Publications by authors named "Veronique Tardy-Guidollet"

7 Publications

  • Page 1 of 1

Exposure to Glucocorticoids in the First Part of Fetal Life is Associated with Insulin Secretory Defect in Adult Humans.

J Clin Endocrinol Metab 2020 03;105(3)

Department of Diabetes and Endocrinology, Lariboisière Hospital, APHP, Paris, France.

Objective: High glucocorticoid levels in rodents inhibit development of beta cells during fetal life and lead to insulin deficiency in adulthood. To test whether similar phenomena occur in humans, we compared beta-cell function in adults who were exposed to glucocorticoids during the first part of fetal life with that of nonexposed subjects.

Research Design And Methods: The study was conducted in 16 adult participants exposed to glucocorticoids during the first part of fetal life and in 16 nonexposed healthy participants with normal glucose tolerance who were matched for age, sex, and body mass index (BMI). Exposed participants had been born to mothers who were treated with dexamethasone 1 to 1.5 mg/day from the sixth gestational week (GW) to prevent genital virilization in children at risk of 21-hydroxylase deficiency. We selected offspring of mothers who stopped dexamethasone before the 18th GW following negative genotyping of the fetus. Insulin and glucagon secretion were measured during an oral glucose tolerance test (OGTT) and graded intravenous (IV) glucose and arginine tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic-clamp.

Results: Age, BMI, and anthropometric characteristics were similar in the 2 groups. Insulinogenic index during OGTT and insulin sensitivity during the clamp were similar in the 2 groups. In exposed subjects, insulin secretion during graded IV glucose infusion and after arginine administration decreased by 17% (P = 0.02) and 22% (P = 0.002), respectively, while glucagon secretion after arginine increased.

Conclusion: Overexposure to glucocorticoids during the first part of fetal life is associated with lower insulin secretion at adult age, which may lead to abnormal glucose tolerance later in life.
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March 2020

Optimized nested PCR enhances biological diagnosis and phylogenetic analysis of human parvovirus B19 infections.

Arch Virol 2019 Nov 10;164(11):2775-2781. Epub 2019 Aug 10.

Hospices Civils de Lyon, Laboratoire de Virologie, Institut des Agents Infectieux, Centre de Biologie et de Pathologie Nord, 103, grande rue de la Croix-Rousse, 69 317, Lyon cedex 04, France.

Diagnosis and epidemiological analysis of human parvovirus B19 (hB19V) infections are essential for disease management in severely ill patients. This study aimed to evaluate the performance of an optimized NS1-VP1u nested PCR for detection and sequencing of viruses in clinical samples using 224 clinical and five reference samples. PCR sensitivity, specificity, and positive and negative predictive values were perfect (100%). While phylogenetic analysis of a 615 bp-long fragment demonstrated that the viruses in all of the samples belonged to genotype 1, this study confirmed that this optimized PCR could detect all known hB19V with high performance.
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November 2019

Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in Gene.

Front Endocrinol (Lausanne) 2018 5;9:491. Epub 2018 Sep 5.

Laboratoire de Biochimie et Biologie Moléculaire Grand Est, UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first rate-limiting step of steroidogenesis. mutations are associated with primary adrenal insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY patients. To define the pathogenicity mechanism for the p.Glu314Lys variant, previously reported, and found in four additional patients with CYP11A1 deficiency. DNA of four patients presenting with delayed PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing. Three mutations were characterized and , and one by mRNA analysis on testicular tissue. All patients were compound heterozygous for the previously described p.Glu314Lys variant. studies predicted this mutation as benign with no effect on splicing but mRNA analysis found that it led to incomplete exon 5 skipping. This mechanism was confirmed by minigene experiment. The protein carrying this mutation without exon skipping should conserve almost normal activity, according to studies. Two other mutations found in , the p.Arg120Gln and p.Arg465Trp, had similar activity compared to negative control, consistent with the studies. We provide biological proof that the p. Glu314Lys variant is pathogenic due to its impact on splicing and seems responsible for the moderate phenotype of the four patients reported herein. The present study highlights the importance of considering the potential effect of a missense variant on splicing when it is not predicted to be disease causing.
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September 2018

News about the genetics of congenital primary adrenal insufficiency.

Ann Endocrinol (Paris) 2018 Jun 13;79(3):174-181. Epub 2018 Apr 13.

Laboratoire de biochimie et biologie moléculaire Grand Est, UM pathologies endocriniennes rénales musculaires et mucoviscidose, groupement hospitalier Est, hospices civils de Lyon, 69677 Bron, France; Université de Lyon, université Claude-Bernard Lyon 1, 69008 Lyon, France.

