CLINICAL BIOCHEMISTRY
Answers to case studies
Chapter 1
Case study 1.1
(a) 0.027
(b) 0.999
(c) The assay has a very low false negative rate (NPV close to 1) and
therefore will classify most women with the disease, correctly; how-
ever, it has a very high false positive rate giving a very low PPV and
will misclassify many women who are disease free. This assay is not
good enough to be used to screen for ovarian cancer.
Case study 1.2
(a) By exchanging samples between the laboratories and compar-
ing results.
(b) Peripheral laboratories should be encouraged to use the same
method as the specialist laboratory or send all requests to them.
Case study 1.3
(a) The sample has not reached the laboratory quickly enough and
intracellular contents have leaked into the plasma. Red cells have
high potassium content and this explains the result.
(b) Request a repeat sample to be taken and transported to the
laboratory for urgent processing.
Case study 1.4
(a) This is a systematic error (a constant shift in one direction).
(b) The most likely cause of the shift is that the incorrect calibrator
has been used.
(c) Re-calibrate the assay using the correct calibrator and check
the QC again.
Case study 1.5
(a) The laboratory cannot produce evidence to confirm that the
reagents have been stored at the recommended temperature and
therefore cannot guarantee that the assay is working.
(b) A procedure must be introduced to check refrigerator tempera-
tures regularly.
(c) Perform another horizontal audit at a later date.
Chapter 3
Case study 3.1
(a) Myoglobin, derived from muscular breakdown (rhabdomyoly-
sis) imparts a red, muddy colour to urine. It is directly toxic to renal
tubular cells, therefore precipitating AKI. Many laboratories offered
a screening test for urinary myoglobin. However, the assay is poorly
specific and sensitive and no quality assessment program existed
for this measurement. Generally it is considered that serum creat-
ine kinase activity is more closely related to the extent of injury and
the renal prognosis.
1 © OXFORD UNIVER SIT Y PRESS 2011
(b) AKI causes a rapid decline in calcium (due to failed vitamin
D synthesis) and increase in serum phosphate concentration
due to renal retention. It is also thought that calcium is seques-
tered by binding to damaged muscle fibres, exacerbating the
hypocalcaemia.
Case study 3.2
(a) Cystinuria is an autosomal recessive condition due to a defect
in proximal tubular cystine transport. Cystinuria should always be
excluded as a cause of stone formation, but the index of suspicion
is raised if stones occur (i) at a young age and/or (ii) there is a family
history of renal stones. Once a cystinuric patient has been identi-
fied, it is important to screen all members of the family.
(b) In the commonest form of cystinuria there is also excess excre-
tion of these dibasic amino acids, which share the same tubular
transporter as cystine. However, their presence in urine appears
benign.
Chapter 4
Case study 4.1
(a) This is a classical presentation of gout, being of sudden onset,
nocturnal occurrence, and symptoms in a single joint.
(b) He should be treated initially with a non-steroidal anti-inflam-
matory drug such as naproxen and the symptoms should subside
rapidly. Given his family history, signs, and symptoms, three to
four weeks later he should be prescribed allopurinol, a drug which
inhibits xanthine oxidase, the enzyme that mediates the formation
of urate, to prevent further attacks.
Case study 4.2
(a) The patient has a high serum creatinine and a reduced EGFR
consistent with chronic kidney disease. The high serum urea sug-
gests a depletion of the intravascular volume probably caused by
overmedication with diuretic therapy. There is severe hyperuricae-
mia, which is probably mainly caused by over treatment with diu-
retics, but also by the chronic kidney disease.
(b) Acute gout and chronic tophaceous gout.
(c) The diagnosis may be confirmed by microscopic examination
of synovial fluid taken from the knee joint to show the presence of
crystals of monosodium urate.
Chapter 5
Case study 5.1
The plasma sodium is clearly very low, as is the osmolality, indicat-
ing a true hyponatraemia (i.e. not pseudo-hyponatraemia). Creati-
nine and urea are not raised, suggesting renal function is adequate.
In health, the physiological response to such a low plasma osmolal-
ity should be to stop the production of ADH and for dilute urine
of high volume to be produced. Further laboratory tests might
2 ANSWERS TO CASE STUDIES
include tests of endocrine function, including thyroid function tests
and tests for cortisol, but the results are consistent with a diagnosis
of SIADH.
Case study 5.2
The plasma sodium is increased, as is the osmolality. These results
indicate an appropriate degree of sodium excretion and the pro-
duction of concentrated urine in response to dehydration. The
hypernatraemia resolved within three days.
