- Email: [email protected]
Cullin 3 is a partner of Armadillo repeat containing 5 (ARMC5), the product of the gene responsible for primary bilateral macronodular adrenal hyperplasia
Disponible en ligne sur
ScienceDirect www.sciencedirect.com Annales d’Endocrinologie 79 (2018) 184–186
Klotz Communications 2018 : le Cortisol et tous ses dérèglements
Communications orales
CO1
Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome Anne-Lise Lecoq 1,2,3,∗ , Constantine A. Stratakis 4 , Say Viengchareun 1,2 , Ronan Chaligné 5,6 , Lucie Tosca 2,7,8 , Vianney Deméocq 1 , Mirella Hage 1 , Annabel Berthon 4 , Fabio R. Faucz 4 , Patrick Hanna 9 , Hadrien-Gaël Boyer 10 , Nicolas Servant 11,12 , Sylvie Salenave 3 , Gérard Tachdjian 2,7,8 , Clovis Adam 13 , Vanessa Benhamo 5,6 , Eric Clauser 14 , Anne Guiochon-Mantel 1,2,15 , Jacques Young 1,2,3 , Marc Lombès 1,2 , Isabelle Bourdeau 16 , Dominique Maiter 17 , Antoine Tabarin 18 , Jérôme Bertherat 19 , Hervé Lefebvre 10 , Wouter de Herder 20 , Estelle Louiset 10 , André Lacroix 16 , Philippe Chanson 1,2,3 , Jérôme Bouligand 1,2,15 , Peter Kamenick´y 1,2,3 1 Inserm U1185, Le Kremlin Bicêtre, France 2 Université Paris-Sud, université Paris-Saclay, Le Kremlin-Bicêtre, France 3 Service d’éndocrinologie et des maladies de la reproduction, Assistance publique–Hôpitaux de Paris (AP–HP), hôpital de Bicêtre, Le Kremlin-Bicêtre, France 4 Section on endocrinology and genetics, Eunice Kennedy Shriver National, institute of child health and human development, NIH, Bethesda, Maryland, USA 5 Inserm U934, Paris, France 6 Institut Curie, centre de recherche, UMR3215, Paris, France 7 Inserm U935, Villejuif, France 8 AP–HP, hôpital Antoine-Bécle`re, histologie-embryologie-cytogénétique, Clamart, France 9 Inserm U1169, Le Kremlin Bicêtre, France 10 Inserm U1239, université de Rouen, Normandie Université, Rouen, France 11 Inserm U900, Paris, France 12 Institut Curie, centre de recherche, bioinformatique et biologie des systemes, ` Paris, France 13 AP–HP, hôpital de Bicêtre, service d’anatomie pathologique, Le Kremlin-Bicêtre, France 14 AP–HP, hôpital Cochin, service d’oncogénétique, Paris, France 15 AP–HP, hôpital de Bicêtre, service de génétique moléculaire, pharmacogénétique et hormonologie, Le Kremlin-Bicêtre, France 16 Division of endocrinology, department of medicine, centre de recherche du CHUM, université de Montréal, Montréal, Quebec, Canada 17 Service d’endocrinologie et nutrition, cliniques universitaires Saint-Luc, Brusseles, Belgium 18 Service d’endocrinologie, hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France 19 AP–HP, hôpital Cochin, service d’endocrinologie, Paris, France 20 Department of internal medicine, section of endocrinology, Erasmus MC, Rotterdam, The Netherlands ∗ Corresponding author. E-mail address: [email protected] (A.-L. Lecoq)
0003-4266/
Background GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Methods We performed molecular analyses on 14 adrenal samples obtained from 12 patients with overt GIP-dependent Cushing’s syndrome and from one patient with GIP-dependent aldosteronism. Results Nascent RNA FISH showed that GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified by CGH-array somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had 19q duplication only. These duplications were further confirmed by DNA FISH. Among the 5 genes encompassed in the smallest region of overlap, only GIPR was over expressed. We demonstrated in vitro that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in HEK293 T and H295R cells. Conclusion Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. Disclosure of interest competing interest.
The authors have not supplied their declaration of
https://doi.org/10.1016/j.ando.2018.04.002 CO2
Cullin 3 is a partner of Armadillo repeat containing 5 (ARMC5), the product of the gene responsible for primary bilateral macronodular adrenal hyperplasia Isadora P. Cavalcante 1,2,∗ , Eric Clauser 3 , Anna Vaczlavik 1 , Ludivine Drougat 1 , Claudimara Lotfi 2 , Maria Fragoso 4 , Marthe Rizk-Rabin 1 , Jérôme Bertherat 1 , Bruno Ragazzon 1 1 Inserm U1016, CNRS 8104, institut Cochin, Paris Descartes University, Paris, France 2 Department of anatomy, institute of biomedical sciences, university of Sao Paulo, Sao Paulo, Brazil 3 Inserm U970, Paris Cardiovascular Center, Paris Descartes University, Paris, France 4 Laboratory of hormones and molecular genetics LIM/42, adrenal unit, university of Sao Paulo, Sao Paulo, Brazil ∗ Corresponding author. E-mail address: [email protected] (I.P. Cavalcante)
Klotz Communications 2018 : le Cortisol et tous ses dérèglements / Annales d’Endocrinologie 79 (2018) 184–186 Background ARMC5 has been identified as the gene responsible for PBMAH (primary bilateral macronodular adrenal hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5 is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BTB domain, patterns known to play a role in protein-protein interactions. Therefore identification of proteins that interact with ARMC5 and study of the mechanisms of this interaction will help to understand its function. By co-immunoprecipitation followed by mass spectrometry in HEK293 cells we identified a potential interaction between ARMC5 and Cullin3 (Cul3), also suggested in online databases and by 2 Hybrid Assay (Hu et al., 2017). Cul3 is a protein that mediates the ubiquitination process and subsequent degradation of specific protein substrates. Therefore, the aim of this study was to confirm this interaction and to investigate its mechanisms. Methods We used immunoprecipitation experiments with HA-tagged Cul3 and the bioluminescence resonance energy transfer (BRET) proximity assay in HEK293 cells in order to confirm and investigate the interaction of ARMC5 with Cul3. Results ARMC5 co-immunoprecipitated with HA-Cul3 and a hyperbolic BRET saturation curve was observed with YFP-Cul3 and ARMC5-Luc indicating a specific close proximity between these two proteins. We have also observed that a missense mutation in the BTB domain (p.L754P) of ARMC5 disrupts the interaction with Cul3. Altogether, these complementary approaches demonstrate that ARMC5 and Cul3 form a complex involving the BTB domain of ARMC5. Conclusion These data demonstrate that Cul3 is an ARMC5 partner. A likely direct interaction involves the BTB domain of ARMC5 and can be altered by pathogenic ARMC5 missense mutations. This suggests that ARMC5 participates in the ubiquitination process and open new perspectives in the pathophysiology of PBMAH. Disclosure of interest competing interest.
The authors have not supplied their declaration of
Introduction Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy provides a more physiological cortisol profile than conventional thrice-daily (TID) therapy and has demonstrated improved metabolic profile among patients with adrenal insufficiency (AI). The mechanisms by which this metabolic improvement occurs may be due to less total exposure, changed cortisol time exposure profile, but also modified metabolism of cortisol. Objective To study cortisol metabolism during DR-HC and TID. Methods Patients with primary AI received DR-HC or an equal total daily dose of TID in a crossover multi-center study. Cortisol metabolites were measured by gas chromatography/mass spectrometry on 24 h urinary collections after both treatments and in controls. Results Fifty patients (22 females, mean age 47 years) and 124 healthy controls (73 females, mean age 48 years) were included in the study. Total cortisol metabolites were significantly decreased during DR-HC [median: 6380 g/24 h] compared to TID [8825 g/24 h]; P < 0.001] and returned to values similar to controls (6850 g/24 h; P = 0.089). Compared to controls, the urinary THF + 5␣THF/THE ratio reflecting 11HSD1 activity was increased during both DR-HC (P < 0.001) and TID treatment (P < 0.001), being more marked in TID compared to DR-HC (P < 0.05). Urinary F/E reflecting 11HSD2 activity was higher in TID versus controls (P < 0.01), but normalized during DR-HC (P = 0.358). The urinary 5␣THF/THF ratio was increased during both treatments (controls: 1.3; TID: 2.3, P < 0.001; DR-HC: 2, P < 0.001) indicating an increase in 5-reductase activity during replacement therapy. However, the 5␣-reduced, 5␣THF, and the 5-reduced, THF, metabolites decreased significantly with DR-HC compared to TID (P < 0.001). Conclusion The urinary cortisol metabolome may be a more sensitive marker of “optimal cortisol replacement”. Abnormal cortisol metabolites excretion and cortisol metabolism are observed in patients receiving TID. This abnormal profile improves with DR-HC. Especially, reduced 11HSD1 activity during DR-HC may mediate some of the beneficial metabolic effects previously observed with this treatment.
