Weakness in the body: common causes and appropriate tests

Muscle weakness is a generalized feeling of decreased physical strength and endurance, making everyday activities more difficult. It's important to distinguish true muscle weakness, when strength in specific muscle groups is objectively reduced, from general fatigue, when strength "seems to be gone," but strength remains intact during testing. These conditions can coexist, but the causes and diagnostic approaches differ. [1]

Muscle weakness is most often associated with neurological or muscular diseases and has characteristic features: asymmetry, predominantly proximal muscle damage, and increased or decreased reflexes. Fatigue, on the other hand, is most often caused by systemic, metabolic, psychoemotional factors, or sleep disturbances. The first step a doctor always takes is to determine whether true weakness is occurring or simply a feeling of fatigue. [2]

Subjective "fatigue" often masks specific health issues: anemia, thyroid dysfunction, vitamin B12 or folate deficiency, electrolyte imbalances, dehydration, depression, anxiety, sleep apnea, and post-viral conditions, including post-COVID conditions. Proper distinctions between these concepts determine subsequent examinations and treatment. [3]

Sometimes weakness is an alarm signal of an emergency. Sudden weakness of one side of the body, drooping of the corner of the mouth, and slurred speech indicate a stroke and require immediate emergency assistance. Rapidly worsening generalized weakness with difficulty breathing may be a manifestation of Guillain-Barré syndrome or a myasthenic crisis. [4]

Table 1. Terms: what exactly a person feels

Term	Key description	What does the doctor find out during the appointment?	Possible reasons come first
True muscle weakness	Decreased strength on objective testing	Distribution of weakness, reflexes, tone	Neurological and muscular diseases
General fatigue	Feeling exhausted, lacking strength, but still retaining power	Sleep, stress, mood, lifestyle	Anemia, endocrine disorders, sleep apnea, depression
Drowsiness	I feel like sleeping during the day	Sleep hygiene, snoring, respiratory arrest	Obstructive sleep apnea
Shortness of breath on exertion	Shortness of breath with effort	Cardiopulmonary assessment	Heart failure, lung disease
Dizziness	A feeling of spinning or instability	Neurological, vestibular tests	Low blood pressure, imbalance
Source: summarized from clinical guidelines. [5]

The main causes of weakness

Causes are conveniently grouped by system: hematological, endocrine and metabolic, infectious and post-infectious, neurological and muscular, cardiopulmonary, psychoemotional, drug effects, and sleep disorders. Several factors may be present simultaneously in one person, for example, anemia and sleep apnea. [6]

Anemia, especially iron deficiency and vitamin B12 or folate deficiency, often presents with fatigue, decreased endurance, and shortness of breath with exertion. Confirmation requires a complete blood count and assessment of iron stores, and, if necessary, vitamin B12 and folate levels. It is important to remember that ferritin increases with inflammation, so interpretation is based on C-reactive protein. [7]

Endocrine and metabolic causes include hypothyroidism, diabetes mellitus, adrenal insufficiency, and vitamin D deficiency. Electrolyte imbalances, especially sodium and potassium, cause muscle weakness, cramps, and arrhythmias. Dehydration increases weakness, dizziness, and reduces performance. [8]

Sleep disorders and obstructive sleep apnea cause daytime sleepiness, decreased concentration, and persistent fatigue, which patients often describe as weakness. Diagnosis is confirmed by sleep testing, and treatment includes lifestyle modification and positive airway pressure therapy. [9]

Neurological and muscular causes include stroke, polyradiculoneuropathy, myasthenia, and inflammatory myopathies. In such cases, objective neurological signs and often asymmetry are present, while myasthenia is characterized by muscle fatigue that worsens in the evening. Sudden unilateral deficits require immediate action. [10]

