MRCP revision battle 35.1: Graves' disease

Today is going to be a bit of a thyroid binge with a little gap to end on...


MRCP revision battle 35.1: Graves' disease
MRCP revision battle 35.2: Subacute (de Quervain's) thyroiditis
MRCP revision battle 35.3: Hashimoto's thyroiditis
MRCP revision battle 35.4: Drugs causing hypothyoidism
MRCP revision battle 35.5: Thyroid storm
MRCP revision battle 35.6: Anion gap




MRCP revision battle 35.1: Graves' disease


Graves' disease is an autoimmune condition which causes hyperthyroidism.  Autoantibodies against the thyroid gland are present.  This may be antithyroid peroxidase antibodies or antithyroglobulin antibodies (neither are specific as they may also found in Hashimotos)  or TSH receptor antibody (specific)


Features of Graves' disease include:

• eye disease (see revision battle 29.2 to recap which features are Graves' disease specific)
• pretibial myxoedema - only found in Graves
• thyroid acropachy = clubbing, painful toe and finger swelling - also only in Graves
• diffuse thyroid enlargement

Associated with Graves' disease include:

• diabetes 
• vitiligo
• Addisons

Treatment options for Graves are:

1. titrate antithyroid drugs
• start at 40mg carbimazole
• continue for 12-18 months
• less side effects
2. block and replace
• start at 40mg carbimazole, levothyroxine once euthyroid
• treat for 6 to 9 months
• more side effects
3. radioiodine

on to battle 35.2...

MRCP revision battle 35.2: Subacute (de Quervain's) thyroiditis

Subacute (de Quervain's) thyroiditis is the label given to a viral infection which causes a painful goitre and potentially transient hyper or hypo thyroidism.


In addition to a painful goitre the patient may have a fever and dysphagia.


Classically it occurs following a upper respiratory tract infection but it may occur after any viral illness (mumps, adenovirus) and also post-partum.


Histology would show multi-nucleated giant cells.
Radioiodine uptake is typically less than 1% at 24 hrs.


Treatment is with NSAIDs.  It resolves spontaneously.


Onwards to Hashimotos...

MRCP revision battle 35.3: Hashimoto's thyroiditis

Hashimoto's thyroiditis is an autoimmune condition causing hypothyroidism.


It is associated with high titres of antithyroid peroxidase antibodies or antithyroglobulin antibodies (neither are specific as they may also found in Graves' disease)


Patients with Hashimotos have a goitre due to lymphocytic and plasma cell infiltration.  The gotire is firm and non-tender.


Clinically patients' with Hashimotos may be hypothyroid, euthyroid or occasionally initially even hyperthyroid!



So lets move away from this autoimmune cause of hypothyroidism to look at drugs causing hypothyroidism...

MRCP revision battle 35.4: Drugs causing hypothyoidism

Drugs which can cause hypothyroidism include:

• lithium
• interferon
• amiodarone
• phenytoin
• aspirin
• oestrogens
• furosemide

 On  to the final bit of thyroid for the day: thyroid storm

MRCP revision battle 35.5: Thyroid storm

Thyroid storms may be precipitated by:

• recent thyroid surgery
• radioiodine
• infection
• MI
• trauma

Iatrogenic thyroxine excess doesn't usually cause a storm.


Features of a thyroid storm include:

• fever >38.5C
• tachycardia
• confusion
• nausea and vomiting
• hypertension
• heart failure

Treatment:

• treat precipitating event
• propranolol
• antithyroid drugs eg propylthiouracil or carbimazole
• dexamethasone/hydrocortisone - blocks T4 to T3 
• Lugol's solution
• ?digoxin to slow heart.

Thats the end of the thyroid binge - now to 'mind the gap..'

MRCP revision battle 35.6: Anion gap

If you have a patient with metabolic acidosis you need to calculate their anion gap.  This is very simple to do, so long as you can remember the following formula (which unfortunately I never can):

Anion gap = (Na + K) - (Cl + HCO3)

A 'normal' anion gap is 10 to 18mmol/l (which can be recalled as roughly the ages you attend secondary school for)


Causes of a raised anion gap may be recalled as LUKES:

• lactic acid (shock, infection, hypoxia)
• urate (renal failure)
• ketones (diabetes, alcohol)
• ethylene glycol/methanol
• salicylate

A more comprehensive list can be recalled by 'cute dimples' = cyanide, urate, toulene, ethylene glycol, diabetic ketoacidosis, isoniazid, methanol, propylene glycol, lactic acid, salicylates




Causes of a metabolic acidosis with a normal anion gap can be recalled as FUSEDCARS:

• fistula (pancreatic)
• uretogastric conduits
• saline administration
• endocrine (hyperparathyroidism)
• diarrhoea
• carbonic anhydrase inhibitors (acetazolamide)
• ammonium chloride
• renal tubular acidosis
• spironolactone

Hopefully thats demystified the anion gap for you.

