Interactive Cases
Gordon Challand
Royal Berkshire Hospital
Format
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I will present some cases taken from the UK
NEQAS Interpretative Comments scheme
Participants will be asked a range of questions
on each case (totally non-threatening!)
Learning points will be summarised
Case 1: low calcium
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A 16 year old man presenting to his Family Doctor. No clinical
details are given on the request card. Serum results are
Sodium 139 mmol/L; potassium 4.1 mmol/L
Urea 2.1 mmol/L; creatinine 61 umol/L
Albumin 40 g/L; adjusted calcium 1.33 mmol/L
Bilirubin 8 umol/L; ALP 238 IU/L; ALT 20 IU/L
The calcium result was analytically checked, and magnesium and
phosphate were added
Magnesium 0.71 mmol/L; phosphate 2.14 mmol/L
Which of the 3 comments is the
best?
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1: Very low calcium. ? Contamination of sample. Please
send repeat with clinical information
2: Results could be consistent with hypoparathyroidism
or pseudo hypoparathyroidism. Suggest PTH analysis.
Alk Phos appropriate for age
3: Results consistent with PTH deficiency (ALP may be
normal for age). Suggest repeat calcium, albumin and
phosphate; and check PTH and 25-hydroxy vitamin D
at same time. Please give clinical details
And which comment is the worst?
Learning points: Case 1
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Sample contamination with EDTA unlikely with a
normal potassium and normal/raised alkaline
phosphatase
Calcium lower than expected for Vitamin D deficiency
(but this possibility should be mentioned)
Urgent referral to hospital
Repeat adjusted calcium 1.28 mmol/L
PTH elevated at 75.3 pmol/L
On referral, classical clinical history and findings of
pseudohypoparathyroidism
Case 2: high calcium
A 60 year old woman seeing her GP; clinical details
are ‘raised calcium, cause?’
Sodium
136 mmol/L
Potassium 4.0 mmol/L
Urea
3.7 mmol/L
Creatinine 57 umol/L
Adjusted calcium 2.67 mmol/L
Phosphate 1.12 mmol/L
PTH 5.1 pmol/L (1.0-7.2 if normal calcium)
TSH, LFTs within reference limits
Case 2: likeliest diagnosis?
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Please choose a number to select what you
consider to be the likeliest diagnosis
1: Familial hypocalciuric hypercalcaemia
2: Malignancy
3: Primary hyperparathyroidism
4: Hypercalcaemia secondary to thiazides
5: Any other condition
Case 2: which of the 3 is the best
comment?
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1: Calcium remains high. Normal renal function.
Primary hyperparathyroidism excluded. ?on diuretics.
Malignancy should be excluded. ?haematology results
2: PTH inappropriate for calcium. ?primary
hyperparathyroid. ?Fam hypocalciuric hypercalcaemia:
please send paired fasting serum and urine
3: PTH inappropriately high for raised calcium. Possible
primary hyperparathyroidism
Raised calcium: diagnostic
probabilities
Calcium (mmol/L) % likelihood of:1HPTism
malignancy
Vit D toxicity
2.6 – 3.0
55
23
19
3.1 – 3.5
43
41
11
Learning points
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Malignancy is less common than hyperparathyroidism
as a cause of hypercalcaemia in otherwise well patients
Thiazides are a common cause of mild hypercalcaemia
Primary hyperparathyroidism can be indistinguishable
from FHH on the basis of serum calcium and PTH
measurements alone
Debate continues as to whether treatment is required
for either FHH or primary hyperparathyroidism in
asymptomatic patients
Case 3: worried about acne
A 19 year old woman presented to her GP. Clinical
details were ‘worried about acne and lowish weight:
eating well’. Serum results were
Sodium 140 mmol/L
Potassium
3.1 mmol/L
Urea
Creatinine
87 umol/L
Glucose
4.5 mmol/L
7.4 mmol/L
Bicarbonate 36 mmol/L
Albumin
43 g/L
Normal LFTs, TFTs
EQAS participants’ comments included the
following three. Which do you consider the
most appropriate?
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1: Hypokalaemic alkalosis: first consider vomiting,
diuretic/laxative therapy/abuse. If hypertensive,
consider investigate for mineralocorticoid excess.
Euthyroid
2. Clinical picture and hypokalaemic alkalosis may
suggest ectopic ACTH. Suggest referral to
endocrinologist
3. Hypokalaemic alkalosis with mildly raised urea
suggests possibility of recurrent vomiting, laxative or
diuretic abuse
Case 3: other diagnoses suggested by
participants
Cushing’s syndrome
Leukaemia
Bartter’s syndrome
Stress
Gitelman’s syndrome
Pyloric stenosis
Liddle’s syndrome
Case 3: other investigations
suggested by participants
Urine potassium
Androgen profile
Magnesium
Urine chloride
17-OH progesterone
Oestradiol
Renin/aldosterone ratio
09.00 and 24.00 cortisols
etc
Case 3: learning points
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Exclude common conditions first
Diuretics are not easily available
Aldosteronism is probably underdiagnosed
Case 4: jaundiced
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A 54 year old man visited his GP. Clinical
information was ‘jaundice’. Serum results were
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Sodium 144 mmol/L; potassium 3.6 mmol/L
Urea 5.0 mmol/L; creatinine 87 umol/L
Albumin 41 g/L; bilirubin 140 umol/L
ALT 35 IU/L (7-56); Gamma-GT 35 IU/L (15-73)
Alkaline phosphatase 58 IU/L (38-126)
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Which other test would be most
appropriate?
