Question 1#

Which one of the following is a recognized cause of hypokalaemia associated with hypertension?

A. Liddle's syndrome

Correct Answer A: Liddle's syndrome: hypokalaemia + hypertension.

Liddle's syndrome is an autosomal dominant disorder that mimics hyperaldosteronism, resulting in hypokalaemia associated with hypertension. Bartter's syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter in the ascending loop of Henle. It should be noted that it is associated with normotension. Gitelman's syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule. It is associated with hypokalaemia and normotension.

Hypokalaemia and hypertension : For exams it is useful to be able to classify the causes of hypokalaemia in to those associated with hypertension, and those which are not.

1- Hypokalaemia with hypertension:

• Cushing's syndrome
• Conn's syndrome (primary hyperaldosteronism)
• Liddle's syndrome
• 11-beta hydroxylase deficiency*

2- Hypokalaemia without hypertension:

• Diuretics
• GI loss (e.g. Diarrhoea, vomiting)
• Renal tubular acidosis (type 1 and 2**)
• Bartter's syndrome
• Gitelman syndrome

*21-hydroxylase deficiency, which accounts for 90% of congenital adrenal hyperplasia cases, is not associated with hypertension

**type 4 renal tubular acidosis is associated with hyperkalaemia

Question 2#

A 15-year-old girl is investigated for primary amenorrhoea, despite having developed secondary sexual characteristics at 11 years of age. On examination she has well developed breasts with scanty pubic hair and small bilateral groin swellings.

What is the most likely diagnosis?

A. Congenital adrenal hyperplasia

Correct Answer D: Androgen insensitivity syndrome:

Androgen insensitivity syndrome is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome.

Features:

• 'Primary Amennorhoea'
• Undescended testes causing groin swellings
• Breast development may occur as a result of conversion of testosterone to oestradiol

Diagnosis:

• Buccal smear or chromosomal analysis to reveal 46XY genotype

Management:

• Counselling - raise child as female
• Bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
• Oestrogen therapy

 

Question 3#

A 33-year-old woman presents with weight loss and excessive sweating. her partner reports that she is 'on edge' all the time and during the consultation you notice a fine tremor. Her pulse rate is 96/min. A large, non-tender goitre is noted. Examination of her eyes is unremarkable with no evidence of exophthalmos.

What is the most likely diagnosis?

A. Toxic multinodular goitre

Correct Answer E: Graves' disease is the most common cause of thyrotoxicosis.

Only around 30% of patients with Graves' disease have eye disease so the absence of eye signs does not exclude the diagnosis.

Graves' disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30- 50 years.

Features:

• Typical features of thyrotoxicosis
• Specific signs limited to Grave's (see below)

Features seen in Graves' but not in other causes of thyrotoxicosis:

• Eye signs (30% of patients): exophthalmos, ophthalmoplegia
• Pretibial myxoedema
• Thyroid acropachy

Autoantibodies:

• Anti-TSH receptor stimulating antibodies (90%)
• Anti-thyroid peroxidase antibodies (50%)

Question 4#

A 46-year-old man 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. Normal

Correct Answer A: Both the fasting and two-hour glucose are within normal limits.

Diabetes mellitus: diagnosis: The following is based on the World Health Organisation (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 HbAlc 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 5#

A 45-year-old man is referred to the acute medical unit. He had presented earlier in the day to the GP complaining of ongoing fatigue and polydipsia. A BM (finger-prick glucose) taken in the surgery was 22.3 mmol/l. On examination he is an obese man (BMI 36kg/m²) with a pulse of 84 bpm and blood pressure of 144/84 mmHg.

Blood tests reveal the following:

What is the most appropriate initial management?

A. Gliclazide

Correct Answer D: Weight reduction alone would be insufficient in this patient with frank diabetes.

Metformin: Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease.

Mechanism of action:

• Increases insulin sensitivity
• Decreases hepatic gluconeogenesis
• May also reduce gastrointestinal absorption of carbohydrates

Adverse effects:

• Gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
• Reduced vitamin B12 absorption - rarely a clinical problem
• Lactic acidosis* with severe liver disease or renal failure

Contraindications**:

• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 μmol/l and stopping metformin if > 150 μmol/l
• Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis)
• Alcohol abuse is a relative contraindication
• Stop 2 days before general anaesthetic, restart when renal function normal
• Stop prior to IV contrast e.g. Angiography, restart when renal function normal 

*it is now increasingly recognized that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome