Publications by authors named "Jacques Orgiazzi"

43 Publications

Three Consecutive Pregnancies in a Patient with Chronic Autoimmune Thyroid Disease Associated with Hypothyroidism and Extremely High Levels of Anti-Thyrotropin Receptor Antibodies.

Thyroid 2019 05;29(5):743-747

1 Service d'Endocrinologie - Diabète - Nutrition Reims, Centre Hospitalier Universitaire de Reims, Champagne-Ardenne, France.

Thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAb) can be present in chronic autoimmune thyroiditis. Transplacental TRAb transfer can lead to fetal thyroid dysfunction and serious complications. We report the case of a woman with autoimmune hypothyroidism and extremely high TRAb levels, with blocking and stimulating activities (biological activities characterized with Chinese hamster ovary cells expressing TSHR). At week 22 of her first pregnancy, sonography detected fetal growth retardation and cardiac abnormalities (extreme tachycardia, right ventricular dilatation, pericardial effusion). The mother's TRAb level, assayed later, was 4030 IU/L ( < 10). Delivered via caesarean section gestational week 30, the newborn girl had several malformations, signs of malnutrition, goiter and hyperthyroidism associated with elevated TRAb (1200 IU/L). The newborn died 26 days after delivery. Faced with persistently high TRAb levels and a desire to become pregnant again, the woman was treated with three consecutive 740-MBq activities of iodine-131, which resulted in a decrease in TRAb to 640 IU/L. The patient had two subsequent pregnancies 16 and 72 months after the radioiodine administration. During the close follow-ups, fetal development was normal, and initial TRAb levels during the two pregnancies were 680 and 260 IU/L, respectively, which initially decreased but then increased in late pregnancy. In both cases, labor was induced at 34 weeks. The newborns, mildly hyperthyroid at birth, required carbimazole treatment at days 5 and 2, respectively. The mild hyperthyroidism despite high TRAb levels was likely due to the concomitant presence of stimulating and blocking TRAb. The two girls, now aged 12 and 8 years, are in good health. The mother has no detectable thyroid gland tissue and is euthyroid on levothyroxine (175 μg/d). Her TRAb level gradually decreased to 136 IU/L. This remarkable case illustrates the severe consequences of untreated fetal hyperthyroidism and the need to assay and follow-up TRAb levels in women of reproductive age with autoimmune thyroiditis.
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http://dx.doi.org/10.1089/thy.2018.0098DOI Listing
May 2019

Reflections on the Management of Graves' Hyperthyroidism.

Eur Thyroid J 2018 Aug 19;7(4):165-166. Epub 2018 Jul 19.

Hospices Civils de Lyon, Université Claude-Bernard Lyon 1, Lyon, France.

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http://dx.doi.org/10.1159/000491585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140606PMC
August 2018

Treatment of adult Graves' disease.

Ann Endocrinol (Paris) 2018 Dec 16;79(6):618-635. Epub 2018 Aug 16.

Service de médecine nucléaire, Inserm U970, Sorbonne université, groupe hospitalier Pitié-Salpétrière, 75013 Paris, France.

Treatment strategy in Graves' disease firstly requires recovery of euthyroid status by antithyroid therapy. Treatment modalities, precautions, advantages and side-effects are to be discussed with the patient. No particular treatment modality has demonstrated superiority. Pregnancy or pregnancy project affects choice of treatment and monitoring. Graves' orbitopathy is liable to be aggravated by iodine-131 treatment and requires pre-treatment assessment. Iodine-131 treatment aims at achieving hypothyroidism. Thyroid surgery for Graves' disease should preferably be performed by an expert team. In case of recurrence of hyperthyroidism, the various treatment options should be discussed with the patient. Empiric treatment of thyroid dermopathy uses local corticosteroids in occlusive dressing.
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http://dx.doi.org/10.1016/j.ando.2018.08.003DOI Listing
December 2018

Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

Cancer Epidemiol 2018 02 8;52:142-147. Epub 2018 Jan 8.

Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, F-94805, France; Gustave Roussy, Villejuif, F-94805, France; University of Paris-Sud, Villejuif, F-94800, France. Electronic address:

Background: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk.

Methods: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas.

Results: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk.

Conclusion: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.
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http://dx.doi.org/10.1016/j.canep.2017.12.015DOI Listing
February 2018

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

Eur Thyroid J 2016 Jul 21;5(2):132-8. Epub 2016 May 21.

U1018, Centre d'Epidémiologie et de Santé des Populations (CESP), Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Institut Gustave Roussy, Villejuif, France; Université Paris-Saclay, Villejuif, France.

Purpose: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk.

Methods: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status.

Results: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years).

Conclusion: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.
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http://dx.doi.org/10.1159/000445887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949366PMC
July 2016

Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

Am J Epidemiol 2015 Aug 30;182(3):202-14. Epub 2015 Jun 30.

The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer.
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http://dx.doi.org/10.1093/aje/kwv048DOI Listing
August 2015

[Radiation-related health effects of major nuclear events].

Authors:
Jacques Orgiazzi

Rev Prat 2015 Jan;65(1):93-4, 96-8

Three major nuclear events, the Hirosima and Nagasaki bombings and the Chernobyl and Fukushima catastrophes, have been selected to Illustrate the health consequences, observed or anticipated, of irradation of populations. Differences in doses and modalities of irradiation, with the combination of clinical epidemiology and dose estimates, recently revisited, allow for more accurate dose-effect relationship models of the risks. However, extrapolation to the low-doses (< 0.1 Gy) or very low-doses of these models obtained with doses ≥ 0.2 Gy remains hazardous.
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January 2015

Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study.

Am J Epidemiol 2014 Nov 30;180(10):1007-17. Epub 2014 Sep 30.

The incidence of thyroid cancer has increased in eastern Europe since the Chernobyl nuclear power plant accident. Although the radioactive fallout was much less severe and the thyroid radiation dose was much lower in France, a case-control study was initiated in eastern France. The present study included 633 young women who were diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006 and matched with 677 controls. Face-to-face interviews were conducted from 2005 to 2010. Odds ratios were calculated using conditional logistic regressions and were reported in the total group and by histopathological type of cancer ("only papillary" and "excluding microcarcinomas"). The risk of thyroid cancer was higher in women who had a higher number of pregnancies, used a lactation suppressant, or had early menarche. Conversely, breastfeeding, oral contraceptive use, and late age at first pregnancy were associated with a lower risk of thyroid cancer. No association was observed between thyroid cancer and having irregular menstrual cycle, undergoing treatment for menstrual cycle regularity shortly after menarche, having a cessation of menstruation, use of another contraceptive, history of miscarriage or abortion for the first pregnancy, or having had gestational diabetes. This study confirms the role of hormonal and reproductive factors in thyroid cancer, and our results support the fact that exposure to estrogens increases thyroid cancer risk.
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http://dx.doi.org/10.1093/aje/kwu220DOI Listing
November 2014

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

[Autoimmune thyroid diseases, an overview].

Authors:
Jacques Orgiazzi

Rev Prat 2014 Jun;64(6):822-4

Autoimmune thyroid diseases (AITD) are generally of low severity although they can affect significantly the quality of life. Nevertheless, taking into account their high prevalence, a source of considerable medical expenses, it is mandatory that practitioners are well informed on the management of AITD so that they might contribute to curb as much as possible the current costs. Main points discussed are the various clinical and pathophysiological presentations of AITD, as well as their epidemiology and susceptibility/triggering factors. This overview together with the other contributions within this issue should help doctors in the diagnosis and management of AITD.
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June 2014

[Levothyroxine and generics: current reflections].