MRCP revision battle 34.1: The first heart sound

I've just had a whole week off revising.  Very bad from a passing MRCP point of view.  Very good from a remaining sane, keeping friends and staying up-to-date with all the other bits of paper medicine in the UK requires.  Since the exam is now under a month away however I'd better buckle down to it...


MRCP revision battle 34.1: The first heart sound
MRCP revision battle 34.2: The second heart sound
MRCP revision battle 34.3: The third and fourth heart sounds
MRCP revision battle 34.4: Sodium Valproate
MRCP revision battle 34.5: Salicylate overdose
MRCP revision battle 34.6: Haemodialysis in overdose
MRCP revision battle 34.7: Cyanide poisoning
MRCP revision battle 34.8: Phentolamine





MRCP revision battle 34.1: The first heart sound



The first heart sound is made by the closure of the mitral and tricuspid valves.



A loud S1 may be due to:

• mitral stenosis
• hyperdynamic states
• short PR

A soft S1 may be due to:

• long PR
• mitral regurgitation

A    s p l i t  S1 is caused by:

• RBBB
• LBBB
• VT 
• inspiration
• Ebsteins abnormality

A variable S1 is caused by:

• complete heart block
• AF

On to the second heart sound....

MRCP revision battle 34.2: The second heart sound

The second heart sound comprises of the closure of the aortic and pulmonary valves.They usually close <0.05secs apart and in alphabetical order, with the aortic valve closing first.



A loud S2 may be due to:

• systemic hypertension (=loud A2)
• pulmonary hypertension (=loud P2)
• tachycardia

A soft S2 may be due to aortic stenosis.



A  w i d e l y   s p l i t  second heart sound occurs in:

• RBBB
• deep inspiration
• mitral regurgitation
• pulmonary stenosis

A reverse split (=paradoxical split) second heart sound occurs in:

• LBBB
• severe aortic stenosis
• right ventricular pacing
• WPW type 2
• patent ductus arteriosus

Onwards for the third and fourth heart sounds...

MRCP revision battle 34.3: The third and fourth heart sounds

Third heart sound

Third heart sound, AKA gallop rhythm, can be perfectly normal in children and young adults.

It is due to passive filling of the ventricles when the atrioventricular valves open.


In the over 40s it is pathological and may indicate:

• mitral regurgitation
• VSD
• CCF
• constrictive pericarditis

S1          S2  S3

The sound of the 3rd heart sound may be remembered as 'Kentucky' or 'SLOSH-ing in'




Fourth heart sound

A 4th heart sound is caused by atrial contraction against stiff ventricles.

It occurs in:

• aortic stenosis
• HOCM
• hypertension

S4  S1     S2

It can be remembered as 'Tennessee' or  'a STIFF wall'




I thoroughly recommend this website to listen to them http://www.wilkes.med.ucla.edu/Rubintro.htm



Now away from cardiology and to a bit of pharmacology - sodium valproate....

MRCP revision battle 34.4: Sodium valproate

Sodium valproate is a drug used in epilepsy.


It is a P450 inhibitor.


It has the highest risk of birth defects of any of the anti-epileptic drugs.


Sodium valproate also has an impressive plethora of unfortunate side effects which often appear in MRCP questions:

• alopecia
• nausea
• gynaecomastia
• weight gain
• tremor
• hepatitis
• pancreatitis
• tetratrogenic
• ataxia
• thrombocytopenia

As always with long lists of side effects its probable best to try and imprint on your mind a cartoon image of an unfortunate patient who is suffering from all of these side effects.   Personally I have a bald man who has big breasts and a fat, pregnant stomach, who is walking along in an ataxic way, covered in bruises (from his thrombocytopenia and crashing into things with his ataxic gait) while also vomiting and pointing with his trembling fingers to his liver and pancreas.



On that pretty image, lets move on to battle 33.5...