Case study 5.3
The plasma potassium result is below the critical threshold for most
laboratories and should be communicated rapidly to the request-
ing clinician. Hypokalaemia in this case was caused by treatment
with a thiazide diuretic.
Case study 5.4
(a) The electrolyte abnormality is hypokalaemia and this is consist-
ent with Conn’s syndrome.
(b) This could be confirmed by measurement of the plasma aldos-
terone concentration and the plasma renin activity. In Conn’s syn-
drome, the aldosterone will be increased and the renin activity low.
The collection of the samples for the analysis of aldosterone and
renin must be associated with avoidance of hypertensive medica-
tion as these can induce similar biochemical changes.
Case study 5.5
The data set shows electrolyte results that are not compatible with
normal physiology or, indeed, life. The specimen tube was inspected
and found to be one containing sodium fluoride and potassium
oxalate, a preservative and anticoagulant additive used for specimens
requiring glucose analysis. The patient had also had a request for glu-
cose analysis and the two tubes had been inadvertently swapped.
Re-analysis of the tests using the correct tubes was required.
Case study 5.6
(a) The electrolyte abnormality is hyperkalaemia.
(b) The sample is not haemolysed, nor has analysis been delayed;
both of which might falsely elevate the potassium result. The cal-
cium value is within the reference range, which would suggest
the specimen has been collected into an appropriate specimen
collection tube. The urea and creatinine concentrations are also
increased, and together with the potassium value would suggest
the patient has renal failure. The liver function tests are all within
their reference ranges.
(c) In most laboratories such a potassium result would be commu-
nicated to the clinicians managing the patient as soon as possible,
usually by telephone as the increased potassium could lead to car-
diac arrest.
Case study 5.7
(a) This appears to be an example of hyponatraemia. However, the
total protein value of 140 g/L is highly abnormal and will produce
the effect of pseudohyponatraemia.
(b) The difference in sodium values from the main automated
analyser, which employs an indirect ion selective electrode (131
mmol/L) and the direct reading ion selective electrode (144 mmol/L)
is due to the water displacement effect caused by the increased
protein concentration in the sample. The clinically relevant result is
that derived from the direct reading ion selective electrode and, as
such, this patient does not have true hyponatraemia.
Chapter 6
Case study 6.1
(a) Low pH indicates acidaemia. PCO2 and HCO3− are abnormal in
the same direction (both low), therefore less likely to be a mixed
acid-base disorder.
(b) The low HCO3− concentration would indicate a (metabolic) aci-
dosis and is consistent with the low pH, the low PCO2 is not consist-
ent with the acidaemia, but more indicative of the compensatory
response (hyperventilation). As the pH has not returned to normal
there is only partial compensation. This is a partially compensated
metabolic acidosis.
Case study 6.2
(a) The decreased pH indicates acidaemia. PCO2 and HCO3− are
abnormal in the same direction (both low), therefore less likely to
be a mixed acid-base disorder.
(b) The low HCO3− concentration would indicate a (metabolic) aci-
dosis and is consistent with the low pH, the low PCO2 is not consist-
ent with the acidaemia, but more indicative of the compensatory
response (hyperventilation). This is an uncompensated metabolic
acidosis.
(c) The other laboratory tests indicate hyperkalaemia, due to the
movement of potassium out of cells and there is a raised anion gap.
This is consistent with the ingestion of ethylene glycol (antifreeze)
that metabolizes into acidic (anionic) products which increases the
unmeasured anion fraction in the blood.
Case study 6.3
(a) The increased pH indicates alkalaemia. PCO2 is abnormal indi-
cating a respiratory alkalosis.
(b) The HCO3− concentration is still within normal range indicating
that the slower renal compensatory response had not yet begun.
This is an uncompensated respiratory alkalosis.
Case study 6.4
(a) Low pH indicates acidaemia. PCO2 and HCO3− are abnormal in
different directions, which indicates a possible mixed acid-base
disorder.
(b) The results would indicate a respiratory acidosis and a metabolic
acidosis. This is a mixed acid-base disorder: respiratory acidosis and
metabolic acidosis.
(c) Such results are consistent with a patient after cardiac arrest with
impaired respiratory and circulatory functions.
Case study 6.5
The raised pH indicates alkalaemia. PCO2 and HCO3− are abnormal
in the same direction, which indicates a possible respiratory alka-
losis. The HCO3− results would appear to confirm this assumption.
