Cushing's Syndrome

Question 1

Cushing’s syndrome refers to feature of prolonged high levels of..

Answer 1

glucocorticoids

Question 2

What are the 2 groups of corticosteroids?

Answer 2

Glucocorticoids and mineralocorticoids

Question 3

Give an example of a glucocorticoid

Answer 3

cortisol

Question 4

Give an example of a mineralcorticoid

Answer 4

aldosterone

Question 5

Cortisol is the primary natural glucocorticoid hormone and is produced by the…

Answer 5

adrenal glands

Question 6

Cushing’s disease refer to a ______ _______ secreting excessive ____

Answer 6

pituitary adenoma, ACTH

Question 7

How does the increased ACTH in Cushing’s affect the adrenal glands?

Answer 7

Causes excessive cortisol to be released

Question 8

What is the other cause (not Cushing’s disease ie pituitary adenoma) that can cause Cushing’s syndrome?

Answer 8

prolonged use of exogenous corticosteroids like prednisolone or dexamethasone.

Question 9

What are features of Cushing’s syndrome?

Answer 9

Round face (“moon face”)
Central obesity
Proximal limb muscle wasting
Abdominal striae
Enlarged fat pad on upper back (“buffalo hump”)
Male pattern facial hair in women
Easy bruising
Poor skin healing
Hyperpigmentation of skin

Question 10

What are metabolic effects of Cushing’s syndrome?

Answer 10

Hypertension (high levels of cortisol)
Cardiac hypertrophy
T2 DM (cortisol promotes insulin resistance)
Dyslipidaemia
Osteoporosis (cortisol inhibits osteoblasts)

Question 11

What are the causes of Cushing’s Syndrome?

Answer 11

Think CAPE

Cushing’s disease (pituitary adenoma releasing excessive ACTH)

Adrenal adenoma (adrenal tumour secreting excess cortisol)

Paraneoplastic syndrome (a tumour secretes ACTH)

Exogenous steroids (long-term corticosteroids)

Question 12

What does ectopic mean?

Answer 12

In an abnormal place or position

Question 13

What is the ACTH from a tumour other than the pituitary gland (paraneoplastic syndrome) called?

Answer 13

Ectopic ACTH

Question 14

How can hyperpigmentation help you diagnose?

Answer 14

Causes involving excess ATCH will show hyperpigmentation.
Therefore, Cushing’s disease (pituitary adenoma), paraneoplastic syndrome (ectopic ACTH) or Addison’s disease (lots of ACTH) will show hyperpigmentation.

However, there is not excess ACTH in an adrenal adenoma or exogenous steroids so no hyperpigmentation.

Question 15

What test is used to diagnose Cushing’s syndrome caused by a problem in the body (ie not exogenous steroid use)

Answer 15

Dexamethasone suppression test

Question 16

What is the normal response to dexamethasone?

Answer 16

Suppressed cortisol. due to negative feedback.

Dexamethasone suppresses both the CRH released by hypothalamus and the ACTH made by the pituitary gland. Therefore low cortisol level.

Question 17

A lack of _____ suppression in response to dexamethasone suggests Cushing’s syndrome

Answer 17

cortisol

Question 18

What is the low-dose overnight dexamethasone test?

Answer 18

1mg dexamethasone given at night and cortisol checked 9am.
Normal result = suppressed cortisol
Screening test

Question 19

What is the low-dose 48 hour dexamethasone test?

Answer 19

0.5mg dexamethasone given every 6 hours for 8 doses starting 9am.
Cortisol checked before 1st dose at 9am and 9am after last dose.
Normal result = suppressed cortisol

Question 20

What is high-dose 48 hour dexamethasone test?

Answer 20

2mg dexamethasone given every 6 hours for 8 doses.
This higher dose is enough to suppress cortisol in pituitary adenoma (Cushing’s disease) but not from adrenal adenoma or ectopic ACTH.

Question 21

What happens to the level of ACTH when there is excess cortisol from an adrenal tumour or exogenous steroids?

Answer 21

It is suppressed

Question 22

What happens to the level of ACTH when there is a pituitary tumour or ectopic ACTH?

Answer 22

It increases

Question 23

What are other investigations for suspected Cushing’s disease?

Answer 23

Full blood count (may show high WBCs)
U&Es (may show low potassium if adrenal adenoma also secreting aldosterone)
MRI for pituitary adenoma
CT chest for small cell lung cancer (paraneoplastic syndrome)
CT abdomen for adrenal tumours

Question 24

How do treat Cushing’s syndrome?

Answer 24

Surgery: remove adrenal tumour or ectopic ACTH. Trans-sphenoidal surgery for pituitary adenoma.

If surgical removal not possible then could remove both adrenal glands and give life-long steroid replacement therapy.