'Tired all the time': what general practitioners request and find in patients with tiredness/fatigue - an audit... 2025 Murphy et al

Andy

Andy

Retired committee member
Full title: 'Tired all the time': what general practitioners request and find in patients with tiredness/fatigue - an audit against NICE clinical knowledge summary of tiredness/fatigue in adults

Abstract

Background: Tiredness/fatigue is a common presenting complaint. Advice is available from the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) on its investigation. The application of this guidance has not been reported.

Aim: To audit the investigation of tiredness/fatigue in adults in primary care against NICE CKS recommendations.

Methods: We reviewed 16,889 primary care requests in 2019, where clinical details included: ‘tired all the time’ or ‘TATT’; ‘tired(ness)’; ‘fatigue’. We report on how many first-line investigations recommended by the NICE CKS were requested, and, if they were, what the outcome was. We categorised outcomes as normal or abnormal, using relevant laboratory reference intervals.

Results: First-line investigations were requested as follows: full blood count (FBC) 89%, renal function (U&E) 83%, liver function tests (LFT) 80%, thyroid-stimulating hormone (TSH) 80%, bone profile 70%, C-reactive protein (CRP) 66%, plasma viscosity (PV) 46%, ferritin 9.4%, IgA tissue transglutaminase (TTG) 3.2%, creatine kinase (CK) 1.4%. Likelihood of abnormal results was 37% for PV, 26% for ferritin, 25% for LFT, 24% for bone profile, 23% for FBC, 15% for U&E, 14% for CRP, 10% for TSH, 8%, CK, 3% for TTG. (Requesting of diagnostic HbA1c (2.8%) was vetted in accordance with local protocol; 59% of results were in the diabetic range).

Conclusion: This is the first study to audit the application in primary care of NICE CKS advice on investigation of tiredness/fatigue in adults. Our findings provide an insight into 'real-world' primary care requesting.

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InitialConditions said:
So the test most likely to be abnormal was plasma viscosity, which I don't believe I've ever heard of....? I'm assuming it's similar to ESR.
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Plasma viscosity became a popular alternative to ESR in some pathology services probably because it is cheaper and less susceptible to artefacts. It was presented as being of similar significance.

Both tests are based on rises in plasma proteins, mostly globulins, including fibrinogen and IgG/IgM. Fibrinogen goes up as part of the acute phase response so is a sort of poor man's CRP test. Immunoglobulins can go up with inflammation but they are linked to it in more complex ways.

It is probably justified to have a cheap test that picks up almost any shift in plasma proteins associated with disease. The ESR remains useful in addition to CRP because it picks up thing like myeloma. My suspicion is that plasma viscosity is actually less useful as a broad screening test but I have never worked with it.

A 37% abnormality rate on PV is interesting because it suggests that at least a third of people who are fatigued have some identifiable biological abnormality. What is not clear is whether a or not a good proportion of the people studied had other symptoms or sign already pointing to a more specific diagnosis. I doubt audits of this sort tell us much of value.
 
Jonathan Edwards said:
What is not clear is whether a or not a good proportion of the people studied had other symptoms or sign already pointing to a more specific diagnosis. I doubt audits of this sort tell us much of value.
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I guess they stop working through the list at the point where they gain a good enough picture overall to suggest specific avenues, or one of the tests does come back with something.

The only people who go through the entire sheet are probably like me, who at the time of diagnosis had no abnormal results. They were thorough, and the ME/CFS diagnosis only came after (a) they'd run out of other options and (b) determined I fitted the symptom profile.
 
PrairieLights said:
I was thinking the answer is more often "nothing" as the GP accused you of anxiety instead.
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Yes, or FND or <latest meaningless catchphrase>. However, it's important to know the value of those tests for those complaints. There might be situations where a full thyroid test (not just Tsh) should be done, based on other symptoms or signs, and situations where the patient is better off being told "That's a common complaint, and there's really nothing we can do about it, but if you notice <certain signs>, do come in for additional testing." Hmmm, if you mention <certain signs>, some people will see those signs even if they don't really exist. No easy answers.
 
The list of tests should have included Vitamin B12 and Folate too. Low levels of either or both can lead to anaemia. The reference range for Vitamin B12 is outrageously low. High levels of folate, particularly in conjunction with low B12 can lead to cognitive dysfunction. About 50% of the global population can't metabolise folic acid very well and can have high levels of unmetabolised folic acid in their bloodstream. Humans didn't evolve with folic acid as part of their diet. It was first developed in the 1940s, and folic acid is not found to any great extent in food unless it has been fortified.

The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake

Excessive folic acid intake and relation to adverse health outcome

Folate vs. Folic Acid: It Pays to Know the Difference
 
Creekside said:
Yes, or FND or <latest meaningless catchphrase>. However, it's important to know the value of those tests for those complaints. There might be situations where a full thyroid test (not just Tsh) should be done, based on other symptoms or signs, and situations where the patient is better off being told "That's a common complaint, and there's really nothing we can do about it, but if you notice <certain signs>, do come in for additional testing." Hmmm, if you mention <certain signs>, some people will see those signs even if they don't really exist. No easy answers.
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As a hypothyroid patient, despite need, a full thyroid panel has NEVER been done by my GP. I do them myself using a private company.

I feel like even when they run some tests (and I have had loads) not much comes of it.
 
We're not allowed to read the NICE website from outside the UK. Do the guidelines only recommend blood tests, or did the study only look at blood tests? I would have thought sleep studies would have been fairly common too, unless this was for tiredness and fatigue that isn't related to poor sleep.
 
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