Approach to fatigue: Clinical sciences

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. 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. 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. 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. 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 .

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. 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.

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.

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. 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.