Cushing's Syndrome

Question 1

What is cushing’s syndrome?

Answer 1

It is excessive activation of glucocorticoid receptors.

Question 2

What causes Cushing’s?

Answer 2

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.

Question 3

What is cushing’s disease?

Answer 3

It refers to a pituitary adenoma secreting ACTH

Question 4

What is the aetiology of cushing’s?

Answer 4

pituitary-dependent cortisol excess (Cushing’s disease), ectopic ACTH syndrome, adrenal tumour, exogenous steroids

Question 5

What type of cancer produces ectopic ACTH Syndrome?

Answer 5

Small cell bronchial carcinoma

Question 6

What are the symptoms of Cushing’s syndrome?

Answer 6

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

Question 7

What are the signs of it?

Answer 7

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,

Question 8

What causes marked pigmentation?

Answer 8

high ACTH levels are associated with marked pigmentation because of binding to melanocortin 1 receptors on melanocytes in the skin.

Question 9

When is cortisol highest?

Answer 9

In the morning

Question 10

When does cortisol rise?

Answer 10

During times of stress i.e illness

Question 11

How does cortisol cause hypertension and hypernatraemia?

Answer 11

Cortisol can also activate mineralocorticoid receptors

Question 12

What do mineralocorticoids do?

Answer 12

cause Na+ retention and K+ and H+ excretion

Question 13

What causes cortisol release?

Answer 13

Corticotrophin-releasing factor from the hypothalamus stimulates ACTH secretion from the pituitary, which in turn stimulates cortisol and androgen production by the adrenal cortex

Question 14

What produces cortisol?

Answer 14

Zona fasciculata of the adrenal cortex

Question 15

What do excessive glucocorticoids cause?

Answer 15

Gluconeogenesis, glycogenolysis, redistribution of body fat, muscle wasting due to protein catabolism, suppress inflammation, cause osteoporosis

Question 16

What investigations would you carry out in suspected cushing’s?

Answer 16

Dexamethasone suppression test

Additional - electrolytes, glucose, HbA1c, bone mineral density

Question 17

How does the dexamethasone test work?

Answer 17

Give low dose 1mg at night, measure cortisol in the morning

Low cortisol - normal
High/normal cortisol - Cushing’s syndrome

Question 18

How do you localise the cause of cushing’s?

Answer 18

High dose test (8mg dexamethasone)

Low cortisol - cushing’s disease
High cortisol, low ACTH - adrenal cushing’s
High cortisol, high ACTH - ectopic ACTH

Question 19

What treatment can be given for cushing’s syndrome?

Answer 19

Metyrapone and ketoconazole

Question 20

How is cushing’s disease managed?

Answer 20

trans-sphenoidal surgery removing the adenoma

Question 21

How is an adrenal tumour treated?

Answer 21

laproscopic adrenal surgery

Question 22

How is ectopic ACTH syndrome treated?

Answer 22

localised tumours, such as bronchial carcinoid, should be removed surgically

Question 23

What biochemical abnormalities occur in cushing’s?

Answer 23

high cortisol, hyperglycaemia, hypernatremia, hypokalaemia, high bicarbonate

Question 24

How is cushing’s disease diagnosed?

Answer 24

MRI

Question 25

What is a specific sign of a pituitary adenoma?

Answer 25

bitemporal hemianopia

Question 26

How does metryapone work?

Answer 26

blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase.

Question 27

What is 2nd line treatment for cushing’s?

Answer 27

cortisol synthesis inhibitor Metyrapone to reduce adrenal steroid output and then bilateral adrenalectomy.