Professional Documents
Culture Documents
1
years is admitted for cataract surgery. She is taking metformin 500 mg bid,
plain insulin 10 U at night, ramipril 2.5 mg od and bendroflumethiazide
(bendrofluazide) 2.5 mg od. She drinks a glass of whisky to help her sleep at
night. Investigations showed: BM 3.0 mmol/l; urea 10 mmol/l; creatinine 140
.μmol/l; Na+ 130 mmol/l; K+ 3.7 mmol/l
Liver function tests (LFTs) were normal and arterial blood gas measurements
.showed a pH 7.3, p(CO2) 5.1 kPa and HCO3 17 mmol/l
Which one of the following is the most detrimental in these circumstances and should
?be stopped
Ramipril
Metformin
Your answer
Insulin
Alcohol
(Bendroflumethiazide (bendrofluazide
Metformin is a biguanide used as a blood glucose lowering agent. The major toxicity of
metformin is lactic acidosis. It should not be used in patients with renal insufficiency (creatinine
> 133 μmol/l in males and > 124 μmol/l in females), any form of acidosis, congestive heart
failure, liver disease or severe hypoxia. As it is metabolised in the liver, it is contraindicated in
patients with liver disease or a high alcohol intake. Ramipril, an angiotensin-converting enzyme
inhibitor (ACEI), is indicated for the treatment of diabetic nephropathy with albuminuria. It may
potentiate the hypoglycaemic effect of insulin and oral antidiabetic agents, especially during the
first few weeks of use. It should be used under specialist supervision if the creatinine
concentration is > 150 μmol/l, and renal function and potassium levels monitored. This patient
has long-standing diabetes with nephropathy. Hypoglycaemia is common with nephropathy and
is thought to be due to the decreased metabolism of insulin. Decreasing renal function can
cause metabolic acidosis, either of which is a contraindication for treatment with metformin.
.Bendroflumethiazide (bendrofluazide) can be safely continued
Fluids, iv
Insulin
Potassium
Your answer
Bicarbonate
Correct answer
Antibiotics
This patient has diabetic ketoacidosis (DKA), which is more common in type-I than type-2
diabetes mellitus. Inadequate insulin causes lipolysis, leading to ketosis and acidosis. The
common precipitants include inadequate insulin administration, infections (pneumonia, urinary
tract infection (UTI)), myocardial infarct (MI), stroke, peripheral gangrene, etc. Treatment is
directed at the underlying cause and correction of the ketoacidotic state. Here, the underlying
cause, pneumonia, is treated with antibiotics. The most important aspect of treatment is to give
iv fluids, as normal saline, along with regular insulin. When the fluid balance is restored, the
initial high potassium concentration may fall and therefore has to be monitored and
.supplemented as required
The role of HCO3 in DKA is controversial. The acidosis usually corrects itself once the fluid and
electrolyte balance is restored. Some physicians administer HCO3 if severe acidosis (pH < 7) is
.present. However, there is a view that rapid correction of acidosis may impair cardiac function
Normal
Primary polydipsia
Correct answer
Osmotic diuresis
Diabetes insipidus (DI) is suspected when the urine output is > 50 ml/kg per day (3000 ml for a
60-kg female). If the basal urine osmolality is > 300 mOsm/kg, it suggests an osmotic diuresis.
If fluid deprivation causes a urine osmolality > 300 mOsm/kg, it suggests psychogenic
(primary) polydipsia. If not, it is either pituitary or nephrogenic DI. These are differentiated by
the administration of subcutaneous DDAVP which causes an increased urine osmolality > 300
.mOsm/kg in pituitary DI
Marfanoid features
Phaeochromocytoma
Parathyroid hyperplasia
Correct answer
Mucosal neuromas
MEN-1 (multiple endocrine neoplasia type-1; Werner’s syndrome) involves the three P’s:
.parathyroid, pituitary, pancreas
c) insulinoma – hypoglycaemia)
MEN-2 usually involves the thyroid and parathyroid glands and phaeochromocytoma. The mode
of inheritance in MEN-1 is autosomal-dominant. MEN-2A is characterised by medullary thyroid
carcinoma, parathyroid hyperplasia/adenoma and phaeochromocytoma. In addition, MEN-2B
.has mucosal and gastrointestinal (GI) neuromas and marfanoid features
A 35-year-old HIV-positive man, evaluated for weight loss and weakness has.5
been found to have disseminated tuberculosis. On examination, he is
hypotensive and has hyperpigmentation of the mucosa, elbows and skin
.creases. Further investigations confirm a diagnosis of Addison’s disease
?Which of the following is likely in this condition
Increased serum Na
Increased serum Cl
Increased serum K
Your answer
Decreased serum Ca
In adrenal destruction, serum Na, Cl and HCO3 levels are reduced, and serum potassium is
elevated. The hyponatraemia is due to both loss of sodium in the urine (due to aldosterone
deficiency) and to movement into the intracellular compartment. Hyperkalaemia is due to a
combination of aldosterone deficiency, impaired glomerular filtration (due to hypotension) and
acidosis. Mild to moderate hypercalcaemia occurs in 10–20% patients, the cause of which is
.uncertain
A 60-year-old man is referred to the endocrine clinic with a complaint that his.6
shoe size has gone up from size 9 to size 11 and his wedding ring no longer
fits him. He is sweating a lot and his wife complains he is snoring more at
.night
?Which of the tests below is most useful for confirming a diagnosis of acromegaly
Skull X-ray
Random GH level
A 75-g oral glucose tolerance test (OGTT) is the ‘gold standard’ for a diagnosis of acromegaly.
In normal people the growth hormone (GH) level suppresses during the test, but in patients
with acromegaly it is not suppressed. This is because insulin and GH are antagonistic hormones.
Random levels of GH and insulin-like growth factor-1 (IGF-1) may be raised, but as there is a
wide range of normal a single measurement is not sufficient to make the diagnosis. A dynamic
test (the OGTT) is required. Both a skull X-ray and an MRI scan are likely to be abnormal in
patients with acromegaly. Pituitary tumours in acromegaly are usually macroadenomas. As
other secretory and non-secretory tumours of the pituitary can also be macroadenomas these
tests would not confirm the patient had acromegaly, though they would be used in the
.diagnostic work-up
A large goitre
Your answer
Hypertension
Maculopathy
Correct answer
Secondary causes of diabetes occur in other endocrine conditions where hormones with
antagonistic actions to insulin are present in excess amounts. Patients with acromegaly, which
shows elevated growth hormone (GH) levels secondary to a pituitary adenoma, can also have a
goitre, visual field defects and hypertension and diabetes. Those with Cushing’s syndrome, from
glucocorticoid excess, can have visual field defects, hypertension, striae and bruising.
Maculopathy is present in diabetes of long duration and is related to long-term poor glycaemic
control. It could be present in patients with secondary diabetes if they have gone undiagnosed
for some time. However, maculopathy is not related to any of the hormone excesses seen in
.these conditions
A 26-year-old woman attends her GP complaining of feeling tired all the time.8
for the last few months. She has had no period for 6 months and has been
.feeling dizzy first thing in the morning
Which of the following clinical signs would the GP be most likely to find if the
?diagnosis was thought to be glucocorticoid deficiency
Buccal pigmentation
Diminished body hair
Pallor
Postural hypotension
Your answer
Optic atrophy
Hypoadrenalism has many causes including Addison's disease, granulomatous disorders, TB,
tumour (particularly lung) or related to infection (meningococcal septicaemia). Secondary
hypoadrenalism is caused by hypopituitarism or hypothalamic disorders. Pallor is present in
hypopituitarism due to normochromic, normocytic anaemia and a lack of melanocyte-stimulating
hormone (MSH; cleaved from the precursor of ACTH). Buccal pigmentation is also associated
with glucocorticoid deficiency, most commonly from Addison’s disease. ACTH is elevated in
Addison’s disease and results in higher levels of MSH, which causes the skin and buccal
pigmentation found in this condition. Lack of body hair and amenorrhoea are features of
hypogonadism in hypopituitarism. Postural hypotension is related to glucocorticoid deficiency
.regardless of cause
Hypothyroidism
Hyperthyroidism
Pituitary microadenoma
Your answer
Her symptoms are consistent with hyperprolactinaemia. Raised prolactin has many causes
including pituitary tumours (micro- and macroadenomas), drug treatment (some
antidepressants like tricyclic antidepressants, anti-emetics and cimetidine), pregnancy, stress,
hypothyroidism (because thyrotrophin-releasing hormone (TRH) stimulates TSH and prolactin in
primary hypothyroidism) and renal failure (prolactin accumulates in renal failure but not in
hepatic impairment). Hyperthyroidism is not associated with hyperprolactinaemia and
galactorrhoea, although it can cause amenorrhoea and fertility problems. While
hyperprolactinaemia can be present in hypothyroidism it is usually associated with menorrhagia
.rather than amenorrhoea
An 18-year-old young man presents to his GP with thirst and polyuria. Some 6.10
months previously he had a significant head injury as the result of a road
.traffic accident. He is referred to the local endocrine clinic
Which of the following results would be the most useful in confirming a diagnosis of
?diabetes insipidus after a water deprivation test
Diabetes insipidus (DI) can be due to cranial DI with complete or partial deficiency of
antidiuretic hormone (ADH, vasopressin), or renal DI due to renal tubular defects affecting the
action of ADH on water reabsorption from the renal tubules. The plasma sodium can be normal
or elevated, depending on whether the patient can continue to drink freely and so prevent
dehydration. A low plasma sodium concentration is associated with SIADH (syndrome of
inappropriate ADH). The diagnostic test to confirm DI is a water deprivation test. The inability to
concentrate the urine during the test results in the plasma osmolality rises and the urine
osmolality remaining dilute.Normal plasma osmolality is 285–305 mOsm/kg. The higher the
.urine osmolality the more concentrated it is
Small-cell lung tumours can secrete a number of hormones including ADH (vasopressin) and
ACTH. Excess ADH causes SIADH (syndrome of inappropriate ADH) with hyponatraemia and low
plasma osmolality (normal 285–305 mOsm/kg) and concentrated urine (> 500 mOsm/kg).
Excess ACTH would cause a hypokalaemic alkalosis and not hyperkalaemia. Hypercalcaemia
.occurs in squamous-cell lung tumours because of ectopic parathyroid hormone (PTH) secretion
A 54-year old woman is seen for the first time in the diabetes clinic. She is.12
obese, plethoric and has marked bruising on her limbs and fresh striae over
her abdomen. She has a dorsal kyphosis following a vertebral collapse earlier
.in the year
Which of the following results will help to pinpoint the diagnosis if you suspect
?Cushing’s syndrome secondary to adrenal adenoma
Hypercalcaemia
The symptoms he is describing are in keeping with a proximal myopathy. Causes include alcohol
excess (abnormal LFTs and raised MCV), Cushing’s syndrome (failure to suppress 0900-h serum
cortisol level after an overnight dexamethasone suppression test), osteomalacia (low calcium
and raised alkaline phosphatase levels) and thyrotoxicosis (suppressed TSH and raised free T4
levels) or hypothydrodism (elevated TSH and low FT4). The TFTs above are in keeping with
compensated hypothydrodism which isn't associated with proximal myopathy. Low vitamin B12
(eg in pernicious anaemia) causes a number of neurological symptoms including peripheral
.neuropathy and subacute combined degeneration of the spinal cord, but not proximal myopathy
The clinical picture is suggestive of Addison’s disease with hypotension, pigmentation and a
prodromal period with symptoms in keeping with glucocorticoid deficiency in a man with a
history of another autoimmune endocrine disorder. Other disorders that can be associated are
diabetes and pernicious anaemia. Hypoglycaemia, hyponatraemia, hyperkalaemia and an
elevated urea are all present during a hypoadrenal crisis due to steroid deficiency and
subsequent salt and water loss. Although the potassium is elevated it is unusual to find peaked
T-waves on the ECG in patients with hypoadrenalism: the complexes tend to be small, low-
.volume ones
Exercise regimens
Weight-reduction diets
All the above are relevant and each should be discussed. The hirsutism and acne can be very
difficult to deal with and can cause distress from a cosmetic point of view. There are a variety of
treatment options but Dianette (cyproterone acetate) is probably the most effective, along with
cosmetic treatments like waxing, shaving, plucking or electrolysis. Her future risk of type-2
diabetes and associated cardiovascular risk is very important and she should be advised about
the need for lifestyle treatments and the need to lose weight and exercise regularly to reduce
the chance of this happening. It is now recommended that all patients with PCOS have their
fasting blood glucose level measured annually to pick up diabetes at an earlier stage. However,
the most important issue in a woman of her age is fertility, as women with PCOS frequently
require assistance with conception. Her age is against her if she is going to have problems with
fertility and requires help to conceive. The commonest treatment is to induce ovulation with
clomifene. She needs to be advised that pregnancy also carries an increased risk of gestational
.diabetes
Bilateral exophthalmos
Pretibial myxoedema
Graves’ disease is an autoimmune thyroid disorder and is more common in women than men. It
is associated with positive TPO (thyroid peroxidase antibodies) and TSH (thyroid stimulating
hormone) receptor antibodies. The goitre in Graves’ disease is normally diffusely enlarged
rather than nodular. Uptake of radio-isotope is increased in Graves’ disease. In other conditions
causing thyrotoxicosis, like postpartum thyroiditis and viral thyroiditis, the uptake is reduced.
Graves’ disease is associated with a number of other features not found in other causes of
thyrotoxicosis, eg exophthalmos, pretibial myxoedema and thyroid acropachy (a condition that
.affects the nails and looks like finger clubbing). The exophthalmos can be unilateral or bilateral
Thyroidectomy
Your answer
All the above treatments are recognised treatments for thyrotoxicosis. Antithyroid drugs
(carbimazole and propylthiouracil) can be used alone and the dose titrated down or up to keep
the patient euthyroid. Treatment is usually for 12–18 months. However carbimazole has been
associated with aplasia cutis (a scalp defect) in babies born to mothers treated during
pregnancy. The ‘block and replace’ regimen of thyroxine and anti-thyroid drugs is not used in
pregnancy as thyroxine does not cross the placenta. Surgery is an option for people with a large
goitre, or for people who fail on other treatments but would not be first choice in a young
otherwise healthy woman. Radio-iodine is a very effective treatment for thyrotoxicosis but is
contraindicated in women of childbearing age who are contemplating pregnancy within 6
.months
Chromosomal analysis
Your answer
Semen analysis
Myeloma
Metastatic malignancy
Milk–alkali syndrome
Your answer
Primary hyperparathyroidism
Sarcoidosis
All the above diagnoses are causes of hypercalcaemia. Symptoms of hypercalcaemia are
commonly thirst, polyuria, dyspepsia, malaise, bone pain and constipation. Myeloma and
metastatic malignancy cause hypercalcaemia either by direct lytic lesions of bone or by the
production of PTHrP (parathyroid hormone-related protein). Myeloma would be extremely rare
in this age group. There is nothing in the history to suggest bone pain or a diagnosis of
metastatic malignancy. Primary hyperparathyroidism is most commonly found by chance in
elderly women. It can be part of the multiple endocrine neoplasia syndromes and therefore can
be seen in younger people. The normal chest X-ray suggests that sarcoidosis is not the
diagnosis in this case. The age of the patient, the dyspeptic symptoms and the raised
bicarbonate level suggest the most likely diagnosis is the milk–alkali syndrome caused by the
.ingestion of antacids
Hyperprolactinaemia
Turner’s syndrome
Turner’s syndrome (genotype XO) is associated with primary amenorrhoea and short stature.
