Physiology chapters
Adrenal cortex: cortisol and aldosterone
The three zones of the adrenal cortex and their hormones, how cortisol and aldosterone are controlled, their metabolic, permissive and electrolyte actions, and the disorders of too much or too little, including congenital adrenal hyperplasia.
- The cortex has three zones: glomerulosa → aldosterone ("salt"), fasciculata → cortisol ("sugar") and reticularis → androgens ("sex").
- Cortisol is controlled by CRH-ACTH and raises blood glucose (gluconeogenesis), breaks down protein and fat, suppresses inflammation and is permissive for catecholamines and glucagon.
- Aldosterone is controlled mainly by angiotensin II and plasma K+; it makes the collecting duct keep Na+ and lose K+ and H+.
On this page
Overview
The adrenal gland has two parts:
- Cortex (outer): makes steroid hormones from cholesterol.
- Medulla (inner): makes catecholamines; see adrenal medulla.
The cortex makes three groups of hormones: mineralocorticoids (aldosterone), glucocorticoids (cortisol) and adrenal androgens (DHEA).
Zones and hormones
| Zone (outside in) | Main hormone | Main control |
|---|---|---|
| Zona glomerulosa | Aldosterone | Angiotensin II, plasma K+ |
| Zona fasciculata (thickest) | Cortisol | ACTH |
| Zona reticularis | Androgens (DHEA, androstenedione) | ACTH |
"GFR" for glomerulosa, fasciculata, reticularis; and "salt, sugar, sex" for their hormones.
Only the glomerulosa has the enzyme aldosterone synthase, so only it makes aldosterone. ACTH has only a minor role in aldosterone release.
Cortisol
Regulation
Hypothalamus (CRH) → anterior pituitary (ACTH) → zona fasciculata (cortisol).
- Negative feedback: cortisol suppresses CRH and ACTH.
- Circadian rhythm: highest in the early morning, lowest around midnight.
- Stress (physical or mental, injury, infection, surgery) strongly increases CRH and ACTH.
ACTH is cut from a larger precursor, POMC, which also yields MSH (melanocyte-stimulating hormone). This is why high ACTH darkens the skin.
About 90% of cortisol in the blood is bound to cortisol-binding globulin (transcortin) and albumin.
Metabolic actions
| Target | Effect |
|---|---|
| Carbohydrate | ↑ Gluconeogenesis in the liver; ↓ glucose uptake by muscle and fat → raises blood glucose ("adrenal diabetes") |
| Protein | ↑ Breakdown in muscle, bone and skin (supplying amino acids for gluconeogenesis); muscle wasting, thin skin |
| Fat | ↑ Fat breakdown (mobilisation); with excess, fat is redistributed to the face, trunk and back of the neck |
Other actions
- Anti-inflammatory and immunosuppressive: stabilises lysosomes, reduces capillary permeability, blocks prostaglandin and leukotriene formation (via phospholipase A2), reduces lymphocytes and eosinophils.
- Stress resistance: needed to survive severe stress; patients without adrenals can die from minor stress.
- Blood pressure: maintains vascular responsiveness to catecholamines.
- Bone: reduces bone formation; excess causes osteoporosis.
- Raises neutrophils, red cells and platelets; lowers eosinophils and lymphocytes.
- Increases stomach acid; affects mood.
Permissive actions
Cortisol does not cause these effects itself but is needed for other hormones to work fully:
- Catecholamines: vasoconstriction and bronchodilation.
- Glucagon and adrenaline: gluconeogenesis and glycogen breakdown.
Cortisol is permissive for the vascular effects of catecholamines. Without it, blood pressure falls in stress (adrenal crisis).
Aldosterone
Regulation
- Angiotensin II (most important): low blood volume or pressure → renin from the kidney → angiotensin I → angiotensin II (by ACE in the lungs) → aldosterone.
- Raised plasma K+: directly stimulates the glomerulosa.
- ACTH: minor role.
- ANP and high sodium inhibit it.
Actions
Aldosterone acts on the principal cells of the late distal tubule and collecting duct (and on sweat glands, salivary glands and colon):
- ↑ Na+ reabsorption (more ENaC channels and Na+/K+-ATPase); water follows, raising blood volume and pressure.
- ↑ K+ secretion into urine.
