Adrenal Disorders: Too Little (Addison's) and Too Much (Cushing's)
The adrenal gland can fail in two directions. Too little cortisol is Addison's disease — quietly dangerous, and treated by simply replacing the missing hormones. Too much is Cushing's syndrome — and its commonest cause is sitting in the medicine cabinet. Together they complete the adrenal picture and tie the whole steroid story into a neat loop.
Having seen what cortisol does and what happens when we give it as a drug, the two adrenal diseases almost write themselves. If the adrenal makes too LITTLE cortisol (and often too little aldosterone as well), you get Addison's disease — adrenal insufficiency. If there's too MUCH cortisol, from any source, you get Cushing's syndrome. One is a deficiency to be replaced; the other an excess to be removed. And there's a neat twist that links this whole chapter together: by far the commonest cause of Cushing's syndrome isn't a tumour at all — it's the corticosteroid drugs we prescribe.
Addison's disease — too little
Adrenal failure: replace both the glucocorticoid and the mineralocorticoid. In Addison's disease the adrenal glands are damaged (usually by the immune system) and can't make enough of their hormones. Losing cortisol brings tiredness, weight loss, low blood pressure, low glucose and, characteristically, a longing for salt and darkened skin. Losing aldosterone means the kidney can't hold onto sodium and water, worsening the low blood pressure and causing a high potassium. The treatment is pure replacement of both hormones: a glucocorticoid (hydrocortisone, taken to mimic the natural daily cortisol rhythm) AND a mineralocorticoid (fludrocortisone, to replace aldosterone's salt-retaining action). Two safety points are vital. First, exactly like the patient on long-term steroids, an Addison's patient can't mount a stress response, so they must increase their hydrocortisone during illness or surgery (sick day rules again). Second, an Addisonian crisis — a sudden collapse with severe low blood pressure — is a medical emergency treated immediately with intravenous hydrocortisone and fluids. It's the same adrenal-crisis danger we met with abrupt steroid withdrawal, arriving by a different road.
Cushing's syndrome — too much
Cushing's syndrome is the picture of too much cortisol — and you already know its features, because they are exactly the long-term steroid side effects from two articles ago: weight gain with a round 'moon' face and central obesity, thin limbs, high glucose, high blood pressure, thin bruising skin, osteoporosis, and mood changes. The single most important thing to know is the commonest cause: not a tumour, but prescribed corticosteroid drugs (called iatrogenic or exogenous Cushing's) — which is why the previous articles matter so much. When Cushing's is not drug-induced, it comes from the body over-producing cortisol: most often a pituitary tumour making too much ACTH (called Cushing's disease specifically), or an adrenal tumour making cortisol directly, or a tumour elsewhere producing ACTH. Treatment of these depends on the source — usually surgery to remove the responsible tumour, sometimes drugs that block cortisol synthesis (such as metyrapone or ketoconazole) as a bridge. But for the common, drug-induced form, the 'treatment' is to carefully reduce the steroid where possible — by tapering, of course, never abruptly.
- Addison's = adrenal failure: low cortisol + low aldosterone → tiredness, low BP, low Na, high K, dark skin.
- Treat Addison's by replacing BOTH: hydrocortisone (glucocorticoid) + fludrocortisone (mineralocorticoid).
- Addisonian crisis = emergency: IV hydrocortisone + fluids; use sick day rules to prevent it.
- Cushing's = too much cortisol; features = the long-term steroid side effects.
- Commonest cause of Cushing's is prescribed steroids (iatrogenic); other causes are tumours (pituitary/adrenal).
The whole adrenal section closes into a single elegant loop. Cortisol's normal jobs, learned once, generate three things at a stroke: the therapeutic uses of steroids (suppressing inflammation), their side effects (each job over-done), and the features of Cushing's syndrome (which ARE those side effects). Meanwhile the feedback loop generates the deficiency side: why long-term steroids suppress the adrenal, why they can't be stopped suddenly, and why Addison's and steroid withdrawal share the same crisis. Learn cortisol and the feedback loop properly, and you haven't learned four separate topics — you've learned one idea that explains all of them.
- Replacing only the glucocorticoid in Addison's — the mineralocorticoid (fludrocortisone) is also needed.
- Missing an Addisonian crisis — treat immediately with IV hydrocortisone and fluids.
- Forgetting that the commonest Cushing's is drug-induced — always review the steroid history.
- Stopping steroids abruptly in drug-induced Cushing's — taper to avoid a crisis.
What is the most common cause of Cushing's syndrome?
- Addison's = adrenal failure; replace BOTH hydrocortisone and fludrocortisone; beware Addisonian crisis.
- Cushing's = cortisol excess; its features are the long-term steroid side effects.
- Commonest Cushing's cause is prescribed steroids; other causes are pituitary/adrenal tumours.
- Cortisol + feedback explain the uses, side effects, Cushing's and the deficiency crises together.
- Katzung BG. Basic & Clinical Pharmacology — Adrenocorticosteroids & Adrenocortical Antagonists.
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Adrenocortical hormones & antagonists.
- Endocrine Society — Clinical practice guidelines: Addison's disease & Cushing's syndrome.
- Guyton & Hall. Textbook of Medical Physiology — Adrenocortical hormones.
