Endocrine Abstracts

Adrenal incidentalomas (AI) found on axial imaging are common. In ages <20 y the prevalence is <1%, but this increases around 10% of the population aged 70 y. Depending on definitions anything between 10–40% of these tumours exhibit low-grade cortisol excess, but patients are without the classic features of Cushing’s syndrome. This equates to 1–4% of the ageing population.

Independent studies from our own group and others have demonstrated excess mortality and cardiovascular risk in these patients with AI and low-grade cortisol secretion. Numerous cross sectional studies demonstrate increased rates of glucose intolerance, diabetes and osteoporosis. The key question is whether intervening in these patients is associated with patient benefit. Numerous uncontrolled surgical series have shown improvements in co-morbidities in patients who have undergone adrenal surgery in this context, but this is not a uniform finding. Selecting such patients remains an art, with no objective stratification tool available.

In light of this we have used the GR antagonist mifepristone for short durations in such patients to ask whether offsetting the action of cortisol improves parameters that may be cortisol-dependent. We have found that insulin resistance may be improved in some but not all, potentially providing a means to stratify patients to intervention. In 24-hour sampling studies we have established that the cortisol rhythm in AI patients with low grade cortisol secretion differs in the early to late evening and that it is possible to ‘re-set’ this by timed cortisol-lowering medical intervention, resulting in an immediate improvement in key cortisol-dependent parameters, and a rationale for medical therapy or a stratification step. What is needed are large scale intervention studies to formally assess the impact of such medical approaches as these may be of significant relevance to a large number of the ageing population.