Catecholamines Flashcards
What supplies the adrenal medulla?
- Superior
- Middle
- Inferior arteries
- These divide to form medullary, cortical and capsular arterioles
- Cortical arteries also supply medulla to deliver corticosteroids
What veins drain the adrenal gland?
- Medullary venules drain to central vein
- Left adrenal vein drains to left renal vein
- Right adrenal vein to inferior vena cava
What do the granules of chromaffin cells contain?
- ATP
- POMC products
- Chromoganin
- Catecholamines
Describe the formation of catecholamines?
- Tyrosine is taken up into the cell and converted to DOPA by tyrosine hydroxylase (occurs in cytoplasm –> rate limiting step)
- DOPA is converted to dopamine by DOPA decarboxylase (cytoplasm)
- Dopamine converted to NA by dopamine hydroxylase (granules –> store for future use)
- NA released back into cytoplasm and converted to adrenaline by PNMT
- PNMT expression depends on high [cortisol] that are only present in adrenal medulla because of the drainage of venous blood from outer adrenal cortex*
- (cortical arteries passing blood to central vein)*
What is PNMT expression increased by?
- Sympathetic neural outout
- Glucocorticoids
NB. NA neurones lack PNMT
What induces the rate limiting step of synthesis?
Acute sympathetic stimulation
What activates an increase in tyrosine hydroxylase :. increases catecholamines production
Chronic stimulation
What are NA and A broken down by and what are their waste products?
- MOA and COMT
- Metanephrine and VMA (adrenaline and NA)
When look at excess production of catecholamines look at conc. of these waste products as easily detected in urine and blood (broken down quickly)
What do adrenaline and NA conc. depend on:
- Synthesis and secretion
- Uptake and metabolism - controlled by post-ganglionic endocytosis
Uptake is more imp. than metabolism because syntheses and secretion not on as high metabolic control (as NA and A are pre-formed)
What would you give after an adrenalectomy or destruction of medulla?
- Corticosteroid replacement
Adrenaline is short term axis with short half life so easier to administer cortisol as long half life and is a long term axis
What kind of hormones can pheochromocytomas secrete?
- NA
- Adrenaline
- Dopamine
- VMA
- Metanephrines
NB. See increase in both NA and A (as can overproduce both)
What is the difference between an extra-adrenal paraganglioma and intra-adrenal paraganglioma?
- Chromaffin cells outside medulla
- Chromafin cells inside medulla (e.g. pheochromocytoma)
Where do extra-adrenal pheochromocytomas arise?
- in abdomen arise around inferior mesenteric artery (organ of Zuckerland)
- Aortic bifurcation
What is the epidemiology of pheochromocytomas?
- Most are sporadic, unicentric and unilateral when in medulla
- 20-30% are familial, multicentric and bilateral
How would you diagnose pheocytochromas?
- Release is episodic so do assay of 24hr urine sample
- Imaging with uptake scans with meta-iodobenzylguanidine (mIBG)
- Also MRI/PET scanning
What are the steps for surgical prep for pheochromocytoma removal?

Why do you use phenoxybenzamine for preoperative management?
- Non-competitive alpha blockade
- Doxazosin is competitive so can be displaced by high conc. of endogenous catecholamines
- Side effects of phenoxybenzamine:
- Nasal congestion
- Drowsiness
- Fatigue
- Postural hypotension
What are medications which can provoke hypertensive crisis in patients with pheochromocytoma?
- D2 dopamine receptor antagonists
- Non cardioselective beta blockers
- TCAs
- NT uptake blockers
- Sympathomimetics
Why is fluid replacement done 10 days before surgery?
- Blood volume depletion as a result of continued high BP can contribute to hypotension and shock
- Clamping venous drainage of the tumour during surgery can cause abrupt reversal of catecholamines-induced vasoconstriction
What else must be considered before doing surgery?
- Catecholamine-induced cardiomyopathy
- Arrythmias
What are MEN?
- Autosomal dominant mutations
- MENIN gene - tumour supressor gene
- RET gene - proto-oncogene
What is MEN type I defined by?
- 4 parathyroid glands
- Pancreatic islets – e.g. gastrinoma, insulinoma, glucagonoma, vasoactive intestinal peptide tumor (VIPoma), pancreatic polypeptide– producing tumor (PPoma)
- Anterior pituitary – e.g. prolactinoma, somatotropinoma, corticotropinoma, nonfunctioning tumors
- Other associated tumors include lipomas, angiofibromas, and those located in the adrenal gland cortex (rarely, in the adrenal medulla).
What is MEN type IIa defined by?
- Medullary thyroid carcinoma (MTC)
- Pheochromocytoma (~50% of cases)
- Hyperparathyroidism caused by parathyroid gland hyperplasia (~20% of cases).
However, familial MTC is also recognized. Familial MTC is hereditary MTC without other associated endocrinopathies
What is MEN type IIb defined by?
- MTC and pheochromocytoma
- Associated abnormalities include:
- mucosal neuromas
- medullated corneal nerve fibers
- marfanoid habitus.
What is the most common manifestation of Type 1 MEN?
Hyperparathyroidism
What are the symptoms of a pheochromocytoma?
- Extreme hypertension
- Sweating
- Flushing
- Palpitations
- Nausea
What should be evaluated when diagnosing pheocytochromocytomas?
- Plasma free metanephrines
- 24 hour urine for catecholamines/metanephrines