Causes of Fatigue that Slip Through the Cracks

I consider fatigue caused by sinus and nasal issues to be the most common cause of otherwise unexplained chronic fatigue. I’ll describe the evidence for this opinion later but, for now, let’s consider some medical causes that can be missed.

An interesting study examined the amount of iron in the blood of women who were not anemic. Usually an iron deficiency, if severe enough, causes anemia but this study was limited to patients with mild iron deficiency, enough to be noted when examining the blood specifically for iron stores but not enough to cause anemia.

The distinction is an important one. Prior to this study physicians usually thought that iron deficiency would not cause fatigue if the deficiency was not severe enough to cause anemia. The study went on to measure the level of fatigue before and after iron replenishment. The level of fatigue dropped after the iron stores were returned to normal.

Two points are evident from this study: The lack of anemia does not rule out iron deficiency as a cause of fatigue. Additionally, measuring iron stores as simply the level of iron in the blood is inadequate. The iron stores must be measured as “ferritin” a simple and inexpensive blood test but one not always done when evaluating a person for fatigue.

Occasionally low thyroid causes fatigue despite a normal TSH—the usual screening test for low thyroid. TSH comes from the pituitary and increases in the event of a failing thyroid usually providing the earliest clue that the level of thyroid hormone is inadequate.

Occasionally the pituitary is the problem and although the TSH should be climbing as the thyroid fails, it does not. Checking the actual levels of thyroid hormone (T4 and T3) will pick up a thyroid problem even in the event of pituitary insufficiency.

Sometimes an arthritis disease can cause even in the absence of severe arthritis symptoms. Almost always the severity of the arthritic disease seems quite proportionate to the complaint of fatigue. Occasionally this is not so. A person might have rheumatoid arthritis with minor joint problems but have significant fatigue. Treating the rheumatoid arthritis usually causes substantial reduction of fatigue.

A note of caution: The vast majority of individuals with unexplained fatigue and very minor arthritis symptoms do not have positive blood tests for arthritic diseases. Even when the blood tests turn out positive the blood abnormality is, almost always, at a low level, unrelated to the minor arthritis. In these cases treating the person as if the individual did have a serious arthritis disease does not improve the fatigue. In short, arthritis blood tests in the setting of unexplained fatigue are often a “red herring,” but not always.

Occasionally a person may have unexplained fatigue due to a liver problem in the absence of abnormal screening liver function tests. Usually other screening tests, however, denote inflammation.

As mentioned before, the best screening tests to determine if, what appears to be unexplained fatigue, is actually caused by a medical problem are the erythrocyte sedimentation rate (ESR) and the C-reactive protein. Both of these are elevated by any process that causes inflammation. Usually any medical disease that causes fatigue causes inflammation as well.

The ESR and CRP won’t tell you the cause of the problem but do let you know that there is a problem. The absence of ESR or CRP abnormalities does not mean that the cause of fatigue is not physical. However, when these tests are elevated a physical cause of fatigue becomes much more likely.

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Zithromax and Sudden Death

A recent study in the New England Journal of Medicine described an increased risk of death from cardiovascular causes in patients taking azithromycin. Azithromycin (Z-pack, Zithromax) is a very commonly used antibiotic and this warning merits concern.

The increased risk of cardiac death relates to the tendency of azithromycin to increase the risk of an irregular heartbeat. In this study a similar risk of increased cardiac death was noted in patients who took levofloxacin but not in patients who took amoxicillin.

The increased risk was small (47 additional deaths per 1,000,000 courses of treatment) and largely limited to patients with very significant heart problems. This increased risk is probably significantly less than that which had been noted with erythromycin in the past.

Since vulnerability is limited mostly to patients with significant heart problems (the top 10% severity of heart disease in this study) and, presumably, patients taking a number of cardiac medications some caution is needed when prescribing to these patients. Since the blood concentration of azithromycin causes the problem, particular caution is needed in patients with very severe heart disease who are also taking cardiac medications that will raise the blood concentration of azithromycin such as diltiazem and verapamil.

Types of Fatigue

Over 100 years ago William Osler, the father of internal medicine, divided fatigue into three types. The first is the lassitude and malaise associated with systemic illness such as tuberculosis, cancer, rheumatoid arthritis, etc. The second is the weakness associated with muscle and nerve disorders resulting from ordinary exertion. The last is a painful weariness – the cause of which often eludes investigation.

These categories provide a useful framework in attempting to diagnose the cause of an individual’s fatigue. Duration further categorizes the symptom. Most patients with prolonged, unexplained fatigue have the third type of fatigue described by Osler, a painful weariness.

Fatigue that is less than one-month in duration is often due to a passing virus, stress, or other causes that are difficult to define. The relatively brief nature of the problem eliminates the need for an intense medical investigation, and, unless the problem becomes recurrent, it can be dismissed as one of life’s minor problems.

Persistent, significant fatigue, however, is not a minor problem. Even a loss of 10% of a person’s vigor removes enthusiasm and joy from the day’s tasks. Fatigue pulls down the mood and makes everything an effort. Approximately 15% of the general population suffers from chronic fatigue, unrelieved by rest, lacking an adequate medical explanation.

Approximately 25% of patients visiting a medical doctor complain of fatigue. Less than half will be explained by a medical illness.

Fatigue caused by medical conditions has certain characteristics. A serious medical problem will occasionally present itself as unexplained fatigue before other symptoms become apparent but, inevitably, other symptoms will appear. For instance, a person with pancreatic cancer may first notice fatigue before the appearance of abdominal pain and the other symptoms of cancer occur. Therefore, the longer fatigue persists without other symptoms, the less likely a serious medical condition will serve as the eventual explanation.

Fatigue caused by a medical problem has other characteristics as well. Usually patients with typical, diagnosable, medical problems note that their energy is highest in the morning and slowly winds down over the course of the day as if the store of vigor slowly depletes. A nap may recharge the person.

Fatigue that remains unexplained usually has different characteristics. Many times, a person has a bimodal curve of energy, worse in the morning, improving with the day, fading in the afternoon, and, finally, getting a second wind at night. A nap can actually worsen things. Additionally, sleeping a long time can produce an overslept sensation.

Patients with less serious medical problems can, in certain circumstances, have fatigue with the absence of other symptoms, as is the case with hypothyroidism. Patients with low thyroid may notice tiredness before the other symptoms appear. These include dry skin, constipation, cold intolerance, etc. Likewise, a patient with anemia can feel tired before noticing other symptoms such as pale skin or obvious blood loss.

Causes of fatigue are often easy to figure out. Usually a visit to the doctor and a standard panel of blood tests provides a definite answer. If, after a thorough exam and appropriate blood tests, no answer is apparent, it is unlikely that a medical explanation will be found.