No; LDH, ferritin and ESR are "non-specific" tests: they rise in many conditions, and none of them shows cancer on its own [1, 4, 5]. Most of the time a high result is due to infection, inflammation, liver disease or tissue damage; for example, only about 1 in 10 people with a high ferritin have too much iron in the body [4]. But if one of these tests stays high for no clear reason, especially together with weight loss, fever, night sweats, swollen lymph nodes or persistent bone pain, your doctor will look further [1, 11].
Key points
- LDH, ferritin and ESR are not cancer screening tests: a high result does not prove cancer and a normal result does not rule it out [1, 5].
- In a large study, fewer than 4 in 100 people with a raised inflammation test (such as ESR) were diagnosed with cancer within a year [1].
- A high ferritin is usually due to inflammation, fatty liver and obesity, alcohol or liver disease; only about 1 in 10 people have too much iron [4].
- In people already diagnosed with cancer, such as lymphoma, leukaemia, testicular cancer and melanoma, LDH is used to help stage the disease and follow treatment [6].
- A high calcium level is usually due either to an overactive parathyroid gland or to cancer, and its cause should always be found [9].
What does high LDH mean in a blood test?
LDH (lactate dehydrogenase) is an enzyme found in the cells of many body tissues, where it helps to produce energy. When cells are damaged, more LDH leaks into the blood, so LDH rises in many conditions [5]:
- Breakdown of red blood cells (haemolytic anaemia)
- Muscle diseases
- Liver disease, such as acute liver injury
- Heart attack
- Some cancers, especially lymphoma and blood cancers
LDH is not a specific sign of cancer [5]. If your LDH is high, your doctor will read it alongside your symptoms, an examination and other tests such as a blood count (CBC) and liver tests.
What is LDH used for in lymphoma and other cancers?
In someone already diagnosed with cancer, LDH has an important role: in germ cell tumours (such as testicular cancer), lymphoma, leukaemia, melanoma and neuroblastoma it is used to help stage the disease, predict its course and see how it responds to treatment [6].
In aggressive lymphomas, a high LDH is one of the five factors in the "International Prognostic Index" (IPI); the other four are age, the stage of the disease, the patient's physical fitness and the number of organs involved outside the lymph nodes. With this index, the doctor estimates the chance of responding to treatment and chooses the right treatment [7]. In multiple myeloma, a high LDH is also part of staging [8]. Read more: Is lymphoma curable? and What are the symptoms of lymphoma?
High ferritin and cancer
| Cause | Explanation |
|---|---|
| Inflammation and infection | Any kind of inflammation, from infection to COVID-19, raises ferritin [4] |
| Fatty liver, obesity and diabetes (metabolic syndrome) | Common causes of a high ferritin in adults [4] |
| Heavy drinking and chronic liver disease | Damaged liver cells release ferritin; viral hepatitis and cirrhosis also belong in this group [4] |
| Cancer | Blood cancers and solid tumours can also raise ferritin; a ferritin above 1,000 is often seen in cancer that has spread [4] |
| Too much iron in the body | An inherited condition that absorbs too much iron (haemochromatosis), anaemias that load the body with iron, repeated blood transfusions (for example in thalassaemia major) and iron given by infusion [4] |
| Rare conditions | Such as a syndrome of severe immune overactivation (HLH) and Still's disease; usually with a very high ferritin, above 10,000 [4] |
To tell whether there is too much iron, the doctor usually also measures the "transferrin saturation" [4].
A high ferritin on its own is not a reason to worry about cancer; the doctor first checks the common causes [4]. But if it comes with unexplained swollen lymph nodes, fever, night sweats or weight loss, tell your doctor; these symptoms need checking for lymphoma [11]. If your ferritin is low, read: Can anaemia be a sign of cancer?
High ESR and cancer
The ESR (erythrocyte sedimentation rate, or "sed rate") shows how far red blood cells settle in a test tube in one hour. The ESR rises with inflammation, infection, cancer, rheumatic diseases and diseases of the blood and bone marrow [3].
In a large English study, fewer than 4 in 100 people with a raised inflammation test (ESR or similar tests) were diagnosed with cancer within a year; this was more than twice as many as among people whose test was normal [1]. The risk was higher with higher results, at older ages and in men; it rose further when a repeat test was also raised, and fell if the second test came back normal [1]. On the other hand, the ESR was raised in fewer than half of the people who had cancer; so a normal ESR does not rule out cancer [1].
