Cushing's

Question 1

What is Cushing syndrome?

Answer 1

Endocrine disorder with elevated cortisol levels in the blood

Question 2

What is Cushing disease?

Answer 2

Pituitary adenoma making excess ACTH, causing elevated cortisol

Question 3

How are cortisol levels maintained in normal range?

Answer 3

By negative feedback

High levels of cortisol –> hypothalamus and pituitary gland decrease secretion of CRH and ACTH

• -> less CRH tells pituitary to release less ACTH –> zona fasciculata less stimulation to make cortisol
• -> cortisol levels go down

Question 4

Adrenal cortex is divided into…

Answer 4

Zona glomerulosa
Zona fasciculata (widest zone, middle zone)
Zona reticularis

Question 5

Which part of the adrenal cortex releases cortisol?

Answer 5

Zona fasciculata

Question 6

When does cortisol peak?

Answer 6

In morning (“get up and go”), drops in evening

Question 7

Effects of cortisol

Answer 7

Increases gluconeogenesis, proteolysis and lipolysis
Maintains BP
Dampens immune + inflammatory responses 
Unclear effect on mood and memory
Inhibits bone formation

Question 8

How does cortisol maintain BP?

Answer 8

Increasing sensitivity of peripheral blood vessels to catecholamines (adrenaline and noradrenaline) which narrow blood vessel lumen

Question 9

How does cortisol dampen immune/inflammatory response?

Answer 9

Reduces production and release of prostaglandins and ILs

Inhibits proliferation of T lymphocytes

Question 10

Normal process of hypothalamus-pituitary-adrenal axis for cortisol release

Answer 10

Hypothalamus secretes corticotrophin releasing hormone

• -> stimulates pituitary gland to secrete adrenocorticotropic hormone
• -> targets cells in adrenal cortex to secrete cortisol

Question 11

Explain the effects of constantly high cortisol levels (i.e. Cushing syndrome)

Answer 11

Muscle, bone and skin breakdown
Elevated glucose levels which leads to high insulin levels - insulin targets adipocytes in centre of body and activates lipoprotein lipase causing fat accumulation
Hypertension - due to amplifying effect of catecholamines AND binding to mineralocorticoid receptors
Inhibit gondatrophin-releasing hormone
Dampens inflammatory/immune response
Impair brain function

Question 12

What does the zona glomerulosa release?

Answer 12

Mineralocorticoid

Question 13

Mineralocorticoid effect

Answer 13

Increases blood pressure by retaining fluid

Question 14

Exogenous causes of Cushing syndrome

Answer 14

Medications - e.g. steroids

Question 15

Explain how exogenous steriods can cause Cushing syndrome

Answer 15

Similar to cortisol so mimics effects on tissues
Also it has a negative feedback effect, causing less CRH and ACTH and this effects the zona fasciculata
Less cortisol is produced and the zona fasciulata shrinks over time
However, still massive amounts of exogenous steroids so get symptoms of high cortisol

Question 16

Endogenous causes of Cushing syndrome

Answer 16

Excess ACTH - pituitary adenoma (benign), small cell lung cancer
Excess cortisol - adrenal adenoma, adrenal carcinoma

Question 17

Explain how adenal tumours effect cortisol, ACTH, CRH and the size of the zona fasciculata

Answer 17

Cells divide abnormally and secrete excess cortisol
–> less CRH and ACTH from negative feedback
–> effects NORMAL cells in zona fasciculata which produce less cortisol and shrink
BUT…
The abnormal cells are autonomous and so aren’t effected by this negative feedback, so overall net effect = too much cortisol

Question 18

Symptoms/signs of Cushing’s

Answer 18

Muscle wasting
Thin extremities
Skin thinning
Easy bruising
Abdominal striae
Fractures (osteoporosis)
Fat redistribution - round full moon shaped face, buffalo hump, truncal obesity
Hyperglycaemia - can lead to DM
Hypertension
Poor immune system

Question 19

Diagnosis of Cushing’s

Answer 19

24 hour urinary free cortisol
9am and midnight ACTH and cortisol levels
Overnight dexamethasone suppression test
MRI of pituitary, CT adrenals CT chest abdo pelvis (if appropriate)

Question 20

What is low dose dexamethasone suppression test?

Normal result

Answer 20

Given low dose of dexamethasone (1mg at 10pm) –> suppresses ACTH production
Should cause a decrease in serum cortisol levels - measured at 9am

Question 21

Dexamethasone suppression test

- endogenous Cushing’s results

Answer 21

Cortisol remains high

Question 22

Explain HIGH DOSE dexamethasone test

Answer 22

Given 8mg dexamethasone

Pituitary adenoma responds to high dose - reduces ACTH and cortisol

Adrenal adenoma/carcinoma - reduces ACTH, but not cortisol as this is being released autonomously

Small cell lung cancer - stops ACTH from pituitary BUT still have ACTH being released elsewhere, so cortisol still high (and so is overall ACTH)

Question 23

Treatment of Cushing’s

Answer 23

Gradually decrease steroid medications (to avoid adrenal crisis)
Surgical excision of adenoma
Adrenal steroid inhibitors - ketoconazole, metyrapone

Question 24

High dose dexamethasone suppression test results with pituitary adenoma

Answer 24

Low ACTH

Low cortisol

Question 25

High dose dexamethasone suppression test results with adrenal adenoma/carcinoma

Answer 25

Low ACTH

High/normal cortisol

Question 26

High dose dexamethasone suppression test results with small cell lung cancer

Answer 26

High ACTH

High/normal cortisol

Question 27

What acid-base disturbance is seen in Cushing’s and why?

Answer 27

High cortisol acts on mineralocorticoid receptors

• acts in similar way to aldosterone on Na+/K+ pumps in DCT and collecting ducts
• -> hypernatraemia, hypokalaemia
• -> cells try to compensate by taking in H+ and pumping out K+
• -> hypokalaemic metabolic alkalosis