Question 66#

Which of the following results establishes a diagnosis of diabetes mellitus?

A. Asymptomatic patient with fasting glucose 7.9 mmol/L on one occasion

Correct Answer E: Diabetes diagnosis: fasting > 7.0, random > 11.1 - if asymptomatic need two readings.

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 67#

Which one of the following features is not seen in carcinoid syndrome?

A. Flushing

Correct Answer D: Flushing, diarrhoea, bronchospasm, tricuspid stenosis, pellagra --> carcinoid with liver mets - diagnosis: urinary 5-HIAA.

Hypo- not hypertension is seen in carcinoid syndrome secondary to serotonin release.

Carcinoid tumours

Carcinoid syndrome:

• Usually occurs when metastases are present in the liver and release serotonin into the systemic circulation
• May also occur with lung carcinoid as mediators are not 'cleared' by the liver 

Features:

• Flushing (often earliest symptom)
• Diarrhoea
• Bronchospasm
• Hypotension
• Right heart valvular stenosis (left heart can be affected in bronchial carcinoid)
• Other molecules such as ACTH and GHRH may also be secreted resulting in, for example, Cushing's syndrome
• Pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour

Investigation:

• Urinary 5-HIAA
• Plasma chromogranin A y

Management:

• Somatostatin analogues e.g. octreotide
• Diarrhoea: cyproheptadine may help

Question 68#

Which one of the following statements regarding impaired glucose regulation is correct? 

A. All patient should have a repeat oral glucose tolerance test every 2 years

Correct Answer B: 

Impaired glucose regulation

Impaired glucose regulation (IGR) may also be referred to as non-diabetic hyperglycaemia (NDH) or prediabetes. It describes blood glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus. Diabetes UK estimate that around 1 in 7 adults in the UK have IGR. Many individuals with IGR will progress on to developing type 2 diabetes mellitus (T2DM) and they are therefore at greater risk of microvascular and macrovascular complications.

There are two main types of IGR:

• Impaired fasting glucose (IFG) - due to hepatic insulin resistance
• Impaired glucose tolerance (IGT) - due to muscle insulin resistance
• Patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG

Definitions:

• 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
• The role of HbA1c is diagnosing IGR and diabetes is currently under review
• 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.

Management:

• Diabetes UK suggests using the term 'prediabetes' when discussing the condition with patients as research has shown that this term has the most impact and is most easily understood
• Lifestyle modification: weight loss, increased exercise, change in diet
• Drug therapy is not currently licensed or recommended for patients with IGR in the UK
• At least yearly follow-up with blood tests is recommended 

Question 69#

A 47-year-old woman is referred to the general medical clinic. She has gained 10 kg in weight in the past 3 months but her main problem is episodic sweating. These episodes of sweating are associated with double vision and typically occur early in the morning. Clinical examination is unremarkable.

What is the most likely diagnosis?

A. Bronchial carcinoid

Correct Answer E: This is a typical presentation of insulinoma.

Insulinoma:

An insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells.

Basics:

• Most common pancreatic endocrine tumour
• 10% malignant, 10% multiple
• Of patients with multiple tumours, 50% have MEN-1

Features:

• Of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc
• Rapid weight gain may be seen
• High insulin, raised proinsulin:insulin ratio
• High C-peptide

Diagnosis:

• Supervised, prolonged fasting (up to 72 hours)
• CT pancreas

Management:

• Surgery
• Diazoxide and somatostatin if patients are not candidates for surgery

Question 70#

Which one of the following features of haemochromatosis may be reversible with treatment?

A. Cardiomyopathy

Correct Answer A: 

Haemochromatosis: features:
Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. It is often asymptomatic in early disease and initial symptoms often non-specific e.g. lethargy and arthralgia.

Epidemiology:

• 1 in 10 people of European descent carry a mutation genes affecting iron metabolism, mainly HFE
• Prevalence in people of European descent = 1 in 200

Presenting features:

• Early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
• 'bronze' skin pigmentation
• Diabetes mellitus
• Liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
• Cardiac failure (2nd to dilated cardiomyopathy)
• Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
• Arthritis (especially of the hands)

Questions have previously been asked regarding which features are reversible with treatment:

*there are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene

**whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not