- ↑ H+ secretion (intercalated cells).
Aldosterone: keep Na+, lose K+ and H+. Excess causes hypertension, hypokalaemia and metabolic alkalosis.
In primary hyperaldosteronism, plasma sodium is only slightly raised and there is little oedema, because of "aldosterone escape" (pressure natriuresis).
Disorders
Cushing's syndrome (cortisol excess)
Causes: most often steroid medicines; pituitary ACTH-secreting adenoma (Cushing's disease); adrenal tumour; ectopic ACTH (small-cell lung cancer).
What you see: moon face, buffalo hump, central obesity with thin limbs, purple striae, thin skin and easy bruising, muscle weakness, hyperglycaemia, hypertension, osteoporosis, infections and mood change. Diagnosed with the dexamethasone suppression test.
Addison's disease (primary adrenal insufficiency)
Causes: autoimmune destruction (commonest in many countries); tuberculosis (important in Pakistan); bleeding into the adrenals.
What you see: low cortisol and aldosterone: tiredness, weight loss, low blood pressure, hypoglycaemia, low Na+, high K+, and hyperpigmentation of skin, scars, gums and palm creases (high ACTH/MSH from POMC).
Adrenal crisis: sudden shock in stress; treated urgently with IV hydrocortisone and fluids.
Secondary adrenal insufficiency (pituitary failure, or stopping long-term steroids suddenly) causes low ACTH, so there is no pigmentation, and aldosterone is largely preserved (it depends on angiotensin, not ACTH), so K+ is usually normal.
Conn's syndrome (primary hyperaldosteronism)
How it happens: an aldosterone-secreting adenoma or bilateral hyperplasia.
What you see: hypertension, hypokalaemia (weakness), metabolic alkalosis, low renin.
Enzyme deficiencies: congenital adrenal hyperplasia
All cortisol synthesis needs certain enzymes. If one is missing, cortisol falls, ACTH rises, and the adrenals enlarge and push precursors down other pathways.
| Enzyme | Cortisol | Aldosterone | Androgens | Main features |
|---|---|---|---|---|
| 21-hydroxylase (about 90% of cases) | ↓ | ↓ | ↑ | Salt-wasting crisis (low Na+, high K+, shock) in newborns; virilisation of girls (ambiguous genitalia); early puberty in boys |
| 11β-hydroxylase | ↓ | ↓ (but 11-deoxycorticosterone ↑) | ↑ | Hypertension and hypokalaemia (DOC acts like aldosterone); virilisation |
| 17α-hydroxylase | ↓ | ↑ mineralocorticoids | ↓ | Hypertension, hypokalaemia; sexual infantilism (no sex steroids) |
21-hydroxylase deficiency is the commonest form: low cortisol and aldosterone, high androgens, salt-wasting and ambiguous genitalia in girls. 17-OH progesterone is raised.
Expect: the three zones and their hormones, the control of aldosterone (angiotensin II and K+) vs cortisol (ACTH), cortisol's metabolic, anti-inflammatory and permissive actions, aldosterone's effects on Na+, K+ and H+, Addison's vs Cushing's vs Conn's, primary vs secondary insufficiency, and the three enzyme deficiencies of CAH.
Quick revision
- Glomerulosa: aldosterone (angiotensin II, K+). Fasciculata: cortisol (ACTH). Reticularis: androgens.
- Cortisol peaks early morning; ↑ gluconeogenesis, protein breakdown, immunosuppression; permissive.
- Aldosterone: Na+ in, K+ and H+ out.
- Addison's: low Na+, high K+, hypotension, hyperpigmentation.
- Cushing's: central obesity, striae, hyperglycaemia, hypertension.
- Conn's: hypertension, hypokalaemia, low renin.
- 21-hydroxylase deficiency: salt-wasting and virilisation.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What are the zones of the adrenal cortex and their hormones?
Zona glomerulosa makes aldosterone, zona fasciculata makes cortisol, and zona reticularis makes adrenal androgens.
What is the main stimulus for aldosterone secretion?
Angiotensin II, together with a high plasma potassium.
Why does Addison's disease cause hyperpigmentation?
Low cortisol removes feedback, so the pituitary makes more POMC, which yields ACTH and melanocyte-stimulating hormone.
What is the commonest cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency.