Transcript GP LECTURE NOV 2009

GP LECTURE NOV 2009
INTERPRETATION OF BIOCHEMISTRY
RESULTS
POTENTIAL PITFALLS (with short cases)
&
FREQUENT ADVICE TOPICS
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TFT
AUTOIMMUNE TESTS
IRON / FERRITIN / PORPHYRIN
HYPERCALCAEMIA
PROTEINURIA
TUMOUR MARKERS
TEST REPETOIRE
ICE
THYROID FUNCTION TESTS
CAN BE MISLEADING !
SOME ATYPICAL PATTERNS
FEMALE 67Y
CLINICAL PRESENTATION: TACHYCARDIA
INVESTIGATIONS
07/08 FT4 26.7 (9.5-22) FT3 7.8 (<6.5)
DIAGNOSIS
ENDOCRINE REFERRAL
09/08 FT4 25.3 FT3 7.2
CARDIAC SYMPTOMS: TACHYCARDIA
HYPERTHYROIDISM
REVIEW ENDOCRINOLOGIST 2
CHANGE FROM CBZ TO PTU
MONITORING 01/09
FT4 19.7 TSH 7.45
FT4 20.2 TSH 11.09
FEMALE 67Y
CLINICAL PRESENTATION
INVESTIGATIONS
07/08 FT4 26.7 (9.5-22) FT3 7.8 (<6.5)
DIAGNOSIS
ENDOCRINE REFERRAL
09/08 FT4 25.3 FT3 7.2
CARDIAC SYMPTOMS
HYPERTHYROIDISM DIAGNOSED
REVIEW ENDOCRINOLOGIST 2
CHANGE FROM CBZ TO PTU
MONITORING
01/09 FT4 19.7/20.2 TSH 7.45/11.09
TSH 4.73 (0.3-5.5)
TSH 1.41
?? REVIEW DIAGNOSIS ??
DIFFERENTIAL DIAGNOSIS
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FURTHER INVESTIGATION (20/04/09)
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DCH
REF LAB
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HETEROPHILIC ANTIBODIES – NEGATIVE FOR FT4, TSH, FT3
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THYROID HORMONE ANTIBODIES – NEGATIVE FOR FT4, TSH
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FAMILIAL DYSALBUMINAEMIC HYPERTHYROXINAEMIA – NEG
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THYROID HORMONE RECEPTOR - POSITIVE
FT4 22.3 TSH 3.23 FT3 8.5
FT4 26.0 TSH 4.18 FT3 7.4
THYROID HORMONE RESISTANCE
Heterozygous for TRbeta mutation c.728G.A (p.Arg243Gln)
Fluorescent sequencing analysis of exon 7 has detected a single
base change c.728G>A.
This mutation is predicted to result in an abnormal TBbeta
protein (p.Arg243Gln) and has been previously associated
with thyroid hormone resistance (HGMD database).
Screening can be offered to Jennifer's first degree relatives, IF
APPROPRIATE. Relatives having thyroid hormone tests
should be aware of this condition and the importance of a
normal TSH
CASE 2
MALE 43Y PRESENTED TO ENDOCRINE CLINIC
GOITRE AT AGE 19Y
SUBTOTAL THYROIDECTOMY / CARBIMAZOLE 5Y
FREE T4 61.3 (9.5-22.5)
TSH
0.95 ( .3-5.5)
CLINICALLY EUTHYROID
POSSIBILITIES
1 EUTHYROID HYPERTHYROXINAEMIA (Unlikely / T3)
2 ASSAY INTERFERENCE (AUTOANTIBODIES TO THYROXINE)
3 THYROID HORMONE RESISTANCE
FAMILY STUDIES / THYROID HORMONE RESISTANCE
PATIENT AGE
GOITRE
FT4
TSH
TREATMENT
INDEX
43
+
61.3
1.9
Partial thyroidectomy / carbimazole
BROTHER 1
1
2
3
4
51
22
21
19
14
+
-
41.8
67.8
17.1
59.0
16.7
1.95
1.3
2.2
1.3
1.4
Partial thyroidectomy
BROTHER 2 46
+
30.5
1.9
1
+
48.0
1.3
Partial thyroidectomy / carbimazole /
I131
Carbimazole
24
CASE 1
26 Y CAUCASIAN LADY
EIGHT WEEKS PREGNANT WITH HYPEREMESIS
SINGLETON PREGNANCY
Free T4 = 60 pmol/L ( 9.5 - 22.0)
TSH = < 0.1 mu/L
Free T3 = 15 pmol/L (3.5 - 7.5)
IS ANTITHYROID TREATMENT INDICATED ?
