Cushing syndrome Flashcards
What is Cushing’s syndrome?
=> Clinical state of chronic free circulating glucocorticoid excess
=> Loss of normal feedback mechanisms of the hypothalamo-pituitary axis
=> Loss of circadian rhythm of cortisol secretion
What are the causes of Cushing’s syndrome?
What is the most common cause?
Synthetic steroids (iatrogenic) => most common cause
Causes of Cushing’s syndrome can be divided into:
- ACTH-dependent disease:
i) Excess endogenous secretion if ACTH from pituitary adenoma aka Cushing’s disease (65%)
ii) . Ectopic non-pituitary ACTH producing tumour elsewhere in the body (10%) - Non-ACTH dependent disease:
i) Adrenal adenomas - primary excess of endogenous cortisol excretion
ii) Adrenal carcinomas
iii) Exogenous steroids
What is the underlying pathology of Cushing’s disease?
Who does it affect?
What does a dexamethasone test show?
- Bilateral adrenal hyperplasia due to ACTH secreting pituitary adenoma
- Women > men ; peak age 30-50yrs
- Low dose dexamethasone test leads to no change in plasma cortisone => 8mg high dose dexamethasone significantly reduces the morning cortisol
What are some examples of ectopic ACTH production?
What are its related clinical features?
What does a dexamethasone test show?
- Examples of ectopic ACTH e.g. Small cell lung cancer and Carcinoid tumours
- Clinical features:
i. Pigmentation (due to high ACTH)
ii. Hypokalaemia
iii. Metabolic alkalosis (high cortisol leads to mineralocorticoid activity)
iv. Weight loss
v. Hyperglycaemia
* Classical features of Cushing’s are missing - Even high dose dexamethasone fails to suppress cortisol production
Adrenal adenoma/carcinoma:
=> May cause abdo pain ± virilization in female
=> Tumour is autonomous therefore dexamethasone will not suppress cortisol
INFO CARD
What are the symptoms of Cushing’s syndrome?
Weight gain
Mood change i.e. depression, lethargy, irritability, psychosis
Proximal weakness
Gonadal dysfunction (irregular periods, hirsutism, erectile dysfunction)
Acne
Recurrent achilles tendon rupture
What are the signs of Cushing’s syndrome?
i. General signs
ii. Skin signs
iii. Bruises signs
iv. Musculoskeletal signs
General: => Plethoric moon face => Hypertension ; Glycosuria => Central obesity => Buffalo hump => Depression / psychosis => Oedema => Hypokalaemia (due to mineralocorticoid activity of cortisol - common with ectopic ACTH)
Skin: => Thin skin => Supraclavicular fat distribution => Hirsutism => Virilization (male pattern hair growth) in women
Bruises: => Purple abdominal striae => Infection prone => Poor wound healing => Pigmentation (occurs with ACTH dependent causes esp in ectopic ACTH syndromes)
=> Signs of the cause e.g. abdominal mass (in adrenal hyperplasia)
Musculoskeletal: => Osteoporosis => Kyphosis => Rib fractures => Pathological fractures esp vertebrae & ribs => Proximal muscle wasting
Cushing’s investigation
DO NOT do a Random plasma cortisol = misleading because illness, time of day and stress influence results
INFO CARD
What is the 1st line investigation for Cushing’s syndrome?
Overnight dexamethasone suppression test
Dexamethasone 1mg PO at midnight then check serum cortisol at 8am
Normal: cortisol suppression to <50nmol/L
Cushing’s syndrome: no suppression
Overnight dexamethasone suppression test has a high false +ve.
Why is the underlying cause of these false positive tests?
Pseudo-cushing’s seen in:
=> Depression
=> Obesity
=> Alcohol excess
=> Liver enzyme inducers (increases rate of dexamethasone metabolism e.g. phenytoin, phenobarbital, rifampicin)
What is the alternative for overnight dexamethasone suppression test?
24h urinary free cortisol
Normal: <280nmol/24h
If 1st line test is abnormal, move on to the 2nd line test.
What is the 2nd line investigation for Cushing’s syndrome?
I. 48h dexamethasone suppression test:
Give 0.5mg/6h Dexamethasone for 2 days
Measure cortisol at 0 and 48h
Failure to suppress cortisol in Cushing’s (<50nmol/L)
II. 48h high-dose dexamethasone test:
Give 2mg/6h => may distinguish from pituitary cause (suppressed cortisol) to other causes (partly or no suppression)
Circadian rhythm:
After 48h in hospital, cortisol samples taken at 9am and 12am.
Normal: pronounced circadian variation in cortisol
Cushing’s: loss of circadian rhythm
What are the localisation tests for Cushing’s syndrome?
If 1st and 2nd line tests are positive
If ACTH is undetectable => adrenal tumour most likely
=> CT/MRI adrenal glands
=> if no mass, do adrenal vein sampling
If ACTH is detectable => distinguish from a pituitary cause and ectopic ACTH by using:
=> high-dose suppression test
=> corticotropin-releasing hormone test.
What is corticotropin-releasing hormone test?
100mcg ovine or human CRH IV and measure cortisol at 120min
- Cortisol rises in pituitary disease
=> Cushing’s disease is likely => pituitary MRI - No change in cortisol in ectopic ACTH production
=> search for ectopic source
=> IV contract CT chest,
abdomen and pelvis ± MRI of neck, thorax and abdomen e.g. for small ACTH secreting carcinoid tumour
What is the treatment for iatrogenic exogenous cause i.e. steroids in Cushing’s syndrome?
Stop medication