However, such low HCO3− levels are uncommon and not consist-
ent with the relative decrease in PCO2 levels. This would indicate a
respiratory alkalosis superimposed with a metabolic acidosis. This
is a mixed acid-base disorder; respiratory alkalosis and metabolic
acidosis. Also, the serum electrolyte measurements confirm a high
anion gap associated with metabolic acidosis, due to the unmeas-
ured anion metabolites. These results are consistent with a patient
with salicylate overdose. Salicylate stimulates the respiratory centre
to hyperventilate. Salicylate metabolites are acidic, resulting in the
metabolic acidosis. Salicylate determination would be appropriate
to confirm the diagnosis.
Chapter 7
Case study 7.1
(a) The findings on the ECG indicate the chance that this man is
having an MI is very high.
(b) No. Given the chance this man is suffering a MI, treatment
needs to be started as quickly as possible. The changes on the
ECG are sufficient to commence treatment either by immediate
cardiac catheterization or administration of a thrombolytic (clot
busting) drug.

(c) The second troponin value confirms that he has had an AMI.
He has chest pains, changes in his ECG and a rise in his troponin
from undetectable to 1.5 μg/L. This meets the diagnostic criteria
for an AMI.
Case study 7.2
(a) It is difficult to be sure whether this woman is having an MI
although the previous history of heart surgery and the increased
troponin on admission makes this likely. The working diagnosis for
this patient is a suspected ACS and further tests are recommended.
Although she has an elevated troponin she does not meet all the
criteria for a diagnosis of MI.
(b) Yes. This patient had NSTEMI, which was confirmed by the rise
in troponin from the admission to six-hour values. She should be
treated with anti-thrombotic (blood thinning) drugs and considered
for cardiac catheterization at the next convenient opportunity.
Case study 7.3
(a) This is very unlikely. This is a young man and there is evidence
that he has been stabbed. Heart damage from the stabbing is more
likely to be the cause of his collapse than an MI.
(b) He has had damage to his heart from stabbing. This will damage
heart muscle cells and cause the release of troponin. Because
the troponin elevation is due to direct myocardial damage from
trauma, this is a non-ischemic cardiac injury.
Chapter 8
Case study 8.1
The LFTs are indicative of cholestasis, with a low albumin and raised
bilirubin suggestive of a chronic liver disorder. The first line of inves-
tigation would be an abdominal X-ray and liver ultrasound to rule
out gallstones and obstruction due to a tumour in the bile ducts or
pancreas. She is of an age where autoimmune liver disease must be
considered and autoantibodies measured. Her anti-mitochondrial
antibody was positive, consistent with PBC.
Case study 8.2
The AST and ALP results are within reference ranges and suggest
no hepatocellular damage. The urine bilirubin is negative, suggest-
ing that the increased serum bilirubin must be unconjugated in
nature. The normal haemoglobin and reticulocyte count suggest
that haemolysis cannot be responsible for this raised bilirubin. It is
very likely that the mild jaundice is because the individual suffers
from Gilbert’s syndrome. In Gilbert’s syndrome, there is reduced
activity of UDP-glucuronosyl transferase and often reduced uptake
of unconjugated bilirubin by hepatocytes.
Case study 8.3
The recent travel to Africa and the hepatitic pattern of the LFTs
strongly suggest an infective cause of his liver disease. Hepatitis
A is endemic in many parts of the developing world and could
cause these results and the clinical findings. Hepatitis B and C are
less likely as there is no evidence of at-risk behaviour, for example
sexual activity or drug misuse. Other causes of infectious hepatitis
such as Weil’s disease (leptospirosis) or malaria should also be on
the list of possible diagnoses. In fact, he had hepatitis A.
Chapter 9
Case study 9.1
These results show that she has mild subclinical hypothyroidism
and secondary hypercholesterolaemia. After treating her hypothy-
roidism with a small dose of thyroxine, her cholesterol was found
to be 4.2 mmol/L. Given she was healthy and had no risk factors
for heart disease, this cholesterol concentration is satisfactory and
further treatment is unnecessary.
ANSWERS TO CASE STUDIES 3
Case sudy 9.2
(a) Her very high TAGs are due to the presence of chlomicrons and
other TRL particles. She had a genetic predisposition to hypertri-
glyceridaemia, which would be classified as Frederickson type I.
This condition has been exacerbated by dietary indiscretion, exces-
sive alcohol consumption, and poor diabetic control. Dietary advice
was reinforced. She was treated with the triacylglycerol-lowering
drug, fibrate, in addition to her statin treatment.