TRANSIENT HYPERTHYOXINAEMIA ASSOCIATED WITH
PREGNANCY
70
FT4 pmol/L
60
50
40
30
20
10
0
1
2
3
Weeks
4
CLASSIFICATION OF THYROIDITIS
TYPE
AETIOLOGY
CHRONIC AUTOIMMUNE
(Transient variant)
PAIN
-
ESR
TH Ab
%RESOLVED 1Y
N/ ^
+++
0
100
ACUTE
BACTERIAL
++++
HIGH
-
100
SUBACUTE
VIRAL
+++
HIGH
-
95
P/PARTUM
AUTOIMMUNE
N/ ^
+++
80
-
(Painless postpartum thyroiditis may occur in 5 - 9 % unselected women)
TFT’S AND TRANSIENT THYROIDITIS
CASE 6
48Y FEMALE
PRESENTATION WITH WT LOSS / HEAT INTOLERANCE
FREE T4 = 16.5 (9.5 - 22.0)
TSH
= < 0.02 (0.3-5.5)
FREE T3 = 8.5
(3.5-6.5)
COMMENTS ?
CASE 6
48Y FEMALE
PRESENTATION WITH WT LOSS / HEAT INTOLERANCE
FREE T4 = 16.5 (9.5 - 22.0)
TSH
= < 0.02 (0.3-5.5)
FREE T3 = 8.5
(3.5-6.5)
COMMENTS
“ T3 THYROTOXICOSIS “
THYROID EXTRACT PURCHASED OVER INTERNET.
CASE 3
FEMALE 28WEEKS GESTATION
TATT
FREE T4 8.8 (9.5-22.0)
TSH
1.2 (0.3 - 5.5)
IS THYROXINE INDICATED ?
FREE T4 IN PREGNANCY
20
FT4
15
10
5
0
8
12
16
20
24
28
Gestation
32
36
T
CASE 4
TFT REFERRAL FROM GP
28Y FEMALE
CLINICAL INFORMATION TIREDNESS / LOW BP
FREE T4 12.2 (9.5-22)
TSH
0.21 (0.3-5.5)
POSSIBLE CAUSES ?
CASE 4
TFT REFERRAL FROM GP
28Y FEMALE: CLINICAL INFORMATION TIREDNESS / LOW BP
FREE T4 12.2 (9.5-22)TSH
0.21 (0.3-5.5)
POSSIBLE CAUSES
1
2
3
NON THYROIDAL ILLNESS
STEROIDS /DRUGS
HYPOPITUITARISM
INFERTILITY PROFILE / CONSULTANT REFERRAL
PARTIAL HYPOPITUITARISM
DRUGS AFFECTING TSH
TSH DECREASE
TSH INCREASE
Bromocryptine
Carbamazepine *
Corticosteroids **
Cyproheptadine
Dopamine
Heparin
Levodopa
Thyroxine, tri-iodothyronine
Clomiphene
Iodides
Lithium
Metoclopramide
Morphine
Phenothiazines
Amiodarone ***
CASE 5
CLINICAL INFORMATION
68Y MALE
SVT / TIREDNESS
FREE T4
TSH
FREE T3
28.3 (9.5 - 22.0)
1.12 (0.3 - 5.5)
4.5 (3.5 - 6.5)
IS PATIENT HYPERTHYROID ?
WHY IS FT4 RAISED ?
CASE 5
CLINICAL INFORMATION
68Y MALE
SVT / TIREDNESS
FREE T4 28.3 (9.5 - 22.0)
TSH
1.12 (0.3 - 5.5)
FREE T3 4.5 (3.5 - 6.5)
IS PATIENT HYPERTHYROID ? - BIOCHEMISTRY NOT SUPPORTIVE
WHY IS FT4 RAISED ?
