Recent rapid responses

Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on Although a selection of rapid responses will be included as edited readers' letters in the weekly print issue of the BMJ, their first appearance online means that they are published articles. If you need the url (web address) of an individual response, perhaps for citation purposes, simply click on the response headline and copy the url from the browser window.

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We are writing to you regarding the article titled “Tiredness” published in the BMJ 2007:334:1221, which was printed in the 10 minute consultation section. We found the article to be informative concerning a common problem with the various issues, signs, symptoms and an excellent advised plan of action. Many physical causes were mentioned including hypothyroidism, autoimmune disease and malignancy. However, we do believe there was an important omission. This was patient’s medication which plays a significant part in today’s health care system where poly-pharmacy is a growing issue albeit more so in the elderly. Many patients seen in the primary care setting can possibly be on three or more medication for various reasons and tiredness can be a known side effect.Pervasive sense of tiredness can potentially undermine the Doctor -Patient relationship as the medication advised is associated with an undesireable experience.

The British National Formulary (BNF) lists tiredness, fatigue and lethargy caused by many regularly used drug groups. A few of these consist of antihypertensive, lipid regulating medication, corticosteroid, antihistamine, antipsychotic, antidepressant, antiemmetic, opioid analgesic and a few antidiabetic medication. We are writing in part to congratulate you on an impressive article, but also to point out this oversight as reviewing a patient’s medication would be an integral part of a consultation with a patient presenting with tiredness.

Competing interests: None declared

Competing interests: None declared

Zafran Rahman, FY1 psychiatrist

Ananth Puranik

Priority House ME16 9QQ

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Haemochromatosis is a relatively common cause of tiredness in Ireland. It is prudent to include fasting iron studies (especially serum iron and transferrin saturation) in the initial battery of blood tests for investigation of tiredness.

Ray O'Connor

Competing interests: None declared

Competing interests: None declared

Ray F O'Connor, General Practitioner Principal


19 Cregan Avenue, Kileely, Limerick City,

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Moncrieff and Fletcher state that a positive answer to either of two screening questions "suggests depression" (1). Their wording suggests that a positive answer is more or less diagnostic for depression, quoting 97% sensitivity. However, this is a high-sensitivity, low-specificity screening test, not a diagnostic test. Diagnostic criteria for depression should be consulted (2) and a differential diagnosis considered before one can "suggest depression". In everyday General Practice, if someone gives a positive answer to either question, absence of mental illness should be considered as well as other mental problems including bereavement, substance misuse or personality disorder. In General Practice it is good to have a high index of suspicion for depression. However, overdiagnosis of depression equally dangerous. It unduly labels the patient and deprives them of adequate management of the real problem, if there is one.

Also, physical examination is certainly not "unlikely to yield more information" as the authors state. Checking for anaemia and cardiopulmonary disease is necessary. General screening laboratory work should be standard, not "considered". Tiredness can be the only obvious symptom of anaemia, diabetes, hypothyroidism, infectious and inflammatory disease, or early malignancy in the absence of detectable signs.

Moncrieff and Fletcher's assumption seems to be that tiredness is due to depression, at least in a 48-year old woman, unless there is obvious evidence of physical illness. That is a dangerous assumption.

(1) Moncrieff G, Fletcher J. Tiredness. BMJ 2007; 334: 1221. (2) World Health Organisation. The ICD-10 classification of mental and behavioural disorders : diagnostic criteria for research. World Health Organisation, 1993.

Competing interests: None declared

Competing interests: None declared

Wilhelmina J. Rietsema, GP

P.O. Box 7, Oxford, OX1 1TD

Luther Street Surgery

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This article overstates the value of the two questions in diagnosing depression.

The authors state that "A positive answer to either question suggests depression." when in reality far more patients responding positively will not have depression.

The original research by Arroll.B et al showed a high sensitivity (97%) but a low positive predictive value (PPV) (18%)and the post-test probabilities were that there would be 5 false-positives for each true- positive.

This does not mean that the two questions are of no value as the high sensitivity means that they are an excellent method for excluding depression as the cause of tiredness. The chances of a patient with a negative test having depression are only 0.3%.

Without clarification of the PPV of this approach there is a danger that patients will be labelled as depressed incorrectly and more serious illness may be missed.