(b) This case shows that the only present cure for chylomicronae-
mia is not to eat fat. The woman’s HDL remained low because of
increased exchange of HDL cholesterol with TRL. Although the main
clinical problem is pancreatitis, related to her high TAG concentra-
tions, she requires statin medication to lower her LDL because of
the cardiovascular risk associated with her diabetes. This pattern
of dyslipidaemia is usually associated with the accumulation of
atherogenic small dense LDL.
Case study 9.3
(a) This woman had type 3 dyslipidaemia. Most people with the
E2E2 genotype do not develop dyslipidaemia. Usually additional
factors, such as high energy diet, obesity, and diabetes contribute
to its development. The hypertriglyceridaemia is due to the accu-
mulation of IDL particles, which are atherogenic.
(b) Because of the increased cardiovascular risk secondary to her
diabetes.
Chapter 10
Case study 10.1
The patient suffers from hypercalcaemia as confirmed by the high
serum calcium and supported by her clinical features. A possible
explanation for this could be that she took too much of the vitamin
D therapy resulting in hypercalcaemia.
Case study 10.2
(a) 3.46 mmol/L.
(b) She does not suffer from diabetes mellitus as her urine glucose
is negative. She does have hypercalcaemia and this is supported by
her clinical features. Common causes of hypercalcaemia in clinical
practice are primary hyperparathyroidism or malignancy.
(c) Measurements of serum PTH will be high if she suffers from pri-
mary hyperparathyroidism and low in malignancy.
(d) The patient suffers from dehydration as she has a high serum
sodium and urea, and this is likely to be due to the vomiting. Rehy-
dration should be a priority before identifying and treating the
cause of the hypercalcaemia.
Case study 10.3
The results suggest hypocalcaemia but the values for serum calcium
are too low and so this is likely to be artefactual. Such findings are
typical of blood being collected into EDTA tubes. The EDTA chelates
the calcium ions, hence the low reading for calcium. Tubes contain-
ing EDTA as an anticoagulant are commonly used in haematology
laboratories.
Case study 10.4
(a) This patient has hypocalcaemia with hyperphosphataemia,
which is typical of reduced PTH secretion as in hypoparathyroidism.
She had undergone thyroidectomy and this could have resulted in
accidental removal of her parathyroid gland giving rise to hypopar-
athyroidism.
(b) Cataracts occur frequently in patients with hypoparathyroidism
and arise due to precipitation of calcium phosphate in the eye
lens.
4 ANSWERS TO CASE STUDIES
Case study 10.5
(a) This patient has hypocalcaemia and the likely cause of this is
the hypomagnesaemia. A low serum magnesium concentration
can cause hypocalcaemia by reducing action of PTH and partly by
inhibiting secretion of PTH from the parathyroid glands.
(b) She should be placed on calcium and magnesium supple-
ments.
Chapter 11
Case study 11.1
The patient has a normal TSH and free T4 and is biochemically
euthyroid, that is normal thyroid function. However, the cortisol is
<550 nmol/L so it does not exclude adrenal or pituitary dysfunc-
tion. Note, however, that the sample was collected at 2 pm. Before
proceeding with further investigations, the sample should be col-
lected at 9 am for cortisol measurement. If the cortisol concen-
tration in this sample is greater than 550 nmol/L then that would
suggest normal pituitary and adrenal function.
Case study 11.2
(a) The most likely explanation for a suppressed LH/FSH and
increased prolactin in a woman of childbearing age is pregnancy.
(b) Therefore human chorionic gonadotrophin (hCG) should be
measured in this sample to exclude pregnancy.
Case study 11.3
(a) This man presented with classical clinical signs of GH excess. The
patient’s blood glucose is in the diabetic range and his random GH
is detectable although within the normal range. The physician is
therefore considering the diagnosis of acromegaly.
(b) The detectable random GH does not exclude acromegaly even
though it is within the normal range, and it is necessary to establish
if GH can be suppressed following the OGTT.
(c) During the OGTT, the concentration of serum GH does not
decline, supporting the diagnosis of acromegaly.
(d) For further investigation, measurement of serum IGF-1 would
be useful, as would pituitary imaging to check for pituitary mass.
Case study 11.4
(a) The results of the water deprivation test show an increasing
plasma osmolality, with an inappropriately low urine osmolality.
(b) The differential diagnosis is therefore between cranial and
nephrogenic diabetes insipidus.
(c) Following administration of DDAVP, the urine becomes concen-
trated and plasma osmolality returns to normal.
(d) The diagnosis is therefore cranial diabetes insipidus.
