» Articles » PMID: 36761196

Effects of the Therapy Shift from Cortisone Acetate to Modified-release Hydrocortisone in a Group of Patients with Adrenal Insufficiency

Abstract

Objective: Patients with adrenal insufficiency (AI) may be exposed to supraphysiological glucocorticoids levels during standard treatment with cortisone acetate (CA) or immediate-release hydrocortisone (IR-HC). Recent studies, predominantly including patients in IR-HC treatment, suggested that modified-release hydrocortisone (MRH) provide a more physiological cortisol rhythm, improving metabolic control and quality of life. Our primary aim was to assess clinical and biochemical modifications in patients shifted from CA to MRH.

Design/methods: We designed a retrospective longitudinal study, enrolling 45 AI patients (22 primary and 23 secondary AI) treated exclusively with CA thrice daily, shifted to MRH once daily; 29/45 patients concluded at least 18-months follow-up (MRH-group). We recruited 35 AI patients continuing CA as a control group (CA-group). Biochemical and clinical data, including metabolic parameters, bone quality, and symptoms of under- or overtreatment were collected. In 24 patients, a daily salivary cortisol curve (SCC) performed before and one month after shifting to MRH was compared to healthy subjects (HS).

Results: No significant changes in glycometabolic and bone parameters were observed both in MRH and CA-groups during a median follow-up of 35 months. A more frequent decrease in blood pressure values (23.1% vs 2.8%, p=0.04) and improvement of under- or overtreatment symptoms were observed in MRH vs CA-group. The SCC showed a significant steroid overexposure in both CA and MRH-groups compared to HS [AUC (area under the curve) = 74.4 ± 38.1 nmol×hr/L and 94.6 ± 62.5 nmol×hr/L respectively, vs 44.1 ± 8.4 nmol×hr/L, p<0.01 for both comparisons], although SCC profile was more similar to HS in MRH-group.

Conclusions: In our experience, patients shifted from CA to equivalent doses of MRH do not show significant glycometabolic modifications but blood pressure control and symptoms of over-or undertreatment may improve. The lack of amelioration in glucose metabolism and total cortisol daily exposure could suggest the need for a dose reduction when shifting from CA to MRH, due to their different pharmacokinetics.

Citing Articles

Extended-release Hydrocortisone Formulations-Is There a Clinically Meaningful Benefit?.

Steintorsdottir S, Oksnes M, Jorgensen A, Husebye E J Clin Endocrinol Metab. 2024; 110(3):e566-e573.

PMID: 39656185 PMC: 11834724. DOI: 10.1210/clinem/dgae822.

References
1.
Fustinoni S, Polledri E, Mercadante R . High-throughput determination of cortisol, cortisone, and melatonin in oral fluid by on-line turbulent flow liquid chromatography interfaced with liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2013; 27(13):1450-60. DOI: 10.1002/rcm.6601. View

2.
Guarnotta V, Di Stefano C, Santoro A, Ciresi A, Coppola A, Giordano C . Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency. Endocr Connect. 2019; 8(7):853-862. PMC: 6599082. DOI: 10.1530/EC-19-0176. View

3.
Giordano R, Marzotti S, Balbo M, Romagnoli S, Marinazzo E, Berardelli R . Metabolic and cardiovascular profile in patients with Addison's disease under conventional glucocorticoid replacement. J Endocrinol Invest. 2009; 32(11):917-23. DOI: 10.1007/BF03345773. View

4.
Ceccato F, Barbot M, Lizzul L, Selmin E, Saller A, Albiger N . Decrease in salivary cortisol levels after glucocorticoid dose reduction in patients with adrenal insufficiency: A prospective proof-of-concept study. Clin Endocrinol (Oxf). 2017; 88(2):201-208. DOI: 10.1111/cen.13490. View

5.
Delle Cese F, Corsello A, Cintoni M, Locantore P, Pontecorvi A, Maria Corsello S . Switching From Immediate-Release to Fractionated Dual-Release Hydrocortisone May Improve Metabolic Control and QoL in Selected Primary Adrenal Insufficiency Patients. Front Endocrinol (Lausanne). 2021; 11:610904. PMC: 7883639. DOI: 10.3389/fendo.2020.610904. View