Hyperprolactinaemia and PCOS are more commonly associated with secondary amenorrhoea.
Testicular feminisation causes primary amenorrhoea and is caused by either a partial or
complete androgen-receptor defect. Affected patients are genotypically male (XY) but
phenotypically female. Congenital adrenal hyperplasia is most commonly caused by 21-
hydroxylase deficiency. Severe forms present in infancy with salt-losing crises and females can
have ambiguous genitalia. Milder forms cause precocious puberty in boys and virilism, hirsutism
and primary amenorrhoea in girls. Diagnosis is by finding raised serum 17-hydroxyprogesterone
.levels that show a hyperresponsiveness to ACTH. Treatment is with glucocorticoids
An 81-year-old woman is referred to the thyroid clinic with increasing size of a.23
pre-existing goitre. She has had long-standing hypothyroidism and has been
.on a dose of thyroxine of 100 μg daily for many years
?Which of the following primary thyroid cancers is she most likely to have
Thyroid lymphoma
Correct answer
A 52-year-old woman sees her GP complaining of a 4-kg weight gain, dry hair.24
and skin, she feels slow and always has the heating up high. She has a small
diffuse goitre. Her TSH level is 20 mU/l and free thyroxine 5 pmol/l. Thyroid
peroxidase antibody is positive at high titres. She has two sisters who have
.had thyroid disease
?What is the most likely diagnosis
DeQuervain’s thyroiditis
Follicular carcinoma
Hashimoto’s thyroiditis
Your answer
Graves’ disease
Nodular goitre
Hashimoto’s thyroiditis is an autoimmune thyroid disorder found more often in women than
men. It is associated with positive thyroid antibodies and there may be a goitre that tends to be
diffuse rather than multinodular. The gland is infiltrated with lymphocytes and patients can
become hypothyroid. DeQuervain’s thyroiditis is not associated with positive antibodies and
tends to present with painful swelling in the neck. Graves’ disease is also an autoimmune
thyroid disorder but patients usually present with thyrotoxicosis. Follicular carcinoma can
.present with a thyroid swelling but not hypothyroidism
Cushing’s syndrome
Conn's syndrome
Your answer
Phaeochromocytoma
Acromegaly
Conn’s syndrome is a condition where there is a benign adrenal adenoma that is secreting
aldosterone. The renin level is low, and hypokalaemia is one of the common findings as well as
hypertension. Cushing’s syndrome, acromegaly and phaeochromocytoma are all associated with
secondary hypertension, but not with low renin and elevated aldosterone levels. Renal artery
stenosis has high renin levels as well as high aldosterone levels and so causes secondary
hyperaldosteronism. Treatment of Conn’s syndrome is with surgical excision of the adenoma or
.with potassium-sparing diuretics
You are called to see a 36-year-old woman on the surgical ward who is 2 days’.26
post-thyroidectomy. She is complaining of tingling around her mouth and in
.her hands and has developed spasm of her hands
?What immediate treatment can you give that is most likely to resolve her symptoms
Intravenous calcium
Your answer
Intravenous diazepam
Intravenous glucose
Intravenous potassium
Nelson’s syndrome
Prolactinoma
Sheehan’s syndrome
Your answer
Sipple’s syndrome
A BMI of 23
Chlorpropamide
Gliclazide
Your answer
Pioglitazone
Rosiglitazone
Metformin
Gliclazide is a sulphonylurea and can be used alone or in combination therapy for type-2
diabetes mellitus. It acts by increasing insulin release from the pancreatic β-cell. It can be used
in mild to moderate renal failure. Pioglitazone and rosiglitazone are thiazolidinediones, which
promotes insulin sensitivity by their action on the PPARγ receptor (peroxisome proliferator
activated receptor-γ).They are associated with fluid retention and are contraindicated in heart
failure. Chlorpropamide, a sulphonylurea, is rarely used now and is excreted by the kidney.
Metformin is a biguanide and, although its mechanism of action is not entirely clear, it reduces
insulin resistance and hepatic glucose production. It is thought to be able to cause lactic acidosis
in certain circumstances and its use is contraindicated in patients with renal, hepatic or cardiac
.failure
A 27-year-old woman with type-1 diabetes mellitus attends for her routine.30
.review and says she is keen on becoming pregnant
Which of the following is the factor most likely to make you ask her to defer
?pregnancy at this stage
Hb A1C 9.4%
Your answer
Sensory neuropathy
Pregnancy in type-1 diabetes is still associated with a two- to threefold increase in congenital
abnormalities when compared with the background population. It is also associated with higher
neonatal morbidity and mortality and higher operative delivery rates. Prepregnancy counselling
with the aim of bringing the Hb A1c to near-normal levels is associated with better pregnancy
outcomes. Diabetic retinopathy can progress during pregnancy and the eyes must be checked at
least once each trimester; if there is progression that is sight-threatening then the patient
should be referred to an ophthalmologist. Background retinopathy would not be a
contraindication to pregnancy. The microalbumin level is within normal limits. Nephropathy can
also progress during pregnancy, but microalbuminuria would not be a contraindication to
pregnancy and nor would sensory neuropathy. It is important that patients with diabetes take 5
mg folic acid daily prepregnancy (this reduces neural tube defects) and this can be started when
the patient starts trying to conceive, although it should ideally be taken for 3 months
beforehand. The most important thing this woman can do is to improve her glycaemic control
.before trying to conceive
Intravenous bicarbonate
Intravenous fluids
Your answer
Intravenous insulin
Intravenous potassium
The patient has diabetic ketoacidosis, a condition still associated with mortality in patients with
type-1 diabetes mellitus. There is a total body deficit of fluid and electrolytes. The most
important initial treatment is intravenous saline as the hypovolaemia is the factor most likely to
cause the patient to die. Intravenous insulin is required at an early stage; and, although it is
normal, the potassium level will rapidly fall with fluid and insulin treatment and the patient will
require potassium replacement. Intravenous bicarbonate should not be used immediately as it
can cause massive fluid shifts and precipitate cerebral oedema. It can be used if hydrogen ion is
greater than 100 and the patient is not responding to initial measures, in which case small
.volumes of a 1.26% bicarbonate solution should be used
Cataract
Background diabetic retinopathy consists of dot and blot haemorrhages and hard exudates.
Patients do not need to be referred to the ophthalmologist unless these are within 1 disc
diameter of the fovea. This can be monitored annually at the routine clinic. Cataracts appear
about 10 years earlier in type-2 diabetes than in non-diabetic patients. If the vision is
significantly affected the patients warrant routine and not urgent referral to the
ophthalmologist. Soft exudates suggest retinal ischaemia, which would require routine referral
to the ophthalmologist. New vessels anywhere in the fundus are a feature of proliferative
retinopathy and, as new vessels have a risk of haemorrhage and can threaten sight, they should
.be referred urgently to the ophthalmologist
CT brain scan
ECG
Troponin level
Hypoglycaemia in the elderly is a not uncommon problem, even if only treated with oral
hypoglycaemic agents. Glibenclamide has a long half-life and should therefore be avoided in the
elderly. The reduced food intake and the ongoing intake of medication in this patient is likely to
have caused hypoglycaemia, which can be associated with neurological symptoms in the elderly.
The neurological symptoms will resolve promptly with intravenous dextrose. Although a
myocardial infarction or a cerebrovascular accident could have caused his symptoms, they
.would not be immediately reversible
A 43-year-old woman presents with weight loss, palpitations, diarrhoea and a.34
cessation of periods. She has been treated by her GP for anxiety. Examination
reveals a single nodule on the left of her thyroid, about 1.5 cm in diameter.
Thyroid scanning with technetium shows increased uptake within the nodule
with reduced activity throughout the rest of the gland. Thyroid function tests
.(showed a free thyroxine of 30 pmol/l (9–25 pmol/l), TSH < 0.05 mU/l (0.5–5
?Based upon these findings, what would be the definitive treatment
Carbimazole
Surgical excision
Your answer
Propanolol therapy
Toxic thyroid nodules preferentially take up radioactive iodine. This makes them particularly
amenable to radioactive iodine treatment. A dose of 300–500 MBq is usually sufficient to cure
the thyrotoxicosis. Radioiodine therapy is contraindicated in children and women who are
lactating or pregnant, and where the safety of cohabitants from the effects of radioactivity can’t
be guaranteed. Surgery is the next best option for patients in whom radioiodine is
contraindicated or refused. Carbimazole alone or in combination with thyroxine replacement is
used in the medical treatment of Grave’s disease; Propanolol is a useful symptom reliever for
.thyrotoxicosis
A 37-year-old woman presents to A&E after chasing thieves who were stealing.35
her car. Her blood pressure is noted to be 185/110 mmHg on admission. She
admits to episodic headaches and feeling stressed and anxious. She is of
normal appearance, her serum calcium on admission is noted to be 2.95
mmol/l with normal renal function, abdominal ultrasound reveals a possible
.adrenal mass
Carcinoid syndrome
MEN-1
MEN-2a
Correct answer
MEN-2b
MEN-2 (multiple endocrine neoplasia – type 2) is associated with medullary thyroid carcinoma
(almost always), parathyroid chief-cell hyperplasia (10–25%) and phaeochromocytoma (20–
50%). MEN-2b is also associated with a marfanoid appearance, whereas MEN-2a is not. The
cause is an autosomal-dominant inherited genetic mutation on the long arm of chromosome 10.
Correct management of this patient includes appropriate a- and β -blockade prior to surgical
removal of the phaeochromocytoma, screening for medullary thyroid carcinoma with the iv
pentagastrin test and calcitonin assay, then likely thyroidectomy, and probable
parathyroidectomy in the hands of an experienced surgeon. The prognosis of MEN-2 is variable,
.but, overall, the 10-year survival rate is around 65%
Carney complex
Your answer
Prolactinoma
Protein C deficiency
Somatisation disorder
This man has spotty skin pigmentation, probable prolactinoma and a probable left atrial
myxoma. Carney complex is diagnosable with two features out of spotty skin pigmentation,
myxoma, endocrine tumours (commonest being primary pigmented nodular adrenocortical
disease), but it is also associated with Sertoli-cell tumours, growth hormone- or prolactin-
producing pituitary adenomas, thyroid adenomas and ovarian cysts) and psammomatous
melanotic schwannoma (PMS). It is also diagnosable on the presence of one feature and an
affected first-degree relative. It is an autosomal-dominant condition caused by an inactivating
.mutation of protein kinase A on chromosome 17
Clotting disorder
McCune–Albright syndrome
Bartter's syndrome
Gitelman's syndrome
Correct answer
Gordon's syndrome
Conn's syndrome
Liddle's syndrome
Your answer
Bartter’s syndrome
Gitelman’s syndrome
Your answer
Frusemide abuse
Correct answer
Conn’s syndrome
Liddle’s syndrome
This picture could fit Bartter’s syndrome, although Bartter’s syndrome is rare (1 per million),
has an autosomal-recessive pattern of inheritance and commonly presents below the age of 5
years. Features of Bartter’s syndrome include volume depletion, seizures, tetany and muscle
weakness. This woman’s occupation is the clue, which unfortunately makes frusemide abuse
.very much more likely
The suspicion here with hypokalaemia and metabolic alkalosis, and resistant hypertension on
three agents, is that he has primary hyperaldosteronism. ACE inhibitors and angiotensin II-
receptor blockers, diuretics, calcium-channel blockers, b -blockers all ideally require a washout
period of 2 weeks to make the aldosterone: renin ratio assay meaningful. Whilst it may seem
dangerous to wash out, a definitive diagnosis is impossible if you don't. Spironolactone requires
a washout period of 6 weeks. A high aldosterone: renin ratio is suggestive of primary
hyperaldosteronism. The blood sample should be taken in the morning, standing, and with a
normalised potassium concentration (using supplementation) if possible. Urinary potassium
excretion > 30 mmol/24 h may be another useful adjunct in making the diagnosis. Surgery is
the treatment of choice for Conn’s adenoma and leads to resolution of hypertension in around
70% of patients, mitotane may be useful for controlling symptoms of adrenal carcinoma,
.spironolactone is the medical treatment of choice for adrenal hyperplasia
Cushing’s disease
Primary hyperaldosteronism
Your answer
Essential hypertension
Phaeochromocytoma
Waterhouse–Friderichsen syndrome
Your answer
ME
Hypothyroidism
This is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Criteria for
diagnosis are hyponatraemia with an osmolality of less than 270 mOsmol/kg. Inappropriately
raised urine osmolality (> 100 mOsmol/l).High urinary sodium of > 20 mmol/l (reflecting
relative increased concentration due to reduced water loss), and normal renal, adrenal and
thyroid function.Sodium handling by the kidney is not affected in SIADH. Psychiatric drugs,
particularly monoamine oxidase inhibitors and phenothiazines may be possible causes. Other
possible causes include tumours, such as small-cell lung cancer, other chest pathology,
intracerebral haemorrhage or trauma, drugs such as carbamazepine or chlorpropamide and
metabolic causes such as hypothyroidism. Treatment is with fluid restriction or tetracycline-like
.compounds that promote water excretion
Another possible diagnostic consideration in a presentation of hyponatraemia, especially given
the psychiatric aspect here, is that of psychogenic polydipsia. However, in this condition urine is
.maximally dilute (urine osmolality < 100mOsm/kg), in contrast to SIADH
A 44-year-old patient with hypomania is referred for opinion. She is noted to.44
have a sodium concentration of 142 mmol/l, with a urea of 12 mmol/l and a
creatinine of 140 µmol/l. Urine osmolality is 250 mOsmol/l. Fasting plasma
glucose is normal. The nurses have monitored her urine output and found it to
.be 4.4 litres in 24 h
?Which of the following statements best fits with her condition
Urine osmolality rising to > 305 mOsmol/l 4 h after desmopressin in the water
deprivation test is a positive result for cranial diabetes insipidus, it is unlikely to Your
rise in this case answer
Indometacin is of no value
This patient has diabetes insipidus, probably renal in origin related to the use of lithium as
treatment for manic depression. Decompensated diabetes insipidus has features of dehydration
(as in this case), with an inappropriately low urine osmolality. Obviously diabetes mellitus needs
excluding as a cause of polyuria before a diagnosis of diabetes insipidus can be made.
Psychogenic polydipsia is ruled out by the water deprivation test, with urine osmolality rising
appropriately in response to the lack of oral intake. The urine remains dilute in cases of
nephrogenic diabetes insipidus, despite a rising plasma osmolality and urine failing to
concentrate after desmopressin. Desmopressin is unlikely to be effective in this case,
indometacin may be effective. However, if possible, the lithium should be withdrawn in
consultation with a psychiatrist, and another drug such as lamotrigine substituted. Nephrogenic
diabetes insipidus has an autosomal or X-linked recessive pattern of inheritance, whereas
.cranial diabetes insipidus is inherited only with an autosomal-dominant pattern
A 62-year-old man presents with bony pain that has been present for some.45
months, particularly affecting his left femur, pelvis and lower back. Blood
testing reveals a normal serum calcium level, but a raised alkaline
phosphatase. X-rays of the femur and pelvis reveal mixed lytic and sclerotic
.change, with accentuated trabecular markings. Chest X-ray is normal
?What is the likely diagnosis
Secondary carcinoma
Multiple myeloma
Hyperparathyroidism
Hypoparathyroidism
Paget’s disease
Your answer
Paget’s disease is thought to be present in 2% of the population above 55 years of age, with
90% being asymptomatic. It is more common in Caucasian populations and rarer in populations
of African descent. There are said to be three phases associated with the time course of
radiological changes seen in Paget’s disease. Early disease is said to be primarily lytic, then
there are mixed lytic and sclerotic changes, progressing later to primarily sclerotic change with
increasing bony thickening. Goals of treatment are to normalise bone turnover, maintain the
alkaline phosphatase level within the normal range, minimise symptoms and prevent long-term
complications. The mainstay of treatment for this has been use of the bisphosphonates. These
are now often given as intermittent iv courses a few weeks apart. Long-term complications
include deafness (in up to 50% of patients with skull-base Paget’s disease), and vary rarely
.osteogenic sarcoma
A 55-year-old woman presents with her husband to the endocrine clinic. She.47
has distressing symptoms of sweating, and her husband noticed increased
prominence of her jaw when he was archiving photos from recent years. Last
year she was diagnosed with type-2 diabetes. Other past history of note is
.that she has recently been operated on for carpal tunnel syndrome
?Which of the following most likely to fit with her condition
The diagnosis here is acromegaly. A random growth-hormone level of < 1 mU/l excludes the
diagnosis, growth-hormone levels usually remain above 2 mU/l after an oral glucose tolerance
test. There are increased levels of 1, 25-OH vitamin D in some patients. IGF-1 is invariably
elevated in patients with acromegaly. Sweating is present in more than 80% of cases,
hypertension in 40%, impaired glucose tolerance in 40% and frank type-2 diabetes in 20%.
Coarse facial features including prognathism are often noticed by patients on comparing old
photographs, enlargement of the hands and feet and soft tissue swellings are also common
features. Growth hormone-secreting pituitary tumours are usually identified on MRI scanning
.and trans-sphenoidal resection is the treatment of choice
Sheehan’s syndrome
Your answer
Hypothyroidism
Postnatal depression
Dehydration
She has suffered a period of hypotension and blood loss associated with her emergency
caesarean section. This has resulted in pituitary infarction, and she presents now with
symptoms of hypoadrenalism, which include hyponatraemia and potassium at the upper limit of
normal. She, of course, requires fluid rehydration and emergency steroid replacement with iv
hydrocortisone. She will also have pituitary-dependent hypothyroidism and require thyroxine
replacement. Restoration of fertility is more difficult, pulsed delivery of pituitary sex-axis
hormones is usually required. Postnatal depression and simple dehydration are somewhat
.unlikely with this set of blood results
This is polycystic ovarian syndrome (PCOS). The prevalence of PCOS is estimated to range from
8 to 22% of women. Oligo/amenorrhoea is present in 70%, hirsutism in 60%, obesity in 35%
and infertility in 30%. LH is usually markedly raised, as is the LH/FSH ratio. Sex hormone-
binding globulin is low in 50% of sufferers. Due primarily to hyperinsulinaemia.Testosterone and
DHEAS (dehydroepiandrosterone) levels are also usually raised. Up to 40% of women with
PCOS may have impaired glucose tolerance, and up to 10% frank type-2 diabetes mellitus. The
insulin-resistant state is also associated with dyslipidaemia. Management is usually with weight
loss and lifestyle advice. Metformin is a useful treatment for insulin resistance and may help
restore fertility, although clomifene may also be required for ovulation induction. Local creams
.and electrolysis may have a useful role to play if the primary complaint is one of hirsutism
Phaeochromocytoma
Essential hypertension
Simple obesity
Cushing’s syndrome
Your answer
Cushing’s syndrome is associated with a round, plethoric, facial appearance and weight gain – in
particular truncal obesity, buffalo hump and supraclavicular fat pads, skin fragility, proximal
muscle weakness, mood disturbance, menstrual disturbance and reduced libido. Hypertension is
present in more than 50% of patients, impaired glucose tolerance in 30%. Osteopenia and
osteoporosis, and premature vascular disease are an inevitable consequence in untreated
Cushing’s. The annual incidence is approximately 2 per million and the disease is commoner in
women. The disease results from hypercortisolaemia and the cause in 68% of cases is a
pituitary adenoma producing ACTH. Ectopic ACTH production is the cause in 12%, adrenal
adenoma in 10% and adrenal carcinoma in 8%. Diagnosis is made on the results of the 24-h
urinary free-cortisol assay. Differentiation as to the cause is carried out with the
dexamethasone-suppression test and selective venous sampling in cases when a discrete
.tumour cannot be identified on contrast-CT scanning
Pituitary failure
Thyrotoxicosis
The blood picture of elevated FSH, low estradiol and prolonged amenorrhoea fits the picture.
The normal TSH rules out thyrotoxicosis, and the raised FSH makes PCOS unlikely and this does
not fit the picture of an androgen-secreting adrenal tumour. Autoimmune disease is responsible
for 20% of cases of premature ovarian failure, and is prevalent in 10% of women with Addison’s
disease and 25% of women with autoimmune thyroid disease. Spontaneous recovery of fertility
.is unlikely, and put at only 5%
Hyperparathyroidism
Your answer
Hypoparathyroidism
Pseudohypoparathyroidism
She may have diabetes mellitus and requires a fasting blood test the
following day to confirm the diagnosis Your
answer
She probably has impaired glucose tolerance and should undergo a 2-h
glucose tolerance test
A 2-h glucose tolerance test plasma glucose level of 10.5 mmol/l would
confirm diabetes mellitus
A fasting plasma glucose of 7.2 mmol/l the following day would suggest
impaired fasting glucose
The American Diabetes Association (ADA) criteria were developed in 1997, with a suggestion
that a glucose tolerance test should be avoided, if possible, to make diagnosis simpler and
quicker. Three methods of classification of diabetes mellitus were developed: symptoms and a
random plasma glucose of greater than or equal to 11.1 mmol/l; fasting plasma glucose of
greater than or equal to 7.0 mmol/l; and 75-g oral glucose tolerance test 2-h glucose of greater
than or equal to 11.1 mmol/l. These diagnostic criteria still stand the test of time today. Ideally
random raised fasting plasma glucose should be confirmed with a fasting sample. ‘Impaired
fasting glucose’ (analogous to ‘impaired glucose tolerance’), is defined as a plasma glucose level
.of greater than or equal to 5.6 mmol/l and less than 7.0 mmol/l
A 26-year-old woman has been recently diagnosed with type-1 diabetes. She.55
has read a great deal about the prognosis of renal disease in type-1 diabetes
.and has a number of questions to ask
Which of the following statements best describes the renal disease in patients
?with type-1 diabetes
After the serum creatinine level reaches 200 µmol/l, a fall in GFR of 0.5
ml/min per month might be expected
Nephropathy have a 10 times higher mortality rate than age- and sex-
matched controls
In type-1 diabetes microalbuminuria usually occurs 5–15 years after the diagnosis of diabetes
mellitus. The peak incidence of frank albuminuria is around 17 years after diagnosis. It is
reasonable to expect a fall in the glomerular filtration rate (GFR) of 1 ml/min per month once
the serum creatinine level has reached around 200 µmol/traditionally, end-stage renal failure is
said to occur some 7–10 years after a diagnosis of albuminuria, but it is hoped that improved
management of hyperglycaemia and hypertension may stretch this period a little. Unfortunately,
nephropathy carries a 20–100 times higher mortality than that for age- and sex-matched
.controls: 40% of deaths of patients with nephropathy are due to cardiovascular disease
A 70-year-old man is brought unconscious to the emergency department; his.56
blood sugar level is 70 mmol/l. There is no evidence of ketoacidosis. His chest
.X-ray reveals evidence of left-sided consolidation
?What is the most likely diagnosis
Simple pneumonia
Stroke
Glucagonoma
He is most likely to be suffering from hyperosmolar non-ketotic coma, which is associated with
type-2 diabetes and with coexistent infection. The common presentation is often with blood
glucose levels of over 50 mmol/l, a markedly raised serum osmolality and a decreased
conscious level, without ketosis. Management is with iv insulin and isotonic saline infusion,
although the blood glucose level often drops quickly after insulin is initiated. Hyperosmolar
coma may be the initial presentation of diabetes mellitus, and two-thirds of sufferers present
with type-2 diabetes mellitus for the first time. Mortality is high, particularly in elderly sufferers.
.Glucagonoma is vanishingly rare, with an annual incidence of 1/20 million in the UK
A 65-year-old obese woman who has had type-2 diabetes for 4 years presents.57
to the clinic for her annual review. Her current medication is metformin 2
g/day. You decide to add in gliclazide 80 mg po bd because of poor control as
.her Hb A1C is 8.5%
?Which of the following best describes sulphonylureas
Although sulphonylurea therapy was proven by the UKPDS study to have microvascular
benefits, no benefit on macrovascular outcome (cardiovascular disease) was demonstrated: this
was, of course, in contrast to metformin. Sulphonylureas work by stimulating insulin release
from pancreatic beta cells and are associated with mild hypoglycaemia in up to 16% of users,
although hypoglycaemia may be less frequent when short-acting compounds are used. Certain
groups of people (the elderly and those with renal impairment) may be at a higher risk of
.hypoglycaemia. Sulphonylureas have no effect on insulin resistance
There is evidence that all three agents in the glitazone class (troglitazone,
pioglitazone and rosiglitazone) have similar profiles of hepatotoxicity
There are currently two licensed glitazones (insulin sensitisers) world-wide, rosiglitazone and
pioglitazone. Both drugs act at the site of the PPAR-γ receptor, promoting the transcription of
genes predominantly linked to fatty acid metabolism. Fibrates, and some newer dual agonists
currently in development, have activity at the PPAR-α receptor site. Fluid retention may be
precipitated by these drugs, which may (in less than 1% of users) precipitate heart failure.
Experimental evidence has demonstrated that these drugs actually improve myocardial blood
flow and glucose utilisation. Metformin acts primarily by affecting hepatic insulin resistance,
whereas the glitazones act by improving insulin sensitivity and peripheral glucose uptake
.inskeletal muscle and fat. Troglitazone has been withdrawn due to liver side-effects
?Which of the following statements best fits the predisposing factors involved in DKA
The commonest precipitant of diabetic ketoacidosis (DKA) is infection (30–40%). This is closely
followed by non-compliance with treatment (25%), alterations to insulin dose (13%), newly
diagnosed diabetes (10–20%) and myocardial infarction (< 1%). The condition is characterised
by hyperglycaemia, acidosis and ketonuria. DKA is common, with 9.1% of patients in the
EURODIAB study reporting hospitalisation over the period of a year. DKA is caused by insulin
deficiency and counter-regulatory hormone excess. The mortality rate is 2–5%, but up to 50%
.in more elderly patients
A 36-year-old woman who is 28 weeks pregnant attends the midwife clinic for.60
a pregnancy check. She is noted to have glycosuria and has a BMI of 30 You
.understand her mother has Type-2 diabetes
?What is her correct management plan
Observe and follow up in 4 weeks' time with repeat urine glucose testing
Carry out a fasting blood glucose; if it is less than 7.0 mmol/l then repeat
the sample in 4 weeks’ time Your
answer
Carry out a fasting blood glucose; if it is over 5.5 mmol/l then proceed to
administer a 75-g oral glucose tolerance test Correct
answer
Carry out a fasting blood glucose; it is over 7.0 mmol/l then proceed to
administer a 75-g oral glucose tolerance test
A glucose tolerance test is required if the patient’s fasting blood glucose level is over 5.5
mmol/l. Diabetes is defined as a fasting level of > 7.0 mmol/l or > 11.0 mmol/l 2 h after a
glucose tolerance test. Gestational impaired glucose tolerance (IGT) is defined as a fasting blood
glucose level of 6.0–7.8 mmol/l and/or a 2-h level of 9–11 mmol/l. Although initial treatment for
gestational diabetes is with dietary advice, insulin is also required in 10–30% of cases. Insulin
should be considered for those with fasting levels above 6.0 mmol/l after dietary intervention,
or postprandial sugar levels above 8.0 mmol/l. Untreated gestational diabetes is said to carry a
perinatal mortality rate of 4.4–6.4%, compared to 0.5–1.5% in a similarly matched
.normoglycaemic population: hence, good glycaemic control is essential for this reason
Alcohol history
The clue is the fact that her insulin level was raised without a corresponding rise in c-peptide.
