Endo - Cushing's, Phaeochromocytoma, Acromegaly

Question 1

Cushing’s Syndrome - what is it?

Answer 1

Cushing’s syndrome (CS) refers to signs and symptoms that develop after prolonged exposure to excess of glucocorticoids (like cortisol)

Question 2

Cushing’s Syndrome - difference between Cushing’s syndrome and Cushing’s disease?

Answer 2

Cushing’s disease used to refer to specific condition where pituitary adenoma secretes excessive ACTH

Cushing’s Disease can cause Cushing’s Syndrome

Cushing’s syndrome is not always caused by Cushing’s disease

Question 3

Cushing’s Syndrome - clinical features

Answer 3

Round in middle with thin limbs:

1. ‘Moon’ face
2. Central obesity
3. Abdo striae
4. Buffalo hump
5. Proximal limb muscle wasting
6. Hirsutism

High levels of stress hormone:

1. Hyperglycaemia
2. HTN
3. Depression
4. Cardiac hypertrophy

Question 4

Cushing’s Syndrome - causes?

Answer 4

Paraneoplastic Cushing’s - ectopic ACTH released from tumour, stimulates excessive cortisol release, SCLC most common cause

Exogenous steroids - patients on long term high dose steroids

Cushing’s disease - pituitary adenoma

Adrenal adenoma

Question 5

Cushing’s Syndrome - main investigation for Cushing’s

Answer 5

Dexamethasone Suppression Tests - low dose (1mg) and high dose (8mg)

Given at night, measured in morning

Dexamethasone is synthetic glucocorticoid steroid, so giving it should suppress release of cortisol in the morning because of negative feedback on hypothalamus and pituitary

If low dose normal, then Cushing’s excluded, if abnormal, high dose performed to differentiate between different causes

See picture for different causes and their results

Question 6

Cushing’s Syndrome - other investigations

Answer 6

24 hour urinary free cortisol

Scans to check for underlying cause:
MRI brain for pituitary adenoma
Chest CT for SCLC
Abdo CT for adrenal tumours

Question 7

Cushing’s Syndrome - management

Answer 7

Remove underlying cause

Cushing’s Disease: GOLD STANDARD is Trans-sphenoidal (through nose) removal of pituitary adenoma

Surgical removal of adrenal tumour or tumour producing ectopic ACTH

Question 8

Phaeochromocytoma - what is it?

Answer 8

Adrenaline is produced by Chromaffin cells in adrenal medulla of adrenal glands

Phaeochromocytoma is a tumour of the chromaffin cells that secretes excessive amounts of adrenaline

10% are familial and may be associated with multiple endocrine neoplasia type 2 (MEN 2)

Question 9

Phaeochromocytoma - what is adrenaline’s function?

Answer 9

Adrenaline stimulates sympathetic nervous system, and is responsible for fight or flight response

Question 10

Phaeochromocytoma - what is the symptom presentation like timewise?

Answer 10

In patients with a phaeochromocytoma, adrenaline secreted in bursts, therefore periods of worse symptoms followed by more settled periods

Question 11

Phaeochromocytoma - what is the ‘10% rule’?

Answer 11

Used to describe pattern of tumour

10% bilateral
10% cancerous
10% outside adrenal gland

Question 12

Phaeochromocytoma - what is the classical presentation?

Answer 12

HTN (90% of cases)
Palpitations, tachycardia, paroxysmal AF
Sweating
Anxiety
Headaches

Signs and symptoms tend to fluctuate with peaks and troughs

Question 13

Phaeochromocytoma - what are catecholamines?

Answer 13

Catecholamines are hormones made by your adrenal glands

Question 14

Phaeochromocytoma - how do you diagnose?

Answer 14

24 hr urinary collection of metanephrines (sensitivity 97%)

Adrenaline - short half life, few minutes in blood, whereas metanephrines, a breakdown product of adrenaline, have a longer half life

Makes the level of metanephrines less prone to dramatic fluctuations and more reliable

Question 15

Phaeochromocytoma - management

Answer 15

Surgery is definitive management

The patient must first however be stabilized with medical management:

1. alpha-blocker (phenoxybenzamine), given before a
2. beta-blocker (propranolol)

PHaeochromocytoma - give PHenoxybenzamine before beta-blockers

Question 16

Acromegaly - what is it?

Answer 16

Excessive growth hormone production secondary to a pituitary adenoma

or

in minority of cases secondary to ectopic GH producing cancer tumours

Question 17

Acromegaly - presentation

Answer 17

Space occupying lesion:

1. Headaches
2. Bitemporal hemianopia

Overgrowth of tissues:

1. Prognathism - large protruding jaw
2. Macroglossia
3. Large hands + feet
4. Large nose

Organ dysfunction:

1. Cardiomyopathy
2. T2DM
3. HTN
4. Colorectal cancer

Also excessive sweating and oily skin

Question 18

Acromegaly - why do you get bitemporal hemianopia?

Answer 18

1. Optic chiasm sits above pituitary gland, and is where optic nerves crossover
2. Pituitary tumour of sufficient size will press on optic chiasm
3. Causes bitemporal hemianopia
4. Outer half of eye vision loss

Question 19

Acromegaly - investigations

Answer 19

Serum Insulin-like growth factor 1 (IGF-1) - will be increased in acromegaly

If IGF-1 raised, confirm with OGTT and serial GH measurements

MRI brain - pituitary tumour

Question 20

Acromegaly - management

Answer 20

Trans-sphenoidal (through the nose and sphenoid bone) removal of the pituitary tumour is the definitive treatment of acromegaly secondary to pituitary adenomas

If pituitary tumour inoperable or surgery unsuccessful, then medication may be indicated:

1. Pegvisomant - GH receptor antagonist given subcutaneously and daily
2. Somatostatin analogues (Ocreotide) - directly inhibits release of GH
3. Dopamine agonists (Bromocriptine) - blocks GH release

One of the functions of somatostatin is to block GH release from the pituitary gland. Dopamine also has an inhibitory effect on GH release, however not as potent as somatostatin.