Advanced Biomarker Patterns: Reading Panels as Systems

Level 4, Advanced

In brief

Individual test results gain meaning when read together as patterns. Recurring patterns include the insulin resistance pattern, the alcohol pattern, the hypothyroid pattern, the malabsorption pattern, the inflammation pattern, the iron overload pattern and the kidney pattern. Patterns suggest hypotheses rather than diagnoses, must be confirmed through history and targeted testing, and can mislead when a single abnormal value is over interpreted.

A standard panel of blood tests, a blood count, kidney and liver function, lipids, glucose, thyroid function and a few others, contains more information than any single result suggests. Physiology does not respect the boundaries between test groups. Insulin resistance affects liver enzymes, lipids, uric acid and ferritin. Alcohol affects the blood count, liver enzymes and lipids. Malabsorption affects iron, vitamins, albumin and cholesterol. Reading panels as systems means looking across results for recognisable patterns. Earlier articles examined individual panels; this article brings them together.

Principles of pattern reading

  1. Look across groups. Scan the whole panel before focusing on individual results.
  2. Notice values within range but at the edges, especially when several point in the same direction.
  3. Compare with previous results. Trends matter more than single values.
  4. Match the pattern to the history. A pattern suggests a hypothesis; the history supports or refutes it.
  5. Confirm with targeted tests rather than broad panels.
  6. Beware of over interpretation. One mildly abnormal value is often noise.

Common patterns

PatternTypical findingsConfirm with
Insulin resistanceRaised triglycerides, low HDL, fasting glucose or HbA1c at upper range, ALT higher than AST, raised GGT, raised uric acid, mildly raised ferritin, sometimes mildly raised white cell countWaist, blood pressure, fasting insulin, liver imaging and FIB 4
AlcoholRaised MCV, raised GGT, AST higher than ALT, raised triglycerides, raised uric acid, sometimes low platelets and raised HDLCareful alcohol history; liver assessment
HypothyroidRaised LDL, raised creatine kinase, sometimes low sodium, mild macrocytosis or anaemiaTSH and free T4
MalabsorptionLow ferritin, low folate or B12, low vitamin D, low albumin, low cholesterol, sometimes raised ALT and low calcium or magnesiumCoeliac serology, faecal elastase, further gut assessment
InflammationRaised CRP and ESR, raised platelets, raised ferritin, low albumin, low haemoglobin with low iron and transferrin saturationHistory and examination for the source
Iron overloadRaised transferrin saturation, raised ferritin, sometimes raised ALTRepeat fasting transferrin saturation, HFE genotyping
Kidney impairmentReduced eGFR, raised creatinine, raised potassium, low bicarbonate, raised phosphate, anaemiaUrine albumin to creatinine ratio, repeat eGFR, kidney imaging where indicated
Cortisol excess cluesRaised glucose, low potassium, raised neutrophils, low lymphocytes and eosinophilsScreening tests for Cushing syndrome if clinical features suggest it; consider steroid use
DehydrationRaised urea relative to creatinine, raised haemoglobin and albuminClinical assessment; repeat when hydrated
HaemolysisRaised bilirubin, raised LDH, raised reticulocytes, low haptoglobin, anaemiaMedical assessment

Markers often overlooked

Urine albumin to creatinine ratio

Raised urine albumin is an early marker of kidney damage and a strong predictor of cardiovascular risk, particularly in diabetes and hypertension. It is often omitted from routine panels but recommended in these conditions.

Uric acid

Raised uric acid is associated with insulin resistance, fructose and alcohol intake, kidney function and gout, and is part of the metabolic pattern.

GGT

A sensitive but non specific marker that rises with alcohol, fatty liver and enzyme inducing medicines, and is associated with cardiometabolic risk.

Creatine kinase

Raised by exercise, muscle injury, hypothyroidism and statin related muscle effects; helpful in interpreting a raised AST.

Albumin

Reflects nutrition, inflammation, liver function and protein loss; low albumin affects the interpretation of calcium, zinc and other bound substances.

When patterns mislead

  • Overlapping patterns: a patient may have insulin resistance and drink alcohol, with results reflecting both.
  • Medicines: many alter results, such as statins lowering LDL, diuretics altering electrolytes and uric acid, and metformin affecting B12.
  • Acute illness: temporarily alters many markers.
  • Laboratory variation: reference ranges and methods differ.
  • Population differences: for example, lower neutrophil counts in some ancestries.
  • Chance: in a large panel, some results will fall outside the range randomly.

A worked panel

A 49 year old man attends with fatigue. His results include:

TestResultComment
MCV101 fL, slightly raisedMacrocytosis
PlateletsLow normal
GGT3 times upper limit
AST and ALTAST 64, ALT 30AST to ALT ratio above 2
Triglycerides2.8 mmol/L
HDL1.8 mmol/LHigher than expected
Uric acidRaised
HbA1c38 mmol/molNormal
B12 and folateNormal
TSHNormal

No single result is alarming, but together they form a classic alcohol pattern. The practitioner asks about alcohol carefully and without judgement; he drinks around 40 units a week. His doctor arranges liver fibrosis assessment. With support, he reduces his drinking substantially. 3 months later his MCV, GGT, AST, triglycerides and uric acid have all improved, and his fatigue is better.

Systems, not numbers

Pattern reading turns a list of results into a picture of physiology. It helps practitioners notice what individual values hide, ask the right questions and order the right confirmatory tests, while remaining cautious about drawing conclusions from any single result.

Questions about biomarker patterns

Why read results as patterns?
Physiology affects several tests at once, so patterns across a panel reveal more than individual values.
What does an alcohol pattern look like?
Raised MCV, raised GGT, AST higher than ALT, raised triglycerides and uric acid, sometimes low platelets.
Can patterns diagnose conditions?
No. They suggest hypotheses to be confirmed with history and targeted tests.

References

  1. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1).
  2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International. 2024;105(4S).
  3. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement. Circulation. 2009;120(16).
  4. Kaferle J, Strzoda CE. Evaluation of macrocytosis. American Family Physician. 2009;79(3).

Continue your learning

Reading laboratory panels as whole systems

Reading panels as connected systems, rather than lists of numbers, is practised throughout IIFM’s 6 month Functional Medicine and Clinical Nutrition program in case based sessions.

This article is for the education of healthcare professionals. It is not a substitute for individual medical advice, diagnosis or treatment, and does not change any practitioner’s scope of practice. Regulation and guidelines differ between countries.