Table 2. Common causes of weakness by system

System	Common causes	What to look for
Hematopoiesis	Iron deficiency anemia, vitamin B12 deficiency, chronic inflammation	Pallor, shortness of breath with effort, tachycardia
Endocrinology	Hypothyroidism, diabetes, adrenal insufficiency	Chills, weight gain, thirst, hypoglycemia
Electrolytes and water	Hyponatremia, hypokalemia, dehydration	Convulsions, arrhythmia, thirst, dark urine
Dream	Obstructive sleep apnea	Snoring, pauses in breathing, daytime sleepiness
Neurology and muscles	Stroke, Guillain-Barré syndrome, myasthenia gravis, myopathies	Asymmetry, drooping eyelid, difficulty speaking, neck weakness
Mental health	Depression, anxiety	Decreased energy, interest and motivation
Post-viral conditions	Post-COVID state, other post-infectious syndromes	Chronic fatigue, exercise intolerance
Source: clinical guidelines and reviews. [11]

Red Flags: When Urgent Care Is Needed

Seek emergency medical attention immediately if you experience any signs of a stroke, such as sudden facial asymmetry, weakness in one arm, or speech impairment. Even if symptoms resolve, prompt evaluation is necessary, as it may be a transient ischemic attack (TIA). [12]

Signs of progressive generalized weakness with difficulty breathing, choking, a quiet voice, and a weak cough are dangerous. This may indicate Guillain-Barré syndrome or a myasthenic crisis with the risk of respiratory failure and requires hospitalization. [13]

A combination of weakness with fever, night sweats, unintentional weight loss, persistent cough, hemoptysis, and persistent chest pain is worrisome. Such symptoms require prompt referral and further investigation due to suspected infection, cancer, or lung or heart disease. [14]

Emergency signs also include sudden weakness in the legs with impaired sensation and urination, severe headache with neck stiffness, and severe hypoglycemia or hyperkalemia based on laboratory tests. If these symptoms are present, delay increases the risk of complications. [15]

Table 3. Red flags for weakness

Situation	What to do immediately
Signs of a stroke	Call emergency help
Rapidly increasing generalized weakness, poor breathing	Emergency hospitalization
Weakness with fever, night sweats, weight loss	Urgent consultation with a doctor and basic tests
Weakness with chest pain, shortness of breath	Urgent assessment of the heart and lungs
Acute weakness of the legs with impaired sensation and control of urination	Emergency neurosurgical routing
Source: guidelines and clinical reviews. [16]

How does a doctor make a diagnosis?

Step 1. Detailed questionnaire: onset and dynamics of symptoms, daily fluctuations, distribution of weakness, past infections, sleep and snoring, diet and weight loss, medications and supplements, alcohol consumption, comorbidities, mood, and stress. This step allows us to narrow the range of causes and select targeted tests. [17]

Step 2. Physical and neurological examination: assessment of strength in major muscle groups, tone, reflexes, coordination, and gait. Examination of the skin and mucous membranes, thyroid gland, signs of dehydration, pulse and blood pressure measurements, and oxygen saturation. A neurological profile helps localize the lesion and determine whether urgent care is required. [18]

Step 3. Basic laboratory tests for unclear fatigue or suspected systemic cause: complete blood count, ferritin with C-reactive protein, glucose and glycated hemoglobin, creatinine and glomerular filtration rate, sodium and potassium electrolytes, liver enzymes, thyroid-stimulating hormone and free thyroxine, vitamin B12. If indicated, a pregnancy test, creatine kinase, and electrocardiogram are added. [19]

Step 4. Instrumental and extended diagnostics as indicated: polysomnography if sleep apnea is suspected, neuroimaging for focal neurological symptoms, electromyography and nerve conduction studies for neuromuscular disorders, further examination of the causes of anemia, including assessment of iron deficiency and sources of blood loss. [20]

Table 4. Primary laboratory panel for unclear weakness

Test	Task	Comments
Complete blood count	Rule out anemia and inflammation	Interpret together with ferritin
Ferritin and C-reactive protein	Assess iron stores and inflammation	Ferritin may be falsely high when there is inflammation.
Electrolytes sodium and potassium	Eliminate imbalance	Hypokalemia is characterized by weakness and cramps.
Liver enzymes	Rule out liver damage	For systemic causes of fatigue
Creatinine and filtration rate	Evaluation of kidney function	Metabolic causes of weakness
Thyroid-stimulating hormone and free thyroxine	Rule out hypothyroidism	A common reversible cause of fatigue
Vitamin B12	Eliminate the deficit	Neurological symptoms are possible
Glucose and glycated hemoglobin	Rule out diabetes and hypoglycemia	According to clinical indications
Creatine kinase	If myopathy is suspected	According to the readings
Pregnancy test	In women of reproductive age	According to the readings
Source: reviews of fatigue management in primary care. [21]

Differential diagnosis: how to distinguish similar conditions

Weakness is often confused with drowsiness and shortness of breath. Drowsiness indicates sleep disturbances or depression, while shortness of breath suggests cardiopulmonary causes. Distinguishing between complaints and simple tests allows for a quick, targeted examination and avoids unnecessary testing. [22]

In true muscle weakness, localization signs are important: predominance of proximal weakness in myopathies, fatigue with involvement of the oculomotor and bulbar muscles in myasthenia, asymmetric focal deficit in stroke, symmetrical increasing weakness with sensory disturbances in Guillain-Barré syndrome. [23]

Mental disorders, particularly depression and generalized anxiety, often present with decreased energy, sleep, and concentration. It is important to identify and treat these conditions alongside a physical examination, especially in cases of long-term complaints without an obvious organic cause. [24]

Table 5. Weakness, fatigue, drowsiness and shortness of breath: differences

Sign	True weakness	General fatigue	Drowsiness	Dyspnea
Objective force	Reduced	Safe	Safe	Safe
Daily fluctuations	Possible with myasthenia	Often stronger in the evening	He falls asleep during the day	Increases with load
Key Tips	Asymmetry, reflexes	Stress, nutrition, anemia	Snoring, pauses in breathing	Shortness of breath, wheezing, chest pain
First tests	Neurological examination	Complete blood count, ferritin, thyroid hormones	Somnological examination	ECG, chest x-ray as indicated
Source: clinical guidelines. [25]

Medications as a cause of weakness

A number of medications can cause fatigue, muscle weakness, or drowsiness. These include first-generation antihistamines, benzodiazepines, and some antidepressants. Some cardiovascular medications, such as beta-blockers, can cause fatigue in some people. Finally, statins, although rare, can cause muscle symptoms, including myopathy. Never stop taking medications on your own, but be sure to discuss your symptoms with your doctor. [26]

Table 6. Drugs frequently associated with a feeling of weakness

Group	Examples	What does a person feel?	What to do
First-generation antihistamines	Diphenhydramine, promethazine	Drowsiness, a cotton-wool head	Discuss replacement with modern means
Benzodiazepines	Diazepam, lorazepam	Sedative effect, weakness	Review the need and dosage
Antidepressants	Different classes	Fatigue, drowsiness at the beginning	Assess tolerance and adjust the regimen
Beta blockers	Bisoprolol, metoprolol	Fatigue, decreased endurance	Assess the benefit-risk ratio
Statins	Atorvastatin and others	Myalgia, a rare myopathy	Check creatine kinase as indicated
Source: Clinical data and drug safety reviews. [27]

Post-viral weakness and post-COVID state

Following infections, including COVID-19, some people experience persistent fatigue, exercise intolerance, cognitive complaints, and sleep disturbances. The World Health Organization describes post-COVID-19 symptoms as those typically persisting for three months or longer, not explained by another diagnosis, and impairing daily functioning. [28]

The recommendations emphasize the need for an individualized rehabilitation plan, energy management, and gradual, symptom-titrated approaches to activity, taking into account post-exercise deterioration. This differs from rigid, fixed-intensity exercise programs. [29]

