Optimising steroid replacement for patients with adrenal insufficiency

A2002434

Dr. Robert Murray and colleagues are supporting a Specialist Registrar training in Endocrinology to complete studies contributing to his Doctorate degree. The project includes three arms examining the impact of current steroid replacement regimens on various health aspects in adults who cannot produce their own natural steroid, cortisol. The studies also explore ways to improve current treatment regimens to enhance patient well-being, quality of life, and outcomes.

Despite current steroid replacement regimens, patients with Addison’s disease (damaged adrenal glands) face an increased risk of death and impaired well-being. This may be due to the failure of steroid replacements to mimic the natural increase in cortisol that starts around 2 am and peaks just before waking. Cortisol is crucial for normal sleep patterns and maintaining blood sugar levels. The absence of cortisol in Addison’s disease patients may disturb sleep patterns and prevent the maintenance of normal blood sugar levels overnight, contributing to impaired well-being. The team aims to examine these endpoints using non-invasive continuous monitoring of sugar levels (Libre Pro) and sleep monitors (Actiwatch 2). These devices will be worn for two weeks, and changes in sleep and sugar levels will be compared with well-being recorded from patient-completed questionnaires.

Secondly, as part of the National Institute of Health Research-supported multicentre study (HYPER-AID), the team is examining the differences between using a synthetic once-per-day steroid (prednisolone) and the natural steroid, cortisol (hydrocortisone), as replacement therapy in adrenal insufficiency due to pituitary gland damage. Previous studies have shown prednisolone to have negative effects on blood fats, bone thickness, and heart disease risk factors. The HYPER-AID study aims to look at bone markers, body fats, and blood pressure while on prednisolone or the standard hydrocortisone regimen. Additionally, the ‘HYPER-AID plus’ study will collect data on further health aspects, including sleep and blood clotting, in parallel with HYPER-AID.

Lastly, the team has previously conducted an observational study (EU-AIR) documenting adrenal crises, infections, and intercurrent illnesses in patients with adrenal insufficiency. Adrenal crises are life-threatening events characterised by severe illness, very low blood pressure, and an inability to fight off infections. The study aims to utilise data from EU-AIR to determine if these events are more prevalent in those with lower residual cortisol excretion or relate to inappropriate steroid replacement dosages. The team also hopes to determine the socioeconomic status of patients to see if deprivation and health inequalities contribute to the development of adrenal crises.

Lead Researcher	Dr Robert Murray Consultant Endocrinologist & Honorary Associate Professor
Co-Researchers	Dr Nikolaos Kyriakakis Dr Khyatisha Seejore Dr David McLaren Prof Ramzi Aijan MRs Julie Lynch
Host Organisation/ CSU	Emergency & Specialty Medicine Leeds Children’s Hospital Leeds Teaching Hospitals NHS Trust
Grant Amount	£80,000
Start Date	19/09/2023
Estimated Duration	22 months
Status	In Progress
Impact Areas	Innovation & Health Technologies Rare diseases
Tags/key notes	Early Career Researcher Metabolic and endocrine