Question 106#

Which one of the following is least characteristic of Addison's disease?

A. Hypoglycaemia

Correct Answer B: Addison's disease is associated with a metabolic acidosis.

Addison's disease: investigations:

In a patient with suspected Addison's disease the definite investigation is a ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.

Associated electrolyte abnormalities:

• Hyperkalaemia
• Hyponatraemia
• Hypoglycaemia
• Metabolic acidosis

Question 107#

A 62-year-old man who had a myocardial infarction six months ago presents for review.

What should his target cholesterol levels be?

A. Total cholesterol < 3.5 mmol/l; LDL < 1.5 mmol/l

Correct Answer B: NICE adopted the JBS2 targets for secondary prevention in the 2008 guidelines.

Hyperlipidaemia: management:

In 2008 NICE issued guidelines on lipid modification. Key points are summarized below.

Primary prevention:

A systematic strategy should be used to identify people aged 40-74 who are likely to be at high risk of cardiovascular disease (CVD), defined as a 10-year risk of 20% or greater. NICE updated their lipid guidelines so that the following risk models are valid:

• Framingham
• Joint British Society 2 (JBS2)
• QRISK
• ASSIGN (Scotland only)

The 1991 Framingham equations may still be used. It is however recommended that adjustments are made in the following situations:

• First-degree relative with a history of premature coronary heart disease (defined as < 55 years in males and < 65 years in females) - increase risk by 1.5 times if one relative affected or up to 2.0 times if more than one relative affected
• Males of South Asian ethnicity - increase risk by 1.4 times Along with lifestyle changes drug treatment should be considered for patients with a 10-year CVD risk of 20% or greater
• Simvastatin 40mg on is the first line treatment
• There is no target level for total or LDL cholesterol for primary prevention
• Liver function tests should be check at baseline, within 3 months and at 12 months but not again unless clinically indicated 

Secondary prevention:
All patients with CVD should be taking a statin in the absence of any contraindication NICE recommend increasing simvastatin to 80mg if a total cholesterol of less than 4 mmol/litre or an LDL cholesterol of less than 2 mmol/litre is not attained.

Question 108#

A 49-year-old woman is investigated for thyrotoxicosis. On examination she is noted to have a goitre containing multiple irregular nodules. Nuclear scintigraphy with technetium 99m reveals patchy uptake.

What is the treatment of choice? 

A. Corticosteroids

Correct Answer B: 

Toxic multinodular goitre:
Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules that secrete excess thyroid hormones.

Nuclear scintigraphy reveals patchy uptake.

The treatment of choice is radioiodine therapy.

Question 109#

A 52-year-old woman with suspected diabetes mellitus has an oral glucose tolerance test, following the standard WHO protocol. The following results are obtained:

How should these results be interpreted? 

A. Impaired fasting glucose and impaired glucose tolerance

Correct Answer D: 

Diabetes mellitus:

diagnosis The following is based on the World Health Organization (WHO) 2006 guidelines.

Diabetes mellitus:

If the patient is symptomatic:

• Fasting glucose greater than or equal to 7.0 mmol/l
• Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)

If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of diabetes:

• A HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus
• A HbA1c value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
• In patients without symptoms, the test must be repeated to confirm the diagnosis
• It should be remembered that misleading HbA1c results can be caused by increased red cell turnover (for example anaemia, haemoglobinopathies and pregnancy)

Impaired fasting glucose and impaired glucose tolerance:

• A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
• Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour-value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l

Diabetes UK suggests:

• 'People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes
• A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT.'

Question 110#

A 55-year-old woman with type 2 diabetes mellitus is reviewed. A decision is made to start thiazolidinedione therapy.

Which one of the following points is most relevant to consider before starting treatment?

A. History of oesophageal problems

Correct Answer B: There is increasing evidence thiazolidinediones increase the risk of fractures.

Thiazolidinediones:

Thiazolidinediones are a new class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile. The PPAR-gamma receptor is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function. 

Adverse effects:

• Weight gain
• Liver impairment: monitor LFTs
• Fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
• Recent studies have indicated an increased risk of fractures
• Bladder cancer: recent studies have showed an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)

NICE guidance on thiazolidinediones:
Only continue if there is a reduction of > 0.5 percentage points in HbA1c in 6 months