A 56-year-old lady with a BMI of 27 is reviewed in the diabetic clinic due to poor glycaemic control. She is currently being treated with gliclazide 160mg bd. Her latest bloods show:
Which one of the following medications should be added next?
Correct Answer B: Given that she is overweight metformin would be a natural choice to add. The creatinine however is elevated so pioglitazone is the next best option.
One possible drawback of using pioglitazone is that it may lead to weight gain, especially given her BMI is already 27.
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 Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.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 30-year-old female is diagnosed with having Grave's disease.
What is her chance of developing thyroid eye disease?
Correct Answer E: 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.
Thyroid eye disease:
Prevention:
Features:
Management:
A 43-year-old man requests a 'medical' as he is concerned about his risk of heart disease. His father died at the age of 45-years following a myocardial infarction. His lipid profile is as follows:
Clinical examination reveals tendon xanthomata around his ankles.
What is the most likely diagnosis?
Correct Answer A: The presence of tendon xanthomata and cholesterol levels meet the diagnostic criteria for familial hypercholesterolaemia. Homozygous familial hypercholesterolaemia is exceedingly rare - most patients die in their teenage years from a myocardial infarction.
Familial hypercholesterolaemia: Familial hypercholesterolaemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the LDLreceptor protein.
Clinical diagnosis is now based on the Simon Broome criteria:
A 29-year-old female who is 14 weeks into her first pregnancy is investigated for excessive sweating and tremor. Blood tests reveal the following:
What is the most appropriate management?
Correct Answer D: Propylthiouracil is traditionally taught as the antithyroid drug of choice in pregnancy. This approach was supported by the 2007 Endocrine Society consensus guidelines. It also has the advantage of being excreted to a lesser extent than carbimazole in breast milk.
Despite this some endocrinologists use carbimazole and the BNF states both drugs may be used in pregnancy. Carbimazole has rarely been associated with aplasia cutis of the neonate.
Pregnancy: thyroid problems: In pregnancy there is an increase in the levels of thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.
Thyrotoxicosis:
Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart failure and premature labour Graves' disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient gestational hyperthyroidism. HCG levels will fall in second and third trimester.
Hypothyroidism Key points:
A 33-year-old female is referred to endocrinology with thyrotoxicosis. Following a discussion of management options she elects to have radioiodine therapy.
Which one of the following is the most likely adverse effect?
Correct Answer A: It is well documented that radioiodine therapy can precipitate thyroid eye disease but a majority of patients will eventually require thyroxine replacement.
Graves' disease: management: Despite many trials there is no clear guidance on the optimal management of Graves' disease. Treatment options include titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects.
ATD titration:
Block-and-replace:
Radioiodine treatment:
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