The Risk of Adrenal Insufficiency and Cushing Syndrome Associated With Glucocorticoid Therapy in People With Chronic Inflammatory Diseases

Glucocorticoids are widely used for the treatment of chronic inflammatory diseases. Although glucocorticoids are effective in controlling disease symptoms, continuous use of the drugs can lead to suppression of adrenal hormones or excessive cortisol level in the blood stream. That is, excess blood cortisol level due to glucocorticoid exogenous supply can either inhibit the 'hypothalamus-pituitary-adrenal axis' for adrenal hormones production or result in Cushing symptoms.

In the period between 1989 and 2008 in the UK, it was estimated that 0.6%-0.8% of the general adult population were long-term users of oral glucocorticoids. However, there is no data on the risk of adrenal suppression and Cushing syndrome due to chronic use of glucocorticoids in the UK to date.

The aim of the study is to investigate the risk of adrenal insufficiency and Cushing syndrome due to long-term use of glucocorticoids in England.

Study Overview

• Status: Completed
• Conditions: Adrenal; Insufficiency Gluccorticoid-Induced; Cushing; Syndrome or Disease, Glucocorticoid-Induced
• Intervention / Treatment: Drug: Glucocorticoids

Detailed Description

Adrenal insufficiency is a clinical condition that is associated with a deficiency of adrenal hormones, mainly: glucocorticoids and mineralocorticoids. Cushing syndrome is also a condition that stems from the existence of persistent high cortisol level in the body. The majority of Cushing syndrome cases are exogenous (iatrogenic or due to use of medication).

Glucocorticoids are widely used for the treatment of chronic inflammatory diseases. Although glucocorticoids are effective in controlling disease symptoms, continuous use of the drugs can lead to suppression of adrenal hormones or excessive cortisol level in the blood stream. That is, excess blood cortisol level due to glucocorticoid exogenous supply can either inhibit the 'hypothalamus-pituitary-adrenal axis' for adrenal hormones production or result in Cushing symptoms.

In the period between 1989 and 2008 in the UK, it was estimated that 0.6%-0.8% of the general adult population were long-term users of oral glucocorticoids. However, there is no data on the risk of adrenal suppression and Cushing syndrome due to chronic use of glucocorticoids in the UK to date

The aim of the study is to investigate the risk of adrenal insufficiency and Cushing syndrome due to long-term use of glucocorticoids in England. This is a retrospective cohort study of people diagnosed with at least one of six chronic inflammatory diseases (polymialgia rheumatica, giant cell arteritis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis and inflammatory bowel disease).

This study will be based on the analysis of existing primary care health records routinely collected, linked to hospital and mortality data.

• Study Type: Observational
• Enrollment (Actual): 111804

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients registered in CPRD who were eligible for data linkage and had been diagnosed with at least one of six chronic inflammatory diseases (inflammatory bowel diseases, systemic lupus erythematosus, polymyalgia rheumatica, giant cell arteritis, rheumatoid arthritis, and vasculitis) in the period between 1st Jan 1998 and 30th September 2015.

Description

Inclusion Criteria:

• Patients aged 18 years old or over
• Registered in a participating general practice for more than 1 year during the study period
• Minimum of 1 year prior to study entry meeting CPRD data quality
• Diagnosed with at least one of the 6 chronic inflammatory diseases

Exclusion Criteria:

• Patients aged under 18 years during the study period
• Registered in general practices that did not consent to data linkage

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucocorticoid-related adrenal insufficiency	First recorded diagnosis of adrenal insufficiency	18 years
Glucocorticoid-related Cushing syndrome	First recorded diagnosis of Cushing syndrome	18 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Recorded death of any cause	18 years

Collaborators and Investigators

• Sponsor: University of Leeds
• Investigators: Principal Investigator: Mar Pujades-Rodriguez, PhD, University of Leeds

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 1998
• Primary Completion (Actual): January 30, 2015
• Study Completion (Actual): September 30, 2015

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome; Adrenal Insufficiency; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: 16_146

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No