Chapter 12
Case study 12.1
(a) The patient has a suppressed TSH, normal freeT4, and increased
free T3.
(b) T3-toxicosis.
Case study 12.2
Plasma TSH is not a reliable measure of thyroid status in the early
months of treating hyperthyroidism as the response lags behind
the fall in free T4 and free T3 for several weeks. During this time
free T4 and free T3 are the most reliable indicators. In this patient,
the free T4 and free T3 results would support a reduction in the
dose of carbimazole used.
Case study 12.3
(a) The patient has increased free T4 and free T3 with inappropri-
ately high concentrations of TSH. The concentrations of testoster-
one, FSH, and LH are also high.
(b) Imaging of the brain and pituitary which may reveal a pituitary
tumour.
(c) The patient has clinical and laboratory findings consistent with
hyperthyroidism. It is likely the individual has a pituitary tumour
secreting TSH. Most of these tumours secrete TSH alone (72%), but
some tumours can secrete other hormones. The high testosterone
and FSH/LH are consistent with a TSH secreting tumour.
Chapter 13
Case study 13.1
(a) This patient had adrenal insufficiency, hence the low serum
cortisol concentration. Cortisol is an essential counter-regulatory
hormone and glucocorticoid deficient patients are at high risk of
hypoglycaemia. In an acutely ill patient like this, cortisol levels are
usually elevated so the low cortisol was an important pointer to the
diagnosis of adrenal insufficiency. In this case, the adrenal insuf-
ficiency was secondary and due to pituitary disease. However, the
cortisol result was not returned to the ward until after the patient
had died. The initial presentation was hypoglycaemic coma as
confirmed by laboratory glucose measurements. Primary and sec-
ondary adrenal failure should always be considered as a cause for
hypoglycaemia, especially in hypoglycaemic coma. If suspected,
glucocorticoid treatment should be given. This case emphasizes
that cortisol deficiency is a life-threatening condition and unfortu-
nately here had a fatal outcome.
(b) The diagnosis is hypoglycaemia caused by adrenal failure sec-
ondary to pituitary failure.
Case study 13.2
(a) He has developed type 2 diabetes and expresses all the clinical
and biochemical features of the metabolic syndrome.
(b) The results are related to his sedentary lifestyle and his develop-
ing obesity. He is insulin-resistant and his high triacylglycerols are
due to the failure of insulin to regulate his lipoprotein metabolism
as well as his glucose homeostasis. The inflammatory component of
the metabolic syndrome which is related to his adiposity is affecting
his vascular endothelium, contributing to his high blood pressure.
(c) He should be advised to take more exercise and lose weight. As
he is obese, an insulin sensitizing drug such as metformin should
be used. In addition, antihypertensive medication should be given
and because of the increased cardiovascular risk he should be pre-
scribed a statin drug to lower his cholesterol.
Case study 13.3
(a) The diagnosis is severe diabetic ketoacidosis.
(b) She has a low pH because of unregulated lipolysis due to severe
insulin deficiency, increasing the production of keto acids such as
acetoacetate from triacylglycerol stores. Acetoacetate is an end
product of fatty acid metabolism which spontaneously decarboxy-
lates to acetone and can be detected in the urine and smelt on the
breath.
(c) The serum potassium is raised because the acidosis causes
hydrogen ions to enter cells and displace potassium (the major
intracellular cation) into the extracellular space. Additionally, insu-
lin upregulates the cell membrane sodium/potassium exchange
pump which keeps potassium inside and sodium outside cells.

(d) She has thrush, which is a pathological yeast infection caused
by Candida albicans, which thrives in sugar-rich urine. Patients with
diabetes often have chronic candida infections.
(e) She was thirsty because of her need to replace fluid due to high
glucose levels, which were producing an osmotic diuresis.
(f) She had lost weight because in uncontrolled diabetes there is a
large calorie loss in the urine as glucose.
(g) She had a faint rapid pulse on admission because her plasma
volume was reduced due to her fluid loss in the urine.
(h) She should be rehydrated with intravenous saline and soluble
insulin. She will then require stablilizing on a long-term insulin
regime.
Case study 13.4
(a) He is pale and clammy due to the release of catecholamines in
response to the hypoglycaemia. The firm rapid pulse is also a cat-
echolamine mediated effect on the heart.
(b) The laboratory results suggest inappropriate insulin secretion.
The neurological episode followed by unconsciousness is due to
the effects of the hypoglycaemia on the central nervous system.
