tiredness Flashcards
What is the difference between tiredness and fatigue?
Tiredness can be relieved by sleep and rest
Fatigue is when the tiredness is often overwhelming and is not relieved by sleep and rest
In what cases would men and postmenopausal women feel tired due to anaemia?
Ulcer - bleeding of stomach lining → anaemia
Taking NSAIDs - blood loss from intestine or iron deficiency → anaemia
What deficiencies can cause anaemia that leads to tiredness?
Iron, Vitamin B12 and Folate
An overload of which of these minerals can cause tiredness as well?
Iron → Haemochromatosis can lead to tiredness
Haemochromatosis causes pulmonary, pancreatic and hepatic dysfunction, all of which are risk factors for anaemia
What is sleep apnoea and how can this cause tiredness?
Condition where your throat narrows or closes during sleep and repeatedly interrupts your breathing
This leads to loud snoring and drop in blood oxygen levels so you feel tired next day and you wake up often in the night
Who is sleep apnoea most common in?
Overweight middle aged men
What can exacerbate sleep apnoea?
Drinking alcohol - relaxes muscles in throat
Smoking - irritates nose and throat causing swelling here
How can an under-active thyroid cause tiredness?
Low thyroxine –> Tiredness
What other symptoms may present in an under-active thyroid?
Low thyroxine → Weight gain, aching muscles and dry skin (reduced eccrine gland secretion)
What is coeliac disease?
Condition where your immune system attacks your own tissues when you eat gluten
What are other symptoms of coeliac disease?
Diarrhoea, bloating, anaemia, weight loss
Why can coeliac disease be very dangerous?
A lot of people who have it are not aware
What is myalgic encephalomyelitis also known as?
Chronic fatigue syndrome
What is ME?
Severe and disabling fatigue that goes on for at least four months
What are other symptoms that may present with Myalgic encephalomyelitis (ME- Chronic Fatigue Syndrome)?
Muscle or joint pain
What are some of the symptoms of type 1 and 2 diabetes?
Tiredness
Very thirsty, peeing a lot (perhaps at night), weight loss
What is glandular fever and what symptoms does it result in?
Common viral infection causing fatigue, along with fever, sore throat and swollen gland
What category does glandular fever occur commonly in?
Teenagers and young adults
When do symptoms of glandular fever usually clear up?
Symptoms usuallyclear up within4 to6 weeks, but the fatigue can linger for several more months
How can depression make you feel tired?
It can stop you falling asleep or cause you to wake up early in the morning, making you feel more tired during the day
What is Restless Legs Syndrome?
Overwhelming urge to move your legs, which can keep you up at night
You may also have crawling sensation or deep ache in legs
Legs may jerk spontaneously through the night
How does RLS cause tiredness?
Leads to disrupted sleep and poor sleep quality so you feel very tired throughout the day
Does Generalised Anxiety Disorder affect more men or women?
Women
How does GAD affect patients?
They feel worried and irritable and people with GAD often feel tired
What percentage of all GP consultations are due to fatigue?
7% of all GP consultations is due to fatigue
What percentage of patients with fatigue receive a diagnosis?
66% of patients with fatigue receive a diagnosis
What percentage of patients with fatigue receive a diagnosis through blood tests?
<10% of patients with fatigue receive a diagnosis through blood tests
Some cannot be diagnosed with blood tests e.g. Anxiety
What are common red flag causes of tiredness?
- Depression
- Chronic Heart Failure
- Diabetes Mellitus
- COVID-19
- HIV infection
- Acute myocardial ischaemia
- Atrial fibrillation
- COPD
- Tuberculosis
- Stroke
What are common non red flag causes of tiredness?
- Insomnia disorder
- Iron-deficiency anaemia
- Iron-deficiency without anaemia
- Hypothyroidism
- Hyperthyroidism
- EBV infection
- Influenza infection
- Medicine-induced fatigue
- Alcohol dependence
- Drug dependence
- Toxoplasmosis
What are some uncommon red flag causes of tiredness
- Addison’s disease
- Chronic myeloid leukaemia
- Hodgkin’s lymphoma
- Primary biliary cirrhosis
- Underlying malignancy (non-lymphoma)
What are some uncommon non red flag causes of tiredness?
- Obstructive sleep apnoea
- Obesity hypoventilation syndrome
- Restless leg syndrome
- Coeliac disease
- Hypopituitarism
- Myelodysplastic syndrome
- Non-Hodgkin’s syndrome
- Cytomegalovirus
- Lyme disease
- Brucellosis
- Chronic renal disease
- Multiple sclerosis
- Parkinson’s disease
- Fibromyalgia
- Vit D deficiency (osteomalacia)
- Systemic lupus erythematosus
- Chronic fatigue syndrome
- Chronic idiopathic syndrome
- Heavy metal toxicity
How would you classify the tiredness in fatigue?
