FOAM4GP MAP – Tired? Want a blood test?


Thanks to XKCD

So patients present to clinic with fatigue all the time. What do you do? What does the evidence suggest you should be doing? Let’s delve into the literature and see if we can improve some clinical practice!

The NHS homepage on fatigue sums up the issue nicely. It suggests that patients should see their doctor if they have fatigue and have had any of the following:

Confusion, dizziness, blurred vision, weight loss, weight gain, swelling (just… generally I guess), constipation, insomnia, depression, headaches etc.

Ummm. If you haven’t had these at some point you may not actually be a human being. *pinch* – yep, still hurts!

Fatigue/tiredness is a common complaint, occurs regularly in Australian general practice (1.5 in 100 in BEACH (though I am sure I see more than that!)), and while investigations may be used to make some diagnoses and help rule out dangerous conditions, the battery of tests which doctors perform is wide ranging and not always evidence based. Unfortunately, patients will often want ‘tests’ and doctors feel under pressure to order these. They believe that if they refuse and miss a serious condition, the patient may be harmed and there may be medico legal issues.

I want to review some of the main investigations which may help in the Australian patient presenting with fatigue to general practice and briefly talk about some ‘furfy’ (read – not evidence based) diagnoses which I have come across recently.

Thanks Luke

Thanks Luke

Question 1: What actually IS fatigue and what are the related commonly held beliefs by doctors and their patients?

Fatigue is “extreme tiredness resulting from mental or physical exertion or illness.” The precipitating factors for patients to present for consultation are frequently related to stressful life events (which account for 2/3rds of fatigue complaints). 3/4’s of all patients presenting with fatigue will only have an isolated single appointment and will not represent for follow up, and approximately half will be given the diagnosis of ‘tiredness’. Half of all presenting patients will have on average four tests ordered on by their GP. Interestingly, the average patient is female, 34-39yo, and they present to a female GP.

The most commonly ordered tests include: FBC 45%, TSH 32%, Ferritin 21%, LFTs 17%, EUC 15%, and BSL 11%

It is thought that a major reason doctors order tests to relieve their own, and their patients, anxieties. A recent systematic review however, has shown that ordering tests for symptoms with a low pre-test probability of serious illness (as is the case with fatigue) does little to reassure patients or decrease their anxiety

Most patients present because of a precipitating factor. These are primarily stressful life events (underlying about two thirds of fatigue complaints)— for example, work disputes, family problems, bereavement, or financial difficulties.

It has been shown that a limited set of blood tests (haemoglobin, erythrocyte sedimentation rate [ESR], BSL and thyroid stimulating hormone [TSH]) is as useful in diagnosing serious pathology as a more extensive set of investigations; and this will be discussed further below.

Many guidelines for the management of fatigue recommend an initial 4-week postponement of test ordering and subsequent restricted investigation. Delaying investigation has been shown not to affect patient satisfaction or anxiety levels.

Finally, GPs tend to perceive the cause of tiredness as psychological, whereas people with tiredness are more likely to perceive the cause as physical. Don’t trivialise their fatigue – it is a real problem even if it is likely to be self resolving.

Question 2: Is there a test or questionnaire for fatigue?

There appear to be many different types of fatigue tests available (MFIS, FSS, FACIT, Fatigue questionnaire, Short form-36 Vitality… etc.) An old adage by a great mentor of mine once said ‘if there are many ways to do something it means that probably none of them is the best’. Also, as for when or where an Australian GP would use these I am uncertain. If a check-list had a list of red flags this might be beneficial but I could not find one for this. Better off taking a history then!

Question 3: What are the red flags and key issues to consider when a patient presents with fatigue?

NPS Medicinewise – has a great resource listing red flags – Link

RACGP article on fatigue (2014) also has a great table with red flags – Link

While the red flags are important, we must also point out there are times where fatigue may be somewhat appropriate. For example, in pregnancy, children or adults recovering from chemotherapy, or patients with chronic illness. These patients need our understanding and can benefit from small lifestyle changes to improve their energy levels and subsequent health.

Thanks to Luke Surl

Thanks to Luke Surl

Question 4: Tips for history taking:

Remember to elicit what a patient means by ‘fatigue’. Often, just listening and not interrupting your patient initially can give you the answer.

It is important to ask, and acknowledge, the impact of fatigue on their life. This may be affecting their sleep, relationships, and workplace.

Remember to take a full history. Unfortunately, these undifferentiated problems can be the most time consuming as they require a full extensive history to elicit possible causes.

Dr John Murtagh’s famous seven masquerades can be very helpful in these undifferentiated problems. Remember to consider: depression, diabetes, drugs, anaemia, thyroid disorder, spinal dysfunction and urinary tract infections. I would add considering also asking about safety in the home (domestic violence) and about alcohol use (arguably – a drug). Really important other causes of fatigue which can have dire consequences if overlooked.

I really like asking a patient where I cannot find a cause “when was the last time you took some time to yourself or went on a relaxing holiday?” (not a “see as much as we can” type holiday). It is often a nice segway to talking to patients about non physical causes of fatigue such as stress and burn out.

Question 5: Can I wait before ordering any tests?

