An evaluation of the epidemiology and burden of illness of congenital adrenal hyperplasia in the United Kingdom

Date of ISAC Approval: 
Lay Summary: 
Congenital adrenal hyperplasia (CAH) refers to a group of rare inherited conditions affecting the adrenal glands. Most commonly, the glands do not produce enough of the stress hormone cortisol, which can cause the body to experience life-threatening shock in response to physical stress. Lack of cortisol also causes over-production of male sex hormones, leading to the development of male characteristics in girls and early puberty in boys and girls. In one form of CAH, the production of another hormone, aldosterone, responsible for maintaining salt levels in the blood, is also decreased. CAH is treated with steroid drugs to replace the cortisol and, where necessary, aldosterone, but there are concerns that these do not successfully mimic the normal daily patterns of cortisol activity in the body. In this study we wish to use the Clinical Practice Research Datalink to identify patients with CAH and describe its effects on patients' health over their lifetimes and at key life stages. We then wish to match these patients with similar patients who do not have adrenal disease, and compare rates of depression and death and the economic costs of healthcare in the two groups.
Technical Summary: 
We aim to evaluate the burden of congenital adrenal hyperplasia (CAH) in a UK population: analysing the risk of mortality and depression in a retrospective matched cohort study, estimating excess healthcare costs, and describing causes of death, therapy adherence, and clinical manifestations. We will use primary-care data from CPRD GOLD and, where linked, ONS mortality data and inpatient and outpatient data from the Hospital Episode Statistics (HES). Patients with a CAH diagnosis in CPRD GOLD or HES and at least one corticosteroid prescription will be selected and matched 1:10 with non-exposed patients. Risk of death, as recorded in CPRD GOLD, will be compared using a Cox proportional hazards model; a sensitivity analysis will examine deaths from the ONS data. Lifetime prevalence of depression, identified by diagnosis or antidepressant prescription, will be compared by chi-square test; a sensitivity analysis will examine depression identified by diagnosis alone. In HES-eligible patients, rates and costs of health-service use will be compared between CAH patients and controls using the Mann-Whitney U-test. Causes of death in CAH patients, as recorded by the ONS; corticosteroid adherence measured by medical possession ratio; and the clinical manifestations of the condition at key life stages will be tabulated non-comparatively.
Health Outcomes to be Measured: 
All-cause mortality Depressiony Economic cost of healthcare

Professor Craig Currie - Chief Investigator - Pharmatelligence
Dr Christopher Morgan - Researcher - Pharmatelligence
Martin Whitaker - Researcher - University of Sheffield
Richard Ross - Researcher - University of Sheffield
Dr Sara Jenkins-Jones - Corresponding Applicant - Pharmatelligence
Sarah Holden - Researcher - Pharmatelligence

HES Admitted;HES Outpatient;ONS