Step by Step
1
The HPA axis
Stress triggers the hypothalamus to release CRH, which stimulates the anterior pituitary to release ACTH, which stimulates the adrenal cortex (zona fasciculata) to release cortisol. Cortisol then provides negative feedback, suppressing further CRH and ACTH release.
2
Cortisol's metabolic effects
Cortisol raises blood glucose through gluconeogenesis, glycogen breakdown, and decreased glucose uptake in muscle and fat tissue — earning it the label "diabetogenic." It also increases protein catabolism (breaking down muscle) and increases fat mobilization.
3
Cortisol's anti-inflammatory and immune effects
Cortisol is anti-inflammatory (decreasing phospholipase A2, which reduces prostaglandins and leukotrienes, and stabilizing mast cells) and immunosuppressive (decreasing lymphocytes and antibody production). It also has a permissive effect, sensitizing blood vessels to epinephrine.
4
Clinical disorders — too much or too little cortisol
Cushing's syndrome (excess cortisol) causes moon face, buffalo hump, central obesity, hypertension, hyperglycemia, immunosuppression, and osteoporosis. Addison's disease (adrenal insufficiency, too little cortisol) causes fatigue, hypotension, and hyperpigmentation.
Applied Walkthrough
1
In response to a stressful event, the hypothalamus releases CRH, triggering the pituitary to release ACTH, which in turn stimulates the adrenal cortex to release cortisol — raising blood glucose and suppressing inflammation to help the body cope with the stressor.
2
Once cortisol levels rise sufficiently, negative feedback kicks in, suppressing further CRH and ACTH release — keeping the stress response appropriately time-limited under normal conditions.
3
A patient on long-term high-dose corticosteroid medication (mimicking excess cortisol) develops Cushing's syndrome — moon face, central obesity, hypertension, and elevated blood glucose, all direct consequences of cortisol's known metabolic and anti-inflammatory effects taken to an extreme.
4
By contrast, a patient with Addison's disease (insufficient cortisol production) experiences the opposite pattern: fatigue and hypotension, since they lack the metabolic and cardiovascular support cortisol normally provides.
Exam Application
Exams test whether you can trace the full HPA axis (CRH → ACTH → cortisol → negative feedback), whether you know cortisol's wide range of metabolic and immune effects, and whether you can distinguish Cushing's syndrome (excess) from Addison's disease (deficiency) based on their opposite symptom patterns.
⚠ Common Trap
The most common trap is thinking of cortisol only as an anti-inflammatory hormone — it also has major effects on glucose metabolism (raising it), protein catabolism (breaking down muscle), and fat mobilization, all part of its broader stress-response role.
✓ Quick Self-Check
1. What is the correct order of the HPA axis?
Hypothalamus (CRH) → anterior pituitary (ACTH) → adrenal cortex (cortisol) → negative feedback.
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2. How does cortisol affect blood glucose?
It raises it, through gluconeogenesis, glycogen breakdown, and decreased glucose uptake in muscle/fat.
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3. What are cortisol's two immune-related effects?
Anti-inflammatory (via decreased prostaglandins/leukotrienes) and immunosuppressive (via decreased lymphocytes and antibodies).
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4. What condition results from excess cortisol, and what are its symptoms?
Cushing's syndrome; moon face, buffalo hump, central obesity, hypertension, hyperglycemia, immunosuppression, osteoporosis.
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5. What condition results from cortisol deficiency, and what are its symptoms?
Addison's disease; fatigue, hypotension, hyperpigmentation.
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