ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP193 | DOI: 10.1530/endoabs.63.GP193

Comparison of whole-genome expression analysis in patients with secondary adrenal insufficiency treated with conventional treatment versus modified-release hydrocortisone

Tania Pilli1, Sandro Cardinale1, Raffaella Forleo1, Silvia Cantara1, Manuela Ferracin2, Cristian Bassi3, Massimo Negrini3 & Maria Grazia Castagna1

1Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy; 2Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; 3Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.

Background: Conventional treatment (cortisone acetate or hydrocortisone) of adrenal insufficiency (AI) is potentially associated with glycometabolic alterations, bone loss and reduced quality of life. There is an increasing evidence of a more physiological replacement therapy with modified-release hydrocortisone (Plenadren).AimThe objectives of our study were: 1) to compare the gene expression profile of patients under conventional treatment and Plenadren versus healthy controls; 2) to evaluate the effects of Plenadren on glucose, lipid and bone metabolism and clinical parameters.Materials and MethodsEleven patients with primary (PAI) and 13 with secondary (SAI) AI were switched from conventional treatment to Plenadren at equivalent dose. Basally, 1 and 3 months after Plenadren, a whole-genome expression analysis was performed in PBMC of 6 patients with SAI and in 6 age and sex-matched healthy controls. Clinical and metabolic parameters (body weight, BMI, blood pressure, HbA1c, total, HDL and LDL cholesterol, triglycerides) and bone turnover markers (osteocalcin, bone alkaline phosphatase [BAP], serum cross-laps [CTX]) were measured, at baseline and 1, 3, 6, 12, 18 and 24 months after Plenadren in patients with PAI and at baseline, 1 and 3 months after modified-release hydrocortisone in patients with SAI.Results1) The number of genes differentially expressed (mainly involved in inflammation and immune response) in treated patients compared to healthy controls was higher in samples collected under conventional treatment (t0, n=247) than 3 months after Plenadren (t3, n=114) and the global gene expression profile after Plenandren was more similar to healthy subject. 2) On Plenadren treatment we observed a decrease of LDL-cholesterol (up to 27.4%), systolic (3.7%) and diastolic (11.2%) blood pressure, fat mass (13.5%) and an increase of lean mass (+9.2%), CTX and BAP, mainly in patients with PAI at 24 months, while HbA1c and T-score remained stable and triglycerides tended slightly to increase. Conclusions.Modified-release hydrocortisone may restore a normal gene expression profile and improve metabolic and bone parameters in AI patients compared to the conventional therapy.