Differential Diagnostic Report: 5 Causes of Fatigue

Hello everyone,

One of the most common complaints from client’s seeing a medical practitioner is fatigue. It can be caused from a number of reasons, from work-related stress, difficulty sleeping, your body is fighting a virus or even inadequate nutrition. Your practitioner will need to assess you, along with any other signs and symptoms you may be experiencing to determine the cause of fatigue. Below I’ve outlined 5 possible reasons for fatigue, however, It’s important to remember that while fatigue is common, it can be improved when the right diagnosis is made for you.

Possible Cause of Fatigue #1: Iron deficiency Anaemia.

Iron deficiency anaemia results when iron stores within the body are depleted so that the body is unable to make enough of the protein haemoglobin, which is responsible for delivering oxygen to the cells and tissues. Iron deficiency anaemia is a common health problem that can occur in both men and women at any age and ethnicity, although some people that may be at a greater risk than others include women of childbearing age, pregnant and lactating women, people with poor diets, people who donate blood frequently, athletes, babies and toddlers and vegetarians/vegans who don’t replace meat with other iron-rich foods. (Bupa Health Australia, iron-deficiency anaemia, 2014).

When investigating possible iron deficiency anaemia, it’s important to start with a full history and examination. Assess the patient’s symptoms and signs, diet, medicines and other possible causes of iron deficiency. A specific test known as Plasma Ferritin is a measure of iron stores in tissues and is the best test to confirm iron deficiency. A subnormal level is due to an iron deficiency, or, very rarely hypothyroidism or vitamin C deficiency. In difficult cases, it may be necessary to examine a bone marrow aspirate for iron stores. (Walker, Colledge, Ralston, Penman, 2014, pp. 1021-1035).

Some prevailing causes of iron deficiency in adults include an inadequate dietary intake, blood loss in situations such as blood donation, menstrual periods or medications, an increased need for iron in adolescence, pregnant and lactating women, exercise or an inability to absorb iron. The symptoms of iron deficiency anaemia can range from asymptomatic to mild at first, most people don’t realise they have mild anaemia until they have a routine blood test. In a clinical setting other signs and symptoms of a moderate to severe iron deficiency anaemia can include brittle nails, weakness, dizziness, tongue swelling, fatigue, pale skin, headaches, fast or irregular heartbeat, tingling in the legs, decreased immunity and cold hands and feet. (BetterHealthChannel, iron-deficiency-adults, 2016)

Possible Cause of Fatigue #2: Hypothyroidism.

Hypothyroidism is a condition involving a decrease of the hormones T3 and T4 from the thyroid gland that upsets the normal balance of chemical reactions in the body. These hormones have a massive impact on a persons health as they affect all aspects of metabolism. They maintain the rate at which the body utilises fats, carbohydrates and proteins, help control core body temperature and influence the heart rate. There can be a number of causes such as autoimmune diseases, radiation therapy, thyroid surgery and certain medications. The two main risk factors for hypothyroidism are age and sex, as the chances of developing the condition increase with age, and the risk is much greater for women. Besides age and sex, other risk factors that increase the chance of developing the disease are if a person has type 1 diabetes, rheumatoid arthritis, a family history of thyroid disease or any autoimmune diseases, recent thyroid surgery, radiation on the neck or upper chest area and anti-thyroid medication or treatment with radioactive iodine. (Mayo Clinic, 2015).

Hypothyroidism must be evaluated and diagnosed by a physician, usually an endocrinologist or primary care doctor. Many of the signs and symptoms of hypothyroidism are common in people with a normal functioning thyroid gland, so for a diagnosis to be reached it’s important to consider more than just a review of a patient’s clinical features. Other factors a doctor will examine include medical and family history, risk factors, physical examination and blood tests. The blood tests a doctor may order include the most definitive one called the Thyroid Stimulating Hormone (TSH) test, along with free thyroxine or T4, free T4 index or total T4 to aid in the diagnostic process.
(Endocrine Web, Risk Factors for Hypothyroidism, 2015).