1
2
3
4
ANALYTICAL
? THYROID HORMONE REPLACEMENT
EUTHYROID HYPERTHYROXINAEMIA
IMPAIRED CONVERSION OF T4 TO T3
AMIODARONE INDUCED CHANGES
AMIODARONE / THYROID FUNCTION
AMIODARONE INDUCED THYROID DISORDERS
Iodine deficient
Iodine sufficient
Thyroxine Replacement Therapy in
Primary Hypothyroidism
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TSH Level
This Indicates
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< 0.01 miu/L
0.01-0.3 miu/L
Normal
> 3.5 miu/L
Over Replacement
Indicates Possible Over Replacement
Sufficient Replacement
Likely under
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Clinical symptomatology and TSH are the major parameters used in
assessing the adequacy of replacement therapy.
T4 level is an index of recent patient compliance.
TSH may take up to 4-6 weeks to stabilise. Thus, repeat TFT following
alteration of dose should only be performed after this period.
PATHOLOGY HANDBOOK
http://www.pathologydch.co.uk
Special Test Guidelines
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Rheumatic Diseases
SLE Monitoring
Eye Disorders
Vasculitic Diseases
Respiratory Disorders
Renal Disease
Antiphospholipid Disorder’s
Liver Disorders
GI Disorders
Dermatological Disorders
Endocrine Disorders
Addison’s
Primary Ovarian failure
Polyendocrinopathy
Muscle Disorders
Idiopathic Cardiomyopathy, Myocarditis
Allergic Disorders
IMMUNOLOGY TESTS
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Weak positives
Connective tissue ANA
Coeliac
TTG
PBC
M2 Ab
Thyroid
Anti TPO antibodies are present in most
patients with Hashimoto's thyroiditis (95%), primary
myxoedema (90%) and in some patients with Grave's disease
(18%). They are also present in low levels in patients with
colloid goitre, thyroid carcinoma, transiently in de Quervain's
thryoiditis and in normal elderly females. (This is relatively
non specific test)
Thyroid Peroxidase Ab (TPO)
TSH low or normal
TSH elevated
If T4 is normal then Thyroid status is
Normal
If T4 is normal, subclinical
hypothyroidism exists.
Consider T4 replacement if TSH > 10
miu/L.
When the TSH is mildly
elevated ie 5-10 miu/L, positive
TPO antibodies indicate an
increased risk of future
hypothyroidism of 5% per year
If T4 is low consider secondary
If T4 is low, primary hypothyrodism
hypothyroidism (but more commonly Sick
Euthyroid)
TPO: RISK FACTOR FOR HYPOTHYROIDISM
North England - Whickham Survey
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Positive thyroid microsomal antibodies were present in 21% of women
aged 55-65 years and these women have an annual risk of developing
hypothyroidism of 2.6%
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Annual incidence of hypothyroidism was 3.5/1000 women.
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The odds ratio for developing hypothyroidism were:
8 for women and 44 for men with an isolated increase in TSH
8 for women and 25 for men with positive anti-thyroid antibodies
38 for women and 173 for men with an increase in TSH and positive
antibodies
INCIDENCE OF THYROID CARCINOMA
THYROID CARCINOMA: POST ABLATION
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FEMALE 49Y
10/09
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FEMALE 49Y
09/09
FT4 53.0 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
FT4 24.8 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
Other Feb 2008
? OK for monitoring
THYROID CARCINOMA: POST ABLATION
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FEMALE 49Y
10/09
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FEMALE 49Y
09/09
FT4 53.0 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
FT4 24.8 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
Other Feb 2008
? OK for monitoring
THYROGLOBULIN < 0.2 ug/L
([<1.0 post thyroid ablation]
? OK for monitoring
THYROID CARCINOMA: POST ABLATION
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FEMALE 49Y
10/09
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FEMALE 49Y
09/09
FT4 53.0 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
FT4 24.8 pmol/L (8-20)
TSH <0.02 mu/L (0.3-5.5)
Other Feb 2008
? OK for monitoring
THYROGLOBULIN < 0.2 ug/L
([<1.0 post thyroid ablation]
? OK for monitoring
THYROGLOBULIN Ab 2362 (< 20)
ANTI CYCLIC CITRULLINATED PEPTIDE Ab
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Rheumatoid factor = Positive
“Interpret with reference to clinical symptoms as this is non specific marker
which may also be raised in response to infection and other autoimmune
conditions”.