https://doi.org/10.1016/j.ando.2018.04.003
Disclosure of interest competing interest.
CO3
https://doi.org/10.1016/j.ando.2018.04.004
The urinary cortisol metabolome in patients with adrenal insufficiency: Dual-release hydrocortisone is less deleterious than conventional hydrocortisone therapy Stéphanie Espiard 1,∗ , Johanna McQueen 1 , Mark Sherlock 2 , Oskar Ragnarsson 1 , Ragnhildur Bergthorsdottir 1 , Pia Burman 3 , Per Dahlqvist 4 , Bertil Ekman 5 , Britt Edén Engström 6 , Anna G. Nilsson 1 , Stanko Skrtic 1,7 , Jeanette Wahlberg 5 , Paul M. Stewart 8 , Gudmundur Johannsson 1 1 Department of endocrinology, Sahlgrenska University Hospital and institute of medicine, Sahlgrenska Academy, university of Gothenburg, Gothenburg, Sweden 2 Department of endocrinology and diabetes, Beaumont Hospital, Beaumont, Dublin, Ireland 3 Department of endocrinology, Skåne University Hospital Malmö, university of Lund, Lund, Sweden 4 Department of public health and clinical medicine, Umeå University, Umeå, Sweden 5 Department of endocrinology, department of medical and health sciences, department of clinical and experimental medicine, Linköping University, Linköping, Sweden 6 Department of medical sciences, endocrinology and metabolism, university hospital, Uppsala, Sweden 7 AstraZeneca R&D, Mölndal, Sweden 8 Faculty of medicine and health, university of Leeds, Leeds, United Kingdom ∗ Corresponding author. E-mail address: [email protected] (S. Espiard)
185
The authors have not supplied their declaration of
CO4
Comparaison des tests de freinage minute et de « Liddle » dans une population de volontaires saines utilisant une contraception orale oestro-progestative
Tiphaine Carton ∗ , Elise Mathieu , Fleur Wolff , Bernard Corvilain , Natacha Driessens Service d’endocrinologie, hôpital Erasme, université Libre de Bruxelles (ULB), Bruxelles, France ∗ Auteur correspondant. Adresse e-mail : [email protected] (T. Carton) La confirmation du diagnostic de syndrome de Cushing chez un patient présentant une clinique évocatrice nécessite des tests complémentaires. La mesure du cortisol salivaire de minuit, du cortisol libre urinaire de 24 heures (CLU) et le test de freinage minute par 1 mg de Dexaméthasone (DXM) représentent les tests de dépistage classiquement utilisés en première ligne. Chez les femmes utilisant des oestro-progestatifs, le freinage minute est souvent amoindri pouvant engendrer des faux positifs (FP = cortisolémie matinale post-DXM > 50 nmol/L). Le but de notre étude est de comparer le freinage minute et le test de Liddle (DXM 0,5 mg/6 h pendant 48 h) dans un échantillon de 30 volontaires saines utilisant une contraception oestro-progestative. Nous avons également mesuré le cortisol salivaire à minuit et 8 h après chacun des 2 tests. Nous avons également mesuré le CLU au 2e jour du test de Liddle. Nos résultats préliminaires montrent un taux de FP de 62 % (7/18) au freinage minute contre seulement 15 % (2/13) au test de Liddle. Le CLU au second jour du test Liddle élimine les derniers FP (0/12). Le pourcentage de diminution de la cortisolémie est de 95 % pour les 2 tests chez
ScienceDirect www.sciencedirect.com Annales d’Endocrinologie 79 (2018) 184–186
Klotz Communications 2018 : le Cortisol et tous ses dérèglements
Communications orales