An person affected with hypothyroidism can experience other symptoms such as fatigue, drowsiness, thin and brittle nails, excessive weight gain, mentally sluggish and sensitivity to cold temperatures. Advanced hypothyroidism in an adult is known as Myxedem, which commonly occurs in middle-aged women. An individual with this advanced condition can exhibit these clinical features along with other characteristics like swelling, or bloating to the facial tissue, a thickened tongue, and puffy eyelids. Congenital hypothyroidism, Cretinism, causes children to become dwarfed with a short, stocky body build, and a protruding tongue and abdomen. The face becomes abnormal with a broad nose, puffy eyelids and small eyes. Sexual organs fail to develop properly, and muscle growth is slowed to the point where a child cannot stand or walk. (Neighbors, Tannehill-Jones, 2015, pp. 310-311).

Possible Cause of Fatigue #3: Diabetes Mellitus.

Diabetes is a complex condition that can have affects on the entire body. It requires daily self-care and if complications develop, diabetes can have a significant impact on life quality and life expectancy. There are three main types of diabetes including Type 1, Type 2 and Gestational Diabetes. Type 1 diabetes is an autoimmune disease where the immune system of an affect person destroys the cells in the pancreas that produce insulin. Type 1 represents around 10% of all cases of diabetes, it is a genetically acquired condition and is not linked to modifiable factors. (Diabetes Australia, Type 1 Diabetes, 2015).

Type 2 is a progressive condition where the body becomes resistant to the normal effects of insulin and gradually loses the capacity to produce enough insulin in the pancreas. Type 2 is associated with modifiable lifestyle risk factors and has a strong genetic disposition that runs in families. There is no single cause of type 2 diabetes, well-established risk factors include obesity, hypertension, insufficient physical activity, smoking, poor diet, and middle age. (Diabetes Australia, Type 2 Diabetes, 2015).

Gestational Diabetes affects between 5% to 10% of pregnant women in Australia currently between 24-28 weeks gestation. It is diagnosed when higher than normal blood glucose levels first appear during pregnancy, and is now a routine examination for pregnant females. It is idiopathic in development but there are few risk factors that seem to occur amongst pregnancy such as a family history of diabetes, obesity, previously given birth to a large baby, over 25 years age and from an indigenous Australian or Torres Strait Islander background. (Diabetes Australia, Gestational Diabetes, 2015).

Diagnosis of Diabetes Mellitus depends on the findings of hyperglycaemia in a fasting blood sugar test. A general practitioner will assess a patients clinical symptoms that may be commonly found in the disease, but a diagnosis must depend on positive evidence of blood tests. Tests that may be required for the diagnosis include tests for sugar in urine, tests for acetone in urine and blood tests including fasting blood sugar and glucose-intolerance test. If the sugar levels are above 120mg per 100cc of blood, and a glucose-tolerance test that shows blood sugar to be more than 160mg per 100cc of blood, even after two hours, the practitioner may diagnose the case to be Diabetes Mellitus. (Mathur, 2005, pp.24-27).

Additional Signs and Symptoms that may be observed in a clinical setting could include the more common clinical features such as fatigue, frequent and copious urination, abnormal thirst, excessive hunger, dryness of mouth, frequent infections, sensitivity to heat and cold, pyorrhoea alveolaris and xenthoma diabeticum. Over time, the surge and crash of dissolved glucose and insulin that occurs in diabetes can end up causing irreparable damage to many body organs and systems. Serious symptoms of diabetes due to abnormal fat and protein metabolism in advanced cases need to be cared for by a physician such as emaciation and progressive weight loss, vertigo, gangrene, acidosis and dehydration, hypertension, heart disease, kidney disease, nerve damage, cognitive issues, infections in the skin, cardiac symptoms and coma. (Mathur, 2005, pp. 22-23).

Possible Cause of Fatigue #4: Coeliac Disease.

