Question 151#

Which one of the following features is least associated with primary hyperparathyroidism?

A. Depression

Correct Answer C: Primary hyperparathyroidism

In exams primary hyperparathyroidism is stereo-typically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma.

Causes of primary hyperparathyroidism:

• 80%: solitary adenoma
• 15%: hyperplasia
• 4%: multiple adenoma
• 1%: carcinoma

Features - 'bones, stones, abdominal groans and psychic moans':

• Polydipsia, polyuria
• Peptic ulceration/constipation/pancreatitis
• Bone pain/fracture
• Renal stones
• Depression
• Hypertension

Associations:

• Hypertension
• Multiple endocrine neoplasia: MEN I and II

Investigations:

• Raised calcium, low phosphate
• PTH may be raised or normal
• Technetium-MIBI subtraction scan 

Treatment:

• Total parathyroidectomy

Question 152#

A 51-year-old woman is reviewed in the diabetes clinic. She was diagnosed with type 2 diabetes mellitus 12 months ago and still has poor glycaemic control. She has recently had to stop taking gliclazide due to repeated episodes of hypoglycaemia and is only taking maximum dose metformin. Her BMI is 26 kg/m².

What is the most appropriate next step in management? 

A. Add either a thiazolidinedione or a DPP-4 inhibitor

Correct Answer A: Diabetes mellitus: management of type 2

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2009. Key points are listed below: 

Dietary advice: 

• Encourage high fibre, low glycaemic index sources of carbohydrates
• Include low-fat dairy products and oily fish
• Control the intake of foods containing saturated fats and trans fatty acids
• Limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
• Discourage use of foods marketed specifically at people with diabetes
• Initial target weight loss in an overweight person is 5-10%

HbA1c:

• The general target for patients is 48 mmol/mol (DCCT = 6.5%). HbA1c levels below 48 mmol/mol (DCCT = 6.5%) should not be pursued
• However, individual targets should be agreed with patients to encourage motivation
• HbA1c should be checked every 2-6 months until stable, then 6 monthly

Blood pressure:

• Target is < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
• ACE inhibitors are first-line

The NICE treatment algorithm has become much more complicated following the introduction of new therapies for type 2 diabetes. We suggest reviewing this using the link provided. Below is a very selected group of points from the algorithm:

• NICE still suggest a trial of lifestyle interventions first*
• Usually metformin is first-line, followed by a sulfonylurea if the HbA1c remains > 48 mmol/mol (DCCT = 6.5%)
• If the patient is at risk from hypoglycaemia (or the consequences of) then a DPP-4 inhibitor or thiazolidinedione should be considered rather than a sulfonylurea
• Meglitinides (insulin secretagogues) should be considered for patients with an erratic lifestyle
• If HbA1c > 58 mmol/mol (DCCT = 7.5%) then consider human insulin
• Metformin treatment should be continued after starting insulin
• Exenatide should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35 kg/m^2) and the need for high dose insulin is likely. Continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% at 6 months)

Starting insulin:

• Usually commenced if HbA1c > HbA1c > 58 mmol/mol (DCCT = 7.5%)
• NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bedtime or twice daily according to need 

Other risk factor modification:

• Current NICE guidelines suggest giving aspirin to all patients > 50 years and to younger patients with other significant risk factors. However, recent evidence does not support this approach. The 2010 SIGN guidelines do not advocate the use of aspirin for primary prevention in diabetics
• The management of blood lipids in T2DM has changed slightly. Previously all patients with T2DM > 40- years-old were prescribed statins. Now patients > 40-years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obese, normotensive etc) and have a cardiovascular risk < 20%/10 years do not need to be given a statin. We suggest reviewing the NICE T2DM guidelines for further information
• If serum cholesterol target not reach consider increasing simvastatin to 80mg on
• If target still not reached consider using a more effective statin (e.g. Atorvastatin) or adding ezetimibe
• Target total cholesterol is < 4.0 mmol/l
• If serum triglyceride levels are > 4.5 mmol/l prescribe fenofibrate

*many local protocols now recommend starting metformin upon diagnosis.

Question 153#

A 62-year-old male with a history of type 2 diabetes mellitus is investigated for lethargy. Blood tests are as follows:

Which one of the following is most likely to be contributing to the low bicarbonate value?

A. Vomiting due to gastroparesis

Correct Answer D: Whilst the decreased bicarbonate value may be worsened by deteriorating renal function, it is important to exclude lactic acidosis secondary to metformin.

The raised anion gap is against a diagnosis of renal tubular acidosis.

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 recognised 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.