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Anti CCP antibodies
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Improved specificity (98%) and sensitivity (80%) for the detection of
Rheumatoid Arthritis
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Differentiate rheumatoid from similar conditions (polymyalgia, Sjogren’s,
lupus – RhF can be +ve)
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High initial titres are prognostic for subsequent structural damage (target
patients requiring early aggressive therapy)
TSH RECEPTOR Ab (TSH-RAb)
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GESTATIONAL HYPERTHYROIDISM / GRAVE’S
ANTENATAL BOOKING
Very high titre predictive of intrauterine or neonatal thyrotoxicosis
Negative / low need not be measured again
POST THYROIDECTOMY FOR GRAVE’S
High titres TSH-RAb results in concomitant risk of neonatal Grave’s
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EUTHYROID GRAVE’S OPTHALMOPATHY
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NEONATAL TRANSIENT HYPOTHYROIDISM / TSH BLOCKING Ab
Iron deficiency: Iron or ferritin ??
CAUSES OF IRON DEFICINCY
BLOOD LOSS
DECREASED IRON ABSORPTION
Refractive to oral iron therapy
OTHER
Intravascular haemolysis
Pulmonary haemosiderosis
Response erythropoeitin
Gastric bypass /obesity
Peripheral smear from a patient with iron deficiency shows pale small red
cells with just a scant rim of pink haemoglobin; occasional "pencil" shaped
cells are also present. Normal red cells are similar in size to the nucleus of
a small lymphocyte (arrow); thus, many microcytic cells are present in this
smear. Thalassaemia can produce similar findings.
RELIABLE BIOCHEMISTRY !!
MALE 76Y:
RENAL REVIEW
Hb
10.2 g/dL
Iron
2.0 umol/L
UIBC
32 umol/L
Iron Sat 6 %
?? Iron deficient
(13.5-17.5)
(10-28)
(28-64)
(15-40)
RELIABLE BIOCHEMISTRY !!
MALE 76Y:
RENAL REVIEW
Hb
10.2 g/dL
Iron
2.0 umol/L
UIBC
32 umol/L
Iron Sat 6 %
?? Iron deficient
MCV
98.5 fL
(13.5-17.5)
(10-28)
(28-64)
(15-40)
RELIABLE BIOCHEMISTRY !!
MALE 76Y:
RENAL REVIEW
Hb
10.2 g/dL
Iron
2.0 umol/L
UIBC
32 umol/L
Iron Sat 6 %
(13.5-17.5)
(10-28)
(28-64)
(15-40)
?? Iron deficient
MCV
98.5 fL
Ferritin 514 ug/L
(15-300) ??
RELIABLE BIOCHEMISTRY !!
MALE 76Y:
RENAL REVIEW
Hb
10.2 g/dL
Iron
2.0 umol/L
UIBC
32 umol/L
Iron Sat 6 %
(13.5-17.5)
(10-28)
(28-64)
(15-40)
?? Iron deficient
MCV
98.5 fL
Ferritin 514 ug/L
(15-300) ??
CRP
( < 6)
34.9 mg/L
Neutrophils 17.6 x 109
(1.8-7.7)
FACTORS AFFECTING IRON INDICES
IRON
TIBC
FERRITIN
Inflammatory states
Pregnancy / OCP
Anaemia chronic disease
N
N
N
Iron deficiency: which test ?
Observations on ferritin interpretation
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No clinical situation other than iron deficiency in which extremely low ferritin are seen
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Virtually all patients with concentrations less than 10 to 15ug/L are iron deficient
(Sensitivity 59%, specificity 99%)
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25% women with absent stainable bone marrow iron had ferritin > 15ug/L
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Anaemic patients without accompanying infectious or inflammatory disease
Cut off 30ug/L sensitivity 92% specificity 98%
41ug/L sensitivity 98% specificity 98%
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Inflammation elevates ferritin approx threefold (levels <60 may suggest concomitant
iron deficiency)
Serum Transferrin Receptor
Bone marrow erythyroid precursors
Quantitative measure of total erythropoietic activity (inversely prop tiss Fe)
IS THERE A CONSENSUS ?
