ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)
The determination of steroid levels directly in the tissue of bilateral adrenocortical lesions reveals discrepancies with circulating levels
Louis Thomeret 1 , Nesrine Benanteur 1 , Patricia Vaduva 1 , Florian Violon 1,2 , Lucas Bouys 1,3 , Annabel Berthon 1 , Bruno Ragazzon 1 , Karine Perlemoine 1 , Corinne Zientek 4 , Antonin Gouttefarde 4 , Samir Nakib 5 , Martin Gaillard 1,6 , Mathilde Sibony 1,2 , Marie-Claude Menet 7 , Laurence Guignat 3 , Rossella Libe 1,3 , Lionel Groussin 1,3 , Jean Guibourdenche 4 , Anne Jouinot 1 , Guillaume Assié 1,3 , Jérôme Bertherat 1,3 & Fidéline Bonnet-Serrano 1,4
1Team ‘Genomics and Signaling of Endocrine Tumors’, Institut Cochin, INSERM U1016-UMR8104-Université Paris-Cité, Paris, France; 2Pathology department, Hôpital Cochin, Paris, France; 3Endocrinology department, Hôpital Cochin, Paris, France; 4Hormonology department, Hôpital Cochin, Paris, France; 5Biochemistry department, Hôpital Cochin, Paris, France; 6Visceral and Digestive Surgery department, Hôpital Cochin, Paris, France; 7Institut de Chimie Physique, Université Paris-Saclay-CNRS, UMR8000, Orsay, France
JOINT844
Introduction: Bilateral adrenocortical lesions, either primary including macronodular adrenocortical disease (BMAD) and pigmented nodular adrenocortical dysplasia (PPNAD), or secondary to Cushing’s disease (CD), are responsible for steroid hypersecretion of variable intensity, evaluated by plasma or urine assays. In a subgroup of BMAD, ARMC5 pathogenic variants are associated with more severe clinical, radiological and biological phenotypes. The aim of our work was to better describe steroidogenesis alterations in these bilateral lesions by directly assessing steroid content in the adrenocortical tissue.
Material and methods: An intratissular profile of 14 steroids (4 glucocorticoids, 3 mineralocorticoids, 5 androgens, 2 precursors) was determined using LC–MS/MS (Thermo Fisher TM) on 38 fresh-frozen tissue samples collected from patients undergoing adrenalectomy (6 ARMC5-WT BMAD, 7 ARMC5-altered BMAD, 9 PPNAD including 8 with PRKAR1A pathogenic alteration, 7 from adrenal hyperplasia due to CD), and 9 normal adrenals (NA) as controls).
Results: CD presented higher intratissular glucocorticoids and androgens concentrations than NA, in accordance with circulating levels. Intratissular steroids levels were globally lower in ARMC5-altered BMAD than in ARMC5-WT BMAD (cortisol: median [IQR] =5976 [3201–16741] vs. 26971 [18069–44509] nmol/kg of tissue, P=0.02). Surprisingly, intratissular testosterone was elevated (between 256 and 595 nmol/kg vs. 40.3 [15.6–99.7] nmol/kg of tissue in NA) in 4/9 PPNAD (2F/2M) despite neither evidence of clinical nor biological hyperandrogenism. Intratissular concentrations of mineralocorticoids precursors in BMAD were higher than in PPNAD.
Discussion: Our results confirm the hypothesis of a less efficient steroidogenesis in ARMC5-altered BMAD, in which the higher tumoral mass may contribute to systemic hypercortisolism. Despite normal plasmatic concentrations, we observed elevated intratissular levels of testosterone in some PPNAD, as well as mineralocorticoid precursors in BMAD. These discrepancies between intratissular and circulating steroid concentrations might reflect the underlying and little-known mechanisms leading to steroidogenesis alterations in these bilateral adrenocortical nodular diseases, and also raise the question of a specific steroid export dysregulation.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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