This essentially rules out insulinoma, and suggests that the patient is either injecting excess
insulin herself or is taking sulphonylureas. In fact, on further questioning her aunt has type-2
diabetes; she has been struggling with her studies and taking sulphonylureas to precipitate the
attacks as a ‘cry for help’. Standard work-up for hypoglycaemia should include laboratory blood
glucose (not test strips) measurement, liver function tests to rule out significant liver
dysfunction, blood alcohol and alcohol history, cortisol ± Synacthen testing, insulin and c-
.peptide levels taken during an attack as well as a chest X-ray to exclude occult malignancy
A 68-year-old man attends his GP on the insistence of his wife because his left.62
forefoot has become increasingly unstable and abnormally shaped with bony
swelling. He has a long history of diabetes mellitus and his control has been
.erratic, with Hb A1C in the range of 9–10%
Which of the following pieces of information best fits the pathology or management of
?Charcot’s foot
This man has a Charcot left foot. This is a rare condition now, with the average general hospital
clinic seeing a maximum of 10 Charcot’s patients. Chronic untreated Charcot’s foot results in
either ‘rocker-bottom’ foot due to downward displacement and subluxation of the tarsus, or
medial convexity due to talonavicular joint displacement or dislocation of the tarsometatarsal
joints. Management involves tight glycaemic control, reduction of oedema and orthotic and
chiropody involvement. Intravenous bisphosphonate treatment may be of benefit in some
patients. Although plain radiographs may be normal in the early stages of the disease, they
.later show joint destruction, osteolysis, joint reorganisation and subluxation
A 56-year-old patient on gliclazide for his type-2 diabetes presents with an.63
.acute, central, crushing chest pain. He is diagnosed with myocardial infarction
Which of the following best fits the outcome or management of myocardial infarction
?associated with type-2 diabetes
Use of ACE inhibition after MI improves the 6-week mortality rate by 50%
Diabetics may be up to twice as likely to die from myocardial infarction as non-diabetics, and
are more likely to suffer an MI in the first place. The DIGAMI study used iv insulin for 24 h
followed by sc insulin for patients who had suffered an MI. Risk reductions equalled 7.5% at 1
year and 11% at 3.5 years compared to controls. There is now significant doubt about this
result as the study was repeated in the DIGAMI-2 study. This showed no advantage in terms of
cardiac outcomes for patients treated for a prolonged period with insulin. Use of ACE inhibitors
(GISSI-3 Diabetic Subgroup Study) is associated with a 30% relative-risk reduction in the 6-
week mortality rate (8.7% vs. 12.4%). Blood pressure reduction should be aggressively
targeted, aiming for 130/80 mmHg, and all patients with diabetes who are over 40 years of age
should be started on statin treatment unless there is a contraindication, (Joint British Societies
.(Guidelines
Diabetic amyotrophy is said to occur most commonly in men in their fifties with type-2 diabetes
treated with oral hypoglycaemic agents. It is a mixed motor and sensory proximal neuropathy
said to cause severe pain, which is responsible for anorexia and weight loss. Some 50% of
patients recover fully from this condition, usually within 3–4 months. The mainstay of treatment
.is supportive care and transference to insulin therapy
A 63-year-old man presents to the diabetes clinic for review. He attends with.66
his wife who has accused him of a lack of interest in her as he is no longer
.able to sustain an erection
Which of the following statements is most strongly associated with impotence in type-
?2 diabetes
Estimates say that 20% of men with diabetes mellitus of more than 6
years’ duration are affected Your answer
Libido is rarely affected, which makes the condition all the more frustrating for affected men.
Between 30 and 50% of men with diabetes of more than 6 years’ duration are affected. There is
an association with other autonomic neuropathies such as postural hypotension and
gastroparesis. The condition is not usually associated with pain, and may be exacerbated by
both β -blockers and thiazide diuretics. PDE-5 inhibitors are now available as oral therapies for
impotence, but these are often required at high dose. Alprostadil and vacuum devices are
.alternative methods. Estimates put successful treatment at only around 70%
A 54-year-old woman presents to the diabetes clinic for review. She has .67
suffered from diabetes mellitus for many years and has now progressed from
sulphonylurea treatment to insulin therapy. A past history of gallstones is
noted and she failed to tolerate metformin due to chronic diarrhoea. She has
been slowly losing weight over the past few months and has mild anaemia.
Ultrasound scan of her liver reveals a suggestion of a number of small
.metastases within the liver
When considering that this woman has a primary pancreatic tumour, which of the
?following statements best fits the condition
There is a suggestion that this patient has a glucagonoma, 90% of which are associated with
the characteristic skin rash – necrolytic migratory erythema. The annual incidence of
glucagonoma is estimated at 1 in 20 million. Over 70% of glucagonomas are malignant, but,
because of their indolent presentation, the diagnosis is often overlooked for many years. Due to
insulin antagonism over 90% are associated with impaired glucose tolerance, and eventually
weight loss due to protein catabolism. Surgical cure rate is as low as 5%, due to metastases
many years prior to presentation. Octreotide improves the skin rash but may have a detrimental
effect on glucose control; combination chemotherapy with streptazocin and 5-fluoruracil (5-FU)
.gives good palliative results, as does hepatic embolisation
A 52-year-old woman is referred for opinion, she has been diagnosed with.69
type-2 diabetes mellitus and is losing weight, her GP is thinking about insulin
therapy. A normochromic, normocytic anaemia is noted. On examination she
has angular stomatitis and a well-demarcated erythematous rash in her groin,
.extending to her lower limbs, buttocks and perineum
?What is the underlying diagnosis
Somatostatinoma
Cushing’s disease
Glucagonoma
Your answer
The skin rash, necrolytic migratory erythema, glucose intolerance, a normochromic, normocytic
anaemia, weight loss and angular stomatitis are all highly suggestive of glucagonoma. The
annual incidence of glucagonoma is estimated at 1/20 million. Over 70% of glucagonomas are
malignant, but because of their indolent presentation, the diagnosis is often overlooked for
many years. Due to insulin antagonism over 90% are associated with impaired glucose
tolerance, and eventually weight loss due to protein catabolism. Surgical cure rate is as low as
5%, as metastases occur many years prior to presentation. Octreotide improves the skin rash
but may have a detrimental effect on glucose control; combination chemotherapy with
.streptazocin and 5-fluoruracil (5-FU) gives good palliative results, as does hepatic embolisation
A 36-year-old man is referred after his first myocardial infarction for your.70
opinion. He has a total cholesterol level of 9.5 mmol/l, with normal
.triglycerides. You note the presence of corneal arcus and tendon xanthomas
Which of the following genetic factors is not likely to be a cause of the
?hypercholesterolaemia
The suspicion with the history of dry skin, hair loss, obesity and sleep apnoea is that she has
hypothyroidism. This would be the cause of her secondary hypercholesterolaemia. Frank
hypothyroidism is said to occur in 4% of patients with dyslipidaemias, and a further 10% of
patients with dyslipidaemia have a raised TSH level, but with a free T4 still within the normal
range. Total cholesterol often improves somewhat with thyroxine therapy, but statins may be
.required in addition
You review a 67-year-old man in the lipid clinic. He is taking pravastatin 40.73
?mg/day.Which of the following drugs should be used with caution
Warfarin
Erythromycin
Correct answer
Digoxin
Antacids
Antifungals
Your answer
Warfarin and digoxin have well-recognised interactions with atorvastatin and simvastatin.
Antacid and antifungal agents are known to interact with atorvastatin. Erythromycin has known
interactions with simvastatin, fluvastatin, atorvastatin and pravastatin. All statins interact with
ciclosporin and nicotinic acid and should be used with caution in patients on fibrate therapy as
.the risk of rhabdomyolysis may be increased
The presence of galactorrhoea is MOST suggestive of which one of the.74
?following conditions
Turner’s syndrome
Hypothyroidism
Your answer
Sheehan’s syndrome
Bromocriptine therapy
Apoprotein E
Your answer
Apoprotein CII
Correct answer
Apoprotein AII
Lipoprotein B
LDL receptor
Dietary triglycerides in cholesterol are packaged by gastrointestinal epithelial cells into large
lipoprotein particles called chylomicrons. After secretion into the intestinal lymph and passage
into the general circulation, chylomicrons bind to the enzyme lipoprotein lipase, which is located
on endothelial surfaces. This enzyme is activated by a protein contained in the chylomicron,
apoprotein CII, liberating free fatty acids and monoglycerides, which then pass through the
endothelial cells and enter adipocyte or muscle cells. Therefore, complete inactivation of either
lipoprotein lipase or apoprotein CII as a result of the inheritance of two defective copies of the
relevant gene results in an accumulation of chylomicrons (type I lipoprotein elevation) owing to
failure of conversion to the chylomicron remnant particle. Patients with familial lipoprotein lipase
deficiency usually present in infancy with recurrent attacks of abdominal pain caused by
pancreatitis. They also have eruptive xanthomas resulting from triglyceride deposition.
Treatment should consist of a low-fat diet that may be supplemented by medium-chain
triglycerides, which are not incorporated into chylomicrons. The absence of functional
apoprotein CII, with consequent failure to activate lipoprotein lipase, presents with a similar
phenotype, although the affected patients are typically detected at a somewhat later age than
.are patients with familial lipoprotein lipase deficiency
A 65-year-old woman known to have chronic low back pain notices severe.76
sharp pain in the left groin after a minor fall and is unable to walk. Left neck of
femur fracture is identified on radiological examination. Routine laboratory
evaluation discloses a serum calcium concentration of 1.9 mmol/l, a serum
phosphorus concentration of 0.68 mmol/l and increased serum alkaline
phosphatase activity. The serum parathyroid hormone level was subsequently
?found to be elevated.The most likely diagnosis is
Primary hyperparathyroidism
Hypervitaminosis D
Osteoporosis
Your answer
Vitamin D deficiency
Correct answer
Acanthosis nigricans
Panniculitis
Ichthyosis
Glucagonoma syndrome (diabetes mellitus, weight loss and anaemia) is associated with a
characteristic skin rash (necrolytic migratory erythema) in 75% of cases. The lesion starts as an
indurated erythema at the perineum, face and nose. Within a few days blisters will cover the
surface of the skin which then crust and heal leaving hyperpigmented skin. This process takes
.7–14 days with lesions developing in one area while others are resolving
A 23-year-old woman presents to her GP after the birth of her second child..78
She complains of extreme tiredness and a persistent hoarse voice that she is
having problems shaking off. Despite breast-feeding her child she is failing to
lose her pregnancy weight. Thyroid autoantibodies are negative. Her TSH is 12
mU/l, with a free T4of 5 pmol/l. There is no thyroid tenderness on
.examination. Her GP notes that her pulse is only 52 beats per minute
?What diagnosis fits best with this clinical picture
Hashimoto’s thyroiditis
Postpartum thyroiditis
Your answer
Atrophic hypothyroidism
Iodine deficiency
Hyperthyroidism
This woman is hypothyroid after the birth of her second child. Her thyroid autoantibodies are
negative and she has no signs of autoimmune disease, which might suggest atrophic
hypothyroidism were they present (eg vitiligo). Iodine deficiency is now rare and tends to occur
in isolated mountain areas. Postpartum thyroiditis is usually transient, and may involve
hyperthyroidism, hypothyroidism or the two in sequence. It is thought to be due to changes in
the immune system after pregnancy and is histologically a lymphocytic thyroiditis. It is usually
.self-limiting
Hashimoto’s thyroiditis
Thyroglossal cyst
Thyroid carcinoma
Grave’s disease
Toxic multinodular goitre usually occurs in women over 55 years of age and is more common
than Grave’s disease in the elderly. Her atrial fibrillation may well be related to this. Her goitre
is obstructing, with significant retrosternal extension, and surgery is the treatment of choice.
.Initially, however, she should be rendered euthyroid with antithyroid drugs such as carbimazole
A 62-year-old man presents for review some 3 months after first being.80
diagnosed with type-2 diabetes. His BMI is 30. Despite having lost about 7 kg
in weight, his morning blood sugars are still around 9 mmol/l; an Hb A1C check
was 8.9%. He is hypertensive and taking ramipril, his triglycerides are raised
.and his HDL cholesterol is low
?Which therapy for his diabetes would be the best initial choice for his hyperglycaemia
Glibenclamide
Gliclazide
Rosiglitazone
Metformin
Your answer
Acarbose
The best initial therapy for this man, who clearly has the metabolic syndrome, is metformin.
This drug should be introduced at a dose of 500 mg per day, with a gradual increase in the dose
.(over a few weeks to around 1.5–2 g total daily dose (divided into morning and evening doses
The UKPDS (United Kingdom Prospective Diabetes Study) showed that for macrovascular risk,
metformin was superior to sulphonylureas or insulin (a statistically significant risk reduction for
myocardial infarction compared to conventional therapy, which was not found in the
sulphonylurea or insulin group). Metformin is a partial insulin sensitiser that works to reduce
hepatic glucose output and also has some anti-inflammatory action, showing positive effects on
plasminogen-activator inhibitor-1 (PAI-1) in particular. PAI-1 is associated with an increased
tendency to blood clotting and may be associated with an increased vascular risk in sufferers of
.the metabolic syndrome
Acarbose
Glargine
Pioglitazone
Correct answer
Chlorpropamide
Glibenclamide
Your answer
Stopping smoking
Rapid improvement in blood glucose levels may be associated with worsening of diabetic eye
disease. Both the Diabetes Control and Complications Trial (DCCT) in type-1 diabetes and the
UKPDS (United Kingdom Prospective Diabetes Study) in type-2 diabetes have demonstrated the
long-term benefits of reducing blood sugar levels in controlling future microvascular
complications. All diabetic patients should be offered yearly eye screening, preferably with a
digital retinal camera. Rapidly deteriorating visual acuity, hard exudates encroaching on the
macula, preproliferative changes or new-vessel formation are all reasons for early referral to an
.ophthalmologist
Diabetic retinopathy has been known for many years to be the leading cause of blindness in the
UK in people of working age, but progression to blindness is now slowing and tailing off due to
.improved ophthalmic care. Smoking has no effect on the prognosis of retinopathy
Blood glucose
Serum cortisol
Prolactin
Microprolactinoma
Your answer
Macroprolactinoma
Psychogenic impotence
Hypothyroidism
Acromegaly
Men with prolactinoma tend to present substantially later than women, the latter presenting
with cessation of periods and galactorrhoea. Macroprolactinoma is unlikely given his normal
visual fields. Prolactinoma is the most common pituitary tumour; microadenomas are more
common in women, whereas macroadenomas appear more commonly in men. Treatment is
surgical (via the trans-sphenoidal route) or medical (microprolactinomas) using dopamine
agonists such as bromocriptine or cabergoline to suppress prolactin release. Trans-sphenoidal
cure rates are around 50–75%. Up to 20% of microprolactinomas resolve during long-term
.dopamine agonist treatment
A 23-year-old woman with type-1 diabetes presents with an unusual lesion on.86
her shin. It began as a patch of spreading erythema, but now looks yellow and
.has begun to ulcerate
?What diagnosis best fits this lesion
Acanthosis nigricans
Dermatitis herpetiformis
Granuloma annulare
Your answer
Necrobiosis lipoidica
Correct answer
Xanthoma
Necrobiosis lipoidica occurs in patients with type-1 diabetes, beginning as a patch of erythema
that spreads across the shin, begins to yellow and then may ulcerate. Acanthosis nigricans is
associated with insulin resistance and may occur in those with type-2 diabetes and is usually
found in the axillas. Granuloma annulare is normally diffuse in diabetes and occurs as a ring of
papules. Dermatitis herpetiformis is, of course, associated with coeliac disease (gluten
.(enteropathy
Hyperparathyroidism
Hypoparathyroidism
Milk-alkali syndrome
In this case, parathyroid hormone is virtually in the normal range and his renal function is
normal, so there is nothing to suggest a diagnosis of the milk–alkali syndrome. Hypercalcaemia
is found in 10% of established cases of sarcoid, and may eventually lead to nephrocalcinosis.
