Cushing's syndrome

Question 1

ACTH dependent causes?

Answer 1

• Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
• ectopic ACTH production (5-10%): e.g. small cell lung cancer

Question 2

ACTH independent causes?

Answer 2

• iatrogenic: steroids
• adrenal adenoma (5-10%)
• adrenal carcinoma (rare)
• Carney complex: syndrome including cardiac myxoma
• micronodular adrenal dysplasia (very rare)

Question 3

What is Pseudo-Cushing’s and what is it often due to?

Answer 3

• mimics Cushing’s

* often due to alcohol excess or severe depression

Question 4

What test can be used to differentiate Pseudo-Cushing’s from Cushing’s syndrome?

Answer 4

Perform an insulin stress test.

Question 5

What is the issue with investigating Pseudo-Cushing’s?

Answer 5

Pseudo-Cushing’s causes false positive dexamethasone suppression tests or 24 hr urinary free cortisol

Question 6

What abnormalities may be seen in bloods and ABG?

Answer 6

A hypokalaemic metabolic alkalosis along with an impaired glucose tolerance.

Question 7

What cause of Cushing’s is most characteristically associated with very low potassium levels?

Answer 7

Ectopic ACTH secretion (e.g. secondary to small cell lung cancer)

Question 8

What is the main diagnostic test?

Answer 8

Overnight dexamethasone suppression test

Question 9

What other investigative test is there?

Answer 9

24 hr urinary free cortisol

Question 10

What is the first line localisation test?

Answer 10

9am and midnight plasma ACTH (and cortisol) levels. If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma.

Question 11

What is petrosal sinus sampling of ACTH and what is it used for?

Answer 11

Inferior petrosal sinus sampling (IPSS) is an invasive procedure in which adrenocorticotropic hormone (ACTH) levels are sampled from the veins that drain the pituitary gland; these levels are then compared with the ACTH levels in the peripheral blood to determine whether a pituitary tumor (as opposed to an ectopic ACTH tumour is producing raised ACTH)

Question 12

For low and high dose dexamethasone supression test, if results are:
Low dose: no change
High dose: no change
What is the suspected pathology?

Answer 12

Cushing’s syndrome caused by adrenal tumor
or
Cushing’s syndrome related to ectopic ACTH-producing tumor

Question 13

For low and high dose dexamethasone supression test, if results are:
Low dose: no change
High dose: normal suppression
What is the suspected pathology?

Answer 13

Cushing’s Syndrome caused by pituitary tumor (Cushing’s Disease)