MRCP revision battle 34.5: Salicylate overdose

Patients who have taken a salicylate overdose are potentially more interesting than those who have taken a paracetamol overdose as salicylate poisoning actually has early clinical features you can look out for,  such as:

• sweating
• tinnitus
• dizziness
• pyrexia
• hyperventilation

A blood gas should show a mixed respiratory alkalosis and metabolic acidosis, and potentially a low potassium.


The sweating and pyrexia are due to uncoupling of oxidative phosphorylation.




The effects of salicylate are dose related:

• 150mg/kg: mild
• 250mg/kg: moderate
• >500mg/kg: severe

Later features of salicylate poisoning include:

• renal failure
• hypo or hyperglycaemia
• seizures
• acidosis

Treatment:

• activated charcoal if within 1 hr
• correct acidosis with 1.26% sodium bicarb
• haemodialysis if:
• conc >700mg/l
• metabolic acidosis resistant to treatment
• acute renal failure
• pulmonary oedema
• seizures
• urinary alkalinization is rarely used and is contra-indicated in cerebral or pulmonary oedema

Lets move on to consider use of haemodialysis in overdoses in general...

MRCP revision battle 34.6: Haemodialysis in overdose

Haemodialysis is not helpful in removing a drug if:

• the drug has a large volume of distribution (eg amiodarone, paraquat)
• the drug is highly protein-bound (digoxin, phenytoin)

The drugs that are appropriate for haemodialysis can be remembered as BLAST:

• Barbituates
• Lithium
• Alcohol (methanol/ethanol)
• Salicylate
• Theophylline

Charcoal haemoperfusion may be considered for:

• paracetamol
• theophylline

Now for a touch of cyanide poisoning....

MRCP revision battle 34.7: Cyanide poisoning

Cyanide is used in insecticides, photography and found in some metals.


It's toxicity comes from inhibition of oxidising enzymes, which happily is reversible.


The classical features of cyanide poisoning are:

• brick red skin
• smell of bitter almonds

Acute signs of cyanide poisoning include:

• hypotension
• hypoxia
• headache
• confusion

Chronic signs of cyanide poisoning include:

• ataxia
• peripheral neuropathy
• dermatitis

Treatment is with 100% oxygen and IV dicolbalt edetate



Onwards for a very brief final battle of the day: phentolamine

MRCP revision battle 34.8: Phentolamine

Phentolamine is a non-selective alpha-antagonist.

Its main action is vasodilation due to alpha-1 blockade.



In the context of MRCP the most important snippet to remember is that phentolamine is used to treat adrenaline-induced ischaemia (eg idiot houseofficer uses lidocaine with adrenaline in ring block, what ya gonna do? or clumsy dentist stabs little finger with his anaesthetic needle and its going blue, how will you treat it?)


In a broader context it can also be helpful in hypertension due to phaeochromocytoma or cocaine.



Thats all for today, more tomorrow!

MRCP revision battle 33.1: Myeloma

So today is going to be a galavant through the world of paraproteinaemias, taking in 4 of the top 6 causes (myeloma, Waldenstrom's, MGUS and amyloid; lymphoma/leukaemia related are not discussed, nor is heavy chain disease)

While on the topic of paraproteinaemia is seems appropriate to cover hyperviscosity syndrome, which lends itself to a quick forray into polycythaemia and then on to two completely random topics to round off the day.

Enjoy!


MRCP revision battle 33.1: Myeloma
MRCP revision battle 33.2: Hyperviscosity syndrome

MRCP revision battle 33.3: Waldenstrom's macroglobulinaemia
MRCP revision battle 33.4: MGUS
MRCP revision battle 33.5: Amyloidosis
MRCP revision battle 33.6: Polycythaemia
MRCP revision battle 33.7: Levels of evidence
MRCP revision battle 33.8: Holmes Adie pupil



MRCP revision battle 33.1: Myeloma


Myeloma is a malignant monoclonal proliferation of plasma cells.
The commonest subclass is IgG (IgG>IgA>IgM)



Symptoms:

• osteolytic bone lesions --> backache/pathological fractures
• symptoms of hypercalcaemia
• bacterial infections due to immunoparesis
• renal impairment due to light chains

Investigations:

• Bloods:
• normocytic normochromic anaemia
• rouleaux on blood film
• raised calcium (40%)
• raised urea and creatinine
• raised ESR
• Urine
• Bence Jones proteins (=free serum light chains) in urine (66%)
• XR
• ?pepper pot skull, vertebral collapse

The diagnostic criteria for myeloma is:

1. monoclonal protein band in serum or urine electrophoresis
2. increased plasma cells on BM biopsy
3. evidence of end organ damage from myeloma

