Cushing's Flashcards
Define:
• Syndrome associated with chronic inappropriate elevation of free circulating cortisol
Aetiology/risk factors of ACTH dependant:
o Excess ACTH from a pituitary adenoma (Cushing’s disease) – 2nd commonest cause
Adenoma causes bilateral adrenal hyperplasia
o Ectopic ACTH (e.g. small cell lung cancer, pulmonary carcinoid tumours)
Would cause weight loss, pigmentation (ACTH), hypokalaemic metabolic alkalosis, hyperglycaemia
o Rare: ectopic CRF production – some thyroid medullary and prostate cancers
Aetiology/risk factors of ACTH independent:
o Excess ACTH from a pituitary adenoma (Cushing’s disease) – 2nd commonest cause
Adenoma causes bilateral adrenal hyperplasia
o Ectopic ACTH (e.g. small cell lung cancer, pulmonary carcinoid tumours)
Would cause weight loss, pigmentation (ACTH), hypokalaemic metabolic alkalosis, hyperglycaemia
o Rare: ectopic CRF production – some thyroid medullary and prostate cancers
Epidemiology:
- Incidence: 2-4/1,000,000 per year
* Peak incidence 20-40 yrs
Symptoms:
- Increasing weight
- Fatigue
- Muscle weakness – proximal myopathy
- Myalgia
- Thin skin
- Easy bruising
- Poor wound healing
- Fractures
- Gonadal dysfunction – Hirsuitism, irregular menses, erectile dysfunction
- Acne
- Frontal balding
- Recurrent Achilles tendon rupture
- Depression or psychosis
Signs:
- Moon face
- Facial plethora
- Interscapular fat pad – buffalo neck hump
- Supraclavicular fat distribution
- Proximal muscle weakness - myopathy
- Thin skin
- Bruises
- Central obesity
- Pink/purple striae on abdomen/breast/thighs
- Kyphosis (due to vertebral fracture)
- Poorly healing wounds
- Hirsuitism, acne, frontal balding
- Hypertension
- Ankle oedema (due to salt and water retention from the mineralocorticoid effect of excess cortisol)
- Pigmentation in ACTH dependent cases
- Osteoporosis
Investigations:
• Bloods
o U&Es - hypokalaemia due to mineralocorticoid effect
o BM - high glucose
o Urinary free cortisol – 24 hour urine collection
o Late-night salivary cortisol
o Overnight dexamethasone suppression test
o Low dose dexamethasone suppression test (LDDST) - fails to suppress below 50 nmol/L
Investigations for the underlying causes:
o ACTH-independent (adrenal adenoma/carcinoma)
• Low plasma ACTH
• CT or MRI of adrenals
o ACTH-dependent (pituitary adenoma)
• High plasma ACTH
• Pituitary MRI
• High-dose dexamethasone suppression test – would suppress
• Inferior petrosal sinus sampling (SUPERIOR to high-dose dexamethasone suppression test)
Central: peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s disease
o ACTH-dependent (ectopic)
• If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT san
• Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors
Management:
• If iatrogenic - discontinue steroids, use lower dose or use a steroid-sparing agent
o Inhibit cortisol synthesis with metyrapone (11b-hydroxylase inhibitor) or ketoconazole (17a-hydroxylase inhibitor)
o Treat osteoporosis
o Physiotherapy for muscle weakness
o Pituitary Adenomas - trans-sphenoidal adenoma resection
o Adrenal adenoma/carcinoma - surgical removal of tumour. Carcinoma usually requires radiotherapy and adrenolytic drugs (mitotane) to follow.
o Ectopic ACTH - treatment directed at the tumour
Radiotherapy
o Performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour
Bilateral adrenalectomy may be performed in refractory Cushing’s disease
Side effects of drugs that inhibit cortisol:
But metyrapone can cause nausea, vomiting and hypoadrenalism (decreases mineralocorticoid production) so short term use only
Ketoconazole inhibits glucorticoid, mineralocorticoid and sex steroid production so short term too. Can also cause nausea, vomiting, alopecia, liver damage.
Complications:
- Diabetes
- Osteoporosis
- Hypertension
- Pre-disposition to infections
Complications of surgery, radiotherapy and bilateral adrenalectomy :
Surgery: o CSF leakage o Meningitis o Sphenoid sinusitis o Hypopituitarism
Complications of radiotherapy:
o Hypopituitarism
o Radionecrosis
o Increased risk of second intracranial tumours and stroke
Bilateral adrenalectomy may be complicated by the development of Nelson’s syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH secretion
Prognosis:
If untreated the 5 year prognosis is 50%
