Studydroid is shutting down on January 1st, 2019

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Name the naturally occurring catecholamines (3)
  • Norepinephrine (NE)
  • Epinephrine (E)
  • Dopamine
Does synthesis of catecholamines occur only in adrenal medulla?
No
  • Also in SNS (neurons) and CNS (chromaffin cells in abdomen and neck) 
How do catecholamines have biological effect?
Through G-protein coupled receptors (alpha and beta adrenergic receptors)
For each of the following, indicate whether noradrenaline or epinephrine has more effect?
  • Neurotransmitter
  • Vascular system
  • Glucose metabolism
  • Neurotransmitter → N
  • Vascular system → N=E
  • Glucose metabolism → E
For each of the following, indicate the principal catecholamine produced?
  • SNS 
  • Adrenal medulla
  • CNS
  • SNS  → Norepinephrine
  • Adrenal medulla  → Epinephrine
  • CNS  → Dopamine
What is the rate limiting step in the biosynthesis of catecholamines?
Tyrosine  → DOPA
  • Hydroxylation of dopamine 
Name the 5 steps of catecholamine metabolism
  • Tyrosine
  • DOPA
  • Dopamine
  • Norepinephrine
  • Epinephrine 
In adrenal medulla, where is dopamine stored?
Granules
What happens to the dopamine in granules in adrenal medulla?
Metabolized into norepinephrine  by dopamine β-hydroxylase
  • Describe what happens to norepinephrine in catecholamine metabolism
  • What enzyme is involved and what induces this step

  • PNMT methylates norepinephrine to covert it to epinephrine
  • PMNT is induced by cortisol (high concentrations required for induction to occur)
  • Name the products of the 1st step of catecholamine degradation?
  • What enzyme does this?
Products:
  • Metanephrine
  • Normetanephrine
Enzyme:
  • COMT 
  • Name the product of the 2nd step of catecholamine degradation?
  • What enzyme does this?
Product:
  • Vanillyl-mandelic acid (VMA)
Enzyme:
  • MAO 
What regulates the synthesis of epinephrine and norepinephrine?
The hormones regulate their own synthesis by negative feedback inhibition
Name the stimuli that can lead to the release of catecholamines
  • Hypotension
  • Hypoxia
  • Exposure to cold
  • Myocardial infarction
  • Angina
  • Hemorrhage
  • Surgery
  • Hypoglycemia
  • Muscular exertion
  • Pain
  • Emotional disturbances
Describe the specific physiological mechanism that causes release of catecholamines
  • Ach is released from pre-ganglionic fibers
  • Depolarization and influx of calcium triggers exocytosis of storage vesicles 
Pheochromocytoma is usually a benign tumor arising from what type of cell?
Chromaffin cells

Pheochromocytoma:
  • What does it cause?
  • Is it curable? 
  • Rare cause of hypertension, can also cause death from severe hypertensive attacks
  • Surgically curable
Is pheochromocytoma inheritable?
Yes
  • Multiple endocrine neoplasia (MEN)
  • Mutations of succinate dehyodrgenase gene
  • Association with neurofibromatosis and von Hippel-Lindau 
Is pheochromocytoma always benign?
No
  • 10% are malignant 
Describe what pheochromocytomas do?
Release catecholamines in a sustained or episodic fashion
  • Highly variable frequency and duration of episodes, as well as type of hormone secreted
  • What is the most significant finding in pheochromocytoma?
  • What are other common findings
  • Hypertension (90%)
  • Headache, sweating, palpitations, tachycardia, anxiety

Hypotension can also occur
What is the differential diagnosis for a pheochromocytoma?
  • Essential hypertension
  • Anxiety
  • Panic disorder
  • Hyperthyroidism
  • Cardiac arrythmia
What is a common cause of death in pheochromocytoma patients?
Hypertensive or hypotensive crisis
  • Also: Myocardial infarction, strokes, arrythmias, shock, renal failure, dissecting aortic aneurysm

