Cushing's Syndrome Flashcards
Definition
Syndrome associated with chronic inappropriate elevation of free circulating cortisol
Aetiology
It can be divided into ACTH Dependent (80%) and ACTH Independent (20%)
· ACTH Dependent
o Excess ACTH from a pituitary adenoma (Cushing’s disease)
o Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)
· ACTH Independent
o Benign adrenal adenoma
o Adrenal carcinoma
Epidemiology
· Incidence: 2-4/1,000,000 per year
· Peak incidence 20-40 yrs
Presenting symptoms
· Increasing weight · Fatigue · Muscle weakness · Myalgia · Thin skin · Easy bruising · Poor wound healing · Fractures · Hirsuitism · Acne · Frontal balding · Oligomenorrhoea/amenorrhoea · Depression or psychosis
Signs on physical examination
· Moon face · Facial plethora · Interscapular fat pad · Proximal muscle weakness · 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
Investigations (for diagnosis)
· Must be performed on patients with a high pre-test probability
· Bloods
o U&Es - hypokalaemia due to mineralocorticoid effect
o BM - high glucose
· Initial High-Sensitivity Tests
o Urinary free cortisol
o Late-night salivary cortisol
o Overnight dexamethasone suppression test
o Low dose dexamethasone suppression test (LDDST)
· Give 0.5 mg dexamethasone orally ever 6 hrs for 48 hrs
· In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose of dexamethasone fails to suppress below 50 nmol/L
Investigations (to determine underlying cause - ACTH-independent)
o ACTH-independent (adrenal adenoma/carcinoma)
· Low plasma ACTH
· CT or MRI of adrenals
Investigations (to determine underlying cause - ACTH-dependent pituitary)
o ACTH-dependent (pituitary adenoma)
· High plasma ACTH
· Pituitary MRI
· High-dose dexamethasone suppression test
· 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
Investigations (to determine underlying cause - ACTH-dependent ectopic)
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 plan (medical)
· If iatrogenic - discontinue steroids, use lower dose or use a steroid-sparing agent
· Medical
o Used pre-operatively or if unfit for surgery
o Inhibit cortisol synthesis with metyrapone or ketoconazole
o Treat osteoporosis
o Physiotherapy for muscle weakness
Management plan (other)
· Surgical
o Pituitary Adenomas - trans-sphenoidal adenoma resection
o Adrenal adenoma/carcinoma - surgical removal of tumour
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
Possible complications
· Diabetes
· Osteoporosis
· Hypertension
· Pre-disposition to infections
Complications of surgery
· Complications of surgery:
o CSF leakage
o Meningitis
o Sphenoid sinusitis
o Hypopituitarism
· Bilateral adrenalectomy may be complicated by the development of Nelson’s syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH secretion)
Complications of radiotherapy
· Complications of radiotherapy:
o Hypopituitarism
o Radionecrosis
o Increased risk of second intracranial tumours and stroke
Prognosis
· Untreated - 5 yr survival = 50%
· Depression persists for many years following treatment
