Cushing's Syndrome Flashcards
What is cushing’s syndrome?
It is excessive activation of glucocorticoid receptors.
What causes Cushing’s?
It is a clinical state produced by excess glucocorticoid, loss of normal feedback mechanisms of the HPA axis and loss of circadian rhythm of cortisol secretion.
What is cushing’s disease?
It refers to a pituitary adenoma secreting ACTH
What is the aetiology of cushing’s?
pituitary-dependent cortisol excess (Cushing’s disease), ectopic ACTH syndrome, adrenal tumour, exogenous steroids
What type of cancer produces ectopic ACTH Syndrome?
Small cell bronchial carcinoma
What are the symptoms of Cushing’s syndrome?
increased weight, mood change (depression, lethargy, irritability), proximal weakness, gonadal dysfunction, acne, recurrent Achilles tendon rupture, occasional virilisation (development of male characteristics) if female, insomnia
What are the signs of it?
central obesity, plethoric, moon face, buffalo hump, supraclavicular fat distribution, skin and muscle atrophy, bruises, purple abdominal striae (due to weakeness skin making elastin break), osteoporosis, increased BP, hyperglycaemia, infection-prone, poor healing, pigmentation of skin,
What causes marked pigmentation?
high ACTH levels are associated with marked pigmentation because of binding to melanocortin 1 receptors on melanocytes in the skin.
When is cortisol highest?
In the morning
When does cortisol rise?
During times of stress i.e illness
How does cortisol cause hypertension and hypernatraemia?
Cortisol can also activate mineralocorticoid receptors
What do mineralocorticoids do?
cause Na+ retention and K+ and H+ excretion
What causes cortisol release?
Corticotrophin-releasing factor from the hypothalamus stimulates ACTH secretion from the pituitary, which in turn stimulates cortisol and androgen production by the adrenal cortex
What produces cortisol?
Zona fasciculata of the adrenal cortex
What do excessive glucocorticoids cause?
Gluconeogenesis, glycogenolysis, redistribution of body fat, muscle wasting due to protein catabolism, suppress inflammation, cause osteoporosis
What investigations would you carry out in suspected cushing’s?
Dexamethasone suppression test
Additional - electrolytes, glucose, HbA1c, bone mineral density
How does the dexamethasone test work?
Give low dose 1mg at night, measure cortisol in the morning
Low cortisol - normal
High/normal cortisol - Cushing’s syndrome
How do you localise the cause of cushing’s?
High dose test (8mg dexamethasone)
Low cortisol - cushing’s disease
High cortisol, low ACTH - adrenal cushing’s
High cortisol, high ACTH - ectopic ACTH
What treatment can be given for cushing’s syndrome?
Metyrapone and ketoconazole
How is cushing’s disease managed?
trans-sphenoidal surgery removing the adenoma
How is an adrenal tumour treated?
laproscopic adrenal surgery
How is ectopic ACTH syndrome treated?
localised tumours, such as bronchial carcinoid, should be removed surgically
What biochemical abnormalities occur in cushing’s?
high cortisol, hyperglycaemia, hypernatremia, hypokalaemia, high bicarbonate
How is cushing’s disease diagnosed?
MRI
What is a specific sign of a pituitary adenoma?
bitemporal hemianopia
How does metryapone work?
blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase.
What is 2nd line treatment for cushing’s?
cortisol synthesis inhibitor Metyrapone to reduce adrenal steroid output and then bilateral adrenalectomy.