CO1
Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome Anne-Lise Lecoq 1,2,3,∗ , Constantine A. Stratakis 4 , Say Viengchareun 1,2 , Ronan Chaligné 5,6 , Lucie Tosca 2,7,8 , Vianney Deméocq 1 , Mirella Hage 1 , Annabel Berthon 4 , Fabio R. Faucz 4 , Patrick Hanna 9 , Hadrien-Gaël Boyer 10 , Nicolas Servant 11,12 , Sylvie Salenave 3 , Gérard Tachdjian 2,7,8 , Clovis Adam 13 , Vanessa Benhamo 5,6 , Eric Clauser 14 , Anne Guiochon-Mantel 1,2,15 , Jacques Young 1,2,3 , Marc Lombès 1,2 , Isabelle Bourdeau 16 , Dominique Maiter 17 , Antoine Tabarin 18 , Jérôme Bertherat 19 , Hervé Lefebvre 10 , Wouter de Herder 20 , Estelle Louiset 10 , André Lacroix 16 , Philippe Chanson 1,2,3 , Jérôme Bouligand 1,2,15 , Peter Kamenick´y 1,2,3 1 Inserm U1185, Le Kremlin Bicêtre, France 2 Université Paris-Sud, université Paris-Saclay, Le Kremlin-Bicêtre, France 3 Service d’éndocrinologie et des maladies de la reproduction, Assistance publique–Hôpitaux de Paris (AP–HP), hôpital de Bicêtre, Le Kremlin-Bicêtre, France 4 Section on endocrinology and genetics, Eunice Kennedy Shriver National, institute of child health and human development, NIH, Bethesda, Maryland, USA 5 Inserm U934, Paris, France 6 Institut Curie, centre de recherche, UMR3215, Paris, France 7 Inserm U935, Villejuif, France 8 AP–HP, hôpital Antoine-Bécle`re, histologie-embryologie-cytogénétique, Clamart, France 9 Inserm U1169, Le Kremlin Bicêtre, France 10 Inserm U1239, université de Rouen, Normandie Université, Rouen, France 11 Inserm U900, Paris, France 12 Institut Curie, centre de recherche, bioinformatique et biologie des systemes, ` Paris, France 13 AP–HP, hôpital de Bicêtre, service d’anatomie pathologique, Le Kremlin-Bicêtre, France 14 AP–HP, hôpital Cochin, service d’oncogénétique, Paris, France 15 AP–HP, hôpital de Bicêtre, service de génétique moléculaire, pharmacogénétique et hormonologie, Le Kremlin-Bicêtre, France 16 Division of endocrinology, department of medicine, centre de recherche du CHUM, université de Montréal, Montréal, Quebec, Canada 17 Service d’endocrinologie et nutrition, cliniques universitaires Saint-Luc, Brusseles, Belgium 18 Service d’endocrinologie, hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France 19 AP–HP, hôpital Cochin, service d’endocrinologie, Paris, France 20 Department of internal medicine, section of endocrinology, Erasmus MC, Rotterdam, The Netherlands ∗ Corresponding author. E-mail address: [email protected] (A.-L. Lecoq)
0003-4266/
Background GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Methods We performed molecular analyses on 14 adrenal samples obtained from 12 patients with overt GIP-dependent Cushing’s syndrome and from one patient with GIP-dependent aldosteronism. Results Nascent RNA FISH showed that GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified by CGH-array somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had 19q duplication only. These duplications were further confirmed by DNA FISH. Among the 5 genes encompassed in the smallest region of overlap, only GIPR was over expressed. We demonstrated in vitro that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in HEK293 T and H295R cells. Conclusion Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. Disclosure of interest competing interest.
