Approach to fatigue: Clinical sciences

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Introduction0:00–0:56

Fatigue is the feeling of being mentally or physically exhausted. People experiencing fatigue may describe feeling tired, lacking energy, or being unable to carry out their usual daily tasks.
Fatigue can be caused by various conditions, which can be classified into four main groups. The first group covers conditions associated with fatigue and muscle weakness, such as hypercalcemia, hypokalemia, and neuromuscular conditions.
The second one includes exertion-related fatigue, like cardiovascular and pulmonary disease. The third group covers conditions characterized by fatigue and excessive daytime sleepiness, like obstructive sleep apnea.
Finally, the fourth group includes conditions characterized by generalized tiredness, like hypothyroidism, infections, depression, and myalgic encephalomyelitis.When approaching a patient that presents with fatigue, start with a focused history and physical examination.

Muscle weakness0:56–1:16

Next, assess if your patient presents with muscle weakness. If there’s muscle weakness, your next step is to order labs, including BMP and calcium.
Let’s get started! If your patient has a history of constipation, anorexia, nausea, nephrolithiasis, bone pain, and confusion or lethargy, it's a classic presentation of hypercalcemia.

Hypercalcemia1:16–1:52

This symptom combination is often summarized as 'groans, stones, bones, thrones, and psychiatric overtones'. In such cases, labs reveal a serum calcium level higher than 10.5, confirming the diagnosis.On the other hand, your patients may report muscle cramps and palpitations.

Hypokalemia1:52–2:52

Additionally, there might be a history of chronic diarrhea or use of diuretics or laxatives. If labs reveal a serum potassium lower than 3.5, you can make a diagnosis of hypokalemia.Here’s a clinical pearl!
Mild hypokalemia is often asymptomatic, and can be easily corrected by giving oral potassium. However, severe hypokalemia, which occurs when potassium levels drop below 2.5, can lead to neuromuscular weakness and cardiac arrhythmia.
In this case, be sure to correct the potassium level without delay with IV potassium to prevent heart complications! Additionally, don’t forget to order an ECG, which may reveal signs like flattened T waves, depressed ST segments, U waves, and prolonged PR or QT intervals!Next up are neuromuscular diseases.
These include multiple sclerosis, myasthenia gravis, and polymyositis. Your patient may present with muscle weakness and additional neurologic symptoms like numbness, paresthesias, fasciculations, spasticity, or bowel or bladder incontinence.

Neuromuscular diseases2:52–3:33

Keep in mind that in these individuals, labs are usually normal! But, since there are many different etiologies in this category, you might need to order additional tests, including a nerve conduction study, also called .

Exertion-related conditions3:33–3:58

Alright, let’s look at patients with no muscle weakness. In such cases, evaluate if their fatigue is tied to physical activity.
If your patient’s fatigue is worse with exertion and improves with rest, consider conditions that cause decreased exercise tolerance.
To determine the actual cause, start by ordering labs including a CBC. First, let’s focus on cardiovascular diseases.

Cardiovascular disease3:58–5:07

Some important conditions include coronary artery disease, aortic stenosis, bradycardia, or congestive heart failure. These patients typically present with a history of dyspnea on exertion, and may also have chest discomfort.
They could also have risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, and diabetes. Physical exam might reveal systolic ejection murmur, lower extremity edema, and jugular venous distention.
To confirm the diagnosis, order an ECG, a transthoracic echocardiogram or TTE, and an exercise stress test. If ECG reveals arrhythmias or ischemic changes; TTE shows ventricular dysfunction or valve abnormalities; or the exercise stress test is positive for inducible ischemia, you can confirm that the underlying cause of fatigue is cardiovascular disease.

Pulmonary disease5:07–5:56

On the flip side, there’s pulmonary diseases. These include some obstructive lung diseases like COPD, as well as restrictive lung diseases like interstitial lung disease.
History typically reveals a cough and the presence of risk factors for pulmonary diseases, like smoking or occupational exposure.
Physical exam may reveal hypoxemia, wheezing, decreased breath sounds, or crackles; and labs are often normal. Next, order a chest x-ray and spirometry for further evaluation.
If the chest X-ray shows hyperinflated lungs or reticular or nodular opacities, and spirometry reveals an obstructive or restrictive pattern, fatigue is likely caused by pulmonary disease.

Anemia5:56–6:27

Now, fatigue associated with exertion could be caused by anemia. In these individuals, history findings typically include dizziness; pica, meaning the urge to eat non-food items; and history of blood loss from heavy menses or melena.
Physical exam might reveal tachycardia, conjunctival pallor, or a positive fecal occult blood test, while CBC will reveal low hemoglobin and hematocrit.
In this case, you can diagnose anemia. Last but not least, we have deconditioning.

Deconditioning6:27–6:46

If your patient reports gradual onset of fatigue with exertion, and leads a sedentary lifestyle, but no cardiopulmonary issues are found and CBC is normal, you can diagnose fatigue due to deconditioning.Ok, let's switch our focus to fatigue that’s unrelated to exertion.