The cortisol result rules out adrenal insufficiency as a cause of
hypoglycaemia and the negative drug screen makes ingestion of
hypoglycaemic drugs unlikely. The high insulin, together with the
low plasma glucose is referred to as ‘inappropriate’ insulin secre-
tion. It is called inappropriate because normally when glucose is
low insulin is also low. The main causes of inappropriate insulin
secretion are an insulinoma, that is, a pancreatic beta cell tumour
producing insulin, exogenous insulin administration, or ingestion of
sulphonylurea drugs.
(c) C-peptide measurements would be useful and are low in exog-
enous insulin administration but high in an insulinoma. An abdom-
inal CT scan would be useful and may reveal the presence of a
tumour in the pancreas, consistent with an insulinoma.
Chapter 14
Case study 14.1
(a) Salt-losing congenital adrenal hyperplasia due to 21-hydroxy-
lase deficiency is indicated.
(b) If the 17-OHP had been measured in a direct assay, a repeat
measurement in an assay after solvent extraction should be con-
ducted to exclude interference from foetal zone steroids.
(c) Plasma aldosterone would be below the reference range
in CAH due to 21-hydroxylase deficiency, adrenal hypoplasia,
3β-hydroxysteroid dehydrogenase deficiency, and aldosterone
synthase deficiency. These defects could be picked up with a urine
steroid profile analysis. If aldosterone is above the reference range
this would suggest salt loss due to renal disease, aldosterone resist-
ance, or a sodium channel defect.
Case study 14.2
(a) The symptoms, physical findings with hyponatraemia, hyperka-
laemia, and metabolic acidosis are typical of adrenal failure. Diabe-
tes mellitus was excluded by the urine tests.
(b) Plasma ACTH will be raised. A synacthen test can be performed.
You will see low plasma cortisol concentrations basally and no
response to the synacthen if the patient has adrenal failure.
Case study 14.3
(a) High cortisol, with no diurnal rhythm is seen in Cushing’s dis-
ease and Cushing’s syndrome. However, hypercortisolism can also
be seen in stress, depression, and alcoholism.
ANSWERS TO CASE STUDIES 5
(b) The plasma cortisol concentration will be suppressed in a
low dose dexamethasone suppression test in all cases except for
Cushing’s. A high ACTH excludes an adrenal tumour secreting
cortisol.
(c) Plasma cortisol concentration will be suppressed in a high dose
dexamethasone suppression test in most cases of Cushing’s disease
(pituitary tumour secreting ACTH), but not if the ACTH tumour is
ectopic. Cushing’s disease is usually associated with weight gain
around the waste. Ectopic ACTH secreting tumours are aggres-
sive and not all features of cortisol excess are apparent in the time
course of the disease, which is rapidly terminal. A tumour in the
lung was found in this case.
Case study 14.4
(a) These results were suggestive of primary aldosteronism. The fall
in aldosterone concentration on ambulation, with continued low
renin activity, favours an adenoma. If the patient has bilateral adre-
nal hyperplasia the plasma aldosterone increases after ambulation.
(b) A catheterization study may be performed if imaging did not
confirm a unilateral lesion. A dexamethasone suppression test with
normal 18-hydroxycortisol concentrations would exclude gluco-
corticoid remediable aldosteronism.
Chapter 15
Case study 15.1
(a) As her prolactin had normalized and her periods remained
regular this suggests that hyperprolactinaemia was not the cause
of infertility.
(b) A macroprolactin screen was indicated and this should be carried
out at initial presentation in all new cases of hyperprolactinaemia.
In the event the patient was shown to have macroprolactinaemia.
Case study 15.2
(a) Nasreen has all the features of polycystic ovary syndrome.
(b) In an obese patient with PCOS it is appropriate to perform a
glucose tolerance test.
Case study 15.3
(a) The high gonadotrophins suggest a premature menopause,
which was confirmed by ovarian biopsy.
(b) As she is now menopausal and her ovaries contain no viable fol-
licles, Sharon’s principal option for a pregnancy is egg donation.
Chapter 16
Case study 16.1
(a) His albumin is significantly low and his urea and creatinine are
consistent with dehydration as a result of his poor oral intake. His
serum sodium is borderline low.
(b) C-reactive protein to confirm the degree of the acute phase
response. The C-reactive protein level was 220 mg/L. Thus, the
albumin level resulted from an ongoing acute phase response.
(c) In addition to treatment for sepsis, he requires oral nutritional
supplements until his appetite improves.
Case study 16.2
(a) Serum magnesium.
