Endocrinology - Cushing's

Question 1

Presentation of Cushing’s

Answer 1

Central obesity
Round face
Abdominal striae
Fat pad on upper back (buffalo hump)
Proximal limb muscle wasting

High levels of stress hormone causing:

• Hypertension
• Hyperglycaemia (T2DM)
• Depression
• Insomnia

Also:

• Osteoporosis,
• Easy bruising
• Poor wound healing
• Hirsutism

Irregular periods in females

Question 2

Causes of Cushing’s syndrome

Answer 2

Exogenous steroid treatment

Cushing’s disease (pituitary adenoma releasing excessive ACTH)

Adrenal adenoma

Paraneoplastic Cushing’s

Question 3

What is paraneoplastic Cushing’s?

Answer 3

Excess ACTH release from a cancer (which then stimulates excess cortisol release) - most commonly from small cell lung cancer, also carcinoid

Question 4

Diagnostic test for Cushing’s syndrome

Answer 4

Low dose dexamethasone suppression test first
- If abnormal (cortisol not suppressed) - perform high dose dexamethasone suppression test

(24h Urinary free cortisol can be performed as an alternative to Dexa suppression)

Question 5

How is dexamethasone test done?

Answer 5

Dexamethasone given and then cortisol measured after 48h of dexamethasone

Low dose dexamethasone test:

• Normal - cortisol levels suppressed
• Abnormal - cortisol levels not suppressed = Cushing’s syndrome
• If abnormal, perform high-dose dexamethasone test

Question 6

High dose dexamethasone test result meanings

Answer 6

8mg dexamethasone used

In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.

Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisone is not suppressed however ACTH is suppressed due to negative feedback on the hypothalamus and pituitary gland.

Where there is ectopic ACTH (e.g. from a small cell lung cancer), neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland.

Question 7

High dose dexamethasone suppression test shows suppressed cortisol and ACTH…

Answer 7

Cushing’s disease (Pituitary adenoma)

Question 8

High dose dexamethasone suppression test shows not suppressed cortisol but ACTH is suppressed

Answer 8

Adrenal adenoma

Question 9

High dose dexamethasone suppression test shows neither cortisol or ACTH are suppressed

Answer 9

Ectopic ACTH secretion e.g. small cell lung cancer

Question 10

Other investigations in suspected Cushing’s syndrome

Answer 10

BP

FBC - raised white cells) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)

MRI brain (for pituitary adenoma)

CT Thorax (small cell lung cancer)

Abdominal CT (adrenal tumours)

Question 11

Treatment of Cushing’s syndrome

Answer 11

To surgically remove the underlying tumour cause

Trans-sphenoidal (through the nose) removal of pituitary adenoma

Surgical removal of adrenal tumour

Surgical removal of tumour producing ectopic ACTH

Question 12

If surgical removal is not possible…

Answer 12

If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the patient replacement steroid hormones for life.