Coeliac Disease causes the immune system to react abnormally to gluten when ingested affecting the small intestine, which is responsible for absorbing nutrients from food. In a person with coeliac disease the mucosa of the small intestine is damaged causing inflammation of the tiny, finger-like projections called villi. The villous atrophy reduces the surface area, which enables absorption of minerals and vitamins, leading to nutritional deficiencies. The disorder affects people of all ages and sex, people born with the genetic predisposition will develop the condition, however environmental factors play an important role in triggering inflammation in infancy, childhood and later in life. The genes associated with coeliac disease are HLA DQ2 and HLA DQ8, where either one or both of these genes are present. There is a higher risk of a person developing the disease if a first degree relative has been diagnosed. (Better Health Channel, Coeliac disease and gluten sensitivity, 2016).

Coeliac Disease is a serious medical condition with lifelong implications, so it’s important to have a definitive diagnosis made by a practitioner. There are various, simple tests available for the diagnosis of the disease including blood tests, coeliac serology, which measures the antibody levels in the blood that are typically elevated in people with untreated coeliac. These tests are less reliable for children under the age of four years, as their antibody levels can fluctuate, which is why it is suggested to perform the tests on two separate occasions at least three months apart. A small bowel biopsy is essential to confirm diagnosis. This procedure involves a gastroscopy where several tiny samples of the small bowel are taken while the patient is under a light anaesthetic sedation. When the blood or small bowel biopsy results are difficult to interpret, Gene HLA testing can be useful in selective cases. This tests is performed on a blood test or cheek scraping, ordered through a general practitioner. With over 99% of people affected with the disease have HLA DQ2 or HLA DQ8 as part of their genes, a negative tests will effectively rule out coeliac disease. The gene test alone cannot diagnose coeliac disease which is why it’s important to undertake various tests for confirmation before starting a gluten free diet. (Coeliac Australia, Diagnosis, 2016).

The clinical features for coeliac disease can range from minor to sever or even asymptomatic. Some symptoms present can be confused with irritable bowel syndrome or a sensitivity to wheat or other food, which is why some cases go undetected for years. The most common symptoms among adults include anaemia, bloating, nausea, stomach cramps, weight loss, fatigue, vomiting and diarrhoea or constipation. The symptoms among children include symptoms an adult may experience along with bulky-foul-smelling bowel motions, irritability, delayed growth, tiredness, chronic anaemia, delayed puberty and even weight gain in older children. (Better Health Channel, Symptoms for coeliac disease, 2016).

Possible Cause of Fatigue #5: Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Myalgic Encephalopathy/Chronic Fatigue Syndrome affects thousands of people all different ages and ethnicity. It is a severe, debilitating fatigue, painful muscles, disordered sleep, gastric disturbances, poor memory and concentration. In many cases the triggers include viral infections, operations and accidents, although some people experience a slow, insidious onset. ME/CFS has attracted controversy as its been debated as to whether it is actually an illness at all. Although the situation is still not settled, many influential agencies such as The World Health Organisation and The Department of Health, are now in agreement that the condition is real. Loosely the risk factors have been debated as psychiatric, physical or behavioural reasons as to why a person develops the disorder. What also seems possible is that the illness is currently defined as Chronic Fatigue Syndrome is actually a number of different conditions that are characterised by similar signs and symptoms. Until more information is known, there will remain a wide range of people who are affected , as research into causes, treatments and cure options are continued. (ME Association, What is ME/CFS?, 2016).

Clinicians use a diagnostic criteria to provide guidance on the specific sign, symptoms, or test results that indicate the presence of illness and classifying patients into diagnostic categories. The pathology of ME/CFS remains unknown and there is currently no diagnostic test for the disorder, most of the existing diagnostic criteria has been developed through the consensus of experts. One particular example is Fukuda case definition for CFS, established in 1994. Fukuda and colleagues published a case definition for ME/CFS and idiopathic chronic fatigue that was intended to help guide research in adult populations. Fukuda defines chronic fatigue as “self-reported persistent or relapsing fatigue lasting longer six or more consecutive months” and requires a clinical evaluation to identify or rule out any medical or psychological conditions that could explain the chronic fatigue’s presence. To diagnose ME/CFS requires the absence of exclusionary condition, sever chronic fatigue and at least four to eight minor symptoms. (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Board on the Health of Select Populations, Institute of Medicine, 2015).

