Thursday, 14 October 2010

MRCP revision battle 29.1: Hypoglycaemia

After nearly a week away I'm back with a bumper set of battles, the first of which is hypoglycaemia, which has been a recurring theme in both my patients and myself this week!  Enjoy!

MRCP revision battle 29.1: Hypoglycaemia
MRCP revision battle 29.2: Thyroid eye disease
MRCP revision battle 29.3: Hyperlipidaemia
MRCP revision battle 29.4: Lipid-lowering treatment
MRCP revision battle 29.5: Restless legs syndrome
MRCP revision battle 29.6: Histocytosis X
MRCP revision battle 29.7: Bartter's Syndrome
MRCP revision battle 29.8: Gitelman Syndrome
MRCP revision battle 29.9: Liddle's Syndrome

MRCP revision battle 29.1: Hypoglycaemia

Hypoglycaemia is defined as plasma glucose <3mmol/l.

In general in diabetics autonomic symptoms of hypoglycaemia (sweating, anxiety, tremor, palpitations) occur below 3.5mmol and neurological symptoms (confusion, drowsiness, seizures, coma) occur below 2.5mmol.

If a diabetic has frequent hypos they may become 'insensitive' and no longer experience symptoms before becoming unresponsive.  Symptoms may be 'restored' by carefully avoiding hypos for 3 months.

Causes of hypoglycaemia are easy to remember as it "IS PLAIN" to see...
  • Insulin
  • Sulphonyureas/other drugs
  • Pituitary insufficiency
  • Liver failure
  • Addisons disease or alcohol
  • Insulinoma
  • Neoplasms eg retroperitoneal fibrosarcomas than secrete IGF

Take bloods for glucose, insulin, c-peptide and plasma ketones.
Normal/high insulin, no ketones: insulinoma, drugs
Insulin low, no ketones: non-pancreatic neoplasm
Insulin low, ketones high: alcohol, addissons, pituitary insufficiency.

Post-pradial hypoglycaemia can occur post-gastrectomy

Whipples Triad is a set of criteria which if fulfilled suggest a patient's symptoms are due to hypoglycaemia:
  • symptoms suggestive of hypoglycaemia
  • BM < or equal to 2.5
  • symptoms relieved by food.


I'm sure this is all old-hat to you all... get the pt to eat if they can, 1mg IM glucagon if they can't and no IV access (remember glucagon effects only last for 20 mins and may not work at all in alcoholics) and if IV is an option the 50mls of 50% glucose or the more modern 200mls of 10% (less abrasive to the veins)

Now for some TED time...

MRCP revision battle 29.2: Thyroid eye disease

Thyroid eye disease, referred to by its friends as 'TED', can occur in people who are hyperthyroid, hypothyroid or euthyroid.

Thyrotoxicosis from any cause can cause lid lag and lid retraction.

However, only Graves disease causes:
  • periorbital oedema
  • conjunctivial injection
  • proptosis/exophthalmos
  • opthalmoplegia/diplopia
  • papilloedema

(as an aside, I've always been mystified by the difference between proptosis and exophthalmos.  Unfortunately it appears I'm not the only one as some sources suggest the difference is related to the degree of protrusion whilst others say exophthalmos is used if the aetiology is endocrine and proptosis is used if the aetiology is not endocrine...)

25-50% of patients with Grave's disease have TED.

Risk of TED is increased in smokers.

The danger of TED is optic nerve compression.  Symptoms/signs of optic nerve compression include:
  • blurred vision/decrease VA
  • decreased colour vision
  • a relative afferent papillary defect

Treatment for TED is topical lubricants, steroids if severe and possibly even surgery.

Now for a horrid battle with hyperlipidaemia...

MRCP revision battle 29.3: Hyperlipidaemia

This battle is quickly going to get complex and aims only to be an MRCP-focused overview rather than a comprehensive discussion.  It is divided into 5 stages:
  1. The basics
  2. Hypercholesterolaemia
  3. HDL - the good cholesterol
  4. Hypertriglyceridaemia
  5. Mixed

1. The Basics

Hyperlipidaemia = raised lipids.  Lipids come in 4 main 'flavours':

  1. chylomicrons = carry triglyceride
  2. LDL = mainly cholesterol (50%, 10% TG) = the 'bad' flavour
  3. HDL = mainly phospholipid = the 'good' flavour, carry cholesterol back to the liver
  4. VLDL = mainly triglyceride (60%, 20% cholesterol)

  • corneal arcus = grey-white ring around cornea
  • xanthelasma = yellow collection of cholesterol under skin
  • xanthomata = 'lumps' of cholesterol
  • eruptive xanthomata = small yellow-orange papules that appear all over body
  • lipaemia retinalis = 'creamy' appearence of blood vessels on fundoscopy

So lets look first at cholesterol and hypercholesterolaemia.

