Tania Pilli1, Sandro Cardinale1, Silvia Cantara1, Gilda Dalmazio1, Raffaella Forleo1, Marco Capezzone1, Cristian Bassi2, Massimo Negrini2, Manuela Ferracin3, Maria Grazia Castagna4. 1. Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. 2. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. 3. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. 4. Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. m.g.castagna@ao-siena.toscana.it.
Abstract
PURPOSE: Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters. METHODS: Thirteen patients with SAI were switched from CONV to MOD at equivalent dose. Area under curve (AUC) of both formulations was calculated in six patients. Clinical, metabolic and bone parameters were measured at baseline and 3 months after MOD in all patients. In six patients and six age- and sex-matched healthy controls, a whole-genome expression analysis was performed at baseline, 1 month, and 3 months after MOD. RESULTS: (1) The number of genes differentially expressed (n = 235; mainly involved in immune response and metabolism) in SAI patients compared to controls progressively and significantly decreased switching from CONV to MOD (n = 78 at 3 months). (2) Under MOD: AUC of cortisol exposure tended to be smaller and cortisol levels showed a more physiological profile; no significant changes of clinical, metabolic and bone parameters were observed, likely due to the short follow-up, but triglycerides tended slightly to increase. CONCLUSIONS: MOD may restore a normal gene expression profile as soon as 1 month after switching from CONV.
PURPOSE: Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters. METHODS: Thirteen patients with SAI were switched from CONV to MOD at equivalent dose. Area under curve (AUC) of both formulations was calculated in six patients. Clinical, metabolic and bone parameters were measured at baseline and 3 months after MOD in all patients. In six patients and six age- and sex-matched healthy controls, a whole-genome expression analysis was performed at baseline, 1 month, and 3 months after MOD. RESULTS: (1) The number of genes differentially expressed (n = 235; mainly involved in immune response and metabolism) in SAI patients compared to controls progressively and significantly decreased switching from CONV to MOD (n = 78 at 3 months). (2) Under MOD: AUC of cortisol exposure tended to be smaller and cortisol levels showed a more physiological profile; no significant changes of clinical, metabolic and bone parameters were observed, likely due to the short follow-up, but triglycerides tended slightly to increase. CONCLUSIONS:MOD may restore a normal gene expression profile as soon as 1 month after switching from CONV.
Authors: G Johannsson; A G Nilsson; R Bergthorsdottir; P Burman; P Dahlqvist; B Ekman; B E Engström; T Olsson; O Ragnarsson; M Ryberg; J Wahlberg; B M K Biller; J P Monson; P M Stewart; H Lennernäs; S Skrtic Journal: J Clin Endocrinol Metab Date: 2011-11-23 Impact factor: 5.958
Authors: Marianne Øksnes; Sophie Bensing; Anna-Lena Hulting; Olle Kämpe; Annika Hackemann; Gesine Meyer; Klaus Badenhoop; Corrado Betterle; Anna Parolo; Roberta Giordano; Alberto Falorni; Lucyna Papierska; Wojciech Jeske; Anna A Kasperlik-Zaluska; V Krishna K Chatterjee; Eystein S Husebye; Kristian Løvås Journal: J Clin Endocrinol Metab Date: 2011-11-16 Impact factor: 5.958