Hydrocortisone Vs Prednisolone in AI (HYPER-AID)

Recruiting

Interventions: Other: There is no specific intervention other than an individual changing their treatment as part of their usual care

Brief Summary: This study is designed to collect data on individuals with adrenal insufficiency who are changing treatments from hydrocortisone to prednisolone, or vice versa. It will compare anthropometric, biochemical and subjective health outcomes between both treatments.

Detailed Description: In the UK, oral immediate release hydrocortisone divided in three doses daily has been the traditional treatment. The most common regimen in clinical practice uses doses of 10 mg on waking, 5 mg at lunch time and 5 mg in the afternoon. Once daily prednisolone is another regimen in clinical use and now prescribed at less than 5mg daily. It has a longer duration of action and a smoother pharmacokinetic profile compared to hydrocortisone. Moreover, prednisolone is much more cost-effective than hydrocortisone with 5mg tablets. Prednisolone is less commonly used due to perceived concerns regarding loss of bone mineral density leading to osteoporosis, increased insulin resistance leading to steroid induced diabetes, and rises in blood pressure and weight leading to increased cardiovascular risk. This belief is perhaps driven by the fact that most clinicians encounter prednisolone in the context of the treatment of asthma, rheumatoid arthritis etc. where far higher doses are employed. Where effects on bone health have been noted, they have been in association with higher doses of prednisolone (7.5mg) than those employed today (2-5mg).

Although conventionally prednisolone 5 mg is assumed to be bioequivalent to HC 20 mg (ratio 1:4), newer studies suggest that the ratio may be nearer 1:6-8 i.e. lower doses can be used.

Recruitment & Eligibility

Inclusion Criteria

Aged 18 - 85 years
Male or female
Diagnosed with adrenal insufficiency (AI) for over 6 months according to standard diagnostic criteria
Established on stable hydrocortisone or prednisolone replacement, dose not altered for at least 4 months
Individuals taking other hormone replacements are accepted providing that their replacement doses have not altered for at least 3 months;
Individuals who are able and willing to give written informed consent to participate in the study

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Adrenal insufficiency	There is no specific intervention other than an individual changing their treatment as part of their usual care	Individuals who are in the process of changing their treatment from: 1. hydrocortisone to prednisolone or; 2. prednisolone to hydrocortisone

Primary Outcome Measures

Name	Time	Method
P1NP	Minimum 4 months of stable treatment	measurement of bone turnover markers: P1NP,
NTX	Minimum 4 months of stable treatment	measurement of bone turnover markers: NTX

Secondary Outcome Measures

Name	Time	Method
Waist-hip circumference	Minimum 4 months of stable treatment	recording observations- waist-hip circumference ratios
HbA1c	Minimum 4 months of stable treatment	assessed by measuring HBA1c
Heart rate	Minimum 4 months of stable treatment	recording observations- heart rate
Blood pressure	Minimum 4 months of stable treatment	recording observations- blood pressure
High sensitivity CRP	Minimum 4 months of stable treatment	measuring biochemical indicators of cardiovascular risk: high sensitivity CRP
Frequency and severity of steroid replacement related symptoms	Minimum 4 months of stable treatment	assessed by reporting of symptoms of steroid deficiency, their frequency and severity stratified by the patient's current replacement regimen. Symptoms include nausea, lethargy, muscle pain, headaches etc.)
Lipid profile (Total cholesterol, HDL, LDL and triglycerides)	Minimum 4 months of stable treatment	measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides
Glucose	Minimum 4 months of stable treatment	assessed by measuring glucose
Efficacy of replacement and wellbeing	Minimum 4 months of stable treatment	assessed using subjective health questionnaire

Locations (1): Imperial College Healthcare NHS Trust
🇬🇧
London, United Kingdom