(b) In acute excess, alcohol acts as a diuretic, causing a rapid and
large increase in urinary magnesium excretion. In chronic excess,
alcohol depletes the body’s magnesium stores. In addition, alco-
hol abusers often have a poor diet and do not eat sufficient mag-
nesium rich foods (legumes, nuts, green vegetables, and whole
6 ANSWERS TO CASE STUDIES
grains). Magnesium requirements are therefore increased in those
who abuse alcohol.
(c) Magnesium can cause hypocalcaemia by two mechanisms:
(i) reducing the release of PTH and (ii) decreasing the action of PTH
by a post-receptor mechanism. Such hypocalcaemia is resistant
to calcium replacement but is usually responsive to magnesium
replacement without calcium replacement.
Case study 16.3
(a) Whilst technically possible, vitamin C analysis has very special-
ized pre-analytical requirements and the turnaround time would
be several weeks.
(b) Vitamin C deficiency results in scurvy, where there is defective
synthesis of collagen, including that within blood vessel walls.
(c) This can manifest as bleeding from all mucous membranes,
swollen and bleeding gums with loosened teeth; bleeding into
joints, deep tissue, into the skin, or around hair follicles; corkscrew
hair; slow wound-healing; and anaemia.
(d) The consumption of fresh fruit and vegetables (especially citrus
fruit) is the best way to avoid scurvy.
Case study 16.4
(a) His BMI is 36.6 kg/m2 and thus he is obese.
(b) Polyuria, nocturia, and polydipsia.
(c) He has a low HDL-C, giving him a cholesterol:HDL-C ratio of 8.3
and mixed dyslipidaemia (raised cholesterol and raised fasting tri-
acylglycerols). Such a lipid pattern is commonly seen in both obesity
and diabetes mellitus; when the cholesterol:HDL-C ratio ≥6.0. The
2006 Joint British Societies recommendations on the prevention of
cardiovascular disease include treatment of the dyslipidaemia.
Case study 16.5
(a) Her age (nutritional deficiencies are not uncommon at the age
of 75; her pathology (malignant tumour) causing unintentional
weight loss of more than 10% of her body weight; latterly she had
not been eating anything substantial at all.
(b) Significantly low inorganic phosphate with renal impairment
and minor decreases in sodium, potassium, and albumin.
(c) Give intravenous phosphate, arrange a dietetics review, and
reduce her calorific intake.
Chapter 17
Case study 17.1
(a) Diabetes is confirmed by the fasting blood glucose. The low
haemoglobin (hypochromic anaemia) and gastrointestinal symp-
toms would suggest iron malabsorption or blood loss, which could
be confirmed by a test of body iron stores such as serum ferritin.
A test for coeliac disease, a cause of malabsorption, should also
be carried out because of the strong association between coeliac
disease and type 1 diabetes.
(b) The low haemoglobin combined with the low serum fer-
ritin indicates low iron stores. Since there is a strong association
between type 1 diabetes and coeliac disease, the latter is suspected
and confirmed as a strong possibility by the raised serum TTGA.
Coeliac disease was confirmed from a duodenal biopsy which indi-
cated partial villous atrophy.
Case study 17.2
(a) No response to fasting would indicate diarrhoea was unrelated
to dietary constituents and so was most likely secretory.
(b) A gut hormone screen should now be undertaken as an investi-
gation of rare causes of watery diarrhoea. This revealed a VIP level
of 550 pmol/L (<30), with pancreatic polypeptide, gastrin, somato-
statin, and neurotensin being normal. A combination of low serum
potassium and watery diarrhoea is a pointer to secretory diarrhoea,
which is confirmed by the low FOG result. Further testing excludes
laxative abuse, which is a relatively common cause. Elevated VIP
concentration indicates likelihood of a VIPoma (vaso active intesti-
nal peptide tumour as in the Verner Morrison syndrome) and this
was subsequently identified as a pancreatic islet cell tumour con-
firmed by a computed tomography scan and biopsy.
Case study 17.3
(a) Previous surgery and reduced acid production may compromise
vitamin B12 absorption and predispose to bacterial overgrowth of
the small bowel, with malabsorption and diarrhoea.
(b) The normal CRP would not exclude a gastrointestinal inflam-
matory condition, but would indicate malabsorption as being the
most likely cause of weight loss. Basic laboratory tests for small
bowel malabsorption and pancreatic exocrine function were
normal but vitamin B12 concentration was low. Because of previous
gastric surgery, the patient could be predisposed to bacterial colo-
nization. Increase in breath hydrogen was >20 ppm above baseline
and confirmed probable bacterial colonization of the small bowel.
