Standardizing Lab Tests: Urea, Electrolytes, Liver, Calcium/Bone, and Thyroid Functions | Lecture notes Biochemistry

BMJ | 26 MAY 2012 | VOLUME 344 25

ANALYSIS

Time to harmonise common

laboratory test profiles

The composition of routine laboratory test profiles varies between laboratories, causing

confusion and unnecessary expense.

W S A Smellie

describes the Association for Clinical

Biochemistry’s draft proposals for unifying profiles and invites medical opinion

Laboratories can help to limit costs and improve

the quality of healthcare in many ways. Some,

such as avoiding unnecessary testing and the

further investigations and referrals that ensue,

are difficult to achieve and measure. Others are

more straightforward. One such candidate is the

composition of routine laboratory profiles com-

monly known as urea and electrolytes (U&E),

liver function tests (LFT), calcium/bone profiles

(bone), and thyroid function tests (TFT). The tests

included in these profiles vary between laborato-

ries, often for historical reasons.

This variation

has fallen over the past 15 years, at least among

UK subscribers to the comparative national

pathology benchmarking initiative,2 but large

differences remain. For example, there are 11

different profiles for liver function tests listed by

the 49 laboratories subscribing to the initiative.

The ideal profile may not exist, but such dif-

ferences can cause confusion and potentially

affect patient safety. Removing tests that offer

little incremental information would save money,

avoid further investigation of clinically unimpor-

tant minor abnormalities, and remove confusion

for doctors moving between hospitals using dif-

ferent laboratories.3 It could also be an initial

step towards problem based rather than panel

based testing, which might be the ideal solution.

We present proposals for rationalisation drawn

Proposed harmonised test content and some key remaining questions for common blood (usually serum) profiles

Profile Potential content Proposed

Kidney and

electrolytes

Sodium

Potassium

Chloride

Anion gap (now rarely reported)

Urea

Creatinine

eGFR

Sodium

Potassium

Urea (could be omitted in specific situations)

Creatinine

eGFR for primary care

Questionable: eGFR in inpatients and specific

outpatient groups

Liver Bilirubin

Alanine transaminase

Aspartate transaminase

Alkaline phosphatase

γ-glutamyl transferase

Lactate dehydrogenase

Albumin

Total protein

Calculated globulins

Bilirubin

Alanine transaminase

Alkaline phosphatase

Albumin

Questionable: total protein and calculated globulins

Calcium/

bone

profile

Calcium

Albumin

Adjusted calcium

Phosphate

Alkaline phosphatase

Two profiles:

Calcium

Albumin

Adjusted calcium

Bone

Calcium

Albumin

Adjusted calcium

Phosphate

Alkaline phosphatase

Thyroid

function

tests

Thyroid stimulating hormone

(TSH)

Free thyroxine (T4)

Free tri-iodothyronine (T3)

Total T4 or T3 are occasionally

offered as alternatives

TSH and free T4 (+/- fT3 depending on

clinical situation)

TSH alone can be used if laboratory has sufficient

information to determine that fT4 is not needed

eGFR=estimated glomerular filtration rate.

CC STUDIO/SPL

WILL & DEN MCINTYRE/SPL

TEK IMAGE/SPL

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Time to harmonise common

laboratory test profiles

The composition of routine laboratory test profiles varies between laboratories, causing

confusion and unnecessary expense. W S A Smellie describes the Association for Clinical

Biochemistry’s draft proposals for unifying profiles and invites medical opinion

Laboratories can help to limit costs and improve the quality of healthcare in many ways. Some, such as avoiding unnecessary testing and the further investigations and referrals that ensue, are difficult to achieve and measure. Others are more straightforward. One such candidate is the composition of routine laboratory profiles com- monly known as urea and electrolytes (U&E), liver function tests (LFT), calcium/bone profiles (bone), and thyroid function tests (TFT). The tests included in these profiles vary between laborato- ries, often for historical reasons.^1 This variation has fallen over the past 15 years, at least among UK subscribers to the comparative national pathology benchmarking initiative,^2 but large differences remain. For example, there are 11 different profiles for liver function tests listed by the 49 laboratories subscribing to the initiative. The ideal profile may not exist, but such dif- ferences can cause confusion and potentially affect patient safety. Removing tests that offer little incremental information would save money, avoid further investigation of clinically unimpor- tant minor abnormalities, and remove confusion for doctors moving between hospitals using dif- ferent laboratories.^3 It could also be an initial step towards problem based rather than panel based testing, which might be the ideal solution. We present proposals for rationalisation drawn Proposed harmonised test content and some key remaining questions for common blood (usually serum) profiles Profile Potential content Proposed Kidney and electrolytes Sodium Potassium Chloride Anion gap (now rarely reported) Urea Creatinine eGFR Sodium Potassium Urea (could be omitted in specific situations) Creatinine eGFR for primary care Questionable: eGFR in inpatients and specific outpatient groups Liver Bilirubin Alanine transaminase Aspartate transaminase Alkaline phosphatase γ-glutamyl transferase Lactate dehydrogenase Albumin Total protein Calculated globulins Bilirubin Alanine transaminase Alkaline phosphatase Albumin Questionable: total protein and calculated globulins Calcium/ bone profile Calcium Albumin Adjusted calcium Phosphate Alkaline phosphatase Two profiles: Calcium Calcium Albumin Adjusted calcium Bone Calcium Albumin Adjusted calcium Phosphate Alkaline phosphatase Thyroid function tests Thyroid stimulating hormone (TSH) Free thyroxine (T4) Free tri-iodothyronine (T3) Total T4 or T3 are occasionally offered as alternatives TSH and free T4 (+/- fT3 depending on clinical situation) TSH alone can be used if laboratory has sufficient information to determine that fT4 is not needed eGFR=estimated glomerular filtration rate. CC STUDIO/SPL WILL & DEN MCINTYRE/SPL TEK IMAGE/SPL