The cause is increased 1 a-hydroxylation of vitamin D by sarcoid macrophages, in addition to
.that taking place in the kidney
You are asked to review a 54-year-old psychiatric patient by his GP. This.88
patient has been diagnosed with impaired glucose tolerance. He also has a
.history of hypertension, for which he takes ramipril
Which of the following drug classes is most well known as a cause of impaired
?glucose tolerance
Thiazolidinediones
ACE inhibitors
Atypical antipsychotics
Your answer
Biguanides
Sulphonylureas
Older atypical antipsychotic agents have been implicated as a cause of impaired glucose
.tolerance, and are thought to put those taking them at increased risk of type-2 diabetes
Thiazides and β -blockers may also impact negatively on the incidence of new diabetes, and this
combination of antihypertensives is no longer a first choice for patients with a high type-2
.diabetes risk
Ramipril was shown in the HOPE (Healthcare Options Plan Entitlement) study to reduce
progression to type-2 diabetes; this is thought to be mediated by a reduction in insulin
resistance. The LIFE (Longitudinal Interval Follow-up Evaluation) study using losartan has
demonstrated that angiotensin-receptor blockers also probably reduce the incidence of new
.cases of type-2 diabetes
You are asked by a GP to review a 16-year-old girl who presents with primary.89
amenorrhoea. She appears on examination to have minimal body hair but
normal breast development. Examination also reveals a blind-ended vagina.
Biochemistry reveals increased LH, normal FSH, raised estradiol and raised
.testosterone levels
?Which diagnosis fits best with this history and examination
Turner’s syndrome
Asherman’s syndrome
Testicular feminisation
Your answer
Pregnancy
This picture fits a diagnosis of testicular feminisation, in which androgen receptors are defective.
This girl, although having the external phenotype of a female, will have the XY karyotype. These
individuals are, of course, infertile. Patients with testicular feminisation do possess testes, and
.orchidectomy is advised since there is a high risk of testicular malignancy
Girls with Turner’s syndrome usually have the typical Turner’s phenotype of short stature and
webbed neck. Asherman’s syndrome is amenorrhoea due to uterine synechiae after infection;
.there is no history to suggest this and it can be ruled out on the examination findings
A 27-year-old man presents via his GP for review. He wants to start a.90
relationship but is concerned about his small phallus. He also has difficulty
becoming aroused. On examination he is slim and there is gynaecomastia.
There is a general paucity of body hair, his penis is small and he has small
?testes.Which diagnosis fits best with this history and examination
Testicular feminisation
Klinefelter’s syndrome
Your answer
True hermaphroditism
5α -reductase deficiency
This man is likely to have karyotype XXY and has the features of Klinefelter’s syndrome.
Individuals with testicular feminisation are phenotypic females. Karyotypic females with
congenital adrenal hyperplasia may have clitoromegaly and labial fusion, as well as ambiguous
.external genitalia that may appear male; they do not, however, have testes
True hermaphrodites are vanishingly rare and may be XX/XY or mosaic in karyotype; they
.possess both testes and ovaries and usually have male or ambiguous external genitalia
A 54-year-old man presents to the diabetes clinic for review. He has had type-.91
1 diabetes for 30 years. Recently he has suffered a number of falls, which he
describes as attacks where he feels ‘faint’ and loses his footing. He has
suffered from impotence for a number of years and takes antireflux
medication. On examination he has a postural drop of 35 mmHg in his blood
?pressure.Which diagnosis fits best with this history and examination
Arrhythmia
Simple fainting
Somatisation disorder
This man has a marked postural drop, features of GI tract neuropathy and impotence. Further
assessment of his cardiovascular system is likely to reveal tachycardia and impaired
cardiovascular response to the Valsalva manoeuvre. Other symptoms of GI tract involvement
may include diarrhoea and intractable vomiting. Bladder involvement may result in atonic
.bladder and problems with painless urinary retention and recurrent urinary tract infections
Idiopathic hyperaldosteronism
Conn’s adenoma
Your answer
Aldosterone-producing carcinoma
Carcinoid syndrome
To estimate renin and aldosterone levels accurately it may be necessary to wean the patient off
antihypertensive drugs for a period of a few weeks, since most classes of antihypertensives
have effects on the renin–angiotensin axis. CT or MRI scanning may be used to confirm the
.adenoma
After removal of the adenoma, blood pressure is normal in 70% of patients at 1 year. At 5
.years’ postsurgery, 50% of patients remain normotensive
An 18-year-old girl is referred by her GP who is concerned that she may have.93
an underlying endocrine problem. The girl had been taken to the GP by her
mother. She is a good student and has just won a place at university. She
weighs only 38 kg (6 stone) and is 1.78 m (5ft 10 inches) tall. She is
emaciated, her skin is dry and she has excessive growth of lanugo hair. She
has been amenorrhoeic for 9 months. Her cortisol level is elevated, her free T4
is normal. She has an anaemia and associated reduced white cell and platelet
count.Which of the following diagnoses is most likely to fit with this clinical
?picture
Addison’s disease
HIV
Occult carcinoma
Hypothyroidism
Anorexia nervosa
Your answer
Anorexia nervosa has a female to male preponderance of 9:1. It is estimated that around 0.5–
1% of American women between 15 and 30 years of age have anorexia, and the numbers are
likely to be similar in the UK. The aetiology of anorexia is unknown, but it is likely to be an
interaction between environmental and genetic factors, American studies report rates of sexual
abuse as high as 50% in anorexic females. Despite an association with depressive and other
psychiatric illness, demographic studies show no impairment of cognitive level nor educational
achievement in the group of patients with anorexia nervosa as compared to the general
.population
Indeed such patients may fit the profile of being "high achievers", which is what is being hinted
.at in this question
Typical laboratory tests include decreased FSH, LH, oestrogens and 17-OH steroids. Free T4 and
TSH levels are usually normal. Anaemia with decreased white and platelet cell count may also
.occur. There may be metabolic alkalosis, hypocalcaemia, hypokalaemia and hypomagnesaemia
Treatment may involve complex psychotherapy for a number of years, and referral to a
.specialist in the field is recommended
A 60-year-old woman is sent by A&E for endocrine review. During the past 18.94
months she has suffered two Colle’s fractures and a fractured neck of her left
femur. Results of thyroid function testing, serum protein electrophoresis and
serum parathyroid hormone estimation are all normal. Bone densitometry of
the lumbar spine and femoral neck on the non-replaced side reveal a bone
density within the osteoporotic range.Which of the following interventions
?would be most appropriate for her
Initiate HRT
Your answer
This woman has idiopathic osteoporosis, with normal thyroid function and parathyroid hormone
assay ruling out hyperthyroidism and hyperparathyroidism. Her osteoporosis is clearly of clinical
significance in that she has suffered two fractures of the distal radius and a fractured neck of a
femur during the past 19 months. Hormone replacement therapy (HRT) would not be advised in
this age group due to the increased cardiovascular and breast cancer risk. Bisphosphonate
.therapy, which inhibits osteoclast activity, would be the best choice in this patient
The primary mode of action of the bisphosphonates is inhibition of osteoclast activity. With the
results from large-scale HRT studies suggesting an increased risk of carcinoma or cardiovascular
disease, they have become the first-choice therapy for osteoporosis. They may be given orally,
although some clinicians prefer intermittent intravenous use. This class of drugs may be
associated with an increased risk of oesophageal ulceration. When the class was developed
there was initial concern over prolonged inhibition of bone turnover over a number of years, but
.this appears to have been unfounded
Charcot’s ankle
Your answer
Osteomyelitis
Rheumatoid arthritis
Osteoarthritis
Charcot’s joint is said to occur in 1 in every 750 patients with diabetes mellitus, although this is
increased to 5 in every 100 in those with proven neuropathy. However, a Charcot’s joint does
not just occur in those with diabetes but may occur in 20–40% of patients with syringomyelia
and 5–10% of those with long-standing syphilis (although this condition is now very rare).
Management in diabetes includes tight control of blood glucose, appropriate orthotic
.intervention, and there is evidence that bisphosphonates may slow the pace of joint destruction
A 32-year-old merchant banker presents for endocrine review. Apart from a.97
past history of reflux symptoms, her previous medical history is unremarkable.
She gives a history of increasing fatigue, being sometimes unable to leave her
bedroom; she says that she is only able to walk a few steps without feeling
exhausted. She has lost a little weight and gone on long-term sick leave from
her job. She feels unable to concentrate, has headaches, intermittent sore
throats and feels that when she is able to sleep, she awakes unrefreshed. Full
blood count, viscosity, urea and electrolytes, liver function testing, thyroid
function testing and a Synacthen test arranged by her GP have all been
normal. On examination in the clinic there are no abnormal physical findings in
this normal weight, normal height young woman.What diagnosis fits best with
?this clinical picture
Addison’s disease
Hypothyroidism
Myasthenia gravis
The prevalence of chronic fatigue syndrome is estimated at 1–3 per 1000 individuals. The
predominant age at presentation is young adulthood to middle age, and there is a slight female
preponderance. Sufferers often report a short flu-like illness at the point of onset and some
scientists believe that an initial viral trigger may be responsible. Conventional investigation and
physical examination proves normal. Initial hopes centred on the Epstein–Barr virus infection
being that trigger, but concrete proof has not yet been demonstrated. Education, counselling
and goal setting have proved useful in stimulating recovery, and trials have demonstrated
.improvements with amitriptyline use, but many patients take years to return to normal life
Warfarin therapy
Digoxin therapy
Correct answer
Furosemide
Ranitidine
Your answer
Sodium bicarbonate
Digitalis is one of a number of drugs that may be associated with gynaecomastia. Other causes
include oestrogens, cannabis, diamorphine, spironolactone, cimetidine, cyproterone,
gonadotrophins and some cytotoxics. Whilst gynaecomastia is occasionally seen with ranitidine,
this is much less common versus digoxin or cimetidine. Thyrotoxicosis, liver disease, oestrogen-
producing tumours, HCG-producing tumours, starvation/refeeding and carcinoma of the breast
are also associated with gynaecomastia. Surgical removal is occasionally carried out in younger
.men
Hyperprolactinaemia
Androgen-secreting tumour
Cushing’s disease
Type-2 diabetes
PCOS is said to occur in 3% of adult women. Symptoms usually begin around the time of
menarche and the diagnosis is often made in adolescence. Obesity is present in around 40% of
sufferers and there is an increased association with type-2 diabetes due to insulin resistance.
Biochemical abnormalities characteristically include a mildly raised testosterone level and an
increased LH: FSH ratio. Treatment includes weight loss or metformin therapy. Surgical
intervention with wedge ovarian resection may reduce androgen secretion and symptoms. Many
women just require reassurance and effective local treatment for hirsutism. Those who wish to
conceive do so with increased frequency after a trial of metformin therapy, clomifene, or in
.some cases gonadotrophins
A 21-year-old woman presents for review. She is concerned on this occasion .100
because she has not had a period for 5 months. She is 1.76 m in height and
weighs only 43.7 kg (7 stone). A pregnancy test is negative and thyroid
function testing is normal. Which diagnosis fits best with this woman’s clinical
?picture
Gonadotrophin deficiency
Weight-related amenorrhoea
Your answer
Hyperprolactinaemia
A woman needs to maintain a minimum body weight for menstruation, and amenorrhoea may
even be seen at weights considered to be at the lower end of the normal range. The biochemical
picture may be indistinguishable from gonadotrophin deficiency. Gaining body weight to above
the 50th centile for height normally results in the restoration of menstruation, but if this cannot
be achieved then oestrogen replacement may be considered. Amenorrhoea is often seen in
.ballet dancers who maintain a low weight and carry out periods of extreme physical exercise
A 75-year-old woman is admitted in an unconscious state. Her daughter found her.101
on the floor. On examination in casualty she is found to have a core temperature of 33
°C and also to be in left ventricular failure. Her blood glucose level is 5.7 mmol/l,
random cortisol is elevated. By chance you also catch the twice weekly run of thyroid
function testing and her free T4 is 4.4 pmol/l. A CT scan of her brain reveals no focal
lesion and a cursory assessment reveals no gross focal neurology. Which diagnosis
?fits best with this woman’s clinical picture
Hypoglycaemia
Your answer
Addison’s disease
Profound hypothyroidism
Correct answer
Massive stroke
Alcohol excess
This woman has a greatly reduced free T4 concentration, is hypothermic, unconscious and has
evidence of associated heart failure. Mortality associated with this condition used to be as high
as 50%, but with modern intensive care management, survival has improved. T3 is usually given
via a nasogastric (NG) tube or iv injection at the rate of 2.5–5 μ g every 8 h, with conversion to
T4 after the patient regains consciousness. There is a risk of precipitating heart failure if larger
doses are given in the initial period. Other supportive measures include oxygen therapy,
hydrocortisone iv therapy and glucose infusion, but none of these have been effectively proven
.in a randomised, controlled trial setting
You review a 32-year-old woman with relapsed Grave’s disease. TSH is less .103
than 0.05 mU/l, with a free T4of 32.5 pmol/l. She has severe bilateral thyroid
eye disease with marked orbital oedema and proptosis. You are considering
radiotherapy as she has failed drug treatment.Which of the following
?statements best fits the management of her thyroid eye disease
Exacerbation of eye disease is more common after radioiodine treatment (15% vs 3% on drug
therapy alone). Only 5–10% of these worsening cases threaten sight, but discomfort and
deteriorating cosmetic appearance may cause much patient anxiety. Systemic steroids and oral
non-steroidal anti-inflammatory drugs (NSAIDs) may ease the discomfort and decrease
inflammation in severe symptoms. Orbital irradiation should be reserved for all but the most
severe of cases. Corrective eye muscle surgery should be delayed until thyroid eye disease has
.been stable for at least 6 months, but may be of value in improving diplopia
Prolactinoma
Polyglandular syndrome
Sheehan’s syndrome
Your answer
Metastatic carcinoma
Sheehan’s syndrome is well known to occur in women due to postpartum haemorrhage and
hypovolaemic shock, but the risk of it occurring is increased in women with type-1 diabetes who
have microvascular disease, and in patients with sickle-cell anaemia. It is said to occur in 1 in
10,000 deliveries. Initial management includes immediate steroid therapy with later full
endocrine assessment and replacement of pituitary-dependent hormones (eg thyroxine) as
required. Further conception may be difficult and require pulsed gonadotrophin therapy to
.restart ovulation. Diabetes insipidus is not usually associated with the syndrome
Hypothyroidism
Primary hypoadrenalism
Your answer
Psychiatric symptoms
Hypovolaemia
HIV
This woman has a marked postural drop, increased pigmentation due to her high ACTH and a
low cortisol, making primary hypoadrenalism the most likely diagnosis. Free thyroxine may also
be low at time of diagnosis, but thyroid hormone replacement should not be started as this may
worsen the adrenal crisis. Instead, steroid replacement therapy should be started, accompanied
by fluid replacement, and thyroid function reassessed at a later stage. Autoimmune destruction
of the adrenal glands is responsible for 80% of cases. Tuberculosis accounts for a further 15%
of cases. There is a female: male predominance of 2:1, and a prevalence of around 5 per
.100,000
Cushing’s disease
Pseudo-Cushing’s
Your answer
Simple obesity
Essential hypertension
Primary aldosteronism
Obese patients who consume alcohol to chronic excess may acquire a cushingoid appearance. In
this case, this man’s occupation as a publican suggests that he may have easy access to
alcohol. His two screening tests for Cushing’s disease – the dexamethasone suppression test
and 24-h urinary free cortisol – are normal, which effectively rules out option A. His type-2
diabetes is likely to be related to obesity and his sedentary lifestyle, although diabetes mellitus
.could, of course, also be due to alcohol-induced chronic pancreatitis
Management involves lifestyle measures to promote weight loss, and strict control of his alcohol
intake. Metformin would be the ideal treatment for his diabetes, although this would be
.contraindicated in the presence of continued alcohol excess
You are asked to review a 36-year-old man who has suffered a myocardial.107
infarction. He is a non-smoker with no past history of note and is not diabetic.
