302 Pathophysiology and genetics of phaeochromocytomas

Question 1

What are some primary causes of hypertension?

Answer 1

Essential and idiopathic hypertension

Question 2

What are some secondary causes of hypertension?

Answer 2

CHAPS

Cushing’s
Hyperaldosteronism
Aortic coarctation
Pheochromocytoma
Stenosis of renal arteries

Other: pregnancy, drugs

Question 3

What is a Phaeochromocytoma?

Answer 3

An adrenal medullary tumour that secretes excess catecholamines
Eg. adrenaline, noradrenaline and dopamine from chromaffin cells

Question 4

What is a paraganglioma?

Answer 4

Neuroendocrine tumours that arise from sympathetic and parasympathetic ganglia

Sympathetic tumours can secrete excess catecholamines

Question 5

What are the common symptoms of pheochromocytomas and paragangliomas?

Answer 5

Top 40%:
High blood pressure
Headache
Sweating

Other:
Flushing
Anxiety
Palpitations
Abdominal pain
Dizziness
Blurry vision
Diabetes symptoms
Tachycardia
Heart failure

Question 6

What are the 5 P’s for signs and symptoms of phaeochromocytomas?

Answer 6

Pressure (HTN) 90%
Pain (headache) 80%
Perspiration 71%
Palpitation 64%
Pallor 42%

and paroxysms

Question 7

What are Paroxysms?

Answer 7

A sudden strong feeling or expression of emotion that cannot be controlled. a paroxysm of rage

Question 8

Why does a phaeochromocytoma cause hypotension?

Answer 8

There is a loss of postural reflexes due to prolonged catecholamine stimulation

The tumour releases adrenomedullin (vasodilatory neuropeptide)

Question 9

What are the features of having a phaeochromocytoma?

Answer 9

-Abdominal pain
-Severe constipation
-Chest pains
Eg, anxiety, angina
-Hypertension
-Cardiac dysrhythmias
-Hypercalcaemia
-Mild glucose intolerance
-Lipolysis

Question 10

What are some differentials for a phaeochromocytoma?

Answer 10

Hyperthyroidism
Arrhythmias
Hypoglycaemia
Migraine
Panic attacks
Alcohol withdrawal
Recreational medication

Question 11

What are the microscopic sections of an adrenal gland?

Answer 11

Capsule
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla

Question 12

What is the synthesis pathway for catecholamines?

Answer 12

Tyrosine
L-dopa
Dopamine
Noradrenaline
Epinephrine

Each one is produced from the previous one

Question 13

What are the investigations for a phaeochromocytoma?

Answer 13

24 hour urine collection
Catecholamine
VNA
and Metanephrines
Sensitivity: 95-97%; Specificity: 86-95

Or pLasma metanephrines
Sensitivity: 95-99%; Specificity: 89-98%

Question 14

What can cause a false positive of phaeochromocytoma testing?

Answer 14

-Sympathoadrenergic activity/overdrive
-Extreme stress/Critical illness
-Non-supine position
-Renal insufficiency (2-3 fold increased)
-Diet : Coffee, Tea, Bananas, Chocolate, Cocoa, Citrus fruit, Vanilla and Coke
-Medication

Question 15

What imaging can be done for a phaeochromocytoma?

Answer 15

-CT scan
Adrenal pheo sensitivity 93-100%
Extra-adrenal pheo sensitivity 90%

-MRI
Sensitivity greater than CT for extra-adrenal pheo

-MIBG (Meta-iodobenzylguanidine)-chromaffin seeking analogue
Functional modalities
Sensitivity 77-90% specificity 95-100%
Risk of false negative

-FDG PET/CT (Positron emmision tomography
Preferred imaging over metastatic disease
Sensitivity 74 to 100%

Question 16

What pre-operative treatment is given for phaeochromocytomas?

Answer 16

Alpha-adrenergic receptor blockers
Phenoxybenzamine
Start 10mg BD —1mg/kg/d
Daxozocin
2mg/d to 32mg/d

Propanolol can be added if patient is tachycardic
Calcium channel blocker
Metyrosine

Question 17

What are the indications for genetic screening for a phaeochromocytomas?

Answer 17

Bilateral tumours
Paraganglioma (Extra-adrenal)
Unilateral with family history
Unilateral and young age of onset (<45)
Metastasis

Question 18

What are the causes of familial paeochromocytoma?

Answer 18

-MEN 2a- mutation in RET proto-oncogene
50% Pheo (usually bilateral), Medullary, Thyroid carcinoma (MTC) , Parathyroid hyperplasia

-MEN 2b
50% Pheo (usually bilateral), MTC, mucosal neuroma, marfanoid habitus

-Von Hippel-Landau – mutation in the VHL tumour suppressor gene
50% Pheo (usually bilat), retinoblastoma, cerebellar hemangioma, nephroma, renal/pancreas cysts

-NF1 (Von Recklinghausen’s)-mutation in NF1 gene
2% Pheo (50% if NF-1 and HTN)
Café-au-lait spots, neurofibroma, optic glioma

-Familial paraganglioma – SDH mutation

-Familial pheo & islet cell tumor

Other: Tuberous sclerosis, Sturge-Weber, ataxia-telangectgasia, Carney’s Triad (Pheo, Gastric Leiomyoma, Pulm chondroma)