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1: FBC
2: Conjugated bilirubin
3: Haptoglobin
4: LDH
5: Other
Which of these 4 comments is most
appropriate?
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1: Check conjugated bilirubin and consider haemolysis. Could be
biliary despite no elevation in Alk. Phos. and gamma-GT
2: ?massive IV haemolysis ?adverse transfusion reaction (E. coli
unlikely with normal urea). Diffuse hepatocellular damage?
3: Hyperbilirubinaemia with no enzyme abnormality. Gilbert’s
unlikely with a bilirubin of 140. Measure conjugated bilirubin.
?Haemolytic anaemia (HB/FBC) or idiosyncratic reaction to
drug (check drug history)
4: Add conj bili before reporting. If low ‘bilirubin conjugation
problem exacerbated by recent stress?’ If high ‘liver dysfunction
due to drugs, virus or other cause?’
What is the likeliest cause of an
isolated raised bilirubin?
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1: Haemolytic disorder
2: Gilbert’s syndrome
3: Cholestasis
4: Other
Case 4: further information
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A conjugated bilirubin was added which was low
LDH was high
Normal haemoglobin; decreased red cell count
and haematocrit
With this new information, what is the
likeliest cause of the raised bilirubin?
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1: Haemolytic disorder
2: Gilbert’s syndrome
3: Cholestasis
4: Other
Case 4: further action
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The Duty Biochemist asked for a blood film to
be examined
This showed the presence of spherocytes and a
diagnosis of hereditary spherocytosis was made
Case 4: learning points
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It is important to measure conjugated bilirubin
when the cause of a raised total bilirubin is not
clear
Unconjugated bilirubin is high in both
haemolysis and Gilbert’s syndrome
Gilbert’s syndrome is unlikely with such a high
bilirubin
Haematology can help!
Case 5: renal diabetic disease
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A 36 year old woman seeing her GP. Clinical
details were ‘renal diabetic disease’. Results were
Serum creatinine
51 umol/L (62-133)
Urine creatinine
7537 umol/L
Urine flow
1.4 ml/min
Creatinine clearance 214 ml/min (70-120)
Case 5 comment assessment
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Mark each of the following 4 comments on a
scale from 1 (inappropriate) through 2 (no
added value) to 5 (highly appropriate)
Case 5 comments
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More than complete urine collection? Pregnant?
Although hyperfiltration can occur in the early stage of
renal diabetic disease, this clearance seems too high to
be credible. More than complete collection?
Artefactually reduced serum creatinine?
Hyperfiltration consistent with early diabetic renal
disease. Suggest monitor urine albumin.
Measure urine albumin to check diagnosis, as Cr
clearance not consistent with RDD and is unusually
high even if lady were pregnant. Is low Cr simply due
to low muscle mass? Is urine volume correct?
Case 5 learning points
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24 hr urine creatinine output is a reasonable
guide to adequacy of a 24 hour collection
Hyperfiltration can occur in the early stages of
renal diabetic disease
For this patient, it is likely that there is both
hyperfiltration and a more than complete urine
collection
It is important to monitor urine albumin in such
patients
The importance of a comment
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Some clinical activity has a background of ‘I do not know what
is wrong with this patient: I will carry out tests which may
suggest a diagnosis’
Some clinical activity has a background of ‘this is my provisional
diagnosis: what evidence can I gather to prove it right?’
Compared with a conventional approach, the Clinical Biochemist
has to make a conceptual switch: ‘here is some clinical
information and a set of abnormalities: what could cause them?’
Taking account of both laboratory and patient variability, and
giving our opinion on results has an irreplaceable role in patient
care.
The ‘bad’ comment
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Can often be classified as:
Asinine, oBvious, Crass, Dogmatic, Erroneous,
Foolhardy; or Gobbleygook
Often ignores clinical information
Often ignores the recipient of the report
Often contains jargon or incomprehensible
abbreviations
A single foolhardy suggestion can ruin an
otherwise good comment
The ‘good’ comment
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In general, the comment scoring highest tends
to suggest:
The most probable diagnosis or diagnoses
Add-on tests to distinguish between the
diagnostic possibilities
Shows good communication skills and avoids
jargon and incomprehensible abbreviations
Clinical Biochemistry is not easy!
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There is always more than one explanation for
any given findings
Connecting results to clinical information
requires an enormous knowledge base and very
considerable interpretational skills
Our role is unique and of major importance. We
often do not give ourselves enough credit for it!
Thank you for listening