On admission his total cholesterol was 10.2 mmol/l, with triglycerides just
above the normal range, normal HDL and markedly raised LDL cholesterol. His
father died of a myocardial infarction at the age of 43.What is the most likely
?cause of his raised cholesterol
Familial hypertriglyceridaemia
Secondary hyperlipidaemia
Remnant hyperlipidaemia
Secondary hyperlipidaemia
Familial hypercholesterolaemia
Familial hypertriglyceridaemia
Your answer
Hypolipidaemia
Abetalipoproteinaemia
Triglyceride concentrations above 6 mmol/l carry a significant risk of complications, and this
unfortunate man has suffered both a retinal vein thrombosis and acute pancreatitis. Inherited
lipoprotein lipase or apoprotein C-II deficiency may be responsible, but these defects are rare
and normally present in childhood with eruptive xanthomas, lipaemia retinalis, pancreatitis and
retinal vein thrombosis. So-called ‘familial hypertriglyceridaemia’ presenting in this way, with
complications in adulthood and no specific identified genetic defect, is more common. Treatment
.in this case would involve the avoidance of alcohol and use of a fibrate-type agent
Histidase
Homogentisic acid oxidase
Cystathionine synthetase
Correct answer
Vasculitis
Self-neglect
Some 10–15% of patients with diabetes suffer foot ulceration at some stage during their lives;
while 50% of all lower limb amputations are performed on patients with diabetes, effective
.supervision may prevent a number of these from occurring
This man has the features of neuropathy, although he certainly has risk factors for peripheral
vascular disease. The neuropathic foot is said to be painless, or to have abnormal neuropathic
pain, to be high arched with toe clawing. It is often warm with bounding pulses and ulceration
tends to occur on the plantar surface. Peripheral ischaemia is said to be associated with rest
pain in a cold and nearly pulseless foot. There is often gravity-dependent reddening of the foot,
which vanishes if the foot is elevated, ulceration tends to be painful and often presents in the
heal area. Of course, it is perfectly possible for the two conditions to coexist, and for a mixed
.ischaemic/neuropathic pathology to be the underlying cause
Alzheimer’s disease
Coeliac disease
Riboflavin deficiency
Thiamine deficiency
In the presence of hepatic metastases, diarrhoea, facial flushing and a raised urinary 5-HIAA (5-
hydroxyindoleacetic acid), it is highly likely that this woman has the carcinoid syndrome.
Unfortunately during the 2 years that she has been lost to follow-up, it appears that she has
.developed pellagra
Orlistat is a b3-agonist
Orlistat, a pancreatic lipase inhibitor, blocks the breakdown and hence absorption of dietary fat.
In essence, this means that ingested fat continues its passage through the gut. If patients
taking orlistat do not maintain a low-fat diet then they may suffer distressing oily diarrhoea.
This is why it is essential to combine orlistat therapy with an effective patient support
programme. Sibutramine is a centrally acting drug that acts on serotoninergic and
.noradrenergic pathways to encourage earlier satiety and the ingestion of smaller meal portions
A 42-year-old man with long-standing HIV infection presents for review. He.113
has been taking antiretroviral therapy for 5 years and has been relatively free
of associated disease. You notice on examination that he appears to have lost
subcutaneous fat on his arms, legs and face, and has increased deposition of
fat around his abdomen. His lipids are also abnormal, with a raised triglyceride
level and low HDL cholesterol.What is the most likely cause of this clinical
?picture
Antiretroviral-related lipodystrophy
Your answer
HIV wasting
HIV-associated malignancy
You are asked by the psychiatrists to review a 42-year-old woman who has.114
long-standing bipolar disorder for which she takes lithium. During a recent
inpatient stay she appeared to be drinking vast amounts of water and getting
up many times in the night to urinate. Urea and electrolyte testing reveals
elevated sodium and urea concentrations, suggesting possible mild
dehydration. Water deprivation testing reveals a progressively rising serum
osmolality to above 300 mOsm/kg, without increased urine osmolality. Blood
?glucose is normal.What is the most likely cause of this clinical picture
Psychogenic polydipsia
Diabetes mellitus
This woman has nephrogenic diabetes insipidus (DI) secondary to chronic lithium therapy. There
is usually some recovery after withdrawing lithium therapy but many patients suffer some
degree of permanent nephrogenic DI. Lithium therapy should only be discontinued with
psychiatric advice, but at least now there are possible substitute medications including valproate
.and lamotrigine. Other drugs that may cause DI include demeclocycline and glibenclamide
Urgent β-blockade
Urgent surgery
Observation
This woman has a phaeochromocytoma of the right adrenal medulla. The commonest presenting
features are headache (80%), palpitations (70%), hyperhydrosis (60%) and hypertension
(sustained in 55% and paroxysmal in 45% of patients). Drugs that inhibit catecholamine
reuptake, such as tricyclic antidepressants and cocaine, can exacerbate or unmask the
symptoms of this condition. MRI or MIBG (metaiodobenzyl guanidine) scanning are the
definitive methods of localisation. Management involves a-blockade prior to surgery to avoid a
hypertensive crisis. The 5-year survival rate is 95% for patients with benign
phaeochromocytoma, but this falls to 40% in those with malignant disease.
.Phaeochromocytomas are three times more likely to be malignant in women
A 25-year-old woman presents with a lump on the left-hand side of her neck.116
in the thyroid region. Thyroid function is normal, and uptake scanning reveals
it to be a cold nodule. Fine-needle aspiration biopsy reveals architecture
suspicious of follicular carcinoma of the thyroid; this is confirmed on thyroid
.lobectomy
?Which of the following is the most appropriate management plan
No further surgery
Your answer
Total thyroidectomy
Radioiodine therapy
The definitive management for follicular carcinoma of the thyroid without metastases is total
thyroidectomy, followed by radioiodine therapy, with thyroxine replacement to a TSH-
suppressive dose. If metastases are present they usually respond to radioiodine therapy, and
this is added. Metastases are subject to haematological spread, with bone being the commonest
metastatic site. The 5-year survival rate approaches 80% for follicular carcinoma. This is much
higher than for anaplastic carcinoma of the thyroid, which usually occurs in the elderly and only
.carries a 5-year survival rate of 5%
Hypothyroidism
Phaeochromocytoma
Thyroid storm
Your answer
He should not have close contact with children under the age of 11 years for
about 2 weeks after treatment Your
answer
Antithyroid drugs may be recommenced after radioiodine administration, but treatment should
be withdrawn gradually and guided by 6–8 weekly TFTs. Early post-radioiodine hypothyroidism
may be transient. The patient’s TSH level should be monitored every 6 months after radioiodine
therapy to determine late hypothyroidism. Patients should not have close contact with children
under the age of 11 years for about 2 weeks after treatment; this is to prevent exposing
.children to radioactivity. However, there is no overall excess risk of cancer
Any acute stressful precipitating factor such as surgery can result in a thyroid storm or crisis.
This can also occur in patients with acute infections, postpartum and when antithyroid drugs are
being withdrawn. Thyroid crisis is associated with a significant mortality rate (30–50%) and is
best managed in an intensive care unit where close attention can be paid to cardiorespiratory
.status, fluid balance and cooling
Chlorpromazine can be used to treat agitation and, because of its effect in inhibiting central
thermoregulation, it may be useful in treating the hyperpyrexia. Specific treatment includes
propylthiouracil (PTU), potassium iodide (after starting PTU), β-blockers and glucocorticoids.
There is no clinical data comparing PTU and carbimazole in this situation. Plasmapheresis and
.peritoneal dialysis may be effective in cases resistant to pharmacological measures
Postpartum thyroiditis is thyroid dysfunction occurring within the first 6 months’ postpartum.
Prevalence ranges from 5 to 7%. It develops in 30–52% of women who have positive TPO
antibodies. Most patients have a complete remission but some may progress to permanent
.hypothyroidism. It is twice as common in patients with type-1 DM
Fluid restriction
Your answer
Desmopressin
Glucocorticoids
In patients with the syndrome of inappropriate ADH (SIADH) secretion, it is important to restrict
fluids to 500–1000 ml/24 hours. The underlying cause must also be detected and treated. If the
problem is not temporary and long-term fluid restriction is likely to be difficult, then
demeclocycline may be effective by inducing partial nephrogenic diabetes insipidus. In an
emergency, saline infusion may be required; however, great care is required as rapid
.overcorrection of hyponatraemia may cause central pontine myelinolysis
You are called to the psychiatric unit to see an 18-year-old woman with.123
anorexia nervosa. What would you expect to see in the results of her
?biochemical investigations
Increased GnRH
The typical patient with anorexia nervosa is a woman aged < 25 years with weight loss,
amenorrhea and behavioural changes. There is a long-term risk of severe osteoporosis.
Endocrine abnormalities include GnRH deficiency, low LH and FSH, low oestrogen in women,
raised circulating cortisol, low to normal thyroxine, reduced T3, normal TSH and increased
.resting GH levels
A 72-year-old woman recently diagnosed as having hyperparathyroidism has.124
a serum calcium concentration of 3.2 mmol/l.What is the most appropriate
?treatment
Surgery
Your answer
Long-term bisphosphonates
In primary hyperparathyroidism, a patient with a markedly elevated serum calcium > 3 mmol/l
should be referred for surgery, unless this is contraindicated for other reasons. Other indications
for surgery include impaired renal function, renal stones, nephrocalcinosis, reduced bone
mineral density (BMD), substantially elevated urinary calcium excretion of >10 mmol/24 hours.
.Medical management is only indicated if the patient is unsuitable for surgery
What is the commonest cause of death in patients with von Hippel–Lindau .125
?disease
Cerebellar haemangioblastoma
Your answer
Renal carcinoma
Correct answer
Retinal tumours
Myocardial infarction
Phaeochromocytoma
VHL disease is an autosomal-dominant condition, with the VHL gene being located on
chromosome 3. Estimated prevalence is 1/39,000. Retinal angiomatosis is the initial
presentation in 40% patients. Cerebellar haemangioblastoma is a common initial presentation.
Renal carcinoma is the commonest cause of death, with phaeochromocytoma occurring in 40%
.of patients with VHL
A 30-year-old man arrives in A&E in an unconscious state. His initial blood .126
glucose reading by monitor is 2.1 mmol/l.What is the most important
?immediate management of this patient
Oral glucose
Mannitol
glucose into a large vein after first taking a blood sample 50%
Your answer
mg glucagon IM 10
Check his serum ethanol concentration
Hypoglycaemia is defined as a plasma glucose concentration < 2.5 mmol/l and associated with
symptoms of neuroglycopenia. Large-bore venous access should be achieved and blood samples
for serum glucose, liver function, ethanol, cortisol, insulin, C-peptide, proinsulin and
sulphonylurea levels should be sent for testing. If the patient’s Glasgow Coma Score (GCS) is <
13, then 25–50 ml 50% glucose should be given intravenously. Glucagon (1 mg im) may be
.administered if no intravenous access can be obtained
Alcohol
b-Blockers
Diabetes mellitus
Psychological factors
Your answer
Testicular tumour
Erectile dysfunction is present in approximately 10% of all men and >50% of men over the age
of 70 years. Common causes are psychological factors (20%), drugs (25%) and endocrine
causes. Baseline investigations include serum testosterone, prolactin, fasting glucose, LH and
.FSH, thyroid function tests, liver and renal function, lipids and ferritin
Vitreous haemorrhage
Your answer
Cataracts
Drusen
Immediate referral is needed for patients with proliferative retinopathy (as it carries a 40% risk
of blindness if untreated and laser treatment reduces this), rubeosis iridis, vitreous
.haemorrhage, advanced retinopathy with fibrous tissue, retinal detachment or maculopathy
Severe migraine
Liver disease
Pulmonary hypertension
Your answer
Hypothyroidism
Correct answer
Absolute contraindications for OCP includes a history of heart disease, pulmonary hypertension,
history of arterial or venous thrombosis, history of cerebrovascular disease, liver disease, severe
migraine, breast or genital tract cancer and age over 35 years. Hypothyroidism is not a
.contraindication to taking the OCP
A pregnant mother with positive thyroid antibodies, but who is euthyroid, has a higher risk of
spontaneous abortions. There is no risk of neonatal hypothyroidism and the risk of PIH is not
increased. The occasional mother will develop hypothyroidism at the end of pregnancy, so the
TSH level should be checked between 28 and 32 weeks’ gestation, then at 3 months’
.postpartum
Alkaline phosphatase
Echocardiography
Plasma chromogranin A
Correct answer
The most sensitive marker for carcinoid syndrome is plasma chromogranin A, which has been
found in 100% of patients. Although the specificity is lower than for 5-HIAA (5-
hydroxyindoleacetic acid), most tumours with neuroendocrine differentiation are associated with
increased levels of plasma chromogranin A. This test is not widely available for clinical use.
Urinary 5-HIAA has a sensitivity of about 70% and a specificity of 100% in patients with
carcinoid syndrome. Alkaline phosphatase may remain normal despite liver involvement and a
.plasma gut-hormone profile may be useful
What is the most appropriate investigation to confirm a diagnosis of.133
?acromegaly biochemically after initial screening
Increased IGF-1
Your answer
In acromegaly, there is a failure to suppress GH to < 2 mU/l in response to a 75-g oral glucose
load. In contrast, the normal response is GH suppression to undetectable levels. Random GH is
not useful in the diagnosis of acromegaly because, although normal subjects have undetectable
growth hormone levels throughout the day, there are pulses of GH which are impossible to
differentiate from the levels seen in acromegaly. Following a TRH (thyrotrophin-releasing
hormone) test, 80% of patients with acromegaly show increased levels of GH. IGF-1 is useful
for initial screening for acromegaly, as it provides an integrated measure of growth hormone
.levels over time
Radioiodine
Block-and-replace regime
Propylthiouracil
Your answer
ESR
Serum urea
Serum calcium
Hyponatraemia is present in 90% and hyperkalemia in 65% of patients with primary adrenal
insufficiency. Although increased urea, increased ESR and raised TSH levels and mild
hypercalcaemia are seen in Addison’s disease, these are not particularly useful in confirming the
.diagnosis. However, failure to respond following a short Synacthen test suggests adrenal failure
Addison’s disease
Renal failure
Cardiac failure
Cirrhosis
Essential hypertension
Undiagnosed phaeochromocytoma
Your answer
MEN-1
Given her history, she is likely to have been suffering paroxysms of catecholamine release.