Rev Prat 2014 Mar;64(3):304-6

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March 2014

Endocrine side-effects of anti-cancer drugs: the impact of retinoids on the thyroid axis.

Eur J Endocrinol 2014 Jun 10;170(6):R253-62. Epub 2014 Mar 10.

Service d'EndocrinologieCentre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Chemin du grand Revoyet, F 69495 Pierre Bénite, FranceUniversité Claude Bernard Lyon1 - Université de LyonLyon, FranceUnité d'Oncologie Moléculaire et TransfertService de Biochimie et biologie moléculaire sud, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, FranceInserm U1052CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, FranceService de DermatologieCentre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, FranceService d'EndocrinologieCentre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Chemin du grand Revoyet, F 69495 Pierre Bénite, FranceUniversité Claude Bernard Lyon1 - Université de LyonLyon, FranceUnité d'Oncologie Moléculaire et TransfertService de Biochimie et biologie moléculaire sud, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, FranceInserm U1052CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, FranceService de DermatologieCentre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France

Bexarotene (Targretin), approved since 1999 as a second-line treatment for late stage cutaneous T-cell lymphomas, has been shown to induce significant hypothyroidism through TSH suppression. This review revisits, through a case report, mechanisms by which rexinoids repress the expression of TSHB gene as well as αTSH and TRH genes. It appears that rexinoids suppress TSH independently from tri-iodothyronine. Bexarotene also differently affects the gene expression of deiodinases 1 and 2 as well as the peripheral clearance of thyroxine. These data might open new ways of research on the potential interaction between thyroid axis and endogenous rexinoids.
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http://dx.doi.org/10.1530/EJE-13-0920DOI Listing
June 2014

[Thyroid autoimmunity].

Authors:
Jacques Orgiazzi

Bull Acad Natl Med 2013 Jan;197(1):43-59; discussion 60-3

This review of human autoimmune thyroid disease (AITD) focuses mainly on the epidemiology and pathophysiology of this very common disorder, although some specific clinical situations are discussed. One peculiarity of AITD is the existence of two contrasting phenotypes: hypothyroid thyroiditis and hyperthyroid Graves' disease. Graves' disease is characterized by the presence of anti-TSH receptor antibodies capable of activating the TSH receptor, leading to thyroid hypertrophy and hyperfunction. In contrast, autoimmune thyroiditis progresses slowly, through necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis such as postpartum thyroiditis and silent thyroiditis are also described. The aim of this non exhaustive review is to provide the interested reader with basic information required for further investigation.
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January 2013

Thyroid autoimmunity.

Authors:
Jacques Orgiazzi

Presse Med 2012 Dec 17;41(12 P 2):e611-25. Epub 2012 Nov 17.

Hospices civils de Lyon et université Lyon 1, centre hospitalier Lyon-Sud, service d'endocrinologie-diabétologie-maladies métaboliques, 69495 Pierre-Bénite cedex, France.

This overview of the thyroid autoimmunity in human presents the various facets of a very common pathology. Focus is rather on fundamental than clinical aspects, although some specific clinical situations are discussed. Epidemiology, pathophysiology and pathology of AITD are detailed. One of the peculiarities of AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and hyperthyroid Graves' disease. The latter is characterised by the presence of a unique type of autoantibodies, the anti-TSH receptor antibodies. Those are capable to activate the TSH receptor leading to the gland hypertrophy and hyperfunction. On the contrary, the autoimmune thyroiditis processus progressively and slowly tends to the necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis, postpartum thyroiditis and silent thyroiditis are also described. This review, which is not exhaustive, aims at providing a wide scope on the AITD, a basis from which the interested reader or the specialist will be able to find routes towards deeper knowledge.
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http://dx.doi.org/10.1016/j.lpm.2012.10.002DOI Listing
December 2012

Pregnant French women living in the Lyon area are iodine deficient and have elevated serum thyroglobulin concentrations.

Thyroid 2012 May 2;22(5):522-8. Epub 2012 Apr 2.

