Summary

Cushing's Syndrome describes the clinical features of chronic exposure to excess glucocorticoids (Cortisol). It is a multisystem disorder causing central obesity, protein wasting, and metabolic derangement.

• Cushing's Syndrome: The umbrella term for ANY cause of high cortisol (Exogenous steroids are #1).
• Cushing's Disease: The specific condition of an ACTH-secreting Pituitary Adenoma (approx 70% of endogenous cases).

Epidemiology

• Incidence: Rare (2-3 per million/year) for endogenous causes. VERY common for exogenous (steroid users).
• Demographics: Female:Male 3:1 (for pituitary/adrenal causes). Ectopic ACTH is more common in men (Lung Cancer).
• Age: Peak 20-50 years.

Clinical Summary Table

Glossary for Patients

• Pituitary: The "Master Gland" in the brain.
• Adrenal: Two small glands on top of the kidneys.
• ACTH: The hormone that whips the adrenal gland to work.
• Iatrogenic: Caused by doctors/medication.
• Ectopic: In the wrong place (e.g. ACTH coming from the lung).

The "Spot Diagnosis"

Classic Appearance: "Lemon on Toothpicks". Central obesity (Lemon) with proximal muscle wasting giving thin arms/legs (Toothpicks).

Red Flags (Urgent Referral)

• Severe Hypokalaemia: Suggests rapidly progressing Ectopic ACTH (SCLC).
• Visual Field Defect: Bitemporal Hemianopia (Macroadenoma compressing chiasm).
• Fractures: Vertebral compression fractures (Severe Osteoporosis).

1. Exogenous (The Most Common)

• Iatrogenic: Long-term use of Prednisolone, Dexamethasone, or high-dose inhaled steroids.
• Factitious: Surreptitious steroid abuse.

Pseudo-Cushing's State

Look like Cushing's, Test like Cushing's, But NOT Cushing's.

• Definition: Conditions that activate the HPA axis physiologically.
• Causes:
  1. Alcoholism: Chronic ethanol stimulates CRH.
  2. Severe Depression: Stress hormones high.
  3. Obesity/PCOS: Mild hypercortisolism.
  4. Anorexia Nervosa: Starvation stress.
• Differentiation: Insulin Tolerance Test (ITT) or CRH-Dex test is needed.
• Resolution: Fix the underlying cause (Stop drinking), Cortisol normalises.

Mechanism: Alcohol-Induced Pseudo-Cushing's

• Biology: Ethanol stimulates hypothalamic secretion of CRH and impairs hepatic clearance of cortisol.
• Feature: Features are identical (moon face, liver enlargement).
• Test: Admission to hospital (alcohol abstinence) causes rapid drop in cortisol within 3-5 days.

2. Endogenous (The Rare Stuff)

Cyclical Cushing's (The Diagnostic Nightmare)

• What: Tumour secretes ACTH/Cortisol in cycles (days or weeks).
• Problem: You might test them on a "normal" day.
• Clue: Fluctuating symptoms. "Good days and Bad days".
• Strategy: Measure Hair Cortisol (timeline) or repeat salivary cortisol over weeks.

Genetic Syndromes (When to test DNA)

• MEN1 (Multiple Endocrine Neoplasia Type 1): Pituitary + Parathyroid + Pancreas.
• Carney Complex: Spotty skin, Cardiac Myxomas + Cushing's (PPNAD).
• McCune-Albright: Polyostotic fibrous dysplasia + Cushing's.
• Age Rule: If a child/young adult has Cushing's, think genetic.

Genetic Testing Criteria

The Adrenal Incidentaloma

The scan was for kidney stones, but we found a lump.

• Definition: Mass >1cm found on imaging performed for non-adrenal reasons.
• Prevalence: 3-5% of all CT scans.
• Rule 1: Is it functional? (Check Metanephrines [Phaeochromocytoma], Aldosterone [Conn's], Cortisol [Cushing's]).
• Rule 2: Is it Malignant? (Size >4cm, irregular -> Surgery).
• Subclinical Cushing's: Many incidentalomas secrete low-level cortisol (Autonomous Cortisol Secretion). Causes fragility but not full Cushing's features.

Take Home Message: > 1. Don't Stop Suddenly: If you are on long term steroids, stopping abruptly can kill you (Addisonian Crisis). > 2. Patience: Recovery after surgery takes a year. The body has to "learn" to make cortisol again. > 3. Medic Alert: Wear a bracelet saying "Steroid Dependent" post-op.

Steroid Tapering Guide (Rough Rule of Thumb)

For patients on long-term Prednisolone.

• Step 1: Reduce by 2.5mg-5mg every 1-2 weeks until 10mg/day.
• Step 2: Reduce by 1mg every 2-4 weeks.
• Step 3 (The Danger Zone): When <5mg/day, the Adrenal axis must wake up. Measure 9am Cortisol.
• Sick Day Rules: If you get a fever/vomiting while tapering, DOUBLE your dose and call a doctor.

Safety Net (When to call 999)

• Adrenal Crisis: Severe dizziness, vomiting, confusion. (Occurs if you stop steroids or forget sick day rules).
• Vision Loss: Post-pituitary surgery (Haematoma).
• Severe Headache: Pituitary Apoplexy.

Steroid Withdrawal Syndrome

The body hurts when you stop.

• Symptoms: Severe fatigue, joint pain (arthralgia), muscle pain, nausea.
• Cause: Relative cortisol deficiency (the body was used to high levels).
• Differentiation: Check BP and Electrolytes. If normal, it's withdrawal (just persevere). If Hypotensive/Hyponatraemic, it's True Adrenal Insufficiency (Need more steroids).

Frequently Asked Questions

• "Why is my face round?": Fat redistribution. It goes away slowly after cure.
• "Am I diabetic now?": Often yes, but it may reverse after surgery.

Lifestyle & Diet

• Protein: High protein intake to combat muscle wasting.
• Calcium/Vitamin D: Essential for bone recovery (1000mg/800IU daily).
• Salt: Restrict sodium to help BP control.
• Exercise: Resistance training is better than cardio for rebuilding muscle mass.
• Driving: DVLA/DMV rules apply if you have visual field defects (Homonymous/Bitemporal Hemianopia). You must stop driving until cleared by ophthalmology.

Support & Resources

• The Pituitary Foundation: Patient booklets and helpline.
• Addison's Disease Self-Help Group (ADSHG): For post-op adrenal insufficiency management.
• Medikidz: Explaining Cushing's to children.

Key Learning Points (The Pearls)

1. It's Rare: Most "Cushingoid" looking patients just have Metabolic Syndrome.
2. Screen Twice: Cortisol is pulsatile. One test is never enough.
3. Check Potassium: If it's low, panic. It's Ectopic ACTH until proven otherwise.
4. Taper Slowly: The HPA axis takes months to wake up.
5. Mental Health: Do not ignore the psychiatric symptoms. They are part of the disease.

Evidence Check: Outcomes and Survival

• Untreated: 5-year mortality is 50% ( Cardiovascular disease, Stroke, Infection).
• Post-Surgery: 5-year recurrence rate is 10-20% for Pituitary, <5% for Adrenal.
• QoL: Quality of life often remains impaired even after biochemical cure (Cognitive fog, Myopathy recovery time).