Cushing Syndrome

 

• Pathophysiology and causes

  Chronic glucocorticoid (i.e. cortisol) excess, with loss of circadian rhythm of release.

  Physiological effects of cortisol:

  • ↑Glucose via gluconeogenesis
  • ↓Immune function
  • Alters fat, protein, and carbohydrate metabolism.

  Causes of Cushing's:

  • Iatrogenic
  • Basophilic pituitary adenoma: Cushing's disease, with onset usually at age 25-50.
  • Ectopic ACTH syndrome: small cell lung cancer, pancreatic or thymic carcinoid tumour.
  • Adrenal adenoma, though these are more commonly a benign, non-functional incidentaloma.
  • Adrenal adenocarcinoma: onset age <5 or 30-50.

• Signs and symptoms

  Cushions go on BiG SOFAS:

  • ↑BP. Contributes to increased risk of CVD in Cushing's.
  • ↑Glucose
  • Skin: bruising, striae, acne, hyperpigmentation if due to ↑ACTH, poor wound healing.
  • Osteoporosis, achilles tendon rupture, proximal myopathy.
  • Fat: face ('moon face'), central obesity, buffalo hump, wasted legs.
  • Affect: altered mood, lethargy, psychosis.
  • Sex: irregular menstruation, hirsutism, erectile dysfunction.

• Investigations

  Diagnosis

  Several possible diagnostic tests:

  • 24h urine cortisol.
  • Late night salivary cortisol. Midnight serum cortisol is another option.
  • Overnight dexamethasone suppression test: 1 mg at 11pm then cortisol checked at 9am. Failure to suppress is +ve.
  • Low dose dexamethasone suppression test: 0.5 mg 6-hourly for 2 days, then cortisol checked. Failure to suppress is +ve. Less commonly used.

  If 1 is positive, repeat the test – if urine or saliva – and/or confirm with another. Then localise the source:

  • Serum ACTH: ↓ means iatrogenic or adrenal tumour. ↑ requires further test to determine source of ACTH.
  • High dose dexamethasone suppression test: 2 mg 6-hourly for 2 days, then cortisol checked. Substantial suppression (>50%) if pituitary adenoma, but less if ectopic ACTH.
  • CT/MRI to confirm tumour.

  Other tests

  • ↑Glucose
  • ↓K+, as glucocorticoids bind mineralocorticoid receptor too.

• Management

  Iatrogenic:

  • Consider stopping treatment.

  Tumour:

  • Transsphenoidal removal of pituitary tumour.
  • Relapse: metyrapone – inhibits steroid 11-β-hydroxylase to reduce cortisol synthesis – or adrenalectomy as the definitive treatment.
  • Radiotherapy if surgery contraindicated or in relapse.