Interactive CasesInteractive Cases

Gordon ChallandGordon Challand

Royal Berkshire HospitalRoyal Berkshire Hospital

FormatFormat

I will present some cases taken from I will present some cases taken from the UK NEQAS Interpretative the UK NEQAS Interpretative Comments schemeComments scheme

Participants will be asked a range of Participants will be asked a range of questions on each case (totally non-questions on each case (totally non-threatening!)threatening!)

Learning points will be summarisedLearning points will be summarised

Case 1: low calciumCase 1: low calcium A 16 year old man presenting to his Family A 16 year old man presenting to his Family

Doctor. No clinical details are given on the Doctor. No clinical details are given on the request card. Serum results arerequest card. Serum results are

Sodium 139 mmol/L; potassium 4.1 mmol/LSodium 139 mmol/L; potassium 4.1 mmol/L Urea 2.1 mmol/LUrea 2.1 mmol/L; creatinine 61 umol/L; creatinine 61 umol/L Albumin 40 g/L; Albumin 40 g/L; adjusted calcium 1.33 mmol/Ladjusted calcium 1.33 mmol/L Bilirubin 8 umol/L; Bilirubin 8 umol/L; ALP 238 IU/LALP 238 IU/L; ALT 20 IU/L; ALT 20 IU/L The calcium result was analytically checked, and The calcium result was analytically checked, and

magnesium and phosphate were addedmagnesium and phosphate were added Magnesium 0.71 mmol/L; Magnesium 0.71 mmol/L; phosphate 2.14 mmol/Lphosphate 2.14 mmol/L

Which of the 3 comments is Which of the 3 comments is the best?the best?

1: Very low calcium. ? Contamination of 1: Very low calcium. ? Contamination of sample. Please send repeat with clinical sample. Please send repeat with clinical informationinformation

2: Results could be consistent with 2: Results could be consistent with hypoparathyroidism or pseudo hypoparathyroidism or pseudo hypoparathyroidism. Suggest PTH analysis. hypoparathyroidism. Suggest PTH analysis. Alk Phos appropriate for ageAlk Phos appropriate for age

3: Results consistent with PTH deficiency 3: Results consistent with PTH deficiency (ALP may be normal for age). Suggest (ALP may be normal for age). Suggest repeat calcium, albumin and phosphate; repeat calcium, albumin and phosphate; and check PTH and 25-hydroxy vitamin D and check PTH and 25-hydroxy vitamin D at same time. Please give clinical detailsat same time. Please give clinical details

And which comment is the worst?And which comment is the worst?

Learning points: Case 1Learning points: Case 1 Sample contamination with EDTA unlikely Sample contamination with EDTA unlikely

with a normal potassium and normal/raised with a normal potassium and normal/raised alkaline phosphatasealkaline phosphatase

Calcium lower than expected for Vitamin D Calcium lower than expected for Vitamin D deficiency (but this possibility should be deficiency (but this possibility should be mentioned)mentioned)

Urgent referral to hospitalUrgent referral to hospital Repeat adjusted calcium 1.28 mmol/LRepeat adjusted calcium 1.28 mmol/L PTH elevated at 75.3 pmol/LPTH elevated at 75.3 pmol/L On referral, classical clinical history and On referral, classical clinical history and

findings of pseudohypoparathyroidismfindings of pseudohypoparathyroidism

Case 2: high calciumCase 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 Case 2: likeliest diagnosis?diagnosis?

Please choose a number to select what Please choose a number to select what you consider to be the likeliest diagnosisyou consider to be the likeliest diagnosis

1: Familial hypocalciuric hypercalcaemia1: Familial hypocalciuric hypercalcaemia 2: Malignancy2: Malignancy 3: Primary hyperparathyroidism3: Primary hyperparathyroidism 4: Hypercalcaemia secondary to 4: Hypercalcaemia secondary to

thiazidesthiazides 5: Any other condition5: Any other condition

Case 2: which of the 3 is the Case 2: which of the 3 is the best comment?best comment?