It is important to distinguish post-viral fatigue from myalgic encephalomyelitis. The UK guidelines for myalgic encephalomyelitis and chronic fatigue syndrome emphasize that so-called "graded exercise therapy" in the form of fixed, stepwise increases in physical activity time should not be offered, as it may worsen symptoms. [30]

Treatment

Basic principles: treatment is directed at the underlying cause, along with supportive measures. In cases of anemia, iron or vitamin B12 deficiency is corrected and the source of blood loss is eliminated. In cases of hypothyroidism, levothyroxine replacement therapy is initiated under the control of thyroid-stimulating hormone levels. In cases of electrolyte imbalances, the deficiency is replenished and the underlying factors are eliminated. [31]

For sleep disorders, apnea is diagnosed and therapy is prescribed to improve daytime functioning and reduce risks. For depression and anxiety, psychotherapy and pharmacotherapy are effective, often significantly reducing feelings of weakness. [32]

Following viral illnesses and in the post-COVID state, rehabilitation programs are used that include energy management training, sleep modification, breathing techniques, and a gradual increase in activity, strictly based on tolerance. A fixed, forced increase in activity without regard to symptoms is not recommended for myalgic encephalomyelitis. [33]

A review of medication therapy often yields rapid results: discontinuing or replacing sedating antihistamines, adjusting the dosage of psychotropic medications, and discussing alternatives for statin-associated muscle complaints. All changes are made in consultation with a physician, taking into account the risks of the underlying disease. [34]

Table 7. Self-help and medical care: what is appropriate

Situation	What can you do yourself?	When do you need a doctor?
Mild fatigue without red flags	Regular sleep, hydration, balanced diet, moderate physical activity, alcohol limitation, sleep hygiene assessment	If it lasts more than 2 weeks or interferes with work and life
Suspected anemia or hypothyroidism	Don't delay your visit for tests	Prescribing and monitoring therapy
Snoring, pauses in breathing, daytime sleepiness	Weight management, side sleeping, sleep hygiene	Referral to the sleep medicine service
Depressive symptoms	Seeking psychotherapy	Selection of therapy and monitoring
Side effects of medications	Keep a list of medications and symptoms	Shared decision on dose replacement or adjustment
Source: Clinical and patient-centered guidelines. [35]

When to see a doctor

Consult a doctor if weakness persists for more than 2 weeks, interferes with daily activities, is accompanied by fever, weight loss, persistent cough, unexplained pain, sleep disturbances with daytime sleepiness, depressed mood, or if you are taking medications that can cause weakness. This will allow for timely basic testing and clarification of the cause. [36]

Seek emergency medical attention immediately if you experience signs of a stroke, rapidly worsening generalized weakness with difficulty breathing, or severe neurological symptoms. Early treatment saves lives and reduces the risk of disability. [37]

Frequently asked questions

Is it possible to "overcome" weakness with exercise if it's simply fatigue?
Moderate regular activity is beneficial, but for post-viral fatigue and myalgic encephalomyelitis, the intensity is selected individually, focusing on tolerance, avoiding a fixed, forced increase in time. [38]

What tests should be done initially?
Most commonly prescribed are a complete blood count, ferritin with C-reactive protein, electrolytes, creatinine, liver enzymes, glucose and glycated hemoglobin, thyroid-stimulating hormone and free thyroxine, and vitamin B12. The list is then expanded as needed. [39]

How can you tell if it's weakness or drowsiness?
If you feel sleepy during the day, and loved ones notice snoring and pauses in breathing, you likely have a sleep disorder. With true weakness, strength is reduced during testing. A doctor can help differentiate between the two. [40]

Can dehydration cause severe weakness?
Yes, fluid deficiency increases fatigue, dizziness, and reduces performance. Stay hydrated, especially during fever and gastrointestinal illnesses. [41]

What medications most often cause a loss of energy?
Sedating antihistamines, benzodiazepines, some antidepressants, and, in some people, beta-blockers. Statins rarely cause muscle symptoms. Any adjustments to therapy should be made only with the advice of a doctor. [42]