Assessing the Impact of Exogenous Glucocorticoid Exposure on Adrenal Function, Cardiometabolic Risk Factor Profile and Health-Related Quality of Life

Tertiary adrenal insufficiency (TAI) occurs as a result of the negative feedback effect of excess exogenous glucocorticoids on the hypothalamic-pituitary-adrenal axis and is associated with exposure to all forms of glucocorticoid preparations (1). All forms of adrenal insufficiency are associated with the risk of life-threatening adrenal crises (2), and impairment in health-related quality of life (3). Chronic glucocorticoid exposure is also associated with iatrogenic Cushing’s syndrome, and its associated adverse cardiometabolic phenotype (4), which can co-exist with TAI (4). However, despite the potentially serious clinical consequences, the true prevalence of TAI remains unclear, particularly in patients exposed to glucocorticoid doses or preparations traditionally considered to carry a low risk of TAI. The existing literature is limited by heterogenous patient populations with differing exposures, varying methods to assess adrenal function, little cumulative glucocorticoid exposure data and retrospective study design, which carries a potential risk of inclusion bias. 

There is also little published data which addresses the clinical consequences of tertiary adrenal insufficiency, in particular regarding features of co-morbid iatrogenic Cushing’s syndrome, and health-related quality of life.

With this in mind, the aim of this thesis is to investigate the impact of glucocorticoid exposure on adrenal function, cardiometabolic risk factors and health-related quality of life by addressing several research questions.

1. What is the prevalence of TAI in patient populations traditionally considered to be at lower risk?

a. Low-dose oral glucocorticoid exposure (≤5mg prednisolone/day)

b. Inhaled glucocorticoid exposure, with or without intermittent oral glucocorticoid exposure

2. Are patients with TAI at increased risk of an adverse cardiometabolic risk profile compared to patients with intact adrenal function ?

3. What is the impact of TAI on health-related quality of life for patients?

4. How effective is a morning serum or salivary cortisol sample as an initial screening tool for TAI in a glucocorticoid-exposed population?