1: Calcium remains high. Normal renal 1: Calcium remains high. Normal renal function. Primary hyperparathyroidism function. Primary hyperparathyroidism excluded. ?on diuretics. Malignancy should excluded. ?on diuretics. Malignancy should be excluded. ?haematology resultsbe excluded. ?haematology results

2: PTH inappropriate for calcium. ?primary 2: PTH inappropriate for calcium. ?primary hyperparathyroid. ?Fam hypocalciuric hyperparathyroid. ?Fam hypocalciuric hypercalcaemia: please send paired fasting hypercalcaemia: please send paired fasting serum and urineserum and urine

3: PTH inappropriately high for raised 3: PTH inappropriately high for raised calcium. Possible primary calcium. Possible primary hyperparathyroidismhyperparathyroidism

Raised calcium: diagnostic Raised calcium: diagnostic probabilitiesprobabilities

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 pointsLearning points

Malignancy is less common than Malignancy is less common than hyperparathyroidism as a cause of hyperparathyroidism as a cause of hypercalcaemia in otherwise well patientshypercalcaemia in otherwise well patients

Thiazides are a common cause of mild Thiazides are a common cause of mild hypercalcaemiahypercalcaemia

Primary hyperparathyroidism can be Primary hyperparathyroidism can be indistinguishable from FHH on the basis of indistinguishable from FHH on the basis of serum calcium and PTH measurements aloneserum calcium and PTH measurements alone

Debate continues as to whether treatment is Debate continues as to whether treatment is required for either FHH or primary required for either FHH or primary hyperparathyroidism in asymptomatic patientshyperparathyroidism in asymptomatic patients

Case 3: worried about Case 3: worried about acneacne

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 7.4 mmol/L Creatinine 87 umol/L

Bicarbonate 36 mmol/L Glucose 4.5 mmol/L

Albumin 43 g/L

Normal LFTs, TFTs

EQAS participants’ comments EQAS participants’ comments included the following three. included the following three.

Which do you consider the most Which do you consider the most appropriate?appropriate?

1: Hypokalaemic alkalosis: first consider 1: Hypokalaemic alkalosis: first consider vomiting, diuretic/laxative therapy/abuse. If vomiting, diuretic/laxative therapy/abuse. If hypertensive, consider investigate for hypertensive, consider investigate for mineralocorticoid excess. Euthyroidmineralocorticoid excess. Euthyroid

2. Clinical picture and hypokalaemic 2. Clinical picture and hypokalaemic alkalosis may suggest ectopic ACTH. alkalosis may suggest ectopic ACTH. Suggest referral to endocrinologistSuggest referral to endocrinologist

3. Hypokalaemic alkalosis with mildly raised 3. Hypokalaemic alkalosis with mildly raised urea suggests possibility of recurrent urea suggests possibility of recurrent vomiting, laxative or diuretic abusevomiting, laxative or diuretic abuse

Case 3: other diagnoses Case 3: other diagnoses suggested by participantssuggested by participants

Cushing’s syndrome Leukaemia

Bartter’s syndrome Stress

Gitelman’s syndrome Pyloric stenosis

Liddle’s syndrome

Case 3: other investigations Case 3: other investigations suggested by participantssuggested 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 pointsCase 3: learning points

Exclude common conditions firstExclude common conditions first Diuretics are not easily availableDiuretics are not easily available Aldosteronism is probably Aldosteronism is probably

underdiagnosedunderdiagnosed

Case 4: jaundicedCase 4: jaundiced

A 54 year old man visited his GP. A 54 year old man visited his GP. Clinical information was ‘jaundice’. Clinical information was ‘jaundice’. Serum results wereSerum results were

Sodium 144 mmol/L; potassium 3.6 mmol/LSodium 144 mmol/L; potassium 3.6 mmol/L Urea 5.0 mmol/L; creatinine 87 umol/LUrea 5.0 mmol/L; creatinine 87 umol/L Albumin 41 g/L; Albumin 41 g/L; bilirubin 140 umol/Lbilirubin 140 umol/L ALT 35 IU/L (7-56); Gamma-GT 35 IU/L ALT 35 IU/L (7-56); Gamma-GT 35 IU/L

(15-73)(15-73) Alkaline phosphatase 58 IU/L (38-126)Alkaline phosphatase 58 IU/L (38-126)

Which other test would be Which other test would be most appropriate?most appropriate?