The authors have not supplied their declaration of
https://doi.org/10.1016/j.ando.2018.04.002 CO2
Cullin 3 is a partner of Armadillo repeat containing 5 (ARMC5), the product of the gene responsible for primary bilateral macronodular adrenal hyperplasia Isadora P. Cavalcante 1,2,∗ , Eric Clauser 3 , Anna Vaczlavik 1 , Ludivine Drougat 1 , Claudimara Lotfi 2 , Maria Fragoso 4 , Marthe Rizk-Rabin 1 , Jérôme Bertherat 1 , Bruno Ragazzon 1 1 Inserm U1016, CNRS 8104, institut Cochin, Paris Descartes University, Paris, France 2 Department of anatomy, institute of biomedical sciences, university of Sao Paulo, Sao Paulo, Brazil 3 Inserm U970, Paris Cardiovascular Center, Paris Descartes University, Paris, France 4 Laboratory of hormones and molecular genetics LIM/42, adrenal unit, university of Sao Paulo, Sao Paulo, Brazil ∗ Corresponding author. E-mail address: [email protected] (I.P. Cavalcante)
Klotz Communications 2018 : le Cortisol et tous ses dérèglements / Annales d’Endocrinologie 79 (2018) 184–186 Background ARMC5 has been identified as the gene responsible for PBMAH (primary bilateral macronodular adrenal hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5 is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BTB domain, patterns known to play a role in protein-protein interactions. Therefore identification of proteins that interact with ARMC5 and study of the mechanisms of this interaction will help to understand its function. By co-immunoprecipitation followed by mass spectrometry in HEK293 cells we identified a potential interaction between ARMC5 and Cullin3 (Cul3), also suggested in online databases and by 2 Hybrid Assay (Hu et al., 2017). Cul3 is a protein that mediates the ubiquitination process and subsequent degradation of specific protein substrates. Therefore, the aim of this study was to confirm this interaction and to investigate its mechanisms. Methods We used immunoprecipitation experiments with HA-tagged Cul3 and the bioluminescence resonance energy transfer (BRET) proximity assay in HEK293 cells in order to confirm and investigate the interaction of ARMC5 with Cul3. Results ARMC5 co-immunoprecipitated with HA-Cul3 and a hyperbolic BRET saturation curve was observed with YFP-Cul3 and ARMC5-Luc indicating a specific close proximity between these two proteins. We have also observed that a missense mutation in the BTB domain (p.L754P) of ARMC5 disrupts the interaction with Cul3. Altogether, these complementary approaches demonstrate that ARMC5 and Cul3 form a complex involving the BTB domain of ARMC5. Conclusion These data demonstrate that Cul3 is an ARMC5 partner. A likely direct interaction involves the BTB domain of ARMC5 and can be altered by pathogenic ARMC5 missense mutations. This suggests that ARMC5 participates in the ubiquitination process and open new perspectives in the pathophysiology of PBMAH. Disclosure of interest competing interest.
The authors have not supplied their declaration of
Introduction Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy provides a more physiological cortisol profile than conventional thrice-daily (TID) therapy and has demonstrated improved metabolic profile among patients with adrenal insufficiency (AI). The mechanisms by which this metabolic improvement occurs may be due to less total exposure, changed cortisol time exposure profile, but also modified metabolism of cortisol. Objective To study cortisol metabolism during DR-HC and TID. Methods Patients with primary AI received DR-HC or an equal total daily dose of TID in a crossover multi-center study. Cortisol metabolites were measured by gas chromatography/mass spectrometry on 24 h urinary collections after both treatments and in controls. Results Fifty patients (22 females, mean age 47 years) and 124 healthy controls (73 females, mean age 48 years) were included in the study. Total cortisol metabolites were significantly decreased during DR-HC [median: 6380 g/24 h] compared to TID [8825 g/24 h]; P < 0.001] and returned to values similar to controls (6850 g/24 h; P = 0.089). Compared to controls, the urinary THF + 5␣THF/THE ratio reflecting 11HSD1 activity was increased during both DR-HC (P < 0.001) and TID treatment (P < 0.001), being more marked in TID compared to DR-HC (P < 0.05). Urinary F/E reflecting 11HSD2 activity was higher in TID versus controls (P < 0.01), but normalized during DR-HC (P = 0.358). The urinary 5␣THF/THF ratio was increased during both treatments (controls: 1.3; TID: 2.3, P < 0.001; DR-HC: 2, P < 0.001) indicating an increase in 5-reductase activity during replacement therapy. However, the 5␣-reduced, 5␣THF, and the 5-reduced, THF, metabolites decreased significantly with DR-HC compared to TID (P < 0.001). Conclusion The urinary cortisol metabolome may be a more sensitive marker of “optimal cortisol replacement”. Abnormal cortisol metabolites excretion and cortisol metabolism are observed in patients receiving TID. This abnormal profile improves with DR-HC. Especially, reduced 11HSD1 activity during DR-HC may mediate some of the beneficial metabolic effects previously observed with this treatment.