Clinical features associated with Myalgic Encephalopathy/Chronic Fatigue Syndrome include severe fatigue that is persistent/recurrent, that has resulted in a substantial reduction in activity levels, and unexplained by other condition. Other symptoms from the criteria outline in clinical guidelines include difficulty sleeping such as insomnia and hypersomnia, a disturbed sleep-wake cycle, muscle and joint pain, headaches, painful lymph nodes without pathological enlargement sore throat, cognitive dysfunction, physical or mental exertion, general malaise or ‘flu-like’ symptoms,palpitations and difficulties with dizziness and nausea. (ME Research UK, What is ME? 2016)

It’s important to stress that ME/CFS remains a ‘diagnosis of exclusion’, meaning that other possible causes of a patient’s symptoms have been excluded, often by testing before this diagnosis is given. As the NICE Guideline states “A diagnosis should be made after other possible diagnoses have been excluded and the symptoms have persisted for four months in an adult and three months in a child”. (NICE Clinical Guidelines, 2007).

Healthiest regards



Berber, E., Sargis, R.M. (Eds.) (2015). Risk Factors of Hypothyroidism. Could you be at risk of becoming Hypothyroid? Retrieved from http://www.endocrineweb.com/conditions/hypothyroidism/risk-factors-hypothyroidism

Better Health Channel (2016). Iron-Deficiency-adults. Retrieved from https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/iron-deficiency-adults

Bupa Health Australia (2016). Iron-Deficiency Anaemia. Retrieved from

Coeliac Australia (2016). Coeliac Disease Diagnosis. Retrieved from http://www.coeliac.org.au/diagnosis/

Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Board on the Health of Select Populations, Institute of Medicine (2015). Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an illness. [Study], Washington: USA. National Academy of Sciences. Chapter 7, (Recommendations).

Diabetes Australia (2015). About Diabetes. Retrieved from https://www.diabetesaustralia.com.au/what-is-diabetes

The Mayo Clinic (2016). Hypothyroidism: Symptoms and Causes. Retrieved from http://www.mayoclinic.org/diseases-conditions/hypothyroidism/symptoms-causes/dxc-20155382

Mathur, K.N. (Eds) (2005). Diabetes Mellitus. It’s Diagnosis and Homoeopathic Treatment. New Delhi: B. Jain Publisher (P) Ltd. Chapter 9, Diagnosis & Diagnostic Tests pp. 24-27. Chapter 8, Symptoms pp. 22-23.

ME Association (2016). What is ME/CFS? Informing and supporting those affected by ME/CCFS. Retrieved from http://www.meassociation.org.uk/about/what-is-mecfs/

ME Research UK. Scottish Charitable Incorporated Organisation.(2016). What is ME?. Retrieved from http://www.meresearch.org.uk/what-is-me/

National Institute for Health and Care Excellence, NICE. (2007). Assessment and diagnosis of chronic fatigue syndrome myalgic encephalomyelitis. Retrieved from https://www.nice.org.uk/guidance/CG53

Neighbors, M., Tannehill-Jones, R. (Eds) (2015). Human Diseases (4th ed). USA: Cengage Learning. Chapter 14, Endocrine Disease and Disorders pp. 310-311 (Hypothyroidism)

Walker, B., Colledge, NR., Ralston, SH., & Penman, ID. (2014). Davidson’s Principles and Practice of Medicine (22nd edn). Edinburgh: Churchill Livingstone Elsevier, 
Chapter 24, Blood Disease, pp.1021-1035 (Anaemias)


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