Adrenal Medullary Tumours

Question 1

describe the function of the adrenal medulla

Answer 1

consists of neuroendocrine (chromaffin) cells which secrete the major catecholamines: noradrenaline (norepinephrine) and adrenaline (epinephrine)

Question 2

describe the synthesis of noradrenaline and adrenaline

Answer 2

(tyrosine is an amino acid)

Question 3

phaeochromocytoma

Answer 3

rare tumours of the sympathetic nervous system that are derived from the chromaffin cells of the adrenal medulla and secrete catecholamines: noradrenaline and adrenaline

rare cause of secondary hypertension

Question 4

onset of phaeochromocytomas

Answer 4

insidious, mean time of onset of symptoms from diagnosis is 4.5 years

Question 5

what are phaeochromocytomas called when they arise elsewhere in the sympathetic chain

Answer 5

paragangliomas

often found at the aortic bifurcation (chromaffin bodies - the organs of Zuckerlandl)

Question 6

10% rule of phaeochromocytomas

Answer 6

10%:

• malignant
• extra-adrenal (paragangliomas)
• bilateral
• familial

Question 7

what is the only definition for a phaeochromocytoma being malignant

Answer 7

metastases

Question 8

what are the characteristics of familial phaeochromocytomas

Answer 8

occur in younger people and tend to be bilateral

Question 9

genes implicated in familial phaeochromocytomas and paragangliomas

Answer 9

SDH genes

NF1 (neurofibromatosis)

Question 10

succinate dehydrogenase genes

Answer 10

SDH B, C and D

these are mitochondrial genes involved in succinate metabolism and the Kreb’s cycle. they result in accumulation of succinate and activation of hypoxia pathways - stimulate HIF-1a

Question 11

what is associated with SDHD

Answer 11

head and neck paraganglioma

Question 12

what is associated wtih SDHB

Answer 12

malignant paraganglioma

Question 13

what other conditions are phaeochromocytomas associated with

Answer 13

MEN 2 syndrome, neurofibromastosis, tuberous sclerosis and the von Hippel-Lindau syndrome

Question 14

do most phaeochromocytoma tumours release noradrenaline and adrenaline?

Answer 14

yes

although, large and extra-adrenal tumours produce almost entirely noradrenaline

Question 15

what is the classic triad of features

Answer 15

episodic headache, sweating and tachycardia

Question 16

clinical features

Answer 16

pallor

hypertension

palpitations, brady and tachy cardia

pyrexia

breathlessness

constipation

anxiety/fear

weight loss

flushing (uncommon)

Question 17

describe the hypertension

Answer 17

paroxysmal episodes are common, triggered by stress, exercise, posture and palpation of tumour

labile hypertension

Question 18

labile hypertension

Answer 18

(borderline hypertension)

BP may fluctuate abruptly and repeatedly from normal to high

Question 19

what can hypertension be associated with when phaeochromocytomas arise in the bladder

Answer 19

micturition (urination)

Question 20

complications

Answer 20

Cardiac failure (LVF)

Arrhythmias

Myocardial necrosis

Stroke (CVA)

Shock

Paralytic ileus of bowel

Question 21

biochemical abnormalities

Answer 21

hyperglycaemia in adrenaline secreting tumours

low Potassium may be seen

high haematocrit (volume of RBC: total volume of blood - raised Hb concentration)

mild hypercalcaemia

lactic acidosis

Question 22

investigations

Answer 22

detection of urinary catecholamines and metabolites

abdominal CT/MRI to find extra-adrenal masses

MIBG has a lower sensitivity than ^ but is sometimes preferred as it enables whole body imaging

Question 23

diagnosis

Answer 23

Identify the source of catecholamine excess: MRI scan of abdomen and whole body

MIBG

PET scan

Question 24

approach to therapy

Answer 24

full a- and ß- blockade - a before ß to avoid crisis from unopposed a-adrenergic stimulation

• • phenoxybenzamine is an a-blocker used
• • ß blockers too if there is heart disease or tachycardic

fluid and/or blood replacement

careful anaesthetic assessment

surgical

Question 25

surgery

Answer 25

laparoscopic

total excision where possible

tumour debulking

Question 26

long term follow up

Answer 26

genetic testing

family tracing and investigation

malignant recurrence may present late

Question 27

describe the pathology of the masses

Answer 27

range from small to large, adrenal remnants may be seen on the surface

range from yellow/brown to dark and haemorrhagic/necrotic

Question 28

what does potassium dichromate (chrome salts) do to the tumour

Answer 28

turn it dark brown due to oxidation of catecholamines in the tumour chromaffin cells

Question 29

what do the tumour cells stain for

Answer 29

chromogranin A

Question 30

what do malignant tumours tend to look like

Answer 30

dark and necrotic

however, malignancy can only be established on metastases

Question 31

where do adrenal medulllary tumours have a propensity to metastasise to

Answer 31

skeletal

also lymph nodes, lung and liver

Question 32

adrenal neuroblastoma

Answer 32

tumour arising in children from the primitive cells of the medulla

typically presents as a rapdily enlarging abdominal mass

they can show maturation and differentiation towards ganglion cells

age and stage are important for the prognosis

Question 33

amplifications of what in neuroblastomas predict a poor outcome

Answer 33

N-myc and expression of telomerase