Cushing's syndrome Flashcards
What does Cushing’s syndrome comprise
a collection of signs and symptoms caused by a chronic inappropriate elevation of free circulating cortisol
What is the most common cause of Cushing’s syndrome
iatrogenic from excess exogenous glucocorticoids
What can endogenous Cushing’s syndrome be divided into
ACTH dependent (80%) - excess ACTH secreted from a pituitary adenoma (Cushing’s disease) or ACTH secreted from an ectopic source usually tumours, arising from neuroendocrine cells e.g. small cell lung carcinomas, pulmonary, pancreas and thymic carcinoid tumours
ACTH independent (20%) - excess cortisol secreted from a benign adrenal adenoma or excess cortisol secreted from an adrenal carcinoma
What are some physiological causes of hypercortisolism
Stress depression or other psychiatric disorders chronic alcoholism severe obesity poorly controlled diabetes pregnancy
What is often useful in making a diagnosis of Cushing’s syndrome
Older photos of the patient compared to now
What are some symptoms are more discriminatory to Cushing’s syndrome
Easy bruising
proximal muscle weakness
facial plethora
reddish-purple striae on the abdomen, breast or thighs (more than 1cm wide)
weight gain with decreasing growth velocity in children
Name some investigations that can be performed for Cushing’s syndrome
24 hour urinary free cortisol
Overnight dexamethasone and low-dose dexamethasone suppression tests
Late night salivary cortisol measurements
What are some pitfalls of 24 hour urinary free cortisol
It is not recommended in attends with renal failure as levels may be falsely low due to reduced glomerular filtration
High fluid intake may result in false positive results
What are some pitfalls of the dexamethasone tests
Assays measure total cortisol
oestrogen increase cortisol-binding protein levels and therefore increase total cortisol. therefore they need to be stopped for 6 weeks
Dexamethasone metabolism and clearance may be increased by some drugs
Describe the circadian rhythm in Cushing’s syndrome
The circadian rhythm is lost
What are some of the pitfalls of the salivary cortisol measurement
The circadian rhythm may also be blunted in shift-workers
cigarette smoking - tobacco contains an enzyme that metabolises cortisol
What other tests / investigations should be done after the screening tests
Plasma ACTH
High dose dexamethasone suppression
Imaging - MRI
Inferior petrosal sinus sampling
What is the most reliable test for differentiating pituitary and non-pituitary sources
Inferior petrosal sinus sampling
What is the treatment of Cushing’s syndrome due to exogenous glucocorticoid therapy
reduce glucocorticoid dose and discontinue if possible
What is the treatment of choice for Cushing’s disease
trans-sphenoidal surgery