The patient’s symptoms responded well to broad spectrum anti-
biotics.
Case study 17.4
Faecal calprotectin, if normal, may help to exclude inflammatory
bowel disease in younger patients. A test for coeliac disease, which
has a high incidence of <1 in 500 in the general population and is
easily performed, could also be undertaken.
Chapter 18
Case study 18.1
(a) The low IgG would lead to susceptibility to bacterial infection.
(b) The BCG method at the local hospital had overestimated the
albumin concentration.
Chapter 19
Case study 19.1
(a) Urine sodium, serum cortisol, and thyroid function tests should
be carried out.
(b) If the patient had SIADH, the urine sodium would be <300
mmol/L, cortisol and thyroid function tests would be within normal
limits, and the patient would be clinically euvolaemic.
Case study 19.2
(a) The CA 125 was measured too soon after surgery and was raised
due to release from damaged tissue. The CA 125 should not be
measured within two weeks of treatment to avoid such misleading
results.
(b) The clinician should wait and ask for CA 125 measurement at
least two weeks post-surgery to provide information about the
effectiveness of the treatment. The CA 125 could also be used to
monitor this patient for disease recurrence, although we are still
awaiting data as to the usefulness of this.
Chapter 20
Case study 20.1
(a) Classical phenylketonuria due to phenylalanine hydroxylase
deficiency.
(b) Dietary treatment with a low phenylalanine diet.

Case study 20.2
(a) Urea cycle disorders, organic acid disorders.
(b) Quantitative plasma amino acids, acyl carnitines, and urine
organic acids.
Case study 20.3
(a) A non-reducing sugar, for example galactose, fructose, or lactose.
(b) Classical galactosaemia (galactose-1-phosphate uridyl trans-
ferase deficiency).
(c) Assessment of galactose-1-phosphate uridyl transferase activity
in red blood cells (ensure baby has not had a blood transfusion).
Case study 20.4
(a) Hypoglycaemia requires urgent treatment to avoid brain
damage.
(b) Due to storage of excess glycogen in the liver. The infant had gly-
cogen storage disease type 1a (glucose-6-phosphatase deficiency).
(c) Endocrine disorders.
(d) Universal newborn screening for MCADD has been in place in
England since April 2009. It is important to remember that some
patients may have missed screening.
Chapter 21
Case study 21.1
(a) It is possible that the patient took the digoxin just before going
to see his doctor. Digoxin is slowly absorbed and so blood samples
for digoxin measurements should be taken at least six hours after
the last dose.
(b) Serum creatinine to assess renal function as the renal system is
the major route of digoxin clearance in the body, therefore deterio-
rating renal function could account for the high serum concentra-
tion. Patients with hypokalaemia are susceptible to digoxin toxicity
even when digoxin concentrations are within the reference range,
hence the need to measure serum potassium.
ANSWERS TO CASE STUDIES 7
Case study 21.2
This case underlines the importance of collecting samples for TDM
at the appropriate time after the last dose and ensuring clinicians
and nursing staff are made fully aware of the importance. Wherever
possible the laboratory should discuss these results with the ward
pharmacist or senior clinician. For tacromilus, peak concentrations
of 40–50 μg/L can be observed, with the corresponding trough
level often in the range 2–8 μg/L after an oral dose.
Chapter 22
Case study 22.1
The lead was coming from car exhaust fumes. As a result of these
findings laws were put in place to stop the use of lead tetraethyl as
an additive to petrol.
Case study 22.2
(a) The maximum amount ingested = number of tablets unac-
counted for × amount per tablet = (16 −2 − 8) × 300 mg = 1800 mg,
which is equivalent to 90 mg/kg body weight.
(b) No further investigations are required as the aspirin ingested is
only 90 mg/kg of body weight.
Case study 22.3
Yes. Standard tablets contain 500 mg of paracetamol so she
appears to have taken 16 g. Doses of more than 12 g are likely to
cause potentially fatal liver damage. The history is confirmed by the
serum paracetamol concentration at 5.5 hours being above the line
for treatment on the treatment nomogram.
Case study 22.4
The clinical features suggest opiate toxicity from intravenous use.
Plasma ethanol should also be measured in addition to a urine
screen for drugs of abuse, as ethanol is a CNS depressant and
enhances opiate toxicity. A panel of drugs of abuse tests is prefer-
able to a single test for opiates as, more often than not, more than
one drug will be used.