Cushing's disease and Cushing's syndrome

Question 1

Endogenous Cushing’s syndrome

Answer 1

persistently + inappropriately elevated circulating glucocorticoid levels

Question 2

Where are glucocorticoids produced and name some

Answer 2

Zona fasciculata of the adrenal gland

cortisol, hydrocortisone

Question 3

what causes most of Cushing’s syndrome?

Answer 3

Iatrogenic: synthetic steroids or ACTH for Tx of conditions such as asthma

Question 4

ACTH-dependent causes of Cushing’s syndrome

Answer 4

70% are from Cushing’s disease

Ectopic ACTH- producing tumours (SCLC, carcinoid tumours)

Question 5

ACTH independent causes of Cushing’s syndrome

Answer 5

adrenal carcinoma

adrenal adenoma

Question 6

Cushing’s disease

Answer 6

excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary

(usually micro adenoma, less often corticotrophin hyperplasia)

Question 7

Pseudo-Cushing’s syndrome

Answer 7

alcohol excess mimics Cushing’s syndrome clinically + biochemically

unknown why but resolves when alcohol is stopped

Question 8

General clinical features

Answer 8

obese
central fat distribution (buffalo hump)
plethoric complexion (red + ruddy)
moon face

pigmentation with ACTH-dependent cases

Question 9

Clinical features as result of protein-catabolic effect of cortisol

Answer 9

purple striae on abd, breasts + thighs

skin is thin + bruises easily

Question 10

2 principles of investigation

Answer 10

1. confirm cortisol excess

2. determine the cause

Question 11

How to confirm cortisol excess

Answer 11

48hr low-dose dexamethasone suppression test (normal individuals suppress plasma cortisol)

24 hr urinary free cortisol (raised)

Circadian rhythm studies (loss of normal circadian fall of plasma cortisol at 2400 in those with Cushing’s!)

Question 12

Imaging (for cause)

Answer 12

Adrenal CT: adenomas + carcinomas

Pituitary MRI/CT: some pituitary adenomas

Question 13

Significance of plasma ACTH levels

Answer 13

they are low/undetectable in adrenal disease (ACTH independent) –> image adrenals

high –> pituitary disease/ectopic

Question 14

Significant of high-dose dexamethasone suppression test

Answer 14

Those with pituitary-dependent Cushing’s disease suppress plasma cortisol by 48hrs

Failure of suppression –> ectopic source of ACTH or an adrenal tumour

Question 15

What does an exaggerated plasma ACTH response to exogenous CRH suggest? (CRH test)

Answer 15

pituitary-dependent Cushing’s disease

Question 16

Management

Answer 16

Surgical removal (if suitable)

Drugs which inhibit cortisol synthesis

Question 17

How are pituitary tumours removed?

Answer 17

transsphenoidal surgery

Question 18

How to treat iatrogenic Cushing’s syndrome

Answer 18

reduce steroid dosage

use azathioprine (a steroid sparing agent) in combination with a steroid to enable lower steroid doses