Fatigue is a subjective feeling of tiredness and lack of energy during or after physical activity or avoiding/ lack of interest in physical activity. Individuals must be evaluated for medical causes of tiredness and fatigue prior to associating it with psychosocial factors.
Fatigue is a very general term …
It is very difficult to define fatigue since it’s a very general term. Dyspnea or shortness of breath, somnolence or excessive sleeping and muscular weakness are specific terms which need to be differentiated as these terms may be used simultaneously by the patient.
Furthermore, an individual may have fatigue or lethargy in combination with shortness of breath, weakness and other symptoms. Chronic fatigue or chronic fatigue syndrome is another entity in which the symptoms last more than 6 months.
Tiredness or fatigue is a very common symptom, almost everybody has experience at some point in his life.
The most common causes of tiredness include:
- Inadequate sleep
- Increase working hours
- Stress, relationship difficulties, illness in the family,
- Lack of exercise
- Chronic medical conditions
Other than the causes listed above chronic idiopathic fatigue syndrome is also one of the major causes of tiredness and fatigue.
What are the medical causes of tiredness and fatigue?
The following list of medical conditions may lead to lethargy, fatigue or tiredness.
- Hematologic causes – Anemia and leukemias
- Endocrine causes – Hypothyroidism, Addison disease, Cushing syndrome, hypopituitarism, diabetes mellitus, and hypogonadism.
- Electrolyte disturbance – Hypokalemia, hypercalcemia and hyponatremia
- Infectious causes – Hepatitis, endocarditis, tuberculosis, mononucleosis, parasitic infections and, HIV infection.
- Malignant causes – All malignant tumors
- Cardiovascular causes – Heart failure and Hypotension
- Pulmonary causes – Chronic obstructive pulmonary disease and other chronic lung diseases
- Metabolic causes – Chronic renal failure, chronic hepatic failure
- Medications – Sedatives, opiates, antidepressants, and antihypertensive drugs.
- Miscellaneous – Insomnia, Sleep apnea syndrome, gastroesophageal reflux, allergic rhinitis, Myopathy, Dementia and delirium
Few of the very common and important ones will be discussed here:
- Thyroid disorders
- Cushing’s and Addison’s disease
- Chronic infections (Tuberculosis and HIV)
- Chronic renal failure
- Chronic liver disease
- Heart failure
Anemia is a major cause of tiredness:
Patients with anemia may notice progressive Pallor, easy fatigability, tiredness, palpitations, headaches, and shortness of breath.
Anemia in adult females is usually due to iron deficiency because of excessive menstrual blood losses. Iron deficiency anemia in males is usually due to the anemia of blood loss from the gastrointestinal tract.
Other than anemia of iron deficiency patients can have folate deficiency and vitamin B12 deficiency as well. These patients usually are having a chronic diarrheal state like celiac disease, malnutrition or are strict vegetarians.
Anemia apart from the deficiency of enzymes and Minerals can also be secondary to early destruction of red cells, as in hemolytic anemias like thalassemia.
Patients with chronic conditions like malignancies, liver and renal diseases can also have anemia which is usually due to anemia of chronic disease.
In a group of patients, anemia can also be due to inadequate production by the bone marrow as in aplastic anemia.
The WHO cut-offs for a normal hemoglobin in males and females are 13.5 g/l and 12.5 g/l respectively.
Anemia is not a diagnosis!!
Anemia is not a diagnosis and further tests like serum ferritin, Vitamin B12 and folate levels and investigations for the underlying deficiency states should be carried out.
These tests may include:
- Stool for occult blood
- Celiac serology for malabsorption
- Upper and lower gastrointestinal endoscopy
- Bone marrow biopsy
- Reticulocyte count and Coombs test
Treatment of anemia depends upon the cause and the deficiency States. Simple replacement of the hematinics can be sufficient in patients who are malnourished or vegetarians.
Autoimmune Hemolytic anemias require treatment with steroids and immune-modulators. Splenectomy may be considered for hereditary spherocytosis and autoimmune hemolytic anemias.
Blood transfusions and iron chelators to avoid iron overload may be the only treatment options for congenital hemolytic anemias like thalassemia and aplastic anemia. Bonemarrow transplantation may benefit a subset of patients with these disorders.
Thyroid disorders can also cause excessive tiredness. Both hyperthyroid and Hypothyroid States can lead to excessive tiredness and fatigue.
Hypothyroid patients have excessive sleep, cold intolerance, constipation, weight gain, and proximal muscle weakness while patients with hyperthyroidism can have heat intolerance, insomnia, and proximal muscle weakness.
