Cushing's Syndrome & Cushing's Disease

Exam Cram

• Cushing's syndrome = hypercortisolaemia

• Cushing's disease = pituitary adenoma secreting ACTH

• Diagnose hypercortisolaemia: low dose dexamethasone test or 24hr urinary cortisol 

• Localise the source with high dose dexamethasone and ACTH

Cushing's disease vs Cushing's Syndrome

Cushing's Syndrome = Hypercortisolaemia

Cushing's Disease = Pituitary adenoma causing hypercortisolaemia

Workflow

1. Identify presentation concerning for hypercortisolaemia

2. Perform 24hr urinary cortisol or low dose Dexamethasone suppresion test (random cortisol minimal role)

Positive = diagnostic of hypercortisolaemia (Cushing's Syndrome)

Negative = consider other differentials

3. Look for source of raised cortisol: high dose dexamethasone test measuring cortisol and ACTH

Suppressed cortisol = Pituitary source, Cushings Disease

Raised cortisol, low ACTH = Adrenal source

Raised cortisol, raised ACTH = Ectopic ACTH, likely cancer

Ectopic sources produce their own ACTH which stimulates adrenal glands to produce cortisol. 

Adrenal tumours produce cortisol, suppressing the pituitary's ACTH. 

Cushing's Syndrome

Presentation: 

• Lethargy

• Weight gain (centrally)

• Polyuria, polydipsia

New onset or new poor control of 

• Hypertension

• Blood sugars

Investigations

• Na+ upper limit of normal

• K+ lower limit of normal

Diagnosis:

• • Raised 24hr urinary cortisol OR

  • Raised cortisol after low dose dexamethasone 

Management

Find source of hypercortisolaemia

• High dose dexamethasone test &

• ACTH

Management, by Source

Pituitary source (Cushing's disease)

• low cortisol (& low ACTH)

• MRI pituitary

• Surgical referral ?excision

Adrenal source

• low ACTH, high cortisol

• CTAP 

• Surgical referral ?excision

Ectopic: 

• high ACTH, high cortisol

• CTCAP ? location

• If cancerous source- likely require biopsy +/- oncology and endocrine consults

MED REG NOtes

Ectopic cancers typically produce ACTH, stimulating adrenal gland. Interestingly the adrenal gland is not suppressed by a high dose dexamethasone test and listens to the ectopic ACTH instead. 

A random or midnight cortisol have little downside but are of little diagnostic benefit. 

PseudoCushing's

Chronic alcoholism causes induces CYP450, resulting in metabolism of dexamethasone. This results in incomplete suppression of cortisol with dexamethasone suppression. Pseudocushing's requires only lifestyle advice.  A high dose dexamethasone or 24hr urinary cortisol level can be considered. 

Resources and References

Written 2024