%) patients had CaSR autoantibodies. There was no statistically significant difference in the decrease of parathyroid hormone (PTH) level after surgery between patients with or without autoantibodies. Histological examination of parathyroid tissue did not show greater lymphocytic infiltration in patients with autoantibodies than in those without.

Conclusions: This study confirmed that some patients with primary hyperparathyroidism displayed CaSR autoantibodies. The pathophysiological role of these autoantibodies in hyperparathyroidism needs to be further elucidated.
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http://dx.doi.org/10.1016/j.cca.2009.05.023DOI Listing
August 2009

The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease.

Nephrol Dial Transplant 2009 Oct 10;24(10):3120-5. Epub 2009 Jun 10.

Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Bron, France.

Objectives: Osteocalcin, a small peptide secreted by osteoblasts, has been recently described as a circulating hormone involved in the regulation of energy metabolism. In addition, experimental data suggest a regulation of adipocytes by bone, with a stimulation of adiponectin synthesis by osteocalcin and an inverse relationship between serum adiponectin level and bone mineral density (BMD). However, this relationship has not been explored during chronic kidney disease (CKD).

Methods: Osteocalcin, adiponectin and leptin were prospectively measured in a cohort of 61 CKD patients. A new non-invasive 3D bone imaging technique was performed (high-resolution peripheral quantitative computed tomography, HR-pQCT), measuring volumetric BMD (vBMD) and microarchitecture parameters at the distal tibia.

Results: Patients' mean age was 67.2 +/- 13.9 years and mean GFR 33 +/- 12 mL/min/1.73 m(2). We found a positive association between serum osteocalcin and adiponectin (r = 0.29, P = 0.021). Univariate analysis showed inverse correlations between serum adiponectin and total vBMD (r = -0.33, P = 0.01), cortical thickness (r = -0.34, P = 0.008) and trabecular vBMD (r = -0.27, P = 0.04). These associations remained significant in multivariate analysis between serum adiponectin and total vBMD, cortical vBMD and cortical thickness.

Conclusion: We report for the first time an inverse relationship between bone density and adiponectin, as well as a positive association between osteocalcin and adiponectin in CKD II-IV patients.
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http://dx.doi.org/10.1093/ndt/gfp262DOI Listing
October 2009

Prognostic value of modeled PSA clearance on biochemical relapse free survival after radical prostatectomy.

Prostate 2009 Sep;69(12):1325-33

Université de Lyon, Lyon, France.

Purposes: Using population kinetic approach, we modeled PSA decline equations in patients with prostate cancer after radical prostatectomy (RP). We looked for relationships between early PSA decrease profile, characterized by PSA clearance (CL(PSA)) or half-life (HL(PSA)), and the 2-year biochemical relapse free survival (bRFS).

Patients And Methods: We performed a retrospective study on 55 patients treated with RP and with at least 2 PSA measurements in the post-operative month. A population kinetic model was investigated with NONMEM. The prognostic factors regarding bRFS were assessed using univariate and multivariate analyses.

Results: The best model describing the PSA post-operative decrease was bi-compartmental and fit patient data well. Median CL(PSA) was 0.034 (terciles were 0.023 and 0.048). The significant prognostic factors associated with a better bRFS with univariate analysis were lower CL(PSA) terciles (2-year bRFS = 100% vs. 85.1% vs. 66.7% if CL(PSA) < 0.023, 0.023 or= 0.0480, P = 0.006) as well as initial PSA < 7 ng/ml, pT2 stage (vs. pT3), pN0 (vs. pN1) and low main Gleason score (3/5 vs. 4/5). Among these factors, CL(PSA) was the only independent prognostic factor with multivariate analysis regarding bRFS (HR = 0.92, 95%CI = [0.86-0.98], P = 0.0088).

Conclusion: CL(PSA) determined with 4 PSA concentrations in the first month following the RP may predict the biochemical relapse risk of prostate cancer patients, thus enabling early identification of high-risk patients requiring adjuvant treatment. A prospective validation of these results is required.
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http://dx.doi.org/10.1002/pros.20978DOI Listing
September 2009

[Parathormone and chronic kidney disease].

Nephrol Ther 2007 Jul 6;3(4):133-8. Epub 2007 Jun 6.

Département de pédiatrie, centre de référence des maladies rénales héréditaires, hôpital Edouard-Herriot, Lyon, France.

The serum parathyroid hormone (PTH) rises in chronic kidney disease (CKD) and induces renal bone disease as well as other organ damage. The bone disease guidelines were released by the K-DOQI in 2003 in order to help physicians to improve bone management at all different CKD stages. However, many different PTH commercial assays are available today and some questions are raised concerning the interpretation, the validity and the practical choice of these different measurements. After reviewing PTH biosynthesis and metabolism, we will describe the regulation of different PTH fragments (particularly 1-84 and 7-84) and the various types of PTH assays. In compromised clinical situations, bone biopsy still remains the golden standard assessment of bone disease, and it will be helpful to clarify the interest of new 3rd generation PTH measurements. At present, we do not dispose of valid therapeutic recommendations using 3rd generation tests, as well as the relevance of the ratio PTH 1-84/7-84.
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http://dx.doi.org/10.1016/j.nephro.2007.04.003DOI Listing
July 2007

Study of cyfra 21-1, a tumor marker, in head and neck squamous cell carcinoma.

Ann Otol Rhinol Laryngol 2005 Oct;114(10):768-76

Departments of Otolaryngology-Head and Neck Surgery, Lyon-Sud Hospital, Pierre Bénite, France.

Objectives: We performed a prospective study to determine the cutoff value and the prognostic value of Cyfra 21-1, a serum tumor marker, in head and neck squamous cell carcinoma (HNSCC).

Methods: The serum concentration of Cyfra 21-1 was measured in a group of 300 patients (group 1) with HNSCC, in a control group of 71 healthy subjects (group 2), and in a group of 73 patients with a nonmalignant tumor or inflammatory disease (group 3). The concentrations were compared between the various groups and subgroups; the cutoff value was calculated with a receiver operating characteristic curve. Furthermore, the serum concentrations of Cyfra 21-1 before treatment in the group of 300 patients were compared with the stage of the disease and with the evolution of the overall survival rate and the disease-free survival rate. Finally, to determine whether Cyfra 21-1 is an independent prognostic factor, we compared the concentrations, by a Cox model, with the classic prognostic factors of HNSCC.

Results: At the cutoff value of 1 ng/mL, the specificity was 94% and the sensitivity was 72%. The serum concentrations of Cyfra 21-1 were statistically correlated with the stage of the disease. The overall survival rate and the disease-free survival rate were lower in patients with high serum concentrations, and these differences were statistically significant (p < .001). The Cox model allows us to conclude that Cyfra 21-1 is a prognostic marker that is independent of other classic prognostic factors.

Conclusions: Cyfra 21-1 is an interesting tumor marker that could be proposed for the early detection of HNSCC with a cutoff value of 1 ng/mL. Furthermore, Cyfra 21-1 can be considered an independent prognostic marker.
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http://dx.doi.org/10.1177/000348940511401006DOI Listing
October 2005