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Interactive Cases Gordon Challand Royal Berkshire Hospital.

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Presentation on theme: "Interactive Cases Gordon Challand Royal Berkshire Hospital."— Presentation transcript:

1 Interactive Cases Gordon Challand Royal Berkshire Hospital

2 Format I will present some cases taken from the UK NEQAS Interpretative Comments scheme 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!) Participants will be asked a range of questions on each case (totally non-threatening!) Learning points will be summarised Learning points will be summarised

3 Case 1: low calcium A 16 year old man presenting to his Family Doctor. No clinical details are given on the request card. Serum results are 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 Sodium 139 mmol/L; potassium 4.1 mmol/L Urea 2.1 mmol/L; creatinine 61 umol/L Urea 2.1 mmol/L; creatinine 61 umol/L Albumin 40 g/L; adjusted calcium 1.33 mmol/L Albumin 40 g/L; adjusted calcium 1.33 mmol/L Bilirubin 8 umol/L; ALP 238 IU/L; ALT 20 IU/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 The calcium result was analytically checked, and magnesium and phosphate were added Magnesium 0.71 mmol/L; phosphate 2.14 mmol/L Magnesium 0.71 mmol/L; phosphate 2.14 mmol/L

4 Which of the 3 comments is the best? 1: Very low calcium. ? Contamination of sample. Please send repeat with clinical information 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 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 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? And which comment is the worst?

5 Learning points: Case 1 Sample contamination with EDTA unlikely with a normal potassium and normal/raised alkaline phosphatase 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) Calcium lower than expected for Vitamin D deficiency (but this possibility should be mentioned) Urgent referral to hospital Urgent referral to hospital Repeat adjusted calcium 1.28 mmol/L Repeat adjusted calcium 1.28 mmol/L PTH elevated at 75.3 pmol/L PTH elevated at 75.3 pmol/L On referral, classical clinical history and findings of pseudohypoparathyroidism On referral, classical clinical history and findings of pseudohypoparathyroidism

6 Case 2: high calcium A 60 year old woman seeing her GP; clinical details are ‘raised calcium, cause?’ Sodium 136 mmol/L Potassium4.0 mmol/L Urea 3.7 mmol/L Creatinine57 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

7 Case 2: likeliest diagnosis? Please choose a number to select what you consider to be the likeliest diagnosis Please choose a number to select what you consider to be the likeliest diagnosis 1: Familial hypocalciuric hypercalcaemia 1: Familial hypocalciuric hypercalcaemia 2: Malignancy 2: Malignancy 3: Primary hyperparathyroidism 3: Primary hyperparathyroidism 4: Hypercalcaemia secondary to thiazides 4: Hypercalcaemia secondary to thiazides 5: Any other condition 5: Any other condition

8 Case 2: which of the 3 is the best comment? 1: Calcium remains high. Normal renal function. Primary hyperparathyroidism excluded. ?on diuretics. Malignancy should be excluded. ?haematology results 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 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 3: PTH inappropriately high for raised calcium. Possible primary hyperparathyroidism

9 Raised calcium: diagnostic probabilities Calcium (mmol/L) % likelihood of:1HPTismmalignancyVit D toxicity 2.6 – 3.0552319 3.1 – 3.5434111

10 Learning points Malignancy is less common than hyperparathyroidism as a cause of hypercalcaemia in otherwise well patients Malignancy is less common than hyperparathyroidism as a cause of hypercalcaemia in otherwise well patients Thiazides are a common cause of mild hypercalcaemia 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 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 Debate continues as to whether treatment is required for either FHH or primary hyperparathyroidism in asymptomatic patients

11 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 Sodium140 mmol/LPotassium3.1 mmol/L Urea7.4 mmol/LCreatinine87 umol/L Bicarbonate 36 mmol/LGlucose4.5 mmol/L Albumin 43 g/L Normal LFTs, TFTs

12 EQAS participants’ comments included the following three. Which do you consider the most appropriate? 1: Hypokalaemic alkalosis: first consider vomiting, diuretic/laxative therapy/abuse. If hypertensive, consider investigate for mineralocorticoid excess. Euthyroid 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 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 3. Hypokalaemic alkalosis with mildly raised urea suggests possibility of recurrent vomiting, laxative or diuretic abuse

13 Case 3: other diagnoses suggested by participants Cushing’s syndromeLeukaemia Bartter’s syndromeStress Gitelman’s syndromePyloric stenosis Liddle’s syndrome

14 Case 3: other investigations suggested by participants Urine potassiumAndrogen profile MagnesiumUrine chloride 17-OH progesteroneOestradiol Renin/aldosterone ratio09.00 and 24.00 cortisols etc

15 Case 3: learning points Exclude common conditions first Exclude common conditions first Diuretics are not easily available Diuretics are not easily available Aldosteronism is probably underdiagnosed Aldosteronism is probably underdiagnosed