Arroll B, Khin N,Kerse N (2003) Screening for depression in primary care with two verbally asked questions: cross sectional study BMJ 2003;327:1144-1146 (15 November)

Competing interests: None declared

Competing interests: None declared

Julian T Spinks, GP

Strood Kent ME2 2HA

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It pains me to see the concept of Chronic Fatigue Syndrome (CFS) promoted by individuals and organizations alike, including a prestigious US Government Agency such as CDC (Center for Disease Control). I do not recall using CFS as a diagnosis. The reason is simple, I go beyond the CDC criteria in investigating chronic fatigue. In their 10-minute consultation "Tiredness", Drs Moncrieff and Fletcher jump to a speedy conclusion that the patient under discussion has depression. That is exactly what patients dislike about our diagnostic acumen, attributing major symptoms in their life to mental diseases without first exhausting all the underlying physical ailments.

I have yet to see a diagnostic criteria list for fatigue that is complete. This unfortunately includes the diagnostic criteria for Chronic Fatigue Syndrome issued by CDC. No wonder we keep citing CFS as a cause for fatigue when we ourselves fail to pinpoint the diagnosis. In my endocrine practice after ruling out the obvious causes of fatigue (mentioned in this 10-minute consultation, I will also add adrenal insufficiency which is an autoimmune disease not mentioned by name in the mini consultation), I will do the following tests and I almost always find the cause for fatigue: 1. True biological reference range of TSH should be 0.3-2.5. If TSH is > 2.5, especially when Thyroid Peroxidase titer is > 10, the patient might have evolving hypothyroidism. If you go by your laboratory's reference range of 0.5-5, of course you will miss the boat, and resort to the waste basket diagnosis of CFS.

2. Check glucose tolerance test on people who are obese, have family history of diabetes, and have nocturia, or polyuria. The fasting plasma glucose should be <100 mg/dl (5.5 mmol/l).Postprandial plasma glucose should be <140 mg/dl (7.7 mmol/l)at 30-minute, 60-minute, 90-minute, and 120-minute. If you do not use these diagnostic thresholds, you will miss the diagnosis of diabetes, or impaired fasting glucose, or impaired glucose tolerance. The latter 2 are also called pre-diabetes. Pre-diabetes and diabetes both can cause severe fatigue if remained undiagnosed. The mechanism is through loss of glucose (body's fuel) in the urine (Glycosuria>

Check vitamin B12 level. The cutoff reference range is >300 pg/mL (>221 pmol/L), or even higher. Most laboratories in the US have the reference range at 160 or 180, erroneously low. If in doubt, check homocysteine level, the reference range of homocysteine should be between 5 and 15 µmol/L (some authorities use 10 as cutoff). If you rely on outdated reference range, you miss the boat and fall in the trap of CFS.

3. In the Northern regions of the United States and Europe, vitamin D deficiency is rampant. In some cities in the United States 70% of the population in the winter might have vitamin D deficiency (such as Boston). Vitamin D deficiency is responsible for calcium and phosphorus absorption (among other host of other functions). Lack of phosphorus means lack of ATP in the body, which means that you feel tired. I have helped thousands of victims of this type of chronic fatigue through vigorous vitamin D supplementation. Not to mention that vitamin D deficiency causes also severe myalgia and bone pains (osteomalacia), often missed since vitamin D deficiency is not on the list of differential diagnosis of fatigue, including (tragically) the CDC list. Failure to recognize vitamin D deficiency leads you to misdiagnosing patients as CFS and/ or fibromyalgia. Nearly 70% of patients with fibromyalgia have vitamin D deficiency, i.e. misdiagnosed. The true reference range of 25 hydroxy vitamin D is 32-100 ng/ml.

4. Sleep deprivation is a very common cause of fatigue. This was mentioned in the 10-minute consult.

5. Celiac disease is relatively common (~1% of Caucasians have it, most of them undiagnosed). If you don't think of Celiac, you will be an easy victim in the trap of CFS. Celiac can cause pan-malabsorption of iron, vitamin D, B12 (mentioned above) in addition to other nutrients and minerals.

6. If iron saturation is high, perform genetic testing for hemochromatosis. This is another relatively common genetic disease in the Caucasians.

Any list that does not address the above diagnoses (with the reference ranges that I mentioned), would lead to missing the root causes of fatigue. CFS is not a diagnosis; it is merely re-labeling fatigue with a fancier name. It is the time that CDC revisited the criteria of CFS, and included the causes I cited above. I can say with confidence, backed up with data of hundreds, or even thousands of patients with fatigue who I have helped over years, that patients with chronic fatigue syndrome are patients who have not been adequately worked up in accordance with the criteria mentioned above. It is for this reason that CFS is not in my medical vocabulary.

Competing interests: None declared

Competing interests: None declared

Shirwan A. Mirza, MD, FACP, FACE, Pivate Ptactice


Auburn, NY 13021 USA

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