MRCP revision battle 20.1: MEN

Yet another sunny day to try and tempt me outside (who am I kidding, it worked, I've been outside had some sunshine, beer and am now back inside trying to settle)

Todays battles are going to be:

MRCP revision battle 20.1: MEN
MRCP revision battle 20.2: Folate
MRCP revision battle 20.3: Subacute combined degeneration of the spinal cord
MRCP revision battle 20.4: Vitamin B12
MRCP revision battle 20.5: Pernicious anaemia
MRCP revision battle 20.6: Churg Strauss
MRCP revision battle 20.7: ANCA





MRCP revision battle 20.1: MEN

As any of my friends will tell you MEN have frequently been a problem in my life and the condition MEN (=multiple endocrine neoplasia) has been no less troublesome.  Yes, I get that they are genetic syndromes in which there are functioning hormone-producing tumours in multiple organs.  My problem lies in managing to associate the different patterns to the different classes of MEN, which MRCP seems to require you to do rather a lot.


Firstly, 2 key facts to grasp:

1. all MEN can be inherited or sporadic; if inherited they are autosomal dominant
2. all are associated with hypercalcaemia, especially MEN 1

So, to try and learn the subtypes... I've settled on learning "Para pits against the pan men, for which Phaeo gives a medal to the para"  (= parathyroid, pituitary, pancreas (men gene), phaechromocytoma, medullary thyroid, parathyroid)


Which, in more conventional terms:

MEN1

• parathyroid (95%), pituitary (70%) and pancreas (50%)
• caused by mutation of Menin gene (a tumour supressor) on chromosome 10

MEN 2a

• phaechromocytoma (95%), medullary thyroid cancer (70%) and parathyroid (60%)
• ret gene on chromosome 11

MEN 2b

• MEN 2a but without the parathyroid tumours and with a Marfarnoid appearence and mucosal neuromas
• also caused by the ret gene on chromosome 11

Note that the medullary thyroid cancer in MEN is in general less aggressive than the sporadic forms but prophylactic thyroidectomy should still be considered.


As a random aside it might be worth learning that in MEN the mutation in the ret gene is activating, whereas in Hirschsprung's disease, which is also caused by a ret gene mutation, the mutation is inactivating.


So, have you got Para pits against the pan men, for which phaeo gives a medul to the para... not ideal but its the best I've come up with....




Lets move on for a brief encounter with folate....

MRCP revision battle 20.2: Folate

Have you ever been confused by the seemingly random use of either 'folate' or 'folic acid' and wondered what the difference is?  Well, just in case you have, here is the answer: folate is naturally occurring vitamin B9, while folic acid is the artificial form of vitamin B9.   With that cleared up, lets briefly look at folate.


Folate is important in DNA synthesis.  It is also vital in the remethylation of homocysteine, which is a current area of research I'll touch on at the end.


Low folate levels result in a macrocytic anaemia.  In pregnancy they also predispose to neural tube defects.


Good sources of folate include liver, green vegetables and nuts.


Drugs that decrease absorption of folate include phenytoin
Drugs that decrease its metabolism to its active form include trimethoprim, methotrexate and pyrimethamine


If a patient has low folate you should never give folic acid without B12 as doing so may precipitate, or worsen, subacute combined degeneration of the spinal cord (wait for the next battle...)



So just to round up by speaking about folate and homocysteine.  Raised homocysteine levels are associated with increased risk of cardiovascular events, cerebrovascular events and fractures.  Folate lowers homocysteine levels.  Unfortunately, despite this seemingly simple way to decrease risk trials so far have not shown lowering levels to decrease risk.




On that wet blanket of an observation lets progress to subacute combined degeneration of the spinal cord...

MRCP revision battle 20.3: Subacute combined degeneration of the spinal cord

Subacute combined degeneration of the spinal cord is one of those conditions which does exactly what it says on the tin:

• subacute - it's onset is insidious
• combined degeneration - both dorsal and lateral columns affected
• of the spinal cord

The loss of dorsal columns causes sensory and LMN signs, while the lateral (corticospinal) column loss cause motor and UMN signs.


Clinically the classical triad is:

• extensor plantars (UMN)
• absent knee jerks (LMN)
• absent ankle jerks (LMN)

Pain and temperature sensation are preserved as the spinothalamic tracts are preserved.


Subacute combined degeneration of the spinal cord is caused by B12 deficiency.   Treatment is with B12, with varying levels of success.


Now it seems only sensible to have a quick recap of B12....

MRCP revision battle 20.4: Vitamin B12

Vitamin B12 is essential in DNA synthesis.  The body has approximately 4 yrs worth of B12 stored, 'just in case.'

B12 is found in meat and dairy, so other than vegans most people should get enough.


Absorption of B12 is specific; it requires intrinsic factor (which is released from parietal cells in the stomach) to bind to it and it is then absorbed as a complex uniquely in the terminal ileum.


Deficiency of B12 causes a variety of symptoms and signs:

• anaemia
• glossitis
• dementia/depression
• peripheral neuropathy
• subacute combined degeneration of the spinal cord

Investigations will show a macrocytic anaemia, and in severe cases WCC and platelets may also be decreased.


Causes of B12 deficiency can be split into:

• insufficient intake
• vegans
• alcoholics
• anorexics
• lack of absorption
• lack of intrinsic factor
• pernicious anaemia (see next battle)
• gastrectomy
• lack of terminal ileum/absorption space
• crohns
• resection
• giardiasis
• fish tapeworm, Diphyllobothrium 
• drugs interfering with absorption, eg metformin
  

Treatment is to treat the cause/give B12.









  
Lets have a quick look at pernicious anaemia...

MRCP revision battle 20.5: Pernicious anaemia

Pernicious anaemia is an autoimmune atrophic gastritis which leads to achlorhydria and lack of intrinsic factor.


It affects 1:1000 and is commonest in blood group A


Diagnosis may be by:

• parietal cell antibodies - present in 90% of patients with PA - but also 3-10% of people without
• intrinsic factor antibodies - less common but more specific
• the schilling test - click here if it wasn't drummed into you ad nauseum at med school!

Treatment of pernicious anaemia is by B12 injections.


Note gastric cancer is 3x more common in people with PA.



Now for some diversification into the exciting area of small to medium vessel vasculitis...

MRCP revision battle 20.6: Churg Strauss

Churg Strauss is a rare vasculitic disease of unknown aetiology.


The classic triad associated with it is:

• asthma
• eosinophilia
• vasculitis of small and medium vessels

The vasculitis usually affects the lungs, peripheral nerves and skin.


Glomerulonephritis may occur with Churg Strauss but renal failure is rare.


It is pANCA positive.


Treatment is with high-dose steroids.


Now to the final battle of the day, a bit about ANCA...

MRCP revision battle 20.7: ANCA

I had never heard of ANCA until I started my MRCP revision then it seemed to pop up everywhere!


ANCA stands for anti-neutrophil cytoplasmic antibodies.  They are mainly IgG.  They are subdivided into 2 groups based on the patterns produced when they are stained:


1. cANCA

• cytoplasmic, anti PR3
• found in Wegeners (90%), mircroscopic polyangiitis (40%)
• some correlation between level and disease activity

2. pANCA

• perinuclear, anti MPO
• found in churg strauss (60%), crescentic glomerulonephritis (80%), microscopic polyangiitis (60%), Wegeners (60%)
• may also be seen in IBD, RA, SLE, sjogrens, autoimmune hepatitis

Thats it for today, no war at present but I'll try and post one later