Adrenal Medullary Tumours Flashcards
describe the function of the adrenal medulla
consists of neuroendocrine (chromaffin) cells which secrete the major catecholamines: noradrenaline (norepinephrine) and adrenaline (epinephrine)
describe the synthesis of noradrenaline and adrenaline
(tyrosine is an amino acid)
phaeochromocytoma
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
onset of phaeochromocytomas
insidious, mean time of onset of symptoms from diagnosis is 4.5 years
what are phaeochromocytomas called when they arise elsewhere in the sympathetic chain
paragangliomas
often found at the aortic bifurcation (chromaffin bodies - the organs of Zuckerlandl)
10% rule of phaeochromocytomas
10%:
- malignant
- extra-adrenal (paragangliomas)
- bilateral
- familial
what is the only definition for a phaeochromocytoma being malignant
metastases
what are the characteristics of familial phaeochromocytomas
occur in younger people and tend to be bilateral
genes implicated in familial phaeochromocytomas and paragangliomas
SDH genes
NF1 (neurofibromatosis)
succinate dehydrogenase genes
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
what is associated with SDHD
head and neck paraganglioma
what is associated wtih SDHB
malignant paraganglioma
what other conditions are phaeochromocytomas associated with
MEN 2 syndrome, neurofibromastosis, tuberous sclerosis and the von Hippel-Lindau syndrome
do most phaeochromocytoma tumours release noradrenaline and adrenaline?
yes
although, large and extra-adrenal tumours produce almost entirely noradrenaline
what is the classic triad of features
episodic headache, sweating and tachycardia
clinical features
pallor
hypertension
palpitations, brady and tachy cardia
pyrexia
breathlessness
constipation
anxiety/fear
weight loss
flushing (uncommon)
describe the hypertension
paroxysmal episodes are common, triggered by stress, exercise, posture and palpation of tumour
labile hypertension
labile hypertension
(borderline hypertension)
BP may fluctuate abruptly and repeatedly from normal to high
what can hypertension be associated with when phaeochromocytomas arise in the bladder
micturition (urination)
complications
Cardiac failure (LVF)
Arrhythmias
Myocardial necrosis
Stroke (CVA)
Shock
Paralytic ileus of bowel
biochemical abnormalities
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
investigations
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
diagnosis
Identify the source of catecholamine excess: MRI scan of abdomen and whole body
MIBG
PET scan
approach to therapy
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
surgery
laparoscopic
total excision where possible
tumour debulking
long term follow up
genetic testing
family tracing and investigation
malignant recurrence may present late
describe the pathology of the masses
range from small to large, adrenal remnants may be seen on the surface
range from yellow/brown to dark and haemorrhagic/necrotic
what does potassium dichromate (chrome salts) do to the tumour
turn it dark brown due to oxidation of catecholamines in the tumour chromaffin cells
what do the tumour cells stain for
chromogranin A
what do malignant tumours tend to look like
dark and necrotic
however, malignancy can only be established on metastases
where do adrenal medulllary tumours have a propensity to metastasise to
skeletal
also lymph nodes, lung and liver
adrenal neuroblastoma
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
amplifications of what in neuroblastomas predict a poor outcome
N-myc and expression of telomerase
