Cortisol: A Glucocorticoid Hormone
Cortisol is a glucocorticoid hormone, the dominant naturally occurring glucocorticoid in humans, produced in the zona fasciculata of the adrenal cortex. 1
Classification and Chemical Nature
Cortisol is classified as a steroid hormone that functions as both a glucocorticoid (its primary action) and possesses mild mineralocorticoid (salt-retaining) properties 2
It is a lipophilic molecule (pregn-4-ene-3,20-dione,11,17,21-trihydroxy) with molecular weight 362.46, which makes it highly protein-bound in plasma 1, 2
Physiological Characteristics
Protein Binding and Bioavailability
60-80% of cortisol binds to cortisol-binding globulin (CBG), 15-35% binds to albumin, and only approximately 5-10% circulates as free, biologically active hormone 1, 3
The free fraction represents the biologically active component that exerts metabolic effects 3
Production and Regulation
Cortisol production is controlled by the hypothalamic-pituitary-adrenal (HPA) axis: corticotropin-releasing hormone (CRH) from the hypothalamus stimulates adrenocorticotropic hormone (ACTH) from the anterior pituitary, which then stimulates cortisol release 1
Approximately 20 mg of cortisol is released daily under normal conditions, with production increasing up to five-fold (100 mg/day) during major physiological stress such as surgery 1
Cortisol secretion follows a circadian rhythm with pulsatile release: reference ranges are 140-700 nmol/L at 0900 hours but only 80-350 nmol/L at midnight 1
Primary Functions
Metabolic Effects
Cortisol causes profound and varied metabolic effects including regulation of carbohydrate, lipid, and protein metabolism 2
It acts as a catabolic hormone, promoting protein breakdown and gluconeogenesis while affecting energy expenditure 4
Stress Response
Cortisol is released in response to stress and is essential for maintaining health and wellbeing, leading to significant morbidity when deficient or present in excess 3, 5
During stress responses (fight-or-flight), adrenal release of epinephrine and cortisol allows threats to be addressed through physiological changes including increased heart rate and blood pressure 1
Immune Modulation
- Cortisol modifies the body's immune responses to diverse stimuli and possesses potent anti-inflammatory effects 2
Clinical Significance
Cortisol measurement is essential for diagnosing adrenal insufficiency (Addison's disease) and cortisol excess (Cushing's syndrome) 1, 6
Chronic exposure to excessive cortisol is associated with insulin resistance, visceral obesity, and metabolic syndrome 5
In critically ill patients, cortisol levels below 250-276 nmol/L suggest relative adrenal insufficiency, though interpretation must account for reduced binding proteins in severe illness 1