The University of Cape Town invites you to an inaugural lecture by Professor Ian Ross.

The Dichotomous Effects of Cortisol and What We Have Learned from Hypoadrenalism

Cortisol is indispensable for life, yet its effects are dichotomous if either excessive or insufficient. While essential for maintaining glucose availability, cardiovascular function, metabolism, immune regulation and adaptation to stress, excessive or non-physiological glucocorticoid exposure may have important adverse consequences. My academic journey has sought to understand this balance and, ultimately, to restore health in patients with primary hypoadrenalism as closely as possible to normal physiology.

The establishment of the South African Addison’s Disease Study enabled systematic characterisation of patients with this uncommon and potentially fatal disorder. Our work demonstrated frequent delayed presentation, significant cardiovascular risk, hypogonadism, impaired sleep, altered cortisol rhythms, poorer quality of life and cognitive consequences associated with sleep disturbance. We identified evidence of supraphysiological glucocorticoid exposure despite conventional replacement and demonstrated the potential contribution of glucocorticoid receptor polymorphisms to differing hydrocortisone requirements, providing a foundation for personalised therapy.

Our research subsequently expanded across sub-Saharan Africa and the Middle East and North Africa, where physician surveys revealed substantial deficiencies in access to diagnostic investigations and replacement therapy. We also identified important gaps in patients’ practical knowledge of sick-day rules in both South Africa and the United Kingdom, highlighting a potentially preventable contributor to adrenal crisis. In patients with advanced HIV, primary hypoadrenalism was identified in a clinically important proportion, particularly among those with disseminated tuberculosis.

The COVID-19 pandemic provided an unexpected opportunity to examine the consequences of adrenal insufficiency during systemic infection, revealing markedly increased risks of infection and hospitalisation. Studies of tuberculous pericarditis further demonstrated increased local cortisol availability at sites of inflammation, illustrating the dynamic role of cortisol in host defence.

Collectively, this body of work has reinforced that successful treatment of hypoadrenalism extends beyond simply replacing cortisol. It requires earlier diagnosis, improved access to investigations, appropriate glucocorticoid dosing, prevention of adrenal crisis, management of cardiovascular and gonadal complications, optimisation of sleep and consideration of personalised therapy. The overarching mission remains to transform a life-threatening diagnosis into a condition in which patients can achieve longevity, health and quality of life as close to normality as possible.

About the speaker

Professor Ian Ross obtained his primary medical degree at the University of Stellenbosch in 1992.  He began his specialist training in internal medicine, having rotated through multiple special units at Groote Schuur Hospital.  He then undertook training in the United Kingdom at Farnham Hospital in Surrey and King's College Hospital in London.  He obtained his Fellowship of the College of Physicians South Africa in 2000 and sub-specialised in Endocrinology in 2002.  He was the recipient of the Novo Nordisk Travel Award in 2004, where he refined his skills in neuroendocrinology and thyroid cancer at the Queen Elizabeth Hospital in Birmingham University.  He completed his PhD entitled at the University of Cape Town: The aetiopathogenesis, cardiovascular and metabolic complications and pharmacodynamics of Addison's disease in South Africa.  He received his FRCP from London and is a full-time consultant in the Division of Endocrinology and Diabetic Medicine in the Department of Medicine at the University of Cape Town.  He has an active research group specifically in the fields of Addison's disease in Primary Hypoadrenalism.  He has published widely in the fields of hypoadrenalism, pituitary and thyroid disease.  He has supervised several Honours, Master’s and PhD students.  He is internationally known as an expert in adrenal disease and is frequently consulted nationally, across the continent and internationally and he serves on international committees to improve treatment and management for patients with Addison's disease. 

Why this topic?

The title of my lecture, “The Dichotomous Effects of Cortisol and What We Have Learned from Hypoadrenalism,” reflects the central theme of my academic journey. Cortisol is often referred to simply as the “stress hormone”, yet this description does not adequately convey its extraordinary importance. Cortisol is essential for life and normal homeostasis, but too little or too much, or exposure at the wrong time, can have profound consequences for health. Understanding this dichotomy has been a recurring theme throughout my research.

My interest in primary hypoadrenalism, or Addison’s disease, arose from the realisation that patients can die from a condition that is readily treatable once it has been recognised. I became particularly concerned that many patients were being diagnosed late, sometimes only after experiencing an adrenal crisis. This prompted me to ask whether we could improve not only the diagnosis of the disease, but also the quality of life and long-term health of those living with it.

This question became the starting point for an academic odyssey that led to the establishment of the South African Addison’s Disease Study and subsequently to collaborations extending across Africa, Europe and other parts of the world. Through these collaborations, we have examined how patients present, why diagnosis may be delayed, whether conventional hydrocortisone replacement truly reproduces normal physiology, and what happens to patients beyond simply correcting their cortisol deficiency.

During the lecture, I hope to take the audience on this journey—from the physiology and molecular actions of cortisol, through the clinical manifestations of cortisol excess and deficiency, to what we have learned about cardiovascular health, hypogonadism, sleep, cognition, immunity, infection and personalised glucocorticoid replacement.

I will also discuss some of the challenges of conducting clinical research in South Africa, the importance of collaboration, and how careful clinical observation can generate questions that ultimately change our understanding of a disease.

Most importantly, I hope the lecture will demonstrate that treating Addison’s disease should mean more than keeping patients alive. Our goal should be to restore health, function and quality of life as close to normality as far as possible.