Cushing Syndrome Flashcards
Define
Syndrome associated with chronic inappropriate elevation of free circulating cortisol
The adrenal cortex produces steroids:
(1) Glucocorticoids (cortisol), which affect carbohydrate, lipid and protein metabolism
(2) Mineralocorticoids, which control sodium and potassium balance (aldosterone)
(3) Androgens, sex hormones which have weak effect until peripheral conversion to testosterone and dihydrotestosterone
Corticotropin-releasing factor (CRF) from the hypothalamus
→ Stimulates ACTH secretion from the pituitary
→Which in turn stimulates cortisol and androgen production by the adrenal cortex
_Cushing’s syndrome is the clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and loss of circadian rhythm of cortisol secretion (normally highest on waking)
Causes
Main cause is oral steroids
Pituitary adenoma, ↑ACTH (Cushing’s disease)
Ectopic ACTH (common in SC lung cancer)
Specific features: ↑pigmentation, ↓K+ metabolic
alkalosis, weight loss, hyperglycaemia
Adrenal adenoma or carcinoma producing ↑cortisol
Epidemiology
endogenous Cushing’s syndrome more common in WOMEN
Peak incidence 20-40 years
Symptoms
- ↑Weight (↑ fat, ↓protein)
- Mood change: depression, lethargy, irritability
- Proximal myopathy
- Gonadal dysfunction: irregular menses, hirsutism,
- erectile dysfunction)
- Acne
- Recurrent Achilles heel tendon rupture
Signs
- Centripetal obesity, thin legs/arms (lemon-on-sticks)
- Impaired glucose tolerance (diabetes)
- Thin skin and easy bruising
- Skin and muscle atrophy
- Abdominal striae: ↑weight, proteins absent in skin so can’t grow, hence skin tears
- Osteoporosis
- Poor wound healing, infection prone
- Hypertension
- Few months later: moon face, buffalo hump
(intrascapular fat pad)
Investigations
Must be performed on patients with a high pre-test probability
Bloods
- U&Es - hypokalaemia due to mineralocorticoid effect
- BM - high glucose
Initial High-Sensitivity Tests
- Urinary free cortisol
- Late-night salivary cortisol
- Overnight dexamethasone suppression test
- 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
Tests to determine the underlying cause
ACTH-independent (adrenal adenoma/carcinoma)
- Low plasma ACTH
- CT or MRI of adrenals
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
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
Medical
- Used pre-operatively or if unfit for surgery
- Inhibit cortisol synthesis with metyrapone or ketoconazole
- Treat osteoporosis
- Physiotherapy for muscle weakness
Surgical
- Pituitary Adenomas - trans-sphenoidal adenoma resection
- Adrenal adenoma/carcinoma - surgical removal of tumour
- Ectopic ACTH - treatment directed at the tumour
Radiotherapy
- 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
Complications
- Diabetes
- Osteoporosis
- Hypertension
- Pre-disposition to infections
Complications of surgery:
- CSF leakage
- Meningitis
- Sphenoid sinusitis
- Hypopituitarism
Complications of radiotherapy:
- Hypopituitarism
- Radionecrosis
- 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
Untreated - 5 yr survival = 50%
Depression persists for many years following treatment