Excessive daytime sleepiness6:46–7:24

Some patients may describe excessive daytime sleepiness, and increased tendency to fall asleep during wakeful hours. If that’s the case, use a scoring system like the Epworth Sleepiness Scale.
This scale asks patients to rate how likely they are to fall asleep in various situations, such as sitting quietly after lunch, or being the passenger in a car.
Higher scores are consistent with excessive daytime sleepiness, so assess their sleep habits and review their medication list to determine the underlying cause.
Let’s start with obstructive sleep apnea, or OSA. Let’s say your patient has a history of snoring or gasping during sleep, or has been experiencing morning headaches.

OSA7:24–8:06

Additionally, your patient’s sleeping partner may report periods when the patient stops breathing while asleep. Physical exam typically reveals a large neck circumference; or a crowded oropharyngeal airway, meaning narrow airway due to enlarged oropharyngeal structures like the tonsils, uvula, or tongue.
If these findings are present, order polysomnography, and if it reveals frequent episodes of apnea, diagnose your patient with OSA.
However, if your patient reports missed nights of sleep, reduced sleep duration, or frequent nighttime awakenings, you can diagnose fatigue due to insufficient sleep.

Insufficient sleep8:06–8:53

Some important causes of insufficient sleep include an obvious external driver, such as caring for a newborn, working night-shifts, or a student pulling all-nighters - sounds familiar, huh?
But insufficient sleep could also be due to insomnia, which can be primary, or secondary to other conditions like anxiety or depression.
So be sure to help your patient find what’s causing them to get insufficient sleep, and try to come up with a solution when possible.Finally, some patients could report taking a medication with a sedating side effect, such as an antihistamine, opioid, or benzodiazepine, which could be causing their fatigue and excessive daytime sleepiness.

Medication side effect8:53–9:28

However, this diagnosis should be made only when all other potential causes are excluded. To confirm the diagnosis, a trial of temporarily reducing or discontinuing the suspected medication can help assess symptom improvement.
If symptoms improve, you can diagnose fatigue due to medication side effects.Alright, let’s go step back and discuss individuals with no excessive daytime sleepiness.

Generalized tiredness9:28–9:48

In this case, you should consider conditions associated with generalized tiredness, such as hypothyroidism, infection, depression, as well as myalgic encephalomyelitis.Let’s start with hypothyroidism.

Hypothyroidism9:48–10:24

In addition to fatigue, these patients typically report weight gain, constipation, and cold intolerance. Physical exam might reveal the presence of a goiter, dry skin and fragile hair.
Some patients may develop cardiovascular manifestations like bradycardia. These findings are highly suggestive of hypothyroidism, so order labs including a TSH and a free T4.
If labs reveal elevated TSH and low free T4, you can diagnose hypothyroidism. Another cause of fatigue can be an infection.

Infection10:24–11:11

These patients will usually report fever, chills, and malaise. They might also have risk factors for infections, like sexually transmitted infections, or tick-borne illness.
Additionally, the physical exam may reveal lymphadenopathy or a rash. In this case, consider infectious causes, and order labs like a CBC, as well as additional pertinent tests based on your suspicion, such as HIV test, heterophile antibodies, or Lyme disease titers.
The CBC may reveal leukocytosis or leukopenia, or find your patient positive for the suspected pathogen. In this case, you can diagnose fatigue due to infection.Next up is depression.

Depression11:11–11:56

These patients may present with a history of fatigue associated with depressed mood, as well as anhedonia, which is a reduced ability to experience pleasure.
If physical exam is normal, you should consider depression as a cause of fatigue. Next, use a screening tool, such as Patient Health Questionnaire 9, or PHQ 9, to test for depression and assess its severity.
This questionnaire asks patients to rate how often they experience symptoms of depression. A score of 5 or higher indicates that your patient has depression, and the higher the score, the higher the severity.Let’s finish with myalgic encephalomyelitis, or ME, also referred to as chronic fatigue syndrome or CFS, or sometimes ME/CFS.

ME/CFS11:56–13:00

Let’s say your patient reports post-exertional malaise, cognitive impairment, and orthostatic intolerance, meaning their symptoms get worse with standing and improve with lying down.
In this case, consider ME/CFS, and assess the patient using the Institute of Medicine diagnostic criteria.These criteria include a substantial reduction or impairment in their ability to engage in pre-illness levels of activities, presence of symptoms for more than 6 months, fatigue that’s not relieved by rest, presence of post-exertional malaise, unrefreshing sleep, and cognitive impairment or orthostatic intolerance.
If your patient meets these criteria, you can diagnose ME/CFS.Alright, as a quick recap… Fatigue can be caused by many conditions, classified into four main groups.

Review13:00–13:50

The first group covers conditions associated with fatigue and muscle weakness, such as hypercalcemia, hypokalemia, and neuromuscular disease.
The second group is characterized by fatigue associated with exertion, such as cardiovascular and pulmonary diseases, anemia, and deconditioning.
Next up are conditions where fatigue is not associated with exertion, and could be described as excessive daytime sleepiness, like with obstructive sleep apnea, insufficient sleep, and medication side effects.
Finally, the fourth group is characterized by generalized tiredness, like hypothyroidism, infections, depression, and myalgic encephalomyelitis/chronic fatigue syndrome.