FEMALE 16Y PARACETAMOL O/D
HB
(12-16)
MCV
(78-98)
07/09
9.4
69.5
19/10
10.2
70.1
IRON UIBC %SATN
(10-28) (28-64) (15-40)
4.6
79
6
FERRITIN
(15-200)
Pending
LABORATORY TESTS IN IRON DEFICIENCY OF INCREASING SEVERITY
NORMAL
FE DEFICIENCY
NO ANAEMIA
FE DEFICIENCY
MILD ANAEMIA
FE DEF SEVERE
ANAEMIA
Hb
N
N
9 - 12
6-7
Red cell morph.
N
N
N or slight
hypochromia
Hypochromia and
microcytosis
Iron
10 - 28
10 - 28
<10
<7
TIBC
54 - 64
54 - 70
63 - 72
> 74
%Satn
20 - 50
30
< 15
< 10
Ferritin
40 - 200
< 40
< 20
< 10
Other tissue
Nail + epithelia
changes
INCREASED IRON INDICES
61Y MALE - ? HAEMOCHROMATOSIS
IRON 71.4
UIBC 3
%SATN 96 (15-40)
FERRITIN 26O (<300)
ALT
61 (<42)
GGT
69 (<60)
OTHER CAUSES ??
INCREASED IRON INDICES
61Y MALE - ? HAEMOCHROMATOSIS
IRON 71.4
UIBC 3
%SATN 96 (15-40)
POTENTIAL CAUSES
IRON THERAPY ( POISONING)
RPT BLOOD TRANSFUSION
FERRITIN 26O (<300)
ALT
61 (<42)
GGT
69 (<60)
OTHER CAUSES ??
HAEMOLYTIC/OTHER ANAEMIAS
LIVER DISEASE ( EtOH)
REFRACTORY ANAEMIA
THALASSAEMIA
HAEMOCHROMATOSIS
WHAT TESTS FOR DIAGNOSIS : HAEMOCHROMATOSIS ?
ALT (<42)
GGT (<60)
FER (<200/<300)
M/61Y
F/62Y
61
69
260
202
468
1178
BRO/12Y
17
SIS/13Y
15
12
49
Refused H/G gene test
WHAT TESTS FOR DIAGNOSIS : HAEMOCHROMATOSIS ?
M/61Y
F/62Y
61
69
260
202
468
1178
IRON (10-28)
71.4
33
23.3
46.3
UIBC (28-64)
3
20
37
6
%SATN (15-40)
96
63
39
89
ALT (<42)
GGT (<60)
FER (<200/<300)
BRO/12Y
SIS/13Y
15
12
17
49
Refused H/G gene test
WHAT TESTS FOR DIAGNOSIS : HAEMOCHROMATOSIS ?
M/61Y
F/62Y
61
69
260
202
468
1178
IRON (10-28)
71.4
33
23.3
46.3
UIBC (28-64)
3
20
37
6
%SATN (15-40)
96
63
39
89
C282Y
N
N
C282Y/N
H63D
N
ALT (<42)
GGT (<60)
FER (<200/<300)
H63D/H63D
BRO/12Y
SIS/13Y
15
12
17
49
Refused H/G gene test
HD3D/N
C282Y/C282Y
N
WHAT TESTS FOR DIAGNOSIS : HAEMOCHROMATOSIS ?