Laboratory of Hormonology, East Center for Biology and Pathology, East Hospital Group, Civil Hospices of Lyon, 59 boulevard Pinel, Bron, France.

Background: Iodine deficiency (ID) remains common in Europe, and may be especially detrimental during pregnancy. The aim of our study was to assess iodine status and thyroid function in healthy pregnant women in the Lyon metropolitan area.

Methods: In a cross-sectional study, healthy pregnant women (n=228) with no history of thyroid disease were consecutively recruited from an obstetric clinic during all trimesters. Thyrotropin (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO) antibodies, thyroglobulin (Tg), and urinary iodine concentration (UIC) (n=100) were measured. Thyroid functions were compared with those in a control group of nonpregnant adults.

Results: The median (range) UIC was 81 (8-832) μg/L, and 77% of pregnant women had a UIC <150 μg/L, indicating inadequate iodine intake. Overall, 11% of women had abnormal TSH or anti-TPO. The median FT4 (pmol/L) was 14.9, 12.6, and 11.5 in the first, second, and third trimesters, respectively. The median Tg in pregnant women was 16.2 μg/L, did not differ across trimesters, and was significantly higher than in the control group of nonpregnant adults (11.7 μg/L) (p=0.02). Controlling for maternal age and week of gestation, UIC was not a significant predictor of any of the thyroid function tests.

Conclusions: Pregnant women in the Lyon area are iodine deficient and have increased serum Tg concentrations compared with nonpregnant controls, likely due to physiological thyroid hyperstimulation during gestation exacerbated by ID.
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http://dx.doi.org/10.1089/thy.2011.0184DOI Listing
May 2012

[The treatment of Graves' disease: current views and controversies].

Authors:
Jacques Orgiazzi

Presse Med 2011 Dec 9;40(12 Pt 1):1155-62. Epub 2011 Nov 9.

Hospices civils de Lyon, centre hospitalier Lyon-Sud, université Lyon 1, service d'endocrinologie-diabétologie-maladies métaboliques, 69495 Pierre-Bénite, France.

One of the more prevalent among the organ-specific autoimmune diseases, Graves' disease share their chronic evolution and lack of immunomodulatory treatment. Treatment strategy has to consider as opposite options as medical conservatory or ablative approach which requires much expertise and attention to patients' wish. Whatever treatment option, it is mandatory to prevent any risk of iatrogenic hypothyroidism, especially a rise of TSH above normal limit. The long-lasting benefit-risk ratio of treatment options is of primordial importance in this usually benign but enduring disease. Occurrence of Graves' orbitopathy, a significant complication, requires a special multidisciplinary management; the same is true in the case of a current or planned pregnancy. Overall quality-of-life is often markedly affected by Graves' disease; this should not be overlooked. Smoking increases relapse risk after a course of antithyroid drug; it also increases the risk and severity of Graves' orbitopathy. Patients must be made aware of these deleterious effects and encouraged to quit smoking.
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http://dx.doi.org/10.1016/j.lpm.2011.09.012DOI Listing
December 2011

Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy: a questionnaire survey among members of the European Thyroid Association.

Eur J Endocrinol 2012 Feb 4;166(2):247-53. Epub 2011 Nov 4.

Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.

Objective: The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).

Design: A questionnaire-based survey among members of the European Thyroid Association (ETA) who treat GO.

Results: A response was obtained from 128 ETA members of which 115 used GC therapy for GO. The majority of respondents (83/115, 72%) used intravenous (i.v.) GC, with a relatively wide variety of therapeutic regimens. The cumulative dose of methylprednisolone ranged between 0.5 and 12 g (median 4.5 g) for i.v.GC and between 1.0 and 4.9 g (median 2.4 g) for oral GC. Adverse events were often reported during oral GCs (26/32, 81%); most side effects were non-severe, but ten respondents reported severe adverse events (hepatic, cardiovascular, and cerebrovascular complications), including two fatal cases, both receiving a total of 2.3 g prednisone. Adverse events were less common in i.v.GC (32/83 respondents, 39%), but mostly consisted of severe events, including seven fatal cases. All but one fatal event occurred in cumulative i.v.GC doses (>8 g) higher than those currently recommended.