The brilliantly named “VAMPIRE” trial (VAgue Medical Problems In REsearch) run by the Dutch College of General Practitioners looked at postponement of blood tests until 4 weeks after initial presentation. Amusingly, because there were so few people who actually re-presented at 4 weeks in their trial, they were unable to give a statistical answer because of loss of these patients to follow up! They did suggest there were very little differences in the positive test result for blood tests between initial bloods or the 4 week group (though obviously those who would have got a negative result were not unnecessarily tested).

Question 6: What ‘screening’ tests are MOST LIKELY to yield useful clinical information in evaluation of fatigue?

NPS Medicine wise summarises this well in 3 key points: 3% of patients you order tests on will have a somatic cause, repeated testing will yield more false positives, and the majority will self resolve.

First, aim for targeted testing. For example, if a patient presents with weight loss, night sweats, bowel habit change, and PR blood loss – please don’t order the fatigue battery tests – just perform your basic bloods (FBC, Fe studies, ESR) for ?Colon cancer and refer for colonoscopy.

If you perform a full history and examination (remember, a patient seeing a doctor perform a thorough and professional exam and finding nothing CAN be therapeutic) and find no focus, then NPS suggests:

Performing a urine dipstick and fingerprick BSL.

FBC , TSH, Serum Ferritin (not iron studies – which would involve transferrin etc.)

Some guidelines also suggest ordering an ESR. (I am currently writing an article on CRP vs ESR so stay tuned!)


Thanks to XKCD


Question 7: Is there any evidence of any treatment for patients with fatigue but no cause found?

There are several steps you can consider with treatment of fatigue. If not ordering tests, you need to help the patient feel that their fatigue is acknowledged. It is important you highlight that you are planning to help them recover.

UpToDate suggests a stepwise approach to fatigue: 1. Accomplishing activities of daily living 2. Returning to work 3. Maintaining interpersonal relationships 4. Daily exercise

Antidepressants: Only if evidence of depression

Cognitive Behavioural Therapy (CBT): Can be beneficial if fatigue ongoing. This is a common therapy for patients with chronic fatigue and problem solving ways of dealing with fatigue and the patients cognitions and beliefs around their fatigue.

Graded Exercise Therapy (GET): Slow reintroduction of exercise sometimes in consultation with a physiotherapist / exercise physiologist

Sleep hygiene information: Can be very beneficial if sleeping is a significant component of fatigue. Patients often need to control daytime sleepiness and establish appropriate and ongoing sleeping patterns

Patient Education: Can help patients understand their own fatigue, normalise the issues, and possibly begin to build insight into non-organic causes of their fatigue.

Question 8: What patient resources can I use to print out for my patients?

Brilliant handout from NPS – Link

Better health channel has a good handout on simple things people can do to increase their energy levels – Link

Thanks to Webdonuts

Thanks to Webdonuts

Question 9: What about chronic fatigue syndrome or fibromyalgia?

These are ‘rule out’ diagnoses (once you have ruled everything else out). They are difficult to define, difficult to study, and difficult to treat. However, they are expected to be medical conditions with a currently undetermined cause. They could fill a full FOAM4GP Map themselves – so I will currently link to reputable information below and may tackle these further in the future.

Chronic fatigue syndrome (CFS) – MJA 2002 Guideline – Link

Fibromyalgia – AFP article 2013 – Link

Question 10: Time for the fun stuff! What diagnoses do some patients come in ‘insisting’ is the cause for their fatigue; which ‘may not’ be evidence based?

Adrenal Fatigue

What is it stated to be? Allegedly – (From“Adrenal fatigue, also known as adrenal exhaustion or hypoadrenia, is one of the most under diagnosed illnesses in western society. It has been estimated that 80% of adults suffer from adrenal fatigue to some degree. Adrenal fatigue is a decline in adrenal gland function ultimately resulting in diminished production of adrenal hormones which adversely affects your physiology causing exhaustion, etc.” It is a new diagnosis from 1998 by James Wilson.
What it is NOT: This is not adrenal insufficiency (addison’s disease).
What is the evidence?
There is none. There is also no specific test. Some natural practitioners use blood or saliva tests. I could not find what these are?
If patients have a constellation of fatigue symptoms they can be diagnosed with “adrenal fatigue”. (Symptoms said to be due to adrenal fatigue include tiredness, trouble falling asleep at night or waking up in the morning, salt and sugar craving, and needing stimulants like caffeine to get through the day.)
What does professional opinion suggest?
American Endocrine society states:”  “Adrenal fatigue” is not a real medical condition. There are no scientific facts to support the theory that long-term mental, emotional, or physical stress drains the adrenal glands and causes many common symptoms.”
Is it a problem?
Well there are a large amount of treatments for “adrenal fatigue”. Someone is making a lot of money from this diagnosis and I am unsure, given the evidence, of patient benefit.


