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ea0090p13 | Adrenal and Cardiovascular Endocrinology | ECE2023

Prolonged Adrenocortical Blockade Following Interruption of Osilodrostat in ACTH-dependent Cushing’s syndrome

Poirier Jonathan , Bonnet-Serrano Fideline , Thomeret Louis , Bouys Lucas , Bertherat Jerome

Introduction: Osilodrostat is the newest approved steroidogenic inhibitor drug for the treatment of Cushings syndrome (CS). In this presentation, we describe 3 patients who experienced an unexpectedly prolonged adrenal insufficiency following interruption of this treatment.Methods: A monocentric retrospective analysis (October 2019 to January 2023) of ACTH-dependent CS patients controlled with Osilodrostat was performed to identify patients with pr...

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ea0090ep69 | Adrenal and Cardiovascular Endocrinology | ECE2023

Effects of Osilodrostat and Metyrapone on steroidogenesis in adrenocortical H295R tumor cells in vitro

Thomeret Louis , Berthon Annabel , Perlemoine Karine , Poirier Jonathan , Blanchet Benoit , Puszkiel Alicja , Bertherat Jerome , Fideline Bonnet

Introduction: Osilodrostat and Metyrapone are two CYP11B1 inhibitors used for the treatment of patients with Cushing syndrome. Despite their common suspected mechanism of action, the comparison of serum steroid profiles determined in HPLC-MS/MS in patients treated by either Osilodrostat or Metyrapone for an ACTH-dependent Cushing syndrome identified higher levels of 11-deoxycortisol and androgens in patients treated by Metyrapone than in those treated by Osilodrostat (F. B...

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ea0081oc7.4 | Oral Communications 7: Pituitary and Neuroendocrinology 2 | ECE2022

HPLC-MSMS steroidogenic profiles in ACTH-dependent Cushing Syndrome patients treated by osilodrostat or metyrapone suggest differences in the spectrum of steroidogenic enzyme inhibition between the two CYP11B1 inhibitors in clinical care

Fideline Bonnet , Poirier Jonathan , Vaczlavik Anna , Laguillier-Morizot Christelle , Blanchet Benoit , Guignat Laurence , Bessiene Laura , Bricaire Leopoldine , Groussin Lionel , Assie Guillaume , Guibourdenche Jean , Bertherat Jerome

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to metyrapone. It has become increasingly used in recent years for treatment of Cushings Syndrome (CS). However, few in vivo studies are currently available to accurately compare both drugs characteristics. The objective of our study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent CS.Me...

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ea0090oc3.5 | Oral Communications 3: Pituitary and Neuroendocrinology 1 | ECE2023

Interest of serum and salivary cortisol diurnal cycle in the positive diagnostic of Cushing syndrome and in the differential diagnosis of pseudo-Cushing syndrome

Fideline Bonnet , Poirier Jonathan , El Khoury Ralph , Laguillier-Morizot Christelle , Leguy Marie-Clemence , Thomeret Louis , Bouys Lucas , Guignat Laurence , Assie Guillaume , Groussin Lionel , Guibourdenche Jean , Bertherat Jerome

Introduction: Biological diagnosis of Cushing syndrome relies on three parameters: 24 hours-free urinary cortisol; serum cortisol after 1 mg dexamethasone suppression test; late-night serum or salivary cortisol. These tests allow the diagnosis of cortisol excess but do not help in etiological diagnosis, particularly in the distinction between pseudo-Cushing and ACTH-dependent Cushing syndrome, which is often challenging. The aim of this study was to evaluate the performances o...

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ea0093p4 | Guided Poster Tour 1: Adrenal and Neuroendocrine tumors | EYES2023

Decrease in anticortisolic drug osilodrostat plasma exposure in patients treated with mitotane for an adrenocortical carcinoma

Thomeret Louis , Puszkiel Alicja , Balakirouchenane David , Bouys Lucas , Poirier Jonathan , Berthon Annabel , Ragazzon Bruno , Jouinot Anne , Guignat Laurence , Bessiene Laura , Libe Rossella , Bricaire Leopoldine , Groussin Lionel , Assie Guillaume , Blanchet Benoit , Bonnet-Serrano Fideline , Bertherat Jerome

Introduction: The steroidogenesis inhibitor osilodrostat (OSI), indicated for the medical treatment of endogenous Cushings syndrome, exhibits significant interindividual variability regarding the response to treatment (Pivonello et al. 2020). Plasma exposure may contribute to this variability. Our objective was to investigate the effect of concomitant use of mitotane (MIT), a potent inducer of CYP450 (3A4), on circulating OSI concentrations in patients treated f...