A very high ESR (100 or more) almost always has an identifiable cause: in a study of more than 1,000 outpatients, 9 in 10 people with this result had an identifiable disease. The most common cause was infection, followed by cancer, kidney disease and inflammatory diseases [2]. Always follow up an ESR this high with your doctor.
What is the ESR level in leukaemia?
The ESR also rises in diseases of the blood and bone marrow [3], but because it is raised in many other conditions too and stays normal in many cancers, it cannot diagnose leukaemia [1, 3]. In people aged 60 or over with persistent bone pain or an unexplained fracture, the ESR is ordered together with a CBC, calcium and blood protein tests to check for multiple myeloma [11]. Read more: ESR levels in leukaemia and Symptoms of multiple myeloma
High alkaline phosphatase and high calcium: when are they a concern?
ALP (alkaline phosphatase) is one of the liver tests, but it does not come only from the liver; outside the liver, most ALP comes from bone. ALP is naturally higher in children because their bones are growing, in pregnancy, and in older people, especially women over 50 [12]. This is why the doctor first works out whether a high ALP comes from the liver [12]. When ALP has risen much more than the other liver enzymes (ALT and AST), it usually means that the flow of bile is disturbed, and the liver and bile ducts need to be checked [12]. ALP from bone rises in conditions such as bone softening (osteomalacia) and Paget's disease of bone, and sometimes in cancer that started in the bone or has spread to it [12].
A high calcium level is found in about 1 in 100 people. About 9 in 10 people with high calcium have either an overactive parathyroid gland or cancer; other causes include thiazide water tablets, large amounts of calcium or vitamin D supplements, and conditions such as sarcoidosis [9]. Slightly raised calcium usually causes no symptoms, but sometimes causes tiredness and constipation. Very high calcium, or calcium that has risen over days to weeks, causes nausea, vomiting, dehydration, confusion and drowsiness [9].
In an English study of people aged 40 or over, about 1 in 9 men and about 1 in 25 women with high calcium were diagnosed with cancer within a year [10]. The first test to find the cause of high calcium is parathyroid hormone (PTH) [9].
When should these results be investigated further?
Doctors never read these numbers on their own. These situations are worth investigating further:
- A result that is high for no clear reason and stays high on a repeat test [1]
- Symptoms such as unexplained weight loss, fever, night sweats, swollen lymph nodes or persistent bone pain, especially back pain [11]
- Older age: in the large English study, the cancer risk with a raised inflammation test in men over 50 and women over 60 was high enough to call for urgent investigation [1]
These tests are not suitable for finding cancer in healthy people without symptoms [1, 5]. If you are thinking about a cancer check-up, see Which screening tests do I need? and Can a blood test detect cancer? For other blood count results, read: Understanding your CBC results and Low or high platelet count: what does it mean?
When should I contact a doctor?
Go to an emergency department straight away or call your local emergency number if your blood calcium is high and you have vomiting, confusion, severe drowsiness or dehydration [9].
See a doctor within the next few days if:
- Your ESR is 100 or more [2]
- A high LDH, ferritin or ESR comes with unexplained weight loss, fever, night sweats, swollen lymph nodes or persistent bone pain [11]
- You are 60 or over and have persistent back or bone pain, or an unexplained fracture [11]
- Your blood calcium is high, even if you have no symptoms [9, 10]
- You have yellowing of the skin and eyes or dark urine together with a high ALP [12]
Frequently asked questions
Does a high LDH in a blood test mean I have cancer?
Does a high ferritin mean I have cancer?
Not necessarily. A high ferritin is usually due to inflammation, fatty liver and obesity, diabetes, alcohol or liver disease, and only about 1 in 10 people have too much iron [4]. Cancer is one of the causes too, especially when ferritin is very high, but the doctor first checks the more common causes [4].
My ESR is high; what should I do?
The ESR has to be read alongside your symptoms and other tests; inflammation, infection and many other conditions can raise it [3]. The doctor usually looks for the cause and repeats the test; if the second test is normal, cancer is less likely [1]. An ESR of 100 or more almost always has an identifiable cause and should be followed up promptly [2].
Can I have a high ferritin and anaemia at the same time?
Yes. During inflammation the body makes more ferritin and also more of the substances that reduce the use of iron [4]; so you can have a high ferritin and anaemia at the same time. Read: Can anaemia be a sign of cancer?
Does a high LDH in lymphoma mean the disease is advanced?
A high LDH is one of the five factors of the IPI score, which predicts the course of lymphoma; but it is only one of these factors, and the doctor bases treatment decisions on all of them [7]. Read: Is lymphoma curable?