What is it?
Supposedly one of the pyrroles is a breakdown product of poor haemoglobin synthesis. Evidence to support this theory however is lacking. The theory is that this pyrrole binds Vit B6 and Zinc and eliminates it through urine. It was initially theorised in the 1970s through studies on people with schizophrenia, however further studies have failed to detect haemopyrrole and krpytopyrrole in the urine of schizophrenics or controls, and have not correlated it to illness.
What is the evidence?
The initial trials in the early 1970’s suggested high levels in schizophrenic patients. This was not reproducible in multiple further tests. Since that time there has been no further research in pyroluria.
What does professional opinion suggest?
I cannot find a professional society that even has an opinion on it!

Lyme Disease

What is it?
This is a real medical condition caused by the tick-borne spirochaete bacterium, Borrelia burgdorferi. It is a very ‘popular’ diagnosis as the symptoms are very broad and encompass a large amount of non-specific findings. It may be diagnosed in Australia in a traveller from overseas bringing the illness into the country, but there has been no documented cases of primary infection within Australia to date.
What is the evidence?
Within Australia, we do not have the specific ticks known to carry the bacteria. There is a theory that our native ticks could carry a similar type of spirochaete however in a study analysing 12,000 ticks from across Australia, none were found.

Testing for Lyme disease is also controversial. Lyme disease proponents state that if a patient is infected with a local Borrelia species, it won’t show up on Australian tests. US tests previously have been shown to be positive when Australian tests were not. Patients are often referred overseas for expensive testing. The primary test lab in the US is Igenex which was shut down in 2001 over irregularities with documentation requiring fines of nearly $50,000. Patients also often state that their immune systems are too suppressed to show up positive. Australian Microbiologist Stephen Graves however was quoted stating that even if a patient is very ill they will still generate antibodies which can be detected.

What does professional opinion suggest?
Royal College of Pathologists of Australasia (RCPA) has declared there is no evidence that the disease-causing bacteria Borrelia spp is carried by local ticks.

Ok, so Rob after looking at all this, will it change what you do in clinic?

Yes I think it will. I can sometimes get myself caught in the trap of ordering tests to make myself feel better that I am not missing something serious. I understand now that listening, problem solving, and empathising with my patient’s fatigue on the first consult, will make them feel better that this is likely a normal physiological process and make me feel better that I am doing something beneficial for the patient. I will likely suggest that they return to see me in a few weeks time to see how their fatigue levels are going after addressing simple things like rest, exercise, avoidance of alcohol/drugs/smoking, and perhaps some counselling/holiday. If they are still fatigued, or on second presentation have new symptoms, I will perform tests. Ideally I will have focused tests to perform at this stage, but if I do not I will perform: Urine dipstick, fingerprick BSL, and send for FBC, ESR, serum ferritin and TSH.
I will then get the patient back to discuss either pathology, or a continued monitoring plan to readdress the therapeutic problem on a ‘every few weeks’ or monthly basis to see if they generate new symptoms. I may consider making sure the patient is up to date with all possible cancer screening also (as I would with all patients anyway).
Would anyone do anything differently? Any points from anyone? Any interesting other ‘dubious’ causes for fatigue people have heard of? Let me know.
Cheers, Doc Rob.

13 thoughts on “FOAM4GP MAP – Tired? Want a blood test?

  1. this is a great article very well set out, I have shared it with our GPR for discussion. It’s a hard topic for them to get their head around when they start General Practice.

  2. Often the opening lines sets the agenda. “I want you to check my blood Doc Rob”. I wonder of those who have no red flags, obvious diagnosis, abnormal findings one examination and officer tests who are asked to come back in 4 weeks actually do return or wander off to find a less thorough doctor who will just order the tests.

  3. Thanks so much Doc Rob! As a Aussie med student I find your posts so helpful/informative/useful/practical. It acts as a nice introduction &/or a good recap/summary to the topic. The links to articles are great, as are your little words of wisdom (e.g. “when was the last time you went on a relaxing holiday”). Thanks again.

  4. Hello Doc Rob. Lovely review. Just a small bit of feedback… writing about people with schizophrenia is much less pejorative than using the term “schizophrenics” (in your section on pyroluria). See RANZCP guidelines on schizophrenia for examples of how this can be done sensitively and without contributing to stigma.

  5. Thanks Rob, fabulous piece of FOAMED for GP. As a GP registrar dealing with patients presenting with tiredness is always a challenge, and it really helps to have a framework like this.

  6. Thank you for this insightful article! I feel I see this presentation frequently as a female GP registrar. Also enjoyed the cartoons.

  7. Thanks, nice article, researching for student tute on undifferentiated illness.

    My 5c worth.

    20 yrs ago patients who were tired all the time (TATT) had been tired for a couple of years, 10 ago 12 months, teenager last week 4 days.
    As per the NPS article 70% social/psychosocial.

    I show them the NPS pie chart and go through the various areas explaining that though we will exclude “medical” issues the common causes lie in the psyche.

    Usually ask when did they last feel energised and what happened around that time.

  8. Thank you for the great article! I have some difficulty finding the list of red flags from NPS – does anyone here have an electronic (or paper) copy of said list? Thank you in advance 🙂

  9. I’m using this as a teaching tool for GP Supervisors in the NT, thanks Rob.
    This comment doubles up as an ‘Easter egg’ hidden prize for any supervisor at my session who actually reads down this far.

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