2. Hypercholesterolamia

a. Familial
  • LDL receptor dysfunction
    • cholesterol 7.5-16
    • raised LDL
    • tendon xanthomata, corneal arcus and xanthelasma
    • heterozygous prevalance 1/500 --> MI in 40s
    • homozygous --> MI in 20s
  • Polygenic hypercholesterolaemia
    • cholesterol 6.5-9
    • raised LDL
    • xanthelasma and corneal arcus

 b. Acquired
  • nephrotic syndrome
  • renal transplant
  • cholestasis
  • hypothyroidism

3.  HDL

HDL is 'good' cholesterol

It is higher in:
  • thin people
  • exercise
  • oestrogens
  • alcohol
  • low triglycerides

It is lower in:
  • obesity
  • sedentary states
  • post-puberty males
  • smoking

4. Hypertriglyceridaemia

a. Familial
  • failure to metabolise chylomicrcons
  • features include:
    • eruptive xanthomata
    • lipaemia retinalis
    • retinal vein thrombosis
    • pancreatitis
    • hepatosplenomegaly

b. Secondary
  • diabetes
  • obestiy
  • alcohol
  • chronic renal failure
  • liver disease
  • drugs such as thiazides, beta blockers or oestrogens

5. Mixed hyperlipidaemia
  • Look for palar xanthomas and tuberous xanthomas

After that wordy and depressing battle, lets move on to treatment of hyperlipidaemia...

MRCP revision battle 29.4: Lipid-lowering treatment

NICE recommends that all those with a 10 yr cardiovascular risk of >20% should be offered lipid-lowering therapy.

1st line: 40mg simvastatin
Measure LFTs when starting, at 3 months and at 12 months.

In primary prevention there is no 'target' cholesterol
In secondary prevention the target is less than 4mmol/l cholesterol and less than 2mmol/l LDL

If statins are not tolerated consider:
  • fibrates
  • ezetimibe
  • nicotinic acid

Mechanisms of action

Statins are HMG CoA reductase inhibitors.  They therefore work by decreasing the production of cholesterol in the liver.  The decreased production of cholesterol in the liver also results in the liver absorbing and processing more LDL, hence further reducing cholesterol.

Grapefruit juice decreases the metabolism of statins.  Patients on statins are therefore advised to avoid grapefruit juice as it would increase the risk of the rare side effect of rhabdomyolysis

Ezetimibe works by preventing intestinal absorption of cholesterol.

Fibrates are PPAR alpha receptor agonists.  They therefore increase clearance of VLDL and remnant particles and decrease TG secreation.

Fibrates and statins tend not to be used together due to increased risk of rhabdomyolysis.

Nicotinic acid (=vitamin B3) blocks breakdown of fats in adipose tissue. 
It can cause facial flushing.

For the really keen:
NICE lipid modification guide

After those heavy-going battles lets tackle something light - restless legs syndrome...                             

MRCP revision battle 29.5: Restless legs syndrome

Restless legs syndrome, sometimes known as Ekbom's syndrome, is a condition in which a person has unpleasant sensations in their legs and a desire to move them.

Restless legs may be idiopathic or secondary to:
  • pregnancy
  • iron deficiency
  • ureamia
  • diabetes
  • RA

1st line treatments are dopamine agonists such as pramipexole
2nd line treatments include benzodiazepines or gabapentin.

To keep the neurones jumping lets move on to a completely different topic again - histiocytosis X...

MRCP revision battle 29.6: Histiocytosis X

Histocytosis X, aka Langerhans-cell histiocytosis, is a group of disorders in which there is organ infiltration by granulomatous lesions containing clonally proliferated dendrintic (=Langerhams) cells.

The most commonly affected organs are lungs and bones.

Lung histiocytosis tends to affect young adults and is commonest in smokers.

The CXR shows multiple ring shadows with diffuse reticulo-nodular opacities affecting mainly the upper and mid zones.

Biopsy would show characteristic Birbeck granules.

Treatment is ?local excision, ?steroids.

Now onwards for a run of the last 3 short battles of the day, starting with Bartter's Syndrome...

MRCP revision battle 29.7: Bartter's Syndrome

Bartter's Syndrome is an autosomal recessive condition in which there is defective chloride reabsorption in the Na-K-2Cl channels in the loop of Henle resulting in severe hypokalaemia.

It presents in childhood with failure to thrive and polyuria/polydipsia

Blood pressure is normal/low.

There is hyperreninaemia and hypertrophy of the JGA.

Treatment is with potassium replacement and NSAIDs.

Next... Gitelman Syndrome....

MRCP revision battle 29.8: Gitelman Syndrome

Gitelman Syndrome is an autosomal recessive disorder in which there is decreased salt reabsorption in the distal tubule resulting in hypokalaemia due to secondary hyperaldosteronism.

Patients with Gitelman Syndrome have:
  • metabolic alkalosis
  • low potassium
  • low magnesium
  • usually normal blood pressure

Treatment is magnesium and potassium replacement.

Finally - Liddles!

MRCP revision battle 29.9: Liddle's Syndrome

Liddle's syndrome is an autosomal dominant condition caused by enhanced sodium reabsorption in the DCT.

It results in:
  • hypertension
  • hypokalaemia
  • metabolic alkalosis

Treatment is salt restriction, potassium, amiloride.