1: FBC1: FBC 2: Conjugated bilirubin2: Conjugated bilirubin 3: Haptoglobin3: Haptoglobin 4: LDH4: LDH 5: Other5: Other

Which of these 4 comments is Which of these 4 comments is most appropriate?most appropriate?

1: Check conjugated bilirubin and consider haemolysis. 1: Check conjugated bilirubin and consider haemolysis. Could be biliary despite no elevation in Alk. Phos. and Could be biliary despite no elevation in Alk. Phos. and gamma-GTgamma-GT

2: ?massive IV haemolysis ?adverse transfusion reaction 2: ?massive IV haemolysis ?adverse transfusion reaction (E. coli unlikely with normal urea). Diffuse hepatocellular (E. coli unlikely with normal urea). Diffuse hepatocellular damage?damage?

3: Hyperbilirubinaemia with no enzyme abnormality. 3: Hyperbilirubinaemia with no enzyme abnormality. Gilbert’s unlikely with a bilirubin of 140. Measure Gilbert’s unlikely with a bilirubin of 140. Measure conjugated bilirubin. ?Haemolytic anaemia (HB/FBC) or conjugated bilirubin. ?Haemolytic anaemia (HB/FBC) or idiosyncratic reaction to drug (check drug history)idiosyncratic reaction to drug (check drug history)

4: Add conj bili before reporting. If low ‘bilirubin 4: Add conj bili before reporting. If low ‘bilirubin conjugation problem exacerbated by recent stress?’ If conjugation problem exacerbated by recent stress?’ If high ‘liver dysfunction due to drugs, virus or other high ‘liver dysfunction due to drugs, virus or other cause?’cause?’

What is the likeliest cause What is the likeliest cause of an isolated raised of an isolated raised

bilirubin?bilirubin? 1: Haemolytic disorder1: Haemolytic disorder 2: Gilbert’s syndrome2: Gilbert’s syndrome 3: Cholestasis3: Cholestasis 4: Other4: Other

Case 4: further Case 4: further informationinformation

A conjugated bilirubin was added A conjugated bilirubin was added which was lowwhich was low

LDH was highLDH was high Normal haemoglobin; decreased red Normal haemoglobin; decreased red

cell count and haematocritcell count and haematocrit

With this new information, With this new information, what is the likeliest cause of what is the likeliest cause of

the raised bilirubinthe raised bilirubin?? 1: Haemolytic disorder1: Haemolytic disorder 2: Gilbert’s syndrome2: Gilbert’s syndrome 3: Cholestasis3: Cholestasis 4: Other4: Other

Case 4: further actionCase 4: further action

The Duty Biochemist asked for a The Duty Biochemist asked for a blood film to be examinedblood film to be examined

This showed the presence of This showed the presence of spherocytes and a diagnosis of spherocytes and a diagnosis of hereditary spherocytosis was madehereditary spherocytosis was made

Case 4: learning pointsCase 4: learning points

It is important to measure conjugated It is important to measure conjugated bilirubin when the cause of a raised bilirubin when the cause of a raised total bilirubin is not cleartotal bilirubin is not clear

Unconjugated bilirubin is high in both Unconjugated bilirubin is high in both haemolysis and Gilbert’s syndromehaemolysis and Gilbert’s syndrome

Gilbert’s syndrome is unlikely with Gilbert’s syndrome is unlikely with such a high bilirubinsuch a high bilirubin

Haematology can help!Haematology can help!

Case 5: renal diabetic Case 5: renal diabetic diseasedisease

A 36 year old woman seeing her GP. A 36 year old woman seeing her GP. Clinical details were ‘renal diabetic Clinical details were ‘renal diabetic disease’. Results weredisease’. Results were

Serum creatinineSerum creatinine 51 umol/L51 umol/L (62-(62-133)133)

Urine creatinineUrine creatinine 7537 umol/L7537 umol/L Urine flowUrine flow 1.4 ml/min1.4 ml/min Creatinine clearanceCreatinine clearance 214 ml/min (70-214 ml/min (70-

120)120)

Case 5 comment Case 5 comment assessmentassessment

Mark each of the following 4 Mark each of the following 4 comments on a scale from 1 comments on a scale from 1 (inappropriate) through 2 (no added (inappropriate) through 2 (no added value) to 5 (highly appropriate)value) to 5 (highly appropriate)

Case 5 commentsCase 5 comments More than complete urine collection? More than complete urine collection?