M/61Y
F/62Y
61
69
260
202
468
1178
IRON (10-28)
71.4
33
23.3
46.3
UIBC (28-64)
3
20
37
6
%SATN (15-40)
96
63
39
89
C282Y
N
N
C282Y/N
H63D
N
ALT (<42)
GGT (<60)
FER (<200/<300)
FE OVERLOAD
NO
H63D/H63D
SLIGHT
BRO/12Y
SIS/13Y
15
12
17
49
Refused H/G gene test
HD3D/N
MODERATE
C282Y/C282Y
N
SIGNIFICANT
Prevalence of Inherited Liver Diseases
Homozygote
Frequency
Gene
Frequency
Heterozygote
Frequency
Haemochromatosis 1:400
1:20
1:10
α1AT Deficiency
1:1600
1:40
1:20
Cystic Fibrosis
1:2500
1:50
1:25
Wilson's Disease
1:30,000
1:170
1:85
Disease
Leggett et al Brit J. Haem. 1990
Genetics of Haemochromatosis
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Autosomal recessive
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Mutations in HFE gene (C282Y and H63D)
(p.Cys282Tyr pHis63Asp)
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Cause increased intestinal absorption of Fe
C282Y/C282Y and C282Y/H63D are responsible for 90-95%
of genetic haemochromatosis
Clinical Manifestations of
Haemochromatosis
Clinical Manifestations of
Haemochromatosis
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Skin pigmentation
Liver disease
Diabetes mellitus
Arthropathy
Impotence
Fatigue
Cardiomegaly
Screening Strategy for Haemochromatosis
(HFE Associated)
1. Perform transferrin saturation (or UIBC)
2. If  45% - repeat fasting
3. If still  45% - perform HFE testing
4. If C282Y +/+ or C282Y/H63D +/+:
- perform serum ferritin and LFT
- if SF > 1000 and/or LFT abnormal
- Liver biopsy essential
5. If C282Y +/- :
- Counsel re:
 Alcohol
 NASH
 HCV
 PCT
PORPHYRIA CUTANEA TARDA
10/09 MALE 52Y: EtOH
ALT 208 iu/L (<42)
GGT 103iu/L (<60) / MCV 93.8
FERRITIN 1290ug/L (<300)
IRON 58.9umol/L (10-28)
UIBC 5 umol/L (28-64)
SATN 92% (15-40)
PLASMA PORPHYRIN +VE
URINE PORPHYRIN
UROPORPYRIN/HEPTACARBOXYLIC
PORPHYRIA CUTANEA TARDA
10/09 MALE 52Y: EtOH
ALT 208 iu/L (<42)
GGT 103iu/L (<60) / MCV 93.8
FERRITIN 1290ug/L (<300)
IRON 58.9umol/L (10-28)
UIBC 5 umol/L (28-64)
SATN 92% (15-40)
PLASMA PORPHYRIN +VE
URINE PORPHYRIN
UROPORPYRIN/HEPTACARBOXYLIC
GENOTYPE C282Y/C282Y
PORPHYRIN / HAEM PATHWAY
A CASE OF MILD HYPERCALCAEMIA
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FEMALE 80 Y WITH COINCIDENTAL FINDING OF
MILD HYPERCALCAEMIA
CA 2.85
mmol/L (2.15-2.60)
PTH 8.2 / 5.9 pmol/L (1.5-7.6)
? definitely 1o Hyperparathyroidism
A CASE OF MILD HYPERCALCAEMIA
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FEMALE 80 Y WITH COINCIDENTAL FINDING OF
MILD HYPERCALCAEMIA
CA 2.85
mmol/L (2.15-2.60)
PTH 8.2 / 5.9 pmol/L (1.5-7.6)
? definitely 1o Hyperparathyroidism
MG 0.96 mmol/L (0.7-1.0)
Urine calcium 0.6 mmol/24h (2.5-7.5)
A CASE OF MILD HYPERCALCAEMIA
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FEMALE 80 Y WITH COINCIDENTAL FINDING OF
MILD HYPERCALCAEMIA
CA 2.85
mmol/L (2.15-2.60)
PTH 8.2 / 5.9 pmol/L (1.5-7.6)
? definitely 1o Hyperparathyroidism
MG 0.96 mmol/L (0.7-1.0)
Urine calcium 0.6 mmol/24h (2.5-7.5)
Fractional calcium excretion 0.002
(1o HPT >0.02)
(FHH <0.01)
FHH: Inactivating mutation of CaSR
PROTEINURIA
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CKD 3/4/5
DIABETES
HYPERTENSION
CARDIOVASCULAR DISEASE
STRUCTURAL RENAL TRACT DISEASE, MULTIPLE RENAL
CALCULI, PROSTATIC HYPERTROPHY
MULTISYSTEM DISEASE WITH POTENTIAL RENAL
INVOLVEMENT – SLE
FH CKD5 OR HEREDITARY KIDNEY DISEASE
OPPORTUNISTIC DETECTION OF PROTEINURIA
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6 MONTH W/LOAD (APR-SEPT)
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4495 (2008)
7005 (2009)
PROTEINURIA: INTERPRETATION