Mobilisation of the uterus is likely to have precipitated an acute release of large amounts of
catecholamines, causing her catastrophic rise in blood pressure and intraoperative myocardial
infarction. Standard therapy for phaeochromocytoma is aggressive α -blockade prior to surgery,
then surgical excision. The 5-year prognosis for benign tumours approaches 95%, but this falls
.to around 40% in patients with malignant disease
Neurofibromatosis
Carcinoid syndrome
A 45-year-old man presents for review at the type-2 diabetes clinic. He is on.139
maximal metformin and his Hb A1c is still 7.8%. You elect to add in a
peroxisome proliferator-activated receptor (PPAR)-gamma agonist,
pioglitazone.Which of the following best describes the mode of action of PPAR-
?γ agonists
PPAR-γ agonists act by binding to the PPAR-gamma receptor, which binds to a promoter region
of DNA in tandem with the retinoid X-receptor. This then leads to the upregulation of a number
of enzymes concerned with lipid metabolism, bringing about a fall in free fatty acids. The fall in
free fatty acids promotes a reduction in hepatic insulin resistance, a rise in adiponectin and
improved peripheral insulin sensitivity. Retinoid X-receptors are also now under investigation for
their possible action in improving insulin sensitivity. Currently, there are two PPAR-γ agonists
on the market, rosiglitazone and pioglitazone, both with promising data for long-term glycaemic
.control in type-2 diabetes
She has probably suffered an equal mix of cortical and trabecular bone loss
Grave’s disease
Kelp is a very rich source of iodine. In patients with pre-existing thyroid hyperplasia or
adenoma, the ingestion of large amounts of iodine may precipitate thyrotoxicosis. Treatment is
withdrawal of the kelp with monitoring of thyroid function. Thyrotoxicosis affects 2% of women
and 0.2% of men in their lifetimes. Grave’s disease is responsible for around 80% of cases of
thyrotoxicosis; toxic multinodular goitre is the next commonest cause. Patients with Grave’s
disease may be offered radioiodine, if suitable, or a period of medical therapy with antithyroid
drugs and thyroxine replacement. Patients who then fail on medical therapy are offered
.radiotherapy or surgery
Diuretic abuse
Gitelman’s syndrome
Liddle’s syndrome
Bartter’s syndrome
Your answer
Conn’s syndrome
Gordon’s syndrome
Your answer
Bartter’s syndrome
Addison’s disease
Conn’s syndrome
Gitelman’s syndrome
Gordon’s syndrome presents as almost the mirror image of the metabolic abnormalities seen in
Bartter’s syndrome, and is caused primarily by renal sodium retention and volume expansion.
Addison’s disease is, of course, associated with hypotension and hyperkalaemia. Conn’s
syndrome is primary hyperaldosteronism and is associated with hypokalaemia. In general, the
emergency treatment of hyperkalaemia is well documented, with acute administration of
calcium to reduce the risk of arrhythmias, insulin to drive potassium into cells and the use of
.ion-exchange resins to increase the excretion of potassium via the gastrointestinal tract
It is a progesterone-receptor agonist
It is a progesterone-receptor antagonist
It is an oestrogen-receptor agonist
It is an oestrogen-receptor antagonist
The use of tamoxifen after breast cancer is associated with a 25% risk reduction in metastatic
disease, and is also associated with a reduction in the risk of primary breast cancer in high-risk
women. It is a mixed antagonist and partial agonist at the oestrogen receptor. Its partial
agonist action is probably reflected in the increased risk of endometrial carcinoma associated
with chronic tamoxifen use. Tamoxifen has been considered the treatment of choice, although
.positive evidence for other hormone modulators is accumulating
Additional modern selective oestrogen-receptor modifiers now exist, one example being
.raloxifene which is currently used for the treatment of osteoporosis
You are asked to urgently review a 58-year-old woman who presents with a.145
slowly enlarging hard mass in the anterior neck. Thyroid ultrasound reveals
infiltration, and biopsy does reveal dense infiltration of the gland. Free T4 is
low and her TSH is markedly raised, consistent with hypothyroidism. Thyroid
autoantibodies are negative.Which of the following is the most likely diagnosis
?given this clinical picture
Riedel’s thyroiditis
Your answer
Thyroid carcinoma
Hashimoto’s thyroiditis
Grave’s disease
By the nature of its presentation, Riedel’s thyroiditis is often confused with thyroid carcinoma. It
is characterised by marked fibrous infiltration of the thyroid gland, the aetiology of this being as
yet unidentified. Treatment is with thyroxine replacement. Hashimoto’s thyroiditis is
autoimmune in aetiology and is characterised by lymphocytic infiltration and the presence of
antimicrosomal antibodies. Grave’s disease is associated with thyroid-stimulating autoantibodies
and hyperthyroidism. Thyroid ultrasound reveals infiltration but no discrete mass is identified,
.and biopsy does reveal dense infiltration of the gland
You are referred a 15-year-old girl from a family of travellers who has never.146
previously attended medical care. Her mother is concerned that she has short
stature and is still to commence her periods. On examination she is clearly
below the 50th centile for height. She appears to have excess skin around her
neck, and has poor development of secondary sexual characteristics. There is
a murmur suggestive of aortic stenosis. Chromosome analysis reveals a 45 X:
?0 picture. What diagnosis fits best with this clinical picture
Noonan’s syndrome
Turner’s syndrome
Your answer
Testicular feminisation
Congenital lymphoedema
Turner’s syndrome occurs in between 1 in 2500 and 1 in 5000 live births. Rarely, girls with
Turner’s syndrome may still present late if they have limited contact with medical services, as in
this case. In older children, symptoms include slow linear growth, short stature, delayed
development of secondary sexual characteristics and absence of menses. There may also be
dyspraxia, poor spatial awareness or mild intellectual impairment. Associated cardiovascular
defects may include aortic stenosis, bicuspid aortic valve or coarctation of the aorta. Patients
.with Turner’s syndrome also have an increased risk of hypothyroidism
Noonan’s syndrome presents with a similar phenotypic picture to Turner’s syndrome but without
.the absent X chromosome
Rehydration
Your answer
The patient has lactic acidosis and requires close monitoring and should be admitted to an HDU
or ITU ward. The lactate is the cause of the raised anion gap. The mainstay of treatment is
rehydration. Previous commentaries recommended sodium bicarbonate, although no
randomised clinical trials exist to support its use and it may be deleterious. Despite modern fluid
management and aggressive treatment of these patients, mortality still approaches 50%. It is
important to monitor creatinine in patients on metformin as a raised serum creatinine level
significantly increases the risk of lactic acidosis. Many physicians reduce or discontinue
metformin when the serum creatinine level is above 130 µmol/l in women or 150 mmol/lin men,
although the serum creatinine level should always be considered in the context of overall muscle
.mass
Raised levels of proinsulin were shown in the Caerphilly Cohort Study to be independently
.associated with an increased incidence of cardiovascular disease
Intervention trials with proinsulin were also discontinued after a possible CV event signal was
.seen. The reason behind this association has not yet however been clearly elucidated
Raised LDL levels are an independent cardiovascular risk factor and treatment with statins has
.been proven to reduce cardiovascular risk
Increased HDL cholesterol levels are associated with reverse cholesterol transport and increased
.processing of cholesterol by the liver, and are therefore protective
Increased triglyceride levels are associated with increased cardiovascular risk, but their
importance as a cardiovascular risk factor has yet to be proven categorically via an intervention
.study
Insulin resistance, a root cause of type-2 diabetes, is also independently associated with an
increased cardiovascular risk. Whether it is a risk marker or a risk factor in its own right is open
to debate. Results of glitazone intervention to reduce insulin resistance in Type 2 diabetes have
been mixed at best, with the Proactive study demonstrating perhaps a small benefit in reducing
.events, and the RECORD study demonstrating at best a neutral effect
HLA-B47
HLA-B27
HLA-DR3
Your answer
HLA-A28
HLA-DR7
Total fat intake should be restricted to less than 40% of total dietary
energy
Total fat intake should be restricted to less than 30% of total dietary
energy Your answer
The current recommendations in the UK for fat intake are that total fat intake should be
restricted to less than 30% of dietary energy: that monounsaturated fats should provide around
12%, polyunsaturated fats around 6% and that saturated fats should provide no more than
10% of dietary energy. Increased dietary fat intake has an epidemiological association with
cardiovascular disease, cancers, obesity and type-2 diabetes. Essential fatty acid deficiency may
occasionally occur in patients on long-term parenteral nutrition who are given a mix of protein
.and glucose. Alopecia, thrombocytopenia, anaemia and dermatitis may occur
You are asked by the respiratory physicians to see a 74-year-old man who.151
has been admitted from A&E with an abnormal chest X-ray revealing a right
hilar mass. There is a history of 40 years of cigarette smoking. He is noted to
have a markedly raised corrected calcium level of 3.25 mmol/l. Apart from a
mildly raised urea level due to dehydration, his other renal function testing is
normal. He also has a normochromic normocytic anaemia with a haemoglobin
.of 10.0 mg/dl
?What is likely to be the underlying cause of his hypercalcaemia
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
Pseudo-hyperparathyroidism
Parathyroid hormone-related protein (PTH-rp) is a 144 amino acid polypeptide, the initial
sequence of which shows some homology with the biologically active part of PTH. This is being
produced by his bronchial carcinoma. Common primary tumours which may be associated with
hypercalcaemia include bronchial, breast, renal, prostate carcinomas, myeloma and lymphoma.
Treatment involves rehydration and intravenous bisphosphonate therapy. Patients are often
.trialled on prednisolone, but this is rarely successful
A 19-year-old student nurse was admitted after her third collapse in recent.152
months. She was noted to have a blood sugar of 0.9 mmol/l on finger -prick
testing and responded well to intravenous glucose therapy. Venous blood
taken at the same time as obtaining venous access showed a markedly raised
insulin level, but her C-peptide levels were normal.What diagnosis fits best
?with this clinical picture
Insulinoma
Glucagonoma
Self-administration of a short-acting
insulin Your answer
Type-1 diabetes
This woman has hyperinsulinaemia and hypoglycaemia, but her C-peptide levels are normal.
This pattern is strongly suggestive of the fact that she is self-administering insulin. On further
questioning in this case it was determined that her father has type-1 diabetes and she had been
using his Actrapid to induce hypoglycaemia during times of stress at work. If both the insulin
and C-peptide levels were raised, then it would be worth screening her urine for a sulphonylurea
assay. Only after this had been excluded would it be worth pursuing investigation for
.insulinoma
A 35-year-old woman visits you in the paediatric diabetes clinic with her 2-.153
year-old son who has recently developed type-1 diabetes. He has an identical
twin brother and she is concerned about his risk of developing diabetes.What
?advice would you give regarding his future risk
He has a 100% future risk of developing type-1 diabetes
A trial of low-dose insulin in the unaffected child will reduce his future risk
of diabetes
GAD antibodies in the unaffected child are not predictive of the risk of
diabetes
IA-2 antibodies in the unaffected child are not predictive of the risk of
diabetes
Twin studies have suggested that the future risk of diabetes in the unaffected child is 30–50%.
The presence of glutamic acid decarboxylase (GAD), islet-cell or IA-2 antibodies in the
unaffected child increases the likelihood that the child will go on to develop type-1 diabetes.
Children of type-1 diabetic patients have a slightly increased risk of developing the disease (3–
6% risk where the father is diabetic, 2–3% where the mother is diabetic). Twin studies in type-2
diabetes have suggested that if one identical twin develops the disease, then the risk in the
unaffected twin rises to 50% or greater. Maturity-onset diabetes of the young (MODY) is a rare
.variant of type-2 diabetes with a very strong familial pattern of inheritance
You are reviewing a 45-year-old man who has type-2 diabetes. He works a.154
varying shift pattern as a taxi driver and has not tolerated metformin therapy
due to gastrointestinal side-effects. You decide that the postprandial glucose
regulator nateglinide is the most appropriate therapy choice. Which of the
?following best describes the mode of action of nateglinide
It acts by closure of the β-cell K-ATP channel promoting release of insulin. It is short acting and
taken to coincide with meals. Nateglinide is more expensive than sulphonylureas but offers
advantages for shift workers and patients who may fast for a period of time as doses can be
skipped when meals are missed. In these patient groups there may be less incidence of
hyperglycaemia. It appears that the shorter action of duration appears to result in less weight
gain compared to traditional sulphonylureas, and in theory these agents should result in “less
.strain” on the β-cell
Patients with SIAD are usually in sodium balance and sodium excretion is appropriate for intake.