Pregnant?Pregnant? Although hyperfiltration can occur in the early Although hyperfiltration can occur in the early

stage of renal diabetic disease, this clearance stage of renal diabetic disease, this clearance seems too high to be credible. More than seems too high to be credible. More than complete collection? Artefactually reduced complete collection? Artefactually reduced serum creatinine?serum creatinine?

Hyperfiltration consistent with early diabetic Hyperfiltration consistent with early diabetic renal disease. Suggest monitor urine albumin.renal disease. Suggest monitor urine albumin.

Measure urine albumin to check diagnosis, as Measure urine albumin to check diagnosis, as Cr clearance not consistent with RDD and is Cr clearance not consistent with RDD and is unusually high even if lady were pregnant. Is unusually high even if lady were pregnant. Is low Cr simply due to low muscle mass? Is low Cr simply due to low muscle mass? Is urine volume correct?urine volume correct?

Case 5 learning pointsCase 5 learning points

24 hr urine creatinine output is a 24 hr urine creatinine output is a reasonable guide to adequacy of a 24 reasonable guide to adequacy of a 24 hour collectionhour collection

Hyperfiltration can occur in the early Hyperfiltration can occur in the early stages of renal diabetic diseasestages of renal diabetic disease

For this patient, it is likely that there For this patient, it is likely that there is both hyperfiltration and a more is both hyperfiltration and a more than complete urine collectionthan complete urine collection

It is important to monitor urine It is important to monitor urine albumin in such patientsalbumin in such patients

The importance of a The importance of a commentcomment

Some clinical activity has a background of ‘I do Some clinical activity has a background of ‘I do not know what is wrong with this patient: I will not know what is wrong with this patient: I will carry out tests which may suggest a diagnosis’carry out tests which may suggest a diagnosis’

Some clinical activity has a background of ‘this is Some clinical activity has a background of ‘this is my provisional diagnosis: what evidence can I my provisional diagnosis: what evidence can I gather to prove it right?’gather to prove it right?’

Compared with a conventional approach, the Compared with a conventional approach, the Clinical Biochemist has to make a conceptual Clinical Biochemist has to make a conceptual switch: ‘here is some clinical information and a switch: ‘here is some clinical information and a set of abnormalities: what could cause them?’set of abnormalities: what could cause them?’

Taking account of both laboratory and patient Taking account of both laboratory and patient variability, and giving our opinion on results has variability, and giving our opinion on results has an irreplaceable role in patient care.an irreplaceable role in patient care.

The ‘bad’ commentThe ‘bad’ comment

Can often be classified as:Can often be classified as: Asinine, oBvious, Crass, Dogmatic, Asinine, oBvious, Crass, Dogmatic,

Erroneous, Foolhardy; or GobbleygookErroneous, Foolhardy; or Gobbleygook Often ignores clinical informationOften ignores clinical information Often ignores the recipient of the Often ignores the recipient of the

reportreport Often contains jargon or Often contains jargon or

incomprehensible abbreviationsincomprehensible abbreviations A single foolhardy suggestion can ruin A single foolhardy suggestion can ruin

an otherwise good commentan otherwise good comment

The ‘good’ commentThe ‘good’ comment

In general, the comment scoring In general, the comment scoring highest tends to suggest:highest tends to suggest:

The most probable diagnosis or The most probable diagnosis or diagnosesdiagnoses

Add-on tests to distinguish between Add-on tests to distinguish between the diagnostic possibilitiesthe diagnostic possibilities

Shows good communication skills and Shows good communication skills and avoids jargon and incomprehensible avoids jargon and incomprehensible abbreviationsabbreviations

Clinical Biochemistry is not Clinical Biochemistry is not easy!easy!

There is always more than one There is always more than one explanation for any given findingsexplanation for any given findings

Connecting results to clinical Connecting results to clinical information requires an enormous information requires an enormous knowledge base and very knowledge base and very considerable interpretational skillsconsiderable interpretational skills

Our role is unique and of major Our role is unique and of major importance. We often do not give importance. We often do not give ourselves enough credit for it!ourselves enough credit for it!

Thank you for listeningThank you for listening