Should I have these tests as a cancer check-up?
No. These tests are normal in many people who have cancer and raised in many healthy people; that is why they are not suitable for finding cancer in people without symptoms [1, 5]. Have the screening tests that are right for your age: Which screening tests do I need?
Does a high alkaline phosphatase mean cancer?
Not necessarily. ALP rises in liver and bile duct diseases, but it also comes from bone and is naturally higher in children and in pregnancy [12]. The doctor first uses other liver tests to work out whether it comes from the liver or from bone [12]. Cancer that has spread to the liver or bone is one cause of a high ALP, but only one of many [12].
Interpretation and prognostic use (for doctors)
For physicians
Inflammatory markers in primary care. CPRD cohort (160,000 patients tested for CRP, ESR or PV in 2014 and 40,000 untested controls): 1-year cancer incidence 3.53% (95% CI 3.37 to 3.70) with a raised marker vs 1.50% with a normal marker and 0.97% in controls; risk higher with higher levels, older age and in men, higher with an abnormal repeat test and lower when it normalises; above the NICE 3% threshold in men over 50 and women over 60; sensitivity for cancer: CRP 46.1%, ESR 43.6% and PV 49.7%, so they are not useful for ruling out cancer [1]. ESR of 100 mm/h or more (1,006 outpatients, prevalence 4.2%): infection 33%, malignancy 17%, renal disease 17% and inflammatory disorders 14%; low sensitivity (25% for malignancy) but specificity of 96% for malignancy and a PPV of 90% for an identifiable cause [2].
Hyperferritinaemia. Only about 10% of cases in routine practice are associated with iron overload; the rest reflect an acute-phase or reactive rise due to inflammation, metabolic syndrome, alcohol, cell damage, chronic liver disease and malignancy. A ferritin above 1,000 µg/L is non-specific and common in metastatic cancer; above 10,000 µg/L, consider HLH and adult-onset Still's disease, although in adults such levels also occur with kidney disease, liver disease, infection and malignancy. A transferrin saturation above 45% in women and above 50% in men is regarded as raised [4].
LDH. A non-specific marker of cell damage (haemolysis, myopathy, liver injury, MI) and a prognostic factor in many cancers [5]; standard use in germ cell tumours, lymphoma, leukaemia, melanoma and neuroblastoma for staging, prognosis and response to treatment [6]. IPI (2,031 patients with aggressive NHL; age, stage, LDH, performance status and number of extranodal sites): predicted 5-year survival 73%, 51%, 43% and 26% in the four risk groups; age-adjusted IPI (1,274 patients aged 60 or younger; stage, LDH and performance status): 83%, 69%, 46% and 32% [7]. R-ISS (3,060 patients with newly diagnosed myeloma): stage I = ISS I, no high-risk chromosomal abnormality [del(17p), t(4;14) or t(14;16)] and normal LDH; stage III = ISS III with a high-risk abnormality or high LDH; 5-year overall survival 82%, 62% and 40% [8]. Calculators: IPI and ISS, R-ISS and R2-ISS.
Calcium and ALP. Mild hypercalcaemia: total calcium below 12 mg/dL (below 3 mmol/L); severe: 14 mg/dL or more (above 3.5 mmol/L); about 90% due to PHPT or malignancy. PTH is the initial test: a raised or normal PTH points to PHPT and a suppressed PTH (below 20 pg/mL depending on the assay) to other causes. Treatment of symptomatic or severe hypercalcaemia: hydration and intravenous bisphosphonates (zoledronic acid or pamidronate); denosumab and dialysis in kidney failure; corticosteroids when hypercalcaemia is due to excess intestinal calcium absorption (vitamin D intoxication, granulomatous disease, some lymphomas) [9]. In 54,267 primary care patients aged 40 or over, calcium of 2.6 mmol/L or more in 3%; 1-year cancer PPV 11.5% in men and 4.1% in women [10]. NICE NG12: at 60 or over with persistent bone pain (particularly back pain) or an unexplained fracture, a CBC, calcium, ESR or PV, serum protein electrophoresis and serum free light chains (recommendation 1.10.4) [11]. ALP: cholestatic injury means a disproportionate rise in ALP compared with AST and ALT; confirm hepatic origin with GGT or isoenzyme fractionation; the commonest extrahepatic source is bone (osteomalacia, Paget's disease, primary bone malignancy and bone metastases); for an ALP rise of hepatic origin, test for PBC and PSC [12].
Related cancer types
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References
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