Towards the tailoring of glucocorticoid replacement in adrenal insufficiency: the Italian Society of Endocrinology Expert Opinion
- 29 Downloads
Glucocorticoid (GC) replacement therapy in patients with adrenal insufficiency (AI) is life saving. After over 50 years of conventional GC treatment, novel formulations are now entering routine clinical practice.
Given the spectrum of medications currently available and new insights into the understanding of AI, the authors reviewed relevant medical literature with emphasis on original studies, prospective observational data and randomized controlled trials performed in the past 35 years. The Expert Opinion of a panel of selected endocrinologists was sought to answer specific clinical questions. The objective was to provide an evidence-supported guide, for the use of GC in various settings from university hospitals to outpatient clinics, that offers specific advice tailored to the individual patient.
The Panel reviewed available GC replacement therapies, comprising short-acting, intermediate and long-acting oral formulations, subcutaneous formulations and the novel modified-release hydrocortisone. Advantages and disadvantages of these formulations were reviewed.
In the Panel’s opinion, achieving the optimal GC timing and dosing is needed to improve the outcome of AI. No-single formulation offers the best option for every patients. Recent data suggest that more emphasis should be given to the timing of intake. Tailoring of GS should be attempted in all patients—by experts—on a case-by-case basis. The Panel identified specific subgroups of AI patients that could be help by this process. Long-term studies are needed to confirm the short-term benefits associated with the modified-release GCs. The impact of GC tailoring has yet to be proven in terms of hospitalization rate, morbidity and mortality.
KeywordsAdrenal insufficiency Glucocorticoid Addison Hydrocortisone Cortisone acetate Prednisone
The authors thank Marie-Hélène Hayles for her medical writing assistance during the preparation of the manuscript.
No funding was used to produce this manuscript.
Compliance with ethical standards
Conflict of interest
AM.I. has received grants and advisory fees from Takeda and Novartis. G.A. has been Principal Investigator of Research Studies for Novartis; has received research grants from Novartis and Shire; has received speaker fees from Novartis; and has received consulting fees from Novartis and Pfizer, Inc. as board member. M.B. has been Principal Investigator of Research Studies for Novartis; has been Investigator of Research Studies for Novartis, HRA Pharma and ViroPharma; and has received consulting fees from Novartis as board member. AF declares that he has received a speaker honorarium from Shire Italy S.p.A. C.G. has been Principal Investigator of Research Studies for Novo Nordisk and Lilly USA, LLC; has received research grants from Novo Nordisk and Lilly USA, LLC; has been an occasional consultant for Novartis, Pfizer, Inc., Ipsen and Shire; and has received speaker fees from Novo Nordisk, Lilly USA, LLC and Novartis. R.G. has been occasional consultant for Shire. R.P. has been Principal Investigator of Research Studies for Novartis, HRA Pharma, Ipsen, Shire, Corcept Therapeutics, Cortendo AB; Co-investigator of Research Studies for Pfizer; received research grants from Novartis, Pfzer, Ipsen, HRA Pharma, Shire, IBSA; has been an occasional consultant for Novartis, Ipsen, Pfzer, Shire, HRA Pharma, Cortendo AB, Ferring and Italfarmaco; and has received fees and honoraria for presentations from Novartis, Shire. C.S. has been occasional consultant for Shire and Ipsen. C.S. has been Principal Investigator of Research Studies for Novartis, Otsuka and Pfizer, Inc.; has been Co-investigator of Research Studies for Novartis and Lilly USA, LLC; has received research grants from Novartis, Lilly USA, LLC, Otsuka and Pfizer, Inc.; has been an occasional consultant for Novartis and Otsuka; and has received speaker fees for presentations from Otsuka and Lilly USA, LLC. A.L. has received grants and advisory fees from Takeda and Novartis. C.P. and E.S. have no conflicts of interest.
It is an Expert Opinion, with no original experimental or clinical data, and thus no requirement for ethical approval.
For this type of study formal consent is not required.
- 7.OCEBM Table of Evidence Working Group (2011) “The Oxford 2011 Levels of Evidence”. Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653
- 49.Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B et al (2012) Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab 97(2):473–481PubMedCrossRefPubMedCentralGoogle Scholar
- 76.Giordano R, Guaraldi F, Marinazzo E, Fumarola F, Rampino A, Berardelli R et al (2016) Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease. Endocrine 51(2):360–368PubMedCrossRefPubMedCentralGoogle Scholar
- 77.Nilsson AG, Marelli C, Fitts D, Bergthorsdottir R, Burman P, Dahlqvist P et al (2014) Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency. Eur J Endocrinol 171(3):369–377PubMedPubMedCentralCrossRefGoogle Scholar
- 80.Isidori AM, Venneri MA, Graziadio C, Simeoli C, Fiore D, Hasenmajer V et al (2018) Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial. Lancet Diabetes Endocrinol 6(3):173–185PubMedCrossRefGoogle Scholar
- 86.Verma S, Vanryzin C, Sinaii N, Kim MS, Nieman LK, Ravindran S et al (2010) A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 72(4):441–447PubMedCrossRefGoogle Scholar