Question 61#

Liddle's syndrome is associated with each one of the following, except:

A. Alkalosis

Correct Answer D: 

Liddle's syndrome:

Liddle's syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis.

It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.

Treatment is with either amiloride or triamterene

Question 62#

A 62-year-old HGV driver is reviewed. He was diagnosed last year with type 2 diabetes mellitus. Following weight loss and metformin his HbA1c has decreased from 8.8% to 8.4%.

What is the most suitable next step in management? 

A. Add exenatide

Correct Answer E: Pioglitazone is the best option here as it would not put him at risk of hypoglycaemia, which obviously could be dangerous given his job. The NICE guidelines would also support the use of a DPP-4 inhibitor (sitagliptin or vildagliptin) in this situation where the risk of hypoglycaemia must be avoided.

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/m²) 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 63#

A 36-year-old woman who presented with a goitre is diagnosed with autoimmune thyroiditis.

Which one of the following types of thyroid cancer is she predisposed to developing?

A. Anaplastic

Correct Answer B: Hashimoto's thyroiditis is associated with thyroid lymphoma.

Thyroid cancer:
Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones.

Management of papillary and follicular cancer:

• Total thyroidectomy
• Followed by radioiodine (I-131) to kill residual cells
• Yearly thyroglobulin levels to detect early recurrent disease

Question 64#

You review a 68-year-old man who has chronic obstructive pulmonary disease (COPD). Each year he typically has around 7-8 courses of oral prednisolone to treat infective exacerbations of his COPD.

Which one of the following adverse effects is linked to long-term steroid use?

A. Osteomalacia

Correct Answer D: Long-term corticosteroid use is linked to osteopaenia and osteoporosis, rather than osteomalacia.

Corticosteroids:
Corticosteroids are amongst the most commonly prescribed therapies in clinical practice. They are used both systemically (oral or intravenous) or locally (skin creams, inhalers, eye drops, intraarticular). They augment and in some cases replace the natural glucocorticoid and mineralocorticoid activity of endogenous steroids.

The relative glucocorticoid and mineralocorticoid activity of commonly used steroids is shown below: 

Side-effects:
The side-effects of corticosteroids are numerous and represent the single greatest limitation on their usage. Side effects are more common with systemic and prolonged therapy.

Glucocorticoid side-effects:

• Endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia
• Cushing's syndrome: moon face, buffalo hump, striae
• Musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the femoral head
• Immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis
• Psychiatric: insomnia, mania, depression
• Gastrointestinal: peptic ulceration, acute pancreatitis
• Ophthalmic: glaucoma, cataracts
• Suppression of growth in children 

Mineralocorticoid side-effects:

• Fluid retention
• Hypertension

Selected points on the use of corticosteroids:

• Patients on long-term steroids should have their doses doubled during intercurrent illness
• The BNF suggests gradual withdrawal of systemic corticosteroids if patients have: received more than 40mg prednisolone daily for more than one week, received more than 3 weeks treatment or recently received repeated courses

Question 65#

A 51-year-old woman who is known to have poorly controlled type 1 diabetes mellitus is reviewed. Her main presenting complaint is bloating and vomiting after eating. She also notes that her blood glucose readings have become more erratic recently.

Which one of the following medications is most likely to be beneficial?

A. Helicobacter pylori eradication therapy

Correct Answer D: 

Diabetic neuropathy

NICE updated it's guidance on the management of diabetic neuropathy in 2010:

• First-line: oral duloxetine. Oral amitriptyline if duloxetine is contraindicated
• Second-line treatment: if first-line treatment was with duloxetine, switch to amitriptyline or pregabalin, or combine with pregabalin. If first-line treatment was with amitriptyline, switch to or combine with pregabalin
• Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine for localized pain if patients unable to take oral medication

Gastroparesis:

• Symptoms include erratic blood glucose control, bloating and vomiting
• Management options include metoclopramide, domperidone or erythromycin (prokinetic agents)