Primary adrenal insufficiency (PAI) is characterized by impaired production of steroid hormones due to an adrenal cortex defect. This condition incurs a risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relating to oxidative stress have opened the way to research on genes unrelated to the adrenal gland. Identification of causal mutations in a gene responsible for PAI allows genetic counseling, guidance of follow-up and prevention of complications. This is particularly true for stress oxidative anomalies, as extra-adrenal manifestations may occur due to the sensitivity to oxidative stress of other organs such as the heart, thyroid, liver, kidney and pancreas.
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June 2018

Clinical Outcome, Hormonal Status, Gonadotrope Axis, and Testicular Function in 219 Adult Men Born With Classic 21-Hydroxylase Deficiency. A French National Survey.

J Clin Endocrinol Metab 2015 Jun 30;100(6):2303-13. Epub 2015 Mar 30.

University Paris-Sud (C.B., L.E., J.Y.), Assistance Publique Hôpitaux de Paris, Paris, France; Department of Pediatric Endocrinology (C.B., L.E.), Bicêtre Hospital, F-94275 Le Kremlin Bicêtre, France; French Reference Center of Rare Disorders of Sexual Development, (C.B., L.E., A.B.d.l.P., Y.M., V.T.-G., J.Y.), F-94275 Le Kremlin Bicetre, France; Department of Endocrinology (P.R.-P.), Tours Hospital, F-37380 Tours, France; Department of Endocrinology (A.B.d.l.P.), Lyon University Hospital, F-69000 Lyon, France; Department of Endocrinology (F.I.), Angers Hospital, Angers, France; Department of Endocrinology (V.K.), Brest University Hospital, F-29600 Brest, France; Department of Endocrinology (V.P.-V.), Brabois Hospital, F-54200 Nancy, France; Department of Endocrinology (D.Dr.), Nantes University Hospital, F-44000 Nantes, France; Department of Reproductive Endocrinology (S.C.-M.), St-Antoine Hospital, F-75012 Paris, France; Department of Endocrinology (F.G., D.P.), Rennes Hospital, F-35203 Rennes, France; Department of Endocrinology (T.B.), La Timone Hospital, F-13385 Marseilles, France; Department of Endocrinology (Y.R.), Hospital Nacre, Caen, France; Department of Endocrinology (F.S.), Jean Minjoz Hospital, Besançon, France; Department of Endocrinology (X.P.), Poitiers Hospital, Poitiers, France; Department of Endocrinology (G.C.), Strasbourg Hospital, F-67000 Strasbourg, France; Department of Endocrinology (B.D.), Reims Hospital, F-51100 Reims, France; Department of Endocrinology (I.T.), Clermond-Ferrand Hospital, F-63100 Clermond-Ferrand, France; Department of Endocrinology (M.-L.R.-S.), Ambroise Paré Hospital, F-92104 Boulogne-Billancourt, France; Department of Endocrinology (PE), Orléans Hospital, Orléans, France; Department of Endocrinology (J.B.), Cochin Hospital, Paris, France; Department of Endocrinology (J.-M.K.), Rouen Teaching Hospital, F-76031 Rouen, France; Department of Endocrinology, Toulouse Teaching Hospital, F-31059; Department of Pediatric

Context: Outcomes of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women, but less so in men.

Objective: The objective was to analyze data from a network of metropolitan French teaching hospitals on the clinical outcome of classic 21OHD in a large sample of congenital adrenal hyperplasia/21OHD-genotyped adult men, and particularly the impact of 21OHD on the gonadotrope axis, testicular function, and fertility.

Methods: From April 2011 to June 2014, tertiary endocrinology departments provided data for 219 men with 21OHD (ages, 18-70 y; 73.6% salt wasters, 26.4% simple virilizers). Testicular sonography was performed in 164 men, and sperm analysis was performed in 71 men.

Results: Mean final height was 7.8 cm lower than in a reference population. Obesity was more common, and mean blood pressure was lower than in the reference population. None of the patients were diabetic, and lipid status was generally normal. Blood electrolyte status was normal in the vast majority of men, despite markedly elevated ACTH and renin levels. Serum progesterone, 17-hydroxyprogesterone, and androstenedione levels were above normal in the vast majority of cases. Hormonal profiling variously showed a normal gonadotrope-testicular axis, gonadotropin deficiency, or primary testicular insufficiency. Testicular sonography revealed testicular adrenal rest tumors (TARTs) in 34% of 164 men. Serum inhibin B and FSH levels were significantly lower and higher, respectively, in patients with TARTs. Severe oligospermia or azoospermia was found in 42% of patients and was significantly more prevalent in men with TARTs (70%) than in men with normal testes (3.6%; P < .0001). Among men living with female partners, TARTs were significantly more prevalent in those who had not fathered children.

Conclusion: We report the spectrum of testicular/gonadotrope axis impairment in the largest cohort of 21OHD men studied to date. Our results suggest that French men with 21OHD managed in specialized centers frequently have impaired exocrine testicular function but that its reproductive implications are often overlooked.
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June 2015

Late prenatal dexamethasone and phenotype variations in 46,XX CAH: concerns about current protocols and benefits for surgical procedures.

