lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Cortisol and Aldosterone Responses to Insulin-Induced Hypoglycemia and Sodium Depletion in Women with Non-Classic 21-Hydroxylase Deficiency

24 Pages Posted: 31 Mar 2019

See all articles by Peter Kamenicky

Peter Kamenicky

Hôpital de Bicêtre - Service d’Endocrinologie et des Maladies de la Reproduction

Anne Blanchard

Université Paris Sud - Le Kremlin-Bicêtre

Antonin Lamaziere

Université Paris VI Pierre et Marie Curie - Hôpital Saint-Antoine

Céline Piedvache

Unité de Recherche Clinique

Bruno Donadille

Service d'Endocrinologie et des Maladies de la Reproduction

Lise Duranteau

UF de Gynécologie Adolescente et Jeune Adulte

Hélène Bry

Hôpital de Bicêtre

Jean-Francois Gautier

Université Paris IX Dauphine

Sylvie Salenave

Hôpital de Bicêtre

Marie-Laure Raffin-Sanson

Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Parré, Department of Endocrinology

Seray Genc

Hôpital Jean Bernard

Laurence Pietri

Hôpital Saint-Joseph

Sophie Christin-Maitre

Service d'Endocrinologie et des Maladies de la Reproduction

Julien Thomas

Université Paris VI Pierre et Marie Curie - Hôpital Saint-Antoine

Aurelien Lorthioir

Université Paris Sud - Le Kremlin-Bicêtre

Michele Azizi

University of Paris - Georges Pompidou European Hospital

Philippe Chanson

Hôpital de Bicêtre

Yves Le Bouc

UMR_S 938

Sylvie Brailly-Tabard

Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie

Jacques Young

Hôpital de Bicêtre

More...

Abstract

Background: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacological challenges.

Methods: In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 ageand BMI-matched healthy women with 17OHP after Synacthen® <2ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg furosemide under low sodium diet (< 20 mmol during 24 hours), to evaluate renin and aldosterone secretion.

Findings: The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference -47 ng/mL, 90%CI: -66, p=0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (p=0.0039). 24- hours after sodium depletion, blood pressure, plasma sodium, potassium and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (p=0.0044).

Interpretation: Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.

Trial Registration Number: The trial was registered in ClinicalTrials.gov number NCT01862380.

Funding Statement: Institutional grant from APHP AOR11111.  

Declaration of Interests: The authors state that they have nothing to disclose.

Ethics Approval Statement: The study was approved by the local Ethics Committee (Comité de Protection des Personnes Ile de France VII) and the competent authority (ANSM). All subjects gave written informed consent to participate to the study.

Suggested Citation

Kamenicky, Peter and Blanchard, Anne and Lamaziere, Antonin and Piedvache, Céline and Donadille, Bruno and Duranteau, Lise and Bry, Hélène and Gautier, Jean-Francois and Salenave, Sylvie and Raffin-Sanson, Marie-Laure and Genc, Seray and Pietri, Laurence and Christin-Maitre, Sophie and Thomas, Julien and Lorthioir, Aurelien and Azizi, Michele and Chanson, Philippe and Le Bouc, Yves and Brailly-Tabard, Sylvie and Young, Jacques, Cortisol and Aldosterone Responses to Insulin-Induced Hypoglycemia and Sodium Depletion in Women with Non-Classic 21-Hydroxylase Deficiency (March 29, 2019). Available at SSRN: https://ssrn.com/abstract=3362459 or http://dx.doi.org/10.2139/ssrn.3362459

Peter Kamenicky (Contact Author)

Hôpital de Bicêtre - Service d’Endocrinologie et des Maladies de la Reproduction ( email )

France

Anne Blanchard

Université Paris Sud - Le Kremlin-Bicêtre

Le Kremlin-Bicêtre
France

Antonin Lamaziere

Université Paris VI Pierre et Marie Curie - Hôpital Saint-Antoine

Paris
France

Céline Piedvache

Unité de Recherche Clinique

France

Bruno Donadille

Service d'Endocrinologie et des Maladies de la Reproduction

France

Lise Duranteau

UF de Gynécologie Adolescente et Jeune Adulte

France

Hélène Bry

Hôpital de Bicêtre

France

Jean-Francois Gautier

Université Paris IX Dauphine

223 Rue Saint-Honore
Paris, 75775
France

Sylvie Salenave

Hôpital de Bicêtre

France

Marie-Laure Raffin-Sanson

Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Parré, Department of Endocrinology

Paris
France

Seray Genc

Hôpital Jean Bernard

France

Laurence Pietri

Hôpital Saint-Joseph

France

Sophie Christin-Maitre

Service d'Endocrinologie et des Maladies de la Reproduction

France

Julien Thomas

Université Paris VI Pierre et Marie Curie - Hôpital Saint-Antoine

Paris
France

Aurelien Lorthioir

Université Paris Sud - Le Kremlin-Bicêtre

Le Kremlin-Bicêtre
France

Michele Azizi

University of Paris - Georges Pompidou European Hospital

France

Philippe Chanson

Hôpital de Bicêtre

France

Yves Le Bouc

UMR_S 938

Paris
France

Sylvie Brailly-Tabard

Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie

France

Jacques Young

Hôpital de Bicêtre

France