Recipient organisationNIHR Birmingham Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Jan 2026
In plain English
AI plain-English summary
Cortisol-producing adrenal tumours alter the behaviour of immune cells called macrophages, and researchers want to find out exactly how. These tumours are common—affecting 2–3% of people—and can release excess cortisol, either causing full-blown Cushing Syndrome with severe metabolic disease, or a milder form called MACS that still raises risks for diabetes, high blood pressure, and infection. The team has already shown that patients with both conditions have unusual shifts in their monocyte populations, the precursors to tissue macrophages. What remains unknown is whether these changes extend to macrophages in tissues, and whether that contributes to higher infection rates and cardiovascular death. This study will take macrophages from patients with different levels of cortisol excess and test their inflammatory behaviour and function in the lab. If the work confirms that cortisol-driven macrophage dysfunction is a key link to complications, it could open the door to targeted immune therapies that reduce infection risk and metabolic harm in these patients—without needing to treat the tumour itself.
View original technical description
Adrenocortical tumours are among the most frequent human neoplasia (prevalence of 2-3% in the general population)5. Cortisol-producing adenomas (CPA) can produce GC in excess causing Cushing Syndrome (CS), which is characterized by pathognomonic clinical features and severe metabolic sequelae (diabetes, dyslipidaemia, hypertension) that contribute to increased morbidity and mortality5. More frequently, CPA are associated with mild autonomous cortisol secretion (MACS). Whilst the degree of cortisol excess is less marked than in CS patients, it is still frequently accompanied by clinically relevant metabolic and cardiovascular co-morbidities. We have previously demonstrated that patients with CS and MACS also suffer from immune dysregulation with unique changes in white blood cells counts including reduced classical monocyte counts and increased intermediate and non-classical monocyte varieties6. These changes may be driven by both direct GC effects and indirect changes in circulating inflammatory mediators. Whether changes are also apparent in tissue macrophage populations in CS-CPA and MACS-CPA and contribute to increased susceptibility to infection and cardiovascular mortality remains poorly defined. It is now imperative that we better understand how chronically elevated cortisol in CS and MACS impact on tissue macrophage polarization and function and contribute to increased susceptibility to infection and metabolic mortality. Hypothesis: We predict that dysregulation of macrophage maturation and function will correlate with autonomous cortisol secretion and contribute to an altered cellular response to infection and development of comorbidities. Aim: The purpose of our study is to evaluate inflammatory macrophage polarisation and function in vitro in patients with different degrees of endogenous cortisol excess
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know