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Microalbuminuria (ACR > 2.5mg/mmol in men, > 3.5mg/mmol in women)
Protein/creatinine (PCR) (< 15mg/mmol creatinine)
Refer for specialist assessment: (confirmed on early morning sample)
ACR > 29 + haematuria or ACR > 69
PCR 50-99 + haematuria or PCR >99
Protein excr 0.5 – 0.99 g/24h + haematuria or Protein excr >0.99 g/24h
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FALSE POSITIVES: Orthostatic proteinuria, UTI, menstrual bleed
Referral to Specialist
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Stage 4 and 5 CKD
Significant proteinuria (ACR > 70, PCR > 100)
Haematuria and proteinuria (urological problems
excluded)
Declining eGFR (> 5 ml/min/yr or > 10
ml/min/5yr
Poorly controlled HT (4 agents), or suspected
renal artery stenosis
Rare or genetic causes of CKD
Take into account co-morbidity and patient wishes
D
TEST COSTS
REAG
FBC
0.18
(190,000 PA)
U&E
0.20
(195,000)
LFT
0.28
(136,000)
TTG
5.12
(2600)
CA-125
7.63
(1900)
PSA
1.83
(13,000)
PTH
8.64
VITD
28.68
TOTAL
3.41
2.69
2.69
9.58
13.09
7.29
14.10
33.14
IRON/IBC
(7800)
FERRITIN
(6800)
FT4
(52,000)
TSH
REAG
TOTAL
0.28 (3.95 !!) 6.43
1.72
7.18
0.68
6.14
0.68
PRCR
0.34
(940 / 1500)
MALB
1.50
(9,000 / 14,000)
OEST
2.00
2.52
4.60
7.94
TEST REPETOIRE
PATHOLOGY HARMONISATION / COST PRESSURES
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LFT
ALBUMIN-BILIRUBIN-ALT-ALK PHOS
(TOTAL PROTEIN / GAMMA GT)
CAERULOPLASMIN / CU
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TSH ONLY
STABLE REPLACEMENT / ? DYSLIPIDAEMIA
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MENOPAUSE
FSH ONY
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MICROALBUMIN
NOT IF 2+ ON DIP STICK, do PRCR
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UNLABELLED SAMPLES
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TUMOUR MARKERS
(NATIONAL RECOMMENDATIONS)
? FORUM / PCT COMMISSIONING
TUMOUR MARKERS: GI + GYNAE
BMJ OCT 2009 PRESENTATION
CA125
54Y F Swelling abdomen
(ascites)
General malaise
Wt loss 5 kg in 3months
CA125
CEA
CA19-9
1450 (0-35 kU/L)
9 (0-5 ug/L)
69 (0-37 kU/L)
U&E – NORMAL
Albumin
Bilirubin
Alk Phos
ALT
32 (36-48)
27 (7-23)
138 (30-125)
61 (5-45)
TUMOUR MARKERS: none specificity
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CA125 (Ref <23): Guide to interpretation:
Non malignant conditions & malignancy that is not ovarian
Note a raised CA125 result does not necessarily mean the
patient has ovarian cancer.
Endometriosis: rarely exceed 35kU/L except in severe stage
III/IV disease.
Left ventricular failure and pulmonary oedema: upto 100 150kU/L
Congestive cardiac failure: 200 - 300kU/L in almost all cases.
Peritoneal or pleural inflammation/metastases, pleural
effusion, ascites: 500kU/L or higher.
Benign ovarian cysts & fibroma, especially with torsion:
2000kU/L or higher.
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Epithelial ovarian carcinoma
Serum levels above 100kU/L are seen in 75-80% of patients
with this malignancy.
CA125
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NON SPECIFICITY
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PPV 2.3% (50 women undergo laproscopy/laporotomy for 1 Ovarian Ca)
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UK COLLABORATIVE TRIAL OF OVARIAN CA SCREENING
Repeated Ca125 followed by transvaginal U/S
4555 women recalled
42 ovarian or tubal malignancies
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First line:
Follow up:
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Indications: Known disease + abdo mass.
