What is the mechanism of action of thiazolidinediones?
Correct Answer D: Glitazones are agonists of PPAR-gamma receptors, reducing peripheral insulin resistance.
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 Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.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:
NICE guidance on thiazolidinediones:
A 27-year-old female develops eye pain and reduced visual acuity following the initiation of treatment for her recently diagnosed Grave's disease.
Which one of the following treatments is likely to have been started?
Correct Answer A: Radioiodine treatment may lead to the development / worsening of thyroid eye disease in up to 15% of patients with Grave's disease.
Thyroid eye disease: Thyroid eye disease affects between 25-50% of patients with Graves' disease. It is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor, which in turns causes retro-orbital inflammation. The patient may be eu-, hypo- or hyperthyroid at the time of presentation.
Prevention:
Features:
Management:
An obese 48-year-old man presents with lethargy and polydipsia.
What is the minimum HbA1c that would be diagnostic of type 2 diabetes mellitus?
Correct Answer D: Diabetes mellitus - HbA1c of 6.5% or greater is now diagnostic (WHO 2011).
Diabetes mellitus:
Diabetes mellitus: diagnosis:
If the patient is symptomatic:
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:
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:
A 28-year-old woman with polycystic ovarian syndrome consults you as she is having problems becoming pregnant. She has a past history of oligomenorrhea and has previously recently stopped taking a combined oral contraceptive pill. Despite stopping the pill 6 months ago she is still not having regular periods. Her body mass index is 28 kg/m^2. Apart from advising her to lose weight, which one of the following interventions is most effective in increasing her chances of conceiving?
Correct Answer D: Infertility in PCOS - clomiphene is superior to metformin.
Whilst metformin has a role in the management of infertility it should be used second-line to antioestrogens such as clomiphene. Similar questions to this often appear in which clomiphene is not an option, in this case metformin is clearly the right answer.
Polycystic ovarian syndrome: management: Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian dysfunction thought to affect between 5- 20% of women of reproductive age. Management is complicated and problem based partly because the aetiology of PCOS is not fully understood. Both hyperinsulinaemia and high levels of luteinizing hormone are seen in PCOS and there appears to be some overlap with the metabolic syndrome.
Genera:
Hirsutism and acne:
Infertility:
*work by occupying hypothalamic oestrogen receptors without activating them. This interferes with the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion.
A 55-year-old woman is investigated following an osteoporotic hip fracture. The following results are obtained:
Which one of the following autoantibodies is most likely to be present?
Correct Answer A: Anti-TSH receptor stimulating autoantibodies (often referred to as Thyroid Stimulating Immunoglobulins) are almost diagnostic of Graves' disease, the most common cause of thyrotoxicosis in the UK.
Graves' disease: features: Graves' disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30- 50 years.
Features seen in Graves' but not in other causes of thyrotoxicosis:
Autoantibodies:
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