Conclusions: GCs are preferentially administered i.v. for the treatment of GO in Europe. Both oral and i.v.GC may be associated with severe adverse effects, including fatal cases, which are more frequently reported in daily or alternate day i.v.GC. IvGC therapy should be undertaken in centers with appropriate expertise. Patients should be carefully examined for risk factors before treatment and monitored for side effects, which may be asymptomatic, both during and after treatment.
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http://dx.doi.org/10.1530/EJE-11-0779DOI Listing
February 2012

The interface between thyroid and diabetes mellitus.

Clin Endocrinol (Oxf) 2011 Jul;75(1):1-9

Endocrine Unit, Evgenidion Hospital, University of Athens Medical School, Athens, GreeceService d' Endocrinologie-Diabète-Maladies Métaboliques, Centre Hospitalier, Lyon-Sud, FranceDepartment of Endocrinology, The Christie, Manchester Academic Health Science Centre, Manchester, UK.

Thyroid disease and type 1 but also type 2 diabetes mellitus (DM) are strongly associated, and this has important clinical implications for insulin sensitivity and treatment requirements. The pathophysiological basis of this association has only recently been better elucidated. It rests on a complex interaction of common signalling pathways and, in the case of type 1 diabetes and autoimmune thyroid disease, on a linked genetic susceptibility. The pathophysiological mechanisms underlying this linked regulation are increasingly being unravelled. They are exemplified in the regulation of 5' adenosine monophosphate-activated protein kinase (AMPK), a central target not only for the modulation of insulin sensitivity but also for the feedback of thyroid hormones on appetite and energy expenditure. The present review will discuss these concepts and their consequences for the clinical care of patients with DM and thyroid disorders. Moreover, it makes reference to the added effect of metformin in suppressing TSH.
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http://dx.doi.org/10.1111/j.1365-2265.2011.04029.xDOI Listing
July 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

Geographical correlation between incidence of benign disease and that of cancer of the thyroid among the population of the Rhône-Alpes Région of France.

Eur J Endocrinol 2010 Jan 29;162(1):127-35. Epub 2009 Sep 29.

Hospices Civils de Lyon, Registre Rhône Alpin des Cancers thyroïdiens, Fédération d'Endocrinologie et Centre de Médecine Nucléaire Groupement Hospitalier Est, 69677 Bron Cedex, France.

Objective: To analyze, at a population level, the relation between the incidences of benign thyroid diseases in patients submitted to surgery and that of thyroid cancers based on their respective geographical distributions.

Methods: The study included 3169 cases (691 cancers and 2478 benign diseases) operated on in 2002 in the Rhône-Alpes région, which is subdivided into eight départements and 311 cantons.

Results: The total thyroid intervention rate was 54.6/100 000 (23.4 and 86.4), and the annual cancer incidence was 11.9/100 000 (4.7 and 13.8) for men and women respectively. The prevalence of cancer among thyroid surgery was 21.8% and that of cancer discovered in goiters increased with age (44% at 60 years). Intervention rates varied from départment to département. In women, the incidence of microcancers was correlated to the thyroid intervention for benign pathologies rate. In men, the incidence of supracentimetric cancers was related to the TIBR. At the canton level, the relative risk of benign diseases was correlated to that of cancers. TIBR and incidence of cancers were higher in urban cantons than in nonurban ones. The density of endocrinologists influenced the prevalence of cancers among all the cases submitted to surgery.

Conclusion: In the Rhône-Alpes population with high rates of thyroid cancer incidence and of thyroid surgery, a number of correlations were found according to gender and tumor size. However, the general incidence of cancer was not directly related to surgical activity. Geographical variability may be related to the heterogeneous medical and pathological practices.
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http://dx.doi.org/10.1530/EJE-09-0570DOI Listing
January 2010

Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism.

J Clin Endocrinol Metab 2009 Aug 26;94(8):2766-72. Epub 2009 May 26.

Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, Pisa, Italy.

Context: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia.

Objective: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT.

Design: This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk.

Setting: The study was conducted at 23 centers in Europe, the United States, and Canada.

Patients: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter).

Intervention: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted.

Main Outcome Measure: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase.

Results: Mean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias.

Conclusions: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.
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http://dx.doi.org/10.1210/jc.2008-2640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214593PMC
August 2009

Thyroid cancer: is the incidence rise abating?

Eur J Endocrinol 2009 Jan 24;160(1):71-9. Epub 2008 Oct 24.

Hospices Civils de Lyon, Registre Rhône Alpin des Cancers Thyroïdiens, Fédération d'Endocrinologie et Centre de Médecine Nucléaire Groupement Hospitalier Est, Bron, France.

Objective: The aim of the present study was to determine recent trends in thyroid cancer incidence rates and to analyze histopathological characteristics and geographical distribution.

Methods: Histologically proven 5367 cases were collected over the period 1998-2006 in France from the Rhône-Alpes thyroid cancer registry. Geographical variations of incidence were analyzed using a mixed Poisson model.

Results: The average incidence rates, age standardized to the world population, were 3.9/100,000 in men and 12.3/100,000 in women, higher than those previously reported in France. After an initial increase during the first 3 years, a steady level of incidence was observed for the period 2001-2006. The annual incidence rate of microcarcinomas was correlated with that of all cancers in men and women (r=0.78 and 0.89; P<0.01) respectively. Papillary microcarcinomas represented 38% of tumors and two-thirds of them measured less than 5 mm in diameter. They were fortuitously discovered after thyroidectomy for benign diseases in 64% of cases. Histological marks of aggressiveness differed according to the size of the tumor. Despite recent advances in diagnosis, 13% of tumors were diagnosed at advanced stage especially in men. Geographical distribution of incidence based on subregional administrative entities showed lower incidence rates in rural than in urban zones in men (relative rate: 0.72; 95% CI: 0.62-0.84) and women (relative rate: 0.85; 95% CI: 0.73-0.93).

Conclusion: The present study suggests that the rise in thyroid cancer incidence is now abating. It could reflect standardization in diagnostic procedures. Further studies, performed on a more prolonged period, are necessary to confirm these data.
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http://dx.doi.org/10.1530/EJE-08-0624DOI Listing
January 2009

Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy.

Eur J Endocrinol 2009 Jan 10;160(1):1-8. Epub 2008 Oct 10.

Department of Endocrinology and Medicine, Aalborg Hospital, Aalborg, Denmark.

Graves' disease is a common autoimmune disorder in women in fertile ages. The hyperthyroidism is caused by generation of TSH-receptor activating antibodies. In pregnancy both the antibodies and the antithyroid medication given to the mother pass the placenta and affect the foetal thyroid gland. Thyroid function should be controlled not only in the mother with Graves' hyperthyroidism but also in her foetus.The review includes two cases illustrating some of the problems in managing Graves' disease in pregnancy. Major threats to optimal foetal thyroid function are inadequate or over aggressive antithyroid drug therapy of the mother. It should be taken into account that antithyroid drugs tend to block the foetal thyroid function more effectively than the maternal thyroid function, and that levothyroxin (L-T(4)) given to the mother will have only a limited effect in the foetus. Surgical thyroidectomy of patients with Graves' hyperthyroidism does not lead to immediate remission of the autoimmune abnormality, and the combination thyroidectomy+withdrawal of antithyroid medication+L-T(4) replacement of the mother involves a high risk of foetal hyperthyroidism. Conclusion Antithyroid drug therapy of pregnant women with Graves' hyperthyroidism should be balanced to control both maternal and foetal thyroid function. Surgical thyroidectomy of a pregnant woman with active disease may lead to isolated foetal hyperthyroidism.
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http://dx.doi.org/10.1530/EJE-08-0663DOI Listing
January 2009

A child with resistance to thyroid hormone without thyroid hormone receptor gene mutation: a 20-year follow-up.