Diagnosis is confirmed by doing thyroid function tests (TSH, T3, and T4)
Treatment depends upon the condition. Thyroxine replacement in hypothyroidism or antithyroid drugs + – thyroid surgery or radioiodine therapy in hyperthyroid States
Cortisol – The stress hormone:
Cortisol excess also called Cushing syndrome can also lead to proximal muscle weakness and easy fatigability, Diabetes, hypertension, bone fragility, and osteoporosis.
Similarly, cortisol deficiency called adrenal insufficiency or hypo-aldosteronism can also cause fatigue, abdominal pain, nausea, vomiting, and weight loss.
Diagnosis is confirmed by doing an early morning serum cortisol levels, 24-hour urine for cortisol levels, an overnight dexamethasone suppression test, and a short synacthen test for adrenal insufficiency. Treatment depends upon the cause.
Diabetes is the mother of all diseases
Diabetes is one of the major causes of tiredness and fatigue. In diabetic individuals, the blood sugars in the plasma are elevated but the cells, tissues, and organs are starving.
Diabetes also leads to cellular dehydration, nerve dysfunction, early atherosclerotic disease, and chronic renal failure. All these, in turn, can add on to the symptoms of fatigue and lethargy. Diagnosis of Diabetes is discussed in detail.
Diabetes leads to serious complications. These complications include both microvascular and macrovascular complications. Complications of diabetes are discussed in detail. Treatment of diabetes requires an individualized approach.
Electrolytes disturbances – Hypokalemia
Symptoms of hypokalemia can range from muscle cramps, fatigue, lassitude to weakness and muscle paralysis. Hypokalemia can occur in patients due to excessive gut losses, renal losses or malnutrition.
Diarrhea is a common cause of hypokalemia due to gi cause. Causes of hypokalemia due to renal wasting include diuretic use and renal tubular acidosis. Treatment aims at potassium replacement via oral tablets, syrups or in severe cases iv.
Chronic infections cause tiredness too!
Chronic infections like tuberculosis, fungal infections, and HIV infections can lead to asthenia, weight loss, anemia (of chronic disease) and central nervous system manifestations.
Certain drugs used to treat these conditions can also have adverse neurological effects and sedative properties leading to lethargy and tiredness.
Cancers – Important cause of fatigue
Cancer cachexia is the medical term used when patients with a malignant condition develop marked weight loss. The diagnosis of malignancy or cancer itself is a horrible news for the patient and leads to anxiety and depression.
Furthermore, cancers are associated with anorexia, nausea, vomiting, skeletal pains, anemia, and weight loss. In addition, chemotherapeutic drugs have serious adverse effects ranging from bone marrow suppression, oral ulcers, diarrhea (mucositis), electrolyte disturbances like hyponatremia and make the patient prone to opportunistic infections.
Chronic renal failure
Chronic renal failure has subtle symptoms these include symptoms of anemia (like pallor, palpitation, lethargy, and headache), metabolic bone disease (defective vitamin D activation leads to hypocalcemia and hypophosphatemia, proximal muscle weakness and muscle pains), and symptoms of acidosis and uremia.
Chronic liver disease
The liver is a major organ involved in metabolism and detoxification of various waste products. Patients with liver disease develop chronic fatigue, anorexia, and muscle wasting.
Since albumin, proteins and gamma globulins are one of the major synthetic functions of the liver, patients with liver disease may develop hypoalbuminemia and hypoproteinemia. Thus patients develop muscle wasting.
Similarly, elevation of ammonia levels in the blood may lead to an altered sleep pattern, drowsiness, lethargy, and unconscious state. Patients develop anemia as a result of gastrointestinal bleeding and anorexia, further aggravating the problem.
Another cause of anorexia, nausea, and vomiting in these patients is the mechanical effect of ascites on the stomach, stomach ulcer, and varices.
Heart failure – cardiac cachexia
Heart failure is another major cause of fatigue and muscle wasting. Cardiac cachexia is the term used to describe muscle wasting and weight loss in patients with heart failure. These patients have chronic liver congestion that leads to anorexia and decreased protein synthesis.
Patients may also feel tired and lethargic because of the chronically reduced blood and oxygen supply to major organs of the body like the brain, kidneys, liver, and muscles. Drugs used to treat these conditions may potentiate the problem. These include beta blockers, nitrates, and diuretics.
Hypogonadism causes tiredness too!
Apart from the functions related to sexuality, Androgens are required for muscle strength and prevention of osteoporosis. Hypogonadism is often missed in the adults and elderly because of the subtle symptoms.
Common features of hypogonadism include loss of libido, lack of energy and strength, tiredness, early osteoporosis, weight gain, and dyslipidemias. In contrast to elderly individuals, prepubertal individuals have a poor development of secondary sexual characteristics.
Morning serum levels of testosterone confirm the diagnosis in most cases. Replacement of androgens in the form of patches, tablets or injections is the treatment.
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