J Pediatr Urol 2014 Oct 15;10(5):941-7. Epub 2014 Mar 15.

Service d'Urologie Pédiatrique, Hôpital Mère-Enfant, Centre Hospitalo-Universitaire de Lyon, GHE, 59, boulevard Pinel, 69677 Bron Cedex, France. Electronic address:

Objective: To describe the action of prenatal dexamethasone (PreDex) on the anatomy of female congenital adrenal hyperplasia (CAH) genitalia when started at later stages of gestation.

Materials And Methods: Our group follows a large cohort of French CAH patients who underwent PreDex therapy, of whom 258 were recently reported. Four 46,XX patients with a delayed PreDex treatment presented with a virilized genitalia and required surgical reconstruction. This is a retrospective report on genital phenotyping at the time of surgery of these four patients who began PreDex therapy at 8, 12, 20, and 28 weeks of gestation.

Results: Although this series is limited in number, the anatomical description of the length of the genital tubercle, the height of the urethra-vaginal confluence, and the degree of fusion of the genital folds seems to be dependent upon the starting date of PreDex. Most PreDex treatments prescribed up to now have covered the full duration of gestation.

Conclusions: Our findings suggest that PreDex therapy could be limited to the period of the partitioning window. It is hoped that further prospective multicentric clinical studies will obtain ethical approval in order to elucidate the place and protocols of PreDex therapy in the management of CAH.
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October 2014

New management strategy of pregnancies at risk of congenital adrenal hyperplasia using fetal sex determination in maternal serum: French cohort of 258 cases (2002-2011).

J Clin Endocrinol Metab 2014 Apr 28;99(4):1180-8. Epub 2014 Jan 28.

Laboratoire d'Endocrinologie Moléculaire et Maladies Rares (V.T.-G., R.M., Y.M.), Centre de Biologie et de Pathologie Est, Hospices civils de Lyon, 69677 Bron, France; Département de Génétique (J.-M.C), Laboratoire Cerba, 95066 Cergy Pontoise, France; Département d'Endocrinologie, Diabétologie, et Métabolismes Pédiatriques (M.D.), Hôpital Mère-Enfant, HCL, 69677 Bron, France; Unité d'Endocrinologie pédiatrique (C.B.-M.), Centre Hospitalier de Bicêtre, 94275 Le Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Unité de Génétique Clinique (C.B.), Hôpital Robert Debré, AP-HP, 75019 Paris, France; Laboratoire d'Explorations Fonctionnelles (M.H.), Hôpital Trousseau, AP-HP, 75012 Paris, France; Unité d'Endocrinologie et Gynécologie Obstétrique (F.L.), Pôle Femme-Mère-Couple, Hôpital Paule de Viguier, 31059 Toulouse, France; Département de Génétique (N.P.), Hôpital Timone, Assistance Publique-Hôpitaux de Marseille, 13385 Marseille, France; Département de Génétique (S.O.), Hôpital Sud, 35203 Rennes, France; and Département de Génétique (A.G.), Centre Hospitalier UniversitaireAngers, 49033 Angers, France.

Context: Prenatal dexamethasone (DEX) treatment has been proposed since 1984 to prevent genital virilization in girls with congenital adrenal hyperplasia (CAH). DEX is effective in CAH females if initiated before the sixth week of gestation, but its safety in children treated in utero remains controversial regarding cognitive functions.

Objective: To avoid prenatal DEX in males and initiate DEX in due time in CAH females, we proposed in 2002 a protocol for fetal sex determination in the maternal serum (SRY test).

Design And Setting: We conducted a retrospective study of the management of 258 fetuses in the period 2002 through 2011 in pregnancies managed in referent medical centers with an institutional practice.

Patients: A total of 258 fetuses at risk of CAH (134 males and 124 females) were included.

Intervention: DEX was offered after informed consent to pregnant women.

Main Outcome Measure: The sensitivity of an early SRY test was evaluated after data collection.

Results: The SRY test is sensitive from 4 weeks and 5 days of gestation. It avoided prenatal DEX in 68% of males, and this percentage increased over the years. DEX was maintained until prenatal diagnosis in non-CAH females. Virilization was prevented in 12 CAH girls treated at the latest at 6 weeks gestation and minimized in 3 girls treated between 6 and 7 weeks gestation. Maternal tolerance was correct. No fetal malformations were noted in the 154 children treated in utero.

Conclusions: The SRY test is reliable to avoid prenatal DEX in males, but its application must be improved. Prenatal DEX should be maintained to prevent virilization and traumatic surgery in CAH girls after informed consent and information provided to families about the benefit to risk ratio in limiting hyperandrogenism during fetal life. Our large multicentric French cohort has helped to better assess the risks previously reported.
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April 2014