.Very low urine sodium would suggest that hyponatraemia was due to sodium depletion
Failure to concentrate the urine either with water deprivation or following the
administration of desmopressin Your
answer
Significant weight loss, an increase in plasma osmolality and a failure of urinary concentration
during water deprivation are all diagnostic of diabetes insipidus (DI) but do not differentiate
between this being cranial or nephrogenic in origin. In nephrogenic DI, however, there is
typically no response to desmopressin, whereas this causes the urine to become concentrated in
cranial DI. A low plasma osmolality at the end of the investigation, with persistently dilute urine,
suggests prior water loading or continued water intake. Note that cranial DI can be transient
.following head injury
Pituitary adenoma
Phaeochromocytoma
Parathyroid hyperplasia is seen in the vast majority of patients with multiple endocrine
neoplasia type 1 (MEN-1), and the hypercalcaemia that they cause is the most common
presenting feature of the condition. Hypercalcaemia may be discovered incidentally or because it
is symptomatic, but the symptoms are often non-specific. Islet-cell tumours (most frequently
gastrinomas) are present in about 40% of cases. Pituitary tumours occur in about 30% of
patients: over a half are prolactinomas. Medullary-cell carcinomas of the thyroid and
.phaeochromocytomas occur in MEN-2 but not in MEN-1
A 51-year-old man presents with weight loss and is found on examination to.158
have hepatomegaly. He has facial telangiectasia. Urinary 5-HIAA levels are
found to be elevated.Given the diagnosis of carcinoid syndrome, which
?additional clinical feature is the most likely to be present
Abdominal pain
Diarrhoea
Correct answer
Hypertension
Skin rash
Your answer
Wheezing
Diarrhoea and flushing, occurring separately or together, are the most frequent presenting
features of carcinoid syndrome (approximately half of all patients). Abdominal pain occurs in
about 10%. Wheezing is a recognised feature of the condition but is uncommon, and a skin rash
(pellagra) due to niacin deficiency (niacin synthesis may be decreased in carcinoid syndrome) is
.rare. Hypertension is not a feature of the condition
A 73-year-old woman presents with weight loss and is found to have a serum.159
calcium concentration of 3.22 mmol/l. A skeletal survey is normal. Non-
metastatic hypercalcaemia is suspected. Endoscopy reveals a gastric
.carcinoma
Secretion of which of the following substances by the tumour is most likely to be
?responsible
Calcitonin
(Calcitriol (1,25-dihydroxycholecalciferol
Osteoclast-activating cytokines
Your answer
Parathyroid hormone
Parathyroid hormone-related peptide
Correct answer
In patients with solid tumours, non-metastatic hypercalcaemia is most frequently the result of
secretion of parathyroid hormone-related peptide (PTHrP) by the tumour, and is reported in
association with gastric cancer. Non-parathyroid secretion of PTH itself is very rare. Unregulated
production of calcitriol has been described in patients with lymphoma but is rare. Secretion of
calcitonin, either ectopically or by medullary-cell carcinoma of the thyroid, is clinically silent: it
does not perturb calcium homeostasis. Secretion of osteoclast-activating cytokines is an
important cause of hypercalcaemia in patients with myeloma, but this is a relatively uncommon
.malignancy
A 55-year-old man is found incidentally to have hypercalcaemia during a.160
.routine health screen
Which one of the following biochemical findings would be most suggestive of
this being caused by primary hyperparathyroidism rather than any other cause
?of hypercalcaemia
Although parathyroid hormone (PTH) concentrations are often increased in patients with
hyperparathyroidism, they are not always so. PTH secretion should be suppressed by
hypercalcaemia from any other cause, so that a PTH value in the normal range is consistent
with the diagnosis. Urinary calcium excretion is increased in many causes of hypercalcaemia
(except familial hypocalciuric hypercalcaemia), including hyperparathyroidism. Serum alkaline
phosphatase activity can also be elevated with hypercalcaemia, regardless of the cause (with
the exception of myeloma). Serum phosphate concentrations tend to be reduced in
hyperparathyroidism (PTH is phosphaturic) and calcitriol concentrations to be increased (PTH
.(stimulates the formation of this hormone
(Adrenocorticotrophin (ACTH
Growth hormone
Prolactin
Your answer
Prolactinomas are the most frequently occurring functional pituitary tumours; however, prolactin
secretion may be increased in patients with other pituitary tumours because of the interruption
of the inhibitory effect of dopamine secreted by the hypothalamus. ACTH-secreting and growth
hormone-secreting tumours both occur less frequently and TSH- and FSH-secreting tumours are
.uncommon. Non-functional tumours can occur at any age but are more frequent in the elderly
Growth hormone replacement in adults with deficiency of the hormone has numerous effects,
including an increase in vitality and overall quality of life. Lean body mass tends to increase but
body fat decreases, often to a greater extent. Serum total- and LDL-cholesterol concentrations
.and triglycerides tend to decrease but lipoprotein (a) concentration may increase
A 37-year-old man with a diagnosis of hypogonadotrophic hypogonadism is.163
being followed in the endocrine clinic. He does not desire fertility at
?present.Which would be the most appropriate treatment at this stage
A 44-year-old man is surprised to find that he cannot easily get his feet into a.164
pair of shoes that he last wore 5 years ago. He goes to buy a new pair and is
told that his size has increased. He trawls the Internet for an explanation and,
deciding that he may have acromegaly, consults his GP. The GP has not seen
him for several years and thinks his appearance has changed, so refers him to
.the endocrine clinic
?Which of the following would be the most useful first-line test for investigating him
Radiotherapy
Transfrontal surgery
Trans-sphenoidal surgery
Correct answer
Surgery is generally regarded as the first-line treatment for patients with acromegaly. The
trans-sphenoidal route is preferred except with large tumours, which may require a transfrontal
approach. Radiotherapy is sometimes used if surgery does not reduce growth hormone
concentrations to acceptable levels. Medical treatment is used principally as an adjunct to
surgery. Dopamine agonists (eg cabergoline) have been superseded by somatostatin agonists
(eg octreotide) and growth hormone-receptor antagonists (eg pegvisomant) are now becoming
.available
Adrenal adenoma
Your answer
Adrenal carcinoma
Glycosuria
Worsening hypertension
Hypokalaemia
Muscle wasting
Your answer
Weight loss
Correct answer
Glycosuria, hypertension, hypokalaemia and muscle wasting can occur with Cushing’s syndrome
from any cause. The most common manifestation is centripetal fat deposition, often with weight
.gain, but weight loss suggests there is an underlying malignancy
An 18-year-old woman complains of a 2-month history of vague ill health and.168
nausea. She has had several episodes of dizziness and is found to have
postural hypotension.Which of the following investigations is required to best
?demonstrate that these features are the result of adrenal failure
Replacement of mineralocorticoid
All these measures (with the exception of mineralocorticoid replacement) are required in an
addisonian crisis, glucocorticoid and fluid replacements the priority, often given simultaneously
in clinical practice, but the immediate priority is fluid resuscitation. Mineralocorticoid
replacement may be required long term, but is unnecessary in the acute setting because the
.large doses of hydrocortisone used supply mineralocorticoid activity
Diarrhoea
Flushing
Headache
Your answer
Muscle weakness
Tremor
Liddle’s syndrome
Secondary aldosteronism
Adrenal adenomas that secrete aldosterone (now thought to be the less likely cause of
hyporeninaemic hyperaldosteronism) are usually sensitive to ACTH, and aldosterone secretion
falls during the day as ACTH secretion (and that of cortisol) declines. With bilateral adrenal
hyperplasia, however, the aldosterone concentration is usually higher when the patient is erect
than when supine. Hypertension is also a feature of Liddle’s syndrome and steroid 11β
-hydroxylase deficiency, but aldosterone concentrations are low. In secondary aldosteronism,
aldosterone secretion is increased secondary to an increase in renin secretion, and plasma renin
.activity is normal or increased
It is too soon after the last change in dose for a new steady state to have been achieved: it is
usual to wait for a month before reviewing the response. When thyroxine replacement is
started, the TSH concentration often falls to normal more slowly than free thyroxine increases.
Free thyroxine concentrations in clinically euthyroid patients on thyroxine replacement are often
high normal or even slightly elevated, reflecting the lack of production of triiodothyronine (T3)
by the thyroid: peripheral metabolism of thyroxine is the only source of T3. Irregular medication
could explain these results but should not be considered until sufficient time has elapsed for the
.data reliably to reflect the effects of replacement
Triiodothyronine is usually only used in very severe hypothyroidism, when a rapid response to
.treatment is required
A 20-year-old woman presents with anxiety and weight loss with increased .173
appetite. Thyrotoxicosis is suspected and various investigations are
performed.Which of the following findings would most suggest that she has
?Graves’ disease
High ESR
Antibodies to thyroid peroxidase and thyroglobulin are found in the serum of the majority of
patients with Graves’ disease, in which radioisotope uptake is typically increased. A low uptake
occurs in subacute (de Quervain’s) thyroiditis (in which the erythrocyte sedimentation rate
(ESR) is typically elevated). Elevated T3 with a normal T4 (‘T3 toxicosis’) can occur early in the
course of thyrotoxicosis from any cause. The high concentrations of thyroid hormones suppress
TSH secretion to very low levels in thyrotoxicosis due to thyroid disease: detectable (not always
elevated) TSH in thyrotoxicosis suggests that this is caused by a pituitary adenoma secreting
.TSH
Sporadic goitre
Hashimoto thyroiditis
Your answer
Fibromatosis
De Quervain’s thyroiditis
Correct answer
Subacute (or de Quervain’s) thyroiditis is due to thyroid infection by any of a number of viruses,
especially paramyxoviruses (mumps), coxsackieviruses, influenza viruses, adenoviruses and
.echoviruses
The most prominent symptom is pain in the thyroid, often radiating to the ears. A small, tender
goitre can be palpated that is usually diffuse, but there can be asymmetrical involvement.
Systemic upset with fever is variable but sometimes profound, and symptoms of a prodromal
viral infection several weeks earlier may be recalled. There is a granulomatous thyroid
inflammation with follicular destruction, and the release of thyroid hormones often results in a
transient thyrotoxicosis, lasting for 1–4 weeks. Continuing thyroid destruction then leads to a
phase of hypothyroidism once stored hormone is depleted. This lasts 4–12 weeks before
euthyroidism is restored, but relapses occur in 10–20% of cases. Sometimes only one phase of
.thyroid disturbance is seen
Primary hyperparathyroidism
Your answer
Secondary hyperparathyroidism
Vitamin D deficiency
Hyperthyroidism
A detailed clinical history and examination will usually help to differentiate between these two
diagnoses. In primary hyperparathyroidism, the hypercalcaemia is often less than 3 mmol/l,
asymptomatic and may have been present for months or years. However, in malignancy, the
patients are usually acutely ill, often with neurological symptoms, the hypercalcaemia is more
.than 3 mmol/l and the cancer (eg lung, breast or myeloma) is often readily apparent
A 17-year-old young woman has been referred by her gynaecologist. She has.176
been complaining of amenorrhoea for 5 months, although no gynaecological
abnormality has been found. She feels well and is very active but her weight
has decreased from 61 kg to 43 kg in the last 6 months. Her height is 168 cm.
On examination her BP is 90/60 mmHg, heart rate 64 bpm.What is the most
?likely diagnosis
Conn’s syndrome
Crohn’s disease
Anorexia nervosa
Your answer
Hyperthyroidism
Diabetes mellitus
Patients with anorexia nervosa actively maintain an unduly low body weight. For diagnostic
purposes, an ‘unduly low body weight’ may be defined as a weight at least 15% below that
expected for the person’s age, height and sex, or as a body mass index below 17.5.
Amenorrhoea (in postmenarchal women who are not taking an oral contraceptive) is almost
.always present in these patients
A patient has been referred by her GP because she has been complaining of.177
frequent episodes of sweating and palpitations associated with a low blood
glucose level. The family history reveals a brother with type-1 diabetes. A
blood test shows the following results: glucose 1.1 mmol/l, insulin> 500
pmol/l (reference 15–100 pmol/l) and C-peptide of < 0.2 nmol/l (reference
?0.2–1.4 nmol/l).What is the most likely diagnosis
Insulinoma
Pancreatic carcinoma
Add pioglitazone
Add gemfibrozil
Add clopidogrel
Add statins
Your answer
Add ezetimibe
The latest European guidelines suggest that LDL cholesterol should be < 4.5 mmol/l rather than
< 5 mmol/l in secondary prevention, while evidence from primary prevention suggests that
similar targets should also apply to primary prevention. Statins are the medication of choice. As
targets are reduced and further evidence from the low–dose–high-dose statin comparator trials
are announced, it is likely that targets will fall further and that combination therapy for
hyperlipidaemia will become routine as is the case in hypertension. The challenge will still
remain with implementation, but the benefits of satisfactory risk-factor control are that both
.morbidity and mortality from cardiovascular disease will be decreased
Hyperthyroidism
Hypothyroidism
Your answer
Phaeochromocytoma
Hypogonadism
Ultrasound
Correct answer
PET scan
Your answer
Liver biopsy
Serum ceruloplasmin level
Your answer
CRP level
Hepatitis C infection
Wilson’s disease
Your answer
Alcohol abuse
Wilson’s disease may present in childhood, adolescence or early adulthood. Symptoms and signs
may be clinically undetectable under 5 years of age, and few present after the age of 35 years,
although diagnosis over 55 years has been reported. In 90% of patients, the disease presents
with juvenile hepatic disease or with neurological/psychiatric manifestations. In large studies of
patients with Wilson’s disease, initial manifestations were: hepatic (40%); neurological (30%);
psychiatric (10%); haematological (12%); and renal (1%). Some 25% of patients have two or
more organs involved (usually liver and brain) at the initial assessment. Kayser–Fleischer rings
.are almost pathognomonic of Wilson’s disease
Blood transfusion
d-Penicillamine
Your answer
Ciclosporin
Azathioprine
Interferon-alpha
D-Penicillamine is effective in removing copper from patients with Wilson’s disease. The
optimum time for treatment is in the early stages, and all patients with Wilson’s disease should
be treated, even if asymptomatic. Treatment is lifelong, unless the patient undergoes liver
transplantation. The aim of treating a patient with Wilson’s disease is to reduce toxic copper
levels in the body tissues. This can be achieved by increasing the urinary excretion of copper. A
negative copper balance should be monitored carefully since, with an increase in urine and
faecal copper excretion that exceeds copper intake, increased urinary copper may reflect
.(increased plasma non-ceruloplasmin copper (copper in its most damaging form
The effect of any therapy should be regularly monitored by clinical and radiological assessment,
.and by biochemical monitoring of abnormal liver enzymes and liver function
g 10
g 50
g 75
Your answer
g 100
g 150
After an overnight fast, the subject drinks 75 g of anhydrous glucose dissolved in 250 ml water,
venous blood is sampled at baseline and 2 hours later. Food intake should be normal during the
preceding few days: poor nutrition can cause delayed hyperglycaemia with a raised 2-hour
.(value (the ‘lag’ curve
Aspirin
Atenolol
Lisinopril
Your answer
Clopidogrel
Pioglitazone
In patients with type-1 diabetes with a mean entry blood pressure of 122/77 mmHg, a
combined analysis of one European and one American study (total n = 225) showed an adjusted
risk reduction of 63% (95% CI, 16–84%; p = 0.017) for the development of clinical
nephropathy comparing the ACE inhibitor captopril 100 mg/day with placebo. Three smaller
studies in normotensive type-2 patients have reported a similar reduction in the rate of
development of clinical nephropathy. Thus blockade of the renin–angiotensin system by any
.means appears to confer benefit
A patient presents with truncal obesity, insulin resistance and.186
?dyslipidaemia.What additional clinical feature might you expect to be present
Asthma
Renal failure
Hypertension
Your answer
Cancer
Ophthalmoplegia
Metabolic syndrome X is the term given to the co-occurrence of insulin resistance and glucose
intolerance (ranging from mild to overt type-2 diabetes), with truncal obesity, dyslipidaemia
.(raised triglycerides and a high LDL: HDL ratio) and hypertension
Abdominal ultrasound
CT scan abdomen
Hypertension
Respiratory insufficiency
Your answer
Hyperlipidaemia
Hyperthyroidism
Adipositas
Lactic acidosis is best known in diabetic patients as a rare, but often fatal, complication of the
biguanide metformin, which acts mainly by inhibiting hepatic gluconeogenesis. The risk is much
.increased in patients with respiratory insufficiency