https://doi.org/10.1016/j.ando.2018.04.003
Disclosure of interest competing interest.
CO3
https://doi.org/10.1016/j.ando.2018.04.004
The urinary cortisol metabolome in patients with adrenal insufficiency: Dual-release hydrocortisone is less deleterious than conventional hydrocortisone therapy Stéphanie Espiard 1,∗ , Johanna McQueen 1 , Mark Sherlock 2 , Oskar Ragnarsson 1 , Ragnhildur Bergthorsdottir 1 , Pia Burman 3 , Per Dahlqvist 4 , Bertil Ekman 5 , Britt Edén Engström 6 , Anna G. Nilsson 1 , Stanko Skrtic 1,7 , Jeanette Wahlberg 5 , Paul M. Stewart 8 , Gudmundur Johannsson 1 1 Department of endocrinology, Sahlgrenska University Hospital and institute of medicine, Sahlgrenska Academy, university of Gothenburg, Gothenburg, Sweden 2 Department of endocrinology and diabetes, Beaumont Hospital, Beaumont, Dublin, Ireland 3 Department of endocrinology, Skåne University Hospital Malmö, university of Lund, Lund, Sweden 4 Department of public health and clinical medicine, Umeå University, Umeå, Sweden 5 Department of endocrinology, department of medical and health sciences, department of clinical and experimental medicine, Linköping University, Linköping, Sweden 6 Department of medical sciences, endocrinology and metabolism, university hospital, Uppsala, Sweden 7 AstraZeneca R&D, Mölndal, Sweden 8 Faculty of medicine and health, university of Leeds, Leeds, United Kingdom ∗ Corresponding author. E-mail address: [email protected] (S. Espiard)
185
The authors have not supplied their declaration of
CO4
Comparaison des tests de freinage minute et de « Liddle » dans une population de volontaires saines utilisant une contraception orale oestro-progestative
Tiphaine Carton ∗ , Elise Mathieu , Fleur Wolff , Bernard Corvilain , Natacha Driessens Service d’endocrinologie, hôpital Erasme, université Libre de Bruxelles (ULB), Bruxelles, France ∗ Auteur correspondant. Adresse e-mail : [email protected] (T. Carton) La confirmation du diagnostic de syndrome de Cushing chez un patient présentant une clinique évocatrice nécessite des tests complémentaires. La mesure du cortisol salivaire de minuit, du cortisol libre urinaire de 24 heures (CLU) et le test de freinage minute par 1 mg de Dexaméthasone (DXM) représentent les tests de dépistage classiquement utilisés en première ligne. Chez les femmes utilisant des oestro-progestatifs, le freinage minute est souvent amoindri pouvant engendrer des faux positifs (FP = cortisolémie matinale post-DXM > 50 nmol/L). Le but de notre étude est de comparer le freinage minute et le test de Liddle (DXM 0,5 mg/6 h pendant 48 h) dans un échantillon de 30 volontaires saines utilisant une contraception oestro-progestative. Nous avons également mesuré le cortisol salivaire à minuit et 8 h après chacun des 2 tests. Nous avons également mesuré le CLU au 2e jour du test de Liddle. Nos résultats préliminaires montrent un taux de FP de 62 % (7/18) au freinage minute contre seulement 15 % (2/13) au test de Liddle. Le CLU au second jour du test Liddle élimine les derniers FP (0/12). Le pourcentage de diminution de la cortisolémie est de 95 % pour les 2 tests chez