At least 1/3 patients die of one of these complications before they are diagnosed
What proportion of pheochromocytoma are extra-adrenal?
10%
What ages can pheochromocytoma occur at?
Any age
What can trigger attacks with pheochromocytoma?
  • Compression of tumour
  • Change position
  • Exercise
  • Emotional distress
  • How can you diagnose a pheochromocytoma? (3)
  • Which test is the most sensitive

Most sensitive:
  • 24-hour fractionated urinary metanepehrine

Good for confirmation:
  • 24-hour fractionated urinary catecholamines
Also (less sensitive):
  • VMA analysis
What is the most common finding in pheochromocytoma?
Increased norepinephrine or normetanephrine (with smaller increases in epinephrine or norepinephrine)
What is another useful marker that can be used to diagnose pheochromocytoma besides catecholamines and metanephrines?
Chromogranin A
Besides urine tests for metabolites and the chromogranin A marker, what are other tests for pheochromocytoma? (4)
  • Plasma catecholamine
    -High sensitivity, low specificity 
    -Stress from needle can affect results 
  • CT scan
  • Radioisotope imaging (I131 MIBG)
  • Plasma metanephrine
    -Recent interest in testing
    -Hard for laboratory (due to low concentration)
What are indications for testing for a pheochromocytoma? (4)
  • Clinical symptoms
  • Unexplained adrenal mass
  • Family history of MEN
  • Medical history of hypertensive crisis
If clinical suspicion is high, then it is justifiable to order determinations of catecholamines as well as metabolites (metanephrines)
What can interfere in diagnose of pheochromocytoma? (4)
  • Drugs
  • Some foods (caffeine, bananas, peppers)
  • Essential hypertension
  • Severe stress (and certain physiologic stressors: illness, surgery, MI, hypoglycemia)
MEN-1 consists of what triad?
PPP:
  • Parathryoid
  • Pancreatic islet cell
  • (anterior) Pituitary 
What is MEN?
Multiple Endocrine Neoplasia
  • Distinct syndromes featuring tumours of endocrine glands (which may or may not be malignant)
What is the genetic inheritance pattern of MEN-1, MEN-2A and MEN-2B?
All of them are autosomal dominant
  • Most MEN-1 tumours secrete what?
  • What else might they secrete? (2)
MEN-1 tumours mostly secrete prolactin, but also:
  • GH
  • ACTH 
What gene is responsible for MEN-1?
Menin gene
For high risk patients, what biochemical screening is indicated?
Screening relates to the PPP triad:
  • Parathyroid: Calcium, PTH
  • Pancreatic islet cell: Insulin
  • (anterior) Pituitary: Prolactin

Also: gastrin
What is the key component of MEN-2 syndromes with over 95% affected?
Medullary carcinoma of the thyroid
What are the 3 presentations associated with MEN-2?
  • MTC (thyroid carcinoma)
  • Pheochromocytoma
  • Hyperparathyroidism
What are the 3 types of MEN-2?
  • MEN-2A
  • MEN-2B
  • MCT
Which type of MEN-2 has which presentations?
  • MEN-2A: all presentations (MCT, Pheo, Hyper-PTH)
  • MEN-2B: MCT, Pheo
  • MCT: MCT only 
Of all people with MEN-2, what proportion will develop pheochromocytomas?
50%
What additional symptoms are associated with MEN-2B?
  • Ganglioneuromas
  • Neuromas of the lips and tongue
  • Marfinoid features
  • Skeletal anomalies
Which type of MEN-2 is the most benign and has the best prognosis?
MCT = Medullary carcinoma of Thyroid
How does MEN-2 present? (3)
  • Mass in the neck
  • Fine needle biopsy required to confirm diagnosis
  • Elevated calcitonin
Given a patient with MEN-2, who else should be screened?
Screen all first degree relatives of patients with MEN-2
  • DNA testing is available
  • Only those with mutation need to be followed, although thyroid removed because MCL can be fatal at young age
What gene is responsible for all types of MEN-2?
RET proto-oncogene
  • Different mutations in this gene lead to the different types of MEN
What does the RET proto-oncogene code for?
Receptor tyrosine kinase (in neural crest cells)
The RET proto-oncogene is also associated with which disease?
Hirschprung's disease
  • Inactivating mutations 
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