16 Case 4: jaundiced A 54 year old man visited his GP. Clinical information was ‘jaundice’. Serum results were A 54 year old man visited his GP. Clinical information was ‘jaundice’. Serum results were Sodium 144 mmol/L; potassium 3.6 mmol/L Sodium 144 mmol/L; potassium 3.6 mmol/L Urea 5.0 mmol/L; creatinine 87 umol/L Urea 5.0 mmol/L; creatinine 87 umol/L Albumin 41 g/L; bilirubin 140 umol/L Albumin 41 g/L; bilirubin 140 umol/L ALT 35 IU/L (7-56); Gamma-GT 35 IU/L (15-73) ALT 35 IU/L (7-56); Gamma-GT 35 IU/L (15-73) Alkaline phosphatase 58 IU/L (38-126) Alkaline phosphatase 58 IU/L (38-126)

17 Which other test would be most appropriate? 1: FBC 1: FBC 2: Conjugated bilirubin 2: Conjugated bilirubin 3: Haptoglobin 3: Haptoglobin 4: LDH 4: LDH 5: Other 5: Other

18 Which of these 4 comments is most appropriate? 1: Check conjugated bilirubin and consider haemolysis. Could be biliary despite no elevation in Alk. Phos. and gamma-GT 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? 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) 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?’ 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?’

19 What is the likeliest cause of an isolated raised bilirubin? 1: Haemolytic disorder 1: Haemolytic disorder 2: Gilbert’s syndrome 2: Gilbert’s syndrome 3: Cholestasis 3: Cholestasis 4: Other 4: Other

20 Case 4: further information A conjugated bilirubin was added which was low A conjugated bilirubin was added which was low LDH was high LDH was high Normal haemoglobin; decreased red cell count and haematocrit Normal haemoglobin; decreased red cell count and haematocrit

21 With this new information, what is the likeliest cause of the raised bilirubin ? 1: Haemolytic disorder 1: Haemolytic disorder 2: Gilbert’s syndrome 2: Gilbert’s syndrome 3: Cholestasis 3: Cholestasis 4: Other 4: Other

22 Case 4: further action The Duty Biochemist asked for a blood film to be examined 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 This showed the presence of spherocytes and a diagnosis of hereditary spherocytosis was made

23 Case 4: learning points It is important to measure conjugated bilirubin when the cause of a raised total bilirubin is not clear 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 Unconjugated bilirubin is high in both haemolysis and Gilbert’s syndrome Gilbert’s syndrome is unlikely with such a high bilirubin Gilbert’s syndrome is unlikely with such a high bilirubin Haematology can help! Haematology can help!

24 Case 5: renal diabetic disease A 36 year old woman seeing her GP. Clinical details were ‘renal diabetic disease’. Results were A 36 year old woman seeing her GP. Clinical details were ‘renal diabetic disease’. Results were Serum creatinine51 umol/L(62-133) Serum creatinine51 umol/L(62-133) Urine creatinine7537 umol/L Urine creatinine7537 umol/L Urine flow1.4 ml/min Urine flow1.4 ml/min Creatinine clearance214 ml/min (70-120) Creatinine clearance214 ml/min (70-120)

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

26 Case 5 comments More than complete urine collection? Pregnant? 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? 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. 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? 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?

27 Case 5 learning points 24 hr urine creatinine output is a reasonable guide to adequacy of a 24 hour collection 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 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 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 It is important to monitor urine albumin in such patients

28 The importance of a comment 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 ‘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?’ 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?’ 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. Taking account of both laboratory and patient variability, and giving our opinion on results has an irreplaceable role in patient care.

29 The ‘bad’ comment Can often be classified as: Can often be classified as: Asinine, oBvious, Crass, Dogmatic, Erroneous, Foolhardy; or Gobbleygook Asinine, oBvious, Crass, Dogmatic, Erroneous, Foolhardy; or Gobbleygook Often ignores clinical information Often ignores clinical information Often ignores the recipient of the report Often ignores the recipient of the report Often contains jargon or incomprehensible abbreviations Often contains jargon or incomprehensible abbreviations A single foolhardy suggestion can ruin an otherwise good comment A single foolhardy suggestion can ruin an otherwise good comment

30 The ‘good’ comment In general, the comment scoring highest tends to suggest: In general, the comment scoring highest tends to suggest: The most probable diagnosis or diagnoses The most probable diagnosis or diagnoses Add-on tests to distinguish between the diagnostic possibilities Add-on tests to distinguish between the diagnostic possibilities Shows good communication skills and avoids jargon and incomprehensible abbreviations Shows good communication skills and avoids jargon and incomprehensible abbreviations

31 Clinical Biochemistry is not easy! There is always more than one explanation for any given findings 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 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! Our role is unique and of major importance. We often do not give ourselves enough credit for it!

32 Thank you for listening


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