Treatment:

• supportive
• chemo
• younger patients: aggressive (VAD - vincristine, adriamycin, dexamethasone)
• older patients: less aggressive (CDT - cyclophosphamide, dexamethasone, thalidomide)

Complications of myeloma include:

• Hyperviscosity syndrome
• Hyperviscosity syndrome occurs most commonly in IgM myeloma (IgM>IgA>IgG)
• Transfusions should be avoided in hyperviscosity syndrome.
• hypercalcaemia
• spinal cord compression
• acute renal failure
• AL amyloidosis (15%)

Survival with myeloma tends to be 3-4 yrs. 
Higher beta 2 microglobulin implies a worse prognosis.



Onwards for a bit more about hyperviscosity syndrome....

MRCP revision battle 33.2: Hyperviscosity syndrome

Hyperviscosity syndrome is a condition in which the viscosity (='stickiness') of the blood has increased to a degree which prevents easy flow through the microcirculation.



This causes symptoms such as:

• lethargy
• confusion
• headache
• visual disturbances
• spontaneous bleeding

The visual disturbance is described as 'looking through a watery car windscreen'
The optic disc may occur blurred.



Normal plasma viscosity is 1.4-1.8.  Hyperviscosity syndrome develops above around 4.



Causes of hyperviscosity syndrome include:

• myeloma
• Waldenstroms macroglobulinaemia
• leukaemias
• polycythaemia

Treatment depends on the cause; in myeloma/waldenstroms the patient needs plasmaphersis whereas in polycythaemia the treatment is venesection.



So now seems a good time to battle Waldenstrom's macroglobulinaemia...

MRCP revision battle 33.3: Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia, AKA lymphoplasmacytoid lymphoma, is a condition in which monoclonal proliferation of terminally differentiated lymphocytes results in a monoclonal IgM paraprotein.

The significance of this is that IgM carries a high risk of hyperviscosity syndrome.



Treatment for Waldenstom's:

• none if asymptomatic
• plasmapheresis if hyperviscosity
• ? chemo

On to another paraproteinaemia, MGUS...

MRCP revision battle 33.4: MGUS

MGUS stands for monoclonal gammopathy of undetermined significance.
As the name suggests, it is a low-level paraproteinaemia of unknown relevance.

It is common, affecting around 3% of those over 70 yrs of age.


For MGUS to be diagnosed the following diagnostic criteria must be met:

1. low level paraprotein (<30g/l)
2. less than 10% plasma cells on BM
3. no clinical evidence of myeloma.

Around 10% have myeloma at 5yrs so management tends to be yearly observation.


On to amyloidosis...

MRCP revision battle 33.5: Amyloidosis

coming soon....


for now skip on to polycythaemia..

MRCP revision battle 33.6: Polycythaemia

Polycythaemia is a raised red cell count and haemocrit, defined as >0.52 in males or >0.48 in females.


The first thing to establish is if the polycythaemis is 'true/absolute' or 'relative/pseudo'.



Relative/pseudo polycythaemia occurs due to decreased plasma volume.  This may occur due to dehydration (eg vomiting, diarrhoea, diuretics)

A special form of relative polycythaemia is Gaisbocks.  This tends to affect middle-aged men and is attributed to stress (hypertension, smoking, mild obesity) causing a chronically reduced plasma volume.




True/absolute polycythaemis is due to raised red cell mass.
It can be further divided into primary true polycythaemia and secondary true polycythaemia.





Primary true polycythaemia = polycythaemia rubra vera


Polycythaemia rubra vera is associated with JAK2 mutation in 95% of cases.

It peaks in the 6th decade.


Features include:

• hyperviscosity-syndrome symptoms
• pruritis, especially after a hot bath
• splenomegaly
• plethoric features
• hypertension in 1/3
• haemorrhage secondary to abnormal platelets
• DVTs/arterial thrombosis
• peptic ulceration
• gout

WCC/platelets/neutrophil alkaline phosphatase are raised; this helps distinguish primary from secondary polycythaemia.




Secondary polycythaemia 


Secondary polycythaemia is due to raised erythropoietin.

Causes:

• physiological - neonates, high altitude
• congenital cyanotic heart disease
• smoking/COPD
• HbM
• renal cysts
• post renal transplant
• fibroids
• hepatoma

Management of true polycthaemia is:

• venesection
• hydroxyurea to supress erythropoesis
• aspirin

Now for something completely different - levels of evidence...