Clinical examination, routine tests (renal/liver)
(LFT here) – U/S, hepatitis, iron
TUMOUR MARKERS: none specificity
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CA19-9 (Ref 0 – 33): Guide to interpretation:
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Non malignant pancreatic and hepatic disease
Chronic pancreatitis: levels rarely exceed 60kU/L
Hepatobiliary: 20% cases cholecystitis, post necrotic cirrhosis, primary
biliary cirrhosis.
30% cases of chronic and alcoholic pancreatitis.
60% of acute hepatic necrosis.
*Note values above 9,000kU/L can be seen in obstructive jaundice due to
cholelithiasis, returning to normal within 5 weeks of relief of obstruction.
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GI malignancy
Colorectal, stomach, gall bladder, biliary tract and hepatoma
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Pancreatic Carcinoma
Usual presentation at Stage III or IV, concentrations often exceed
2,000kU/L
(See above, levels this high may also be seen in obstructive jaundice).
Levels this high rarely seen in any other malignancy.
TUMOUR MARKERS: none specificity
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CEA (Ref < 5) :
Guide to interpretation
Level 2.5 - 10ug/L are of marginal significance.
Level 11 - 20ug/L suggest malignancy is probable
Level > 20ug/L suggests malignancy of grade III or greater likely
Level > 50ug/L are commonly associated with hepatic metastases and large
bulk disease
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Non malignancy
Modest elevations in smokers, inflammatory bowel (Crohn's, ulcerative
colitis), pancreatitis, gastric ulceration, alcoholic cirrhosis and pulmonary
infections.
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Malignancy
Colorectal, gastric, breast, bronchial and ovarian carcinomas
CEA is a more reliable marker than CA19-9 in hindgut neoplasms.
ICE REQUESTING
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GP PAGES
MITOCHONDRIAL AB
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AUTOIMMUNNITY PAGE – INCOMPLETE !!
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DROP DOWN LISTS – NOT FIND TESTS CA19-9
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CONFUSIONS – ANCA / COELIAC
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REQUESTING PROFILES / PRESENTATIONS
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OTHER
NA
PCO
Rotterdam consensus criteria for the
diagnosis of PCOS
1.
2.
3.
Oligo- and/or anovulation
Clinical/biochemical hyperandrogenism
Ultrasound evidence of polycystic ovaries
PCOS = 2 out of the above 3 criteria
Rotterdam group – sliding scale for
patient pick-up
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Raised FAI% -
93(4)
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Raised FAI + testosterone -
+13=106(7)
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Raised FAI + testo + LH
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Raised FAI + testo + LH + LH/FSH
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Raised FAI + testo + LH + LH/FSH + AD
+1=107(8)
0=107(8)
+13=120(1)
LFT
COMMON CAUSES OF
ABNORMAL LFTS IN THE UK
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Transient mild abnormalities which are
simply impossible to explain
Drugs – eg Statins
Alcohol excess
Hepatitis C
Non-Alcoholic Fatty Liver Disease
(NAFLD)
Gilbert’s Syndrome
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Impaired bilirubin conjugation
Up to 10% of Caucasians, 36% of Africans
Isolated hyperbilirubinaemia
Other LFTs normal
Bilrubin < 100
Unconjugated hyperbilirubinaemia
Exclude haemolysis
Investigation of Abnormal LFTs ALT/AST 2-5x normal (100-200)
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History and Examination
Discontinue hepatotoxic drugs
Continue statins but monitor LFTs monthly
Lifestyle modification (lose wt, reduce alcohol,
diabetic control)
Repeat LFTs at 1 month and 6 months
If still 100-200 at 6 months, Check hepatitis
serology, iron studies, glucose, Autoantibodies and
refer to 2o care
Investigation of Abnormal LFTs
- Raised ALT / AST
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If still abnormal at 6 months:
Consider referral to secondary care
USS
hepatitis serology / iron studies
Autoantibodies & immunoglobulins
Consider caeruloplasmin
Alpha-1- antitrypsin
TFTs, lipids/glucose
Consider liver biopsy esp if ALT > 100)
Investigation of Abnormal LFTs
Indications for early investigation
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Signs of chronic liver disease
ALT/AST - early investigation if >5x
normal (>200)
Jaundice - Bilirubin >25
Alkaline phosphatase > 1.5x normal
(confirm it is hepatic with GGT)
Early USS for jaundice or increased ALP