up by a panel of members of the Association for Clinical Biochemistry. After consultation with members of the association’s clinical practice section, the proposals were debated at its 2011 national scientific meeting, attended by about 100 people. What is a test profile? Current test profiles contain groups of measure- ments that reflect the function or state of an organ system. Not all the included tests, however, are specific to that system—alkaline phosphatase is commonly included in both liver and bone tests; nor are tests always organ oriented—a request for liver function tests on a patient with a non- specific illness may not only be to find liver dis- ease. Some tests may be more useful in specific situations: routine blood bicarbonate measure- ments may be unnecessary in a fit hypertensive patient but are relevant in acutely ill patients. Defining a one size fits all profile is therefore dif- ficult. We suggest that the routine profile should be the minimum set of tests required in everyday practice. These can be supplemented in specific situations. How can we define standard profile content? The evidence for the content of many laboratory profiles is necessarily limited, and their content probably has to be established by professional consensus. That should not prevent us trying to provide a rational and consistent process to determine what they should be. Although reduc- ing the number of tests will produce only mod- est cash savings^3 (most tests cost around £0. each), the millions of tests performed each year make rationalisation important. Box 1 lists the criteria we used to determine whether a test should be included in a routine organ specific profile. Profile proposals Urea and electrolytes This profile contains a variable selection of the tests shown in the table. Sodium, potassium, and creatinine are core measurements of kidney function and seem to meet all our cri- teria. Bicarbonate could be removed from the core profile for non-acute illness because most decisions to adjust treatments such as diuretic therapy are based on other factors. Bicarbonate is, however, relevant in acute illness and advanced renal insufficiency. Chloride measurement rarely adds more information than sodium, and very few clinical decisions are based on a chloride measurement. It costs nothing to measure, however, in many laboratories. Although urea concentration often adds little to the information gained from measuring creati- nine, it can provide information about the under- lying reason for decreased renal function. It rises earlier and more than creatinine in common pre- renal conditions such as hypovolaemia, notably that arising from diuretics and vasoactive drugs. In many routine situations, however (such as patients with a glomerular filtration rate >60 ml/ min), urea is unlikely to add important informa- tion. It may, therefore, be possible to determine rules for when urea needs to be measured. Although the estimated glomerular filtration rate costs nothing to calculate, it raises quality and potential safety concerns. The Renal Asso- ciation and UK General Medical Services contract quality and outcomes framework recommend routine reporting of the estimated glomerular filtration rate using the modification of diet in renal disease (MDRD) equation.^4 5 However, the calculation is invalid in several situations (for example, extreme body morphology, acute changes in renal function, pregnancy, and in amputees^6 ). Further thought is needed about whether this value should be calculated routinely or omitted in particular patient groups. Liver function tests Few of the liver function tests actually reflect liver function, although several reflect liver cell injury or enzyme induction. Alanine transaminase (ALT) is the most specific test of hepatocellular injury, although aspartate transaminase (AST) is also often included. Aspartate transaminase is not hepatospecific and adds little information except in specific situations (such as a marker of alcohol misuse). As a marker of alcohol misuse, it is mostly an opportunistic screening test and should be assessed as such on its own merits. Bilirubin is a test of hepatic excretory function. It is not entirely hepatospecific and additional tests (for example, bilirubin conjugation) may be needed to discriminate between hepatic and extrahepatic causes (notably haemolysis). Alkaline phosphatase, although not specific to liver, is the preferred enzyme marker of hepatic obstruction.^7 Gamma glutamyl transferase (γGT) can be added if the reason for raised alkaline phosphatase activity is not apparent.^8 Although γ-glutamyl transferase is more spe- cific to the liver, it is not clear whether isolated rises are diagnostically or prognostically relevant and whether any interventions have any clinical benefit. Like aspartate transaminase, it may be of value in specific situations such as monitoring abstinence from alcohol. Lactate dehydrogenase (LDH) is not hepat- ospecific and provides little additional informa- tion to the other core tests. Its inclusion seems difficult to justify, and it is now rarely offered routinely. Serum albumin concentration is a test of liver synthetic function, although it can be influenced by malnutrition, increased protein losses, and haemodilution. It helps determine potential underlying causes of oedema and is relevant both diagnostically and prognostically in liver disease. Measurement of total protein has historically been included, mostly to allow total globulins to be calculated (total protein minus albumin concentrations). Globulins rise non-specifically in liver disease and systemic inflammation, and high globulins can also be an indicator of mono- clonal gammopathy of unknown significance or myeloma. Its inclusion is more as an opportun- istic screening test for monoclonal gammopathy, but no specific intervention exists other than watchful waiting. Further research is merited into whether this is a suitable screening test warrant- ing inclusion in a routine profile. Calcium/bone Tests used to investigate calcium and bone metabolism vary depending on whether the presenting question is a disorder of calcium Box 1 | Questions to consider for core tests in a laboratory profile

Is the test specific to the organ or system being investigated?
If not specific, is there another reason for including it?
Does an abnormal result add additional diagnostic or prognostic information to the other tests included?
Does the added information provided by the test justify its cost?
Is there a clinical intervention available that can influence outcome based on the test result? Box 2 | When is thyroid stimulating hormone not sufficient to investigate thyroid function? - New patients with symptoms or features suggestive of thyroid dysfunction (common use of the test) - Confirming a diagnosis of primary hypothyroidism when TSH is raised - Monitoring treatment of hypothyroidism and hyperthyroidism in the early months, or until patients are stabilised on T - Identifying erratic compliance in patients taking T - Diagnosing and monitoring thyroid dysfunction in pregnancy - Diagnosis and monitoring treatment for central hypothyroidism - Confirming a diagnosis of primary hyperthyroidism when TSH <0.1 U/L (T4 and tri-iodothyronine (T3) recommended) to identify severity or to exclude non-thyroidal illness - Identifying patients with end organ thyroid hormone resistance or TSH secreting of pituitary origin - Investigating children (<18 years)

Standardizing Lab Tests: Urea, Electrolytes, Liver, Calcium/Bone, and Thyroid Functions, Lecture notes of Biochemistry

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Download Standardizing Lab Tests: Urea, Electrolytes, Liver, Calcium/Bone, and Thyroid Functions and more Lecture notes Biochemistry in PDF only on Docsity!

Time to harmonise common

laboratory test profiles

The composition of routine laboratory test profiles varies between laboratories, causing

confusion and unnecessary expense. W S A Smellie describes the Association for Clinical

Biochemistry’s draft proposals for unifying profiles and invites medical opinion