Thyroid 2008 Jan;18(1):35-44

Department of Endocrinology, Centre Hospitalier, Chambéry, France.

We report here the 20-year follow-up study of a male subject diagnosed at 15 months of age as a sporadic case of pituitary resistance to thyroid hormone on the combination of clinical hyperthyroidism, elevated serum thyroid hormone (TH) levels and inappropriate thyrotropin (TSH). On D-thyroxine (D-T(4)) therapy from 30 months of age to 12.5 years, hyperactivity and hyperthyroid signs and symptoms as well as growth abnormalities improved, serum L-thyroxine (L-T(4)) enantiomer normalized, and basal and stimulated TSH decreased significantly without complete suppression. After 8 years off D-T(4), at 20 years of age, clinical status was normal despite persisting high TH levels and inappropriate TSH. Evolution of serum markers of TH action and echocardiography measurements followed up from 15 months to 20 years of age either in basal condition or on triiodothyronine (T(3)), as well as the sequential determination of bone mineral density suggest differences in the tissue responses to T(3): normal in bone with a high remodelling rate, heterogeneity for various hepatic markers, and decreased at heart level. No mutations were found in the coding sequence of TRbeta1, TRbeta2, TRalpha1, RXRgamma, SMRT, NCoR1, and NCoA1. In this patient the putative long-term effects of the persisting high bone resorption are unknown.
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http://dx.doi.org/10.1089/thy.2007.0079DOI Listing
January 2008

Evaluation of gene expression profiles in thyroid nodule biopsy material to diagnose thyroid cancer.

J Clin Endocrinol Metab 2008 Apr 22;93(4):1195-202. Epub 2008 Jan 22.

Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 664, Université Lyon 1, Lyon, France.

Context: Detection of thyroid cancer among benign nodules on fine-needle aspiration biopsies (FNAB), which presently relies on cytological examination, is expected to be improved by new diagnostic tests set up from genomic data.

Objective: The aim of the study was to use a set of genes discriminating benign from malignant tumors, on the basis of their expression levels, to build tumor classifiers and evaluate their capacity to predict malignancy on FNAB.

Design: We analyzed the level of expression of 200 potentially informative genes in 56 thyroid tissue samples (benign or malignant tumors and paired normal tissue) using nylon macroarrays. Gene expression data were subjected to a weighted voting algorithm to generate tumor classifiers. The performances of the classifiers were evaluated on a series of 26 sham FNAB, i.e. FNAB carried out on thyroid nodules after surgical resection.

Results: A series of 19 genes with a similar expression in follicular adenomas and normal tissue and discriminating follicular adenomas+normal tissue from the following: 1) follicular thyroid carcinomas (FTCs), 2) papillary thyroid carcinomas (PTCs), or 3) both FTCs and PTCs. These were used to generate four classifiers, the FTCs, PTCs, common (FTC+PTCs), and global classifiers. In 23 of the 26 sham FNAB, the four classifiers yielded a diagnosis in agreement with the diagnosis of the pathologist used as reference; in the three other cases, the correct diagnosis was given by three of four classifiers.

Conclusions: We developed a procedure of molecular diagnosis of benign vs. malignant tumors applicable to the material collected by FNAB. The molecular test complied with a preclinical validation stage; it must be now evaluated on ultrasound-guided FNAB in a large-scale prospective study.
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http://dx.doi.org/10.1210/jc.2007-1571DOI Listing
April 2008