Tired is subjective
Look at frequency (common-uncommon)
Look at consequence (less serious - very serious)
Assessment of fatigue on best practice BMJ
What are 4 differential diagnoses for Mina’s fatigue?
Hypothyroidism - dry skin, weight gain and tiredness, cold intolerance, constipation, problems with periods
Vitamin D - heritable, tiredness
Chronic fatigue syndrome - psychological stress
Anaemia - tired, vegetarian therefore lack of iron
What are less likely diagnoses for Mina?
Sleep apnoea - didn’t mention isssues with sleep
Glandular fever - no lymphadenopathy or toxical insulates, no symptoms of infections
Lupus - no joint pain or muscle aches or pain
Pregnancy - not pregnant
What blood tests would you choose for each of the diagnoses?
- Hypothyroidism
- Anaemia and Haematological abnormalities
- Diabetes
- Vit. D deficiency
- CKD
- Hypothyroidism: TFT (low T4/thyroxine, TSH and T3)
- Anaemia and Haematological abnormalities: FBC (low RBC, low Hb)
- Diabetes: HbA1c (above 48mmol/mol)
- Vit. D deficiency: Vit. D
- CKD: U&E (abnormality in Na+, K+, HCO3-, urea, creatinine, glucose)
What are reasons to not order:
- CRP
- Coeliac screen
- Autoimmune screen
- EBV Serology ?
- CRP - other inflammatory conditions so not very specific
- Coeliac screen - constipated but no other symptoms so would not
- Autoimmune screen - takes time to come back and expensive so need good reason to order it
- EBV Serology - causative for glandular fever but already less likely
What would be the expected TSH, T4 and T3 for the patient if they have hypothyroidism?
TSH - High due to less negative feedback from T4 and T3
T4 - Low due to hypothyroidism
T3 - Low due to hypothyroidism
What are the causes of primary hypothyroidism?
- Iodine deficiency - lack of Thyroxine production
- Hashimoto’s - Antibodies against TSH receptors therefore no TSH effect on thyroid and so lack of thyroxine production
- Viral thyroiditis - due to viral infection, hypo-thyr. is the last stage of this infection and occurs whilst body is resolving infection
- Congenital - hypoplastic
- Thyroidectomy - lack of follicular cells
- Cancer treatments - radiotherapy induced destruction of thyroid gland cells
What are the secondary causes of hypothyroidism?
- Pituitary adenoma - impaired blood flow to normal tissue/ compression of normal tissue so less TSH secreted
- Craniopharyngioma - progressive loss of production of some or all of pituitary hormones such as TSH
- Sheehan’s syndrome - ischaemic necrosis of pituitary gland therefore hypopituitarism and lack of TSH secretion
- Iron overload - Iron causes injury to thyroid followed by development of anti thyroid antibodies and hypothyroidism
- Sarcoidosis - thyroid antibody positive in 20-30% of patients with extensive infiltration by epithelioid granulomas
What does the Antigen Presenting Cell mistake for a foreign antigen in Hashimoto’s Hypothyroidism?
TPO is picked up as an antigen by Antigen Presenting Cell
What does the APC do after it recognises the ‘foreign’ antigen?
Antigen Presenting Cell presents MHC II to the T cell’s
What is the difference in how endogenous and exogenous antigens are recognised in the body?
Endogenous antigens presented by MHC I on the Cytotoxic T cells
Exogenous antigens floating around are ingested by professional APC and then presented by MHC II
What is the co-stimulation required for the T cell to be activated?
APC presents B7 to the T cell’s CD28 as the T cell needs co-stimulation from both the B7 and MHC II
What does the T-cell’s TCR then bind to in the B cell?
MHC II
What is the co-stimulation required by the B cell to become activated?
B cell also needs co-stimulation from the T cell’s CD40 onto it’s CD40L
What is the resultant product that leads to thyroid damage?
Anti-TPO antibodies attack the thyroid gland’s TPO
Which cells are innate cells in the immune system?
- Eosinophil
- Basophil
- Neutrophil
- Macrophage
- Dendritic cell
Why do the innate cells not attack host cells?
Innate cells → Very fast and so they detect molecular patterns on the cell surface of the host cells such as PAMPs
Host cells, physiologically do not release these and so there is no attack on them
What stops the B and T cells from attacking the host cells?
B cells and T cells → AIRE expresses many genes in the body so it is possible for the thymus or bone marrow to produce a variety of antigens through mixing combinations of genes which the B and T cells interact with during development and if they are autoimmune then they are destroyed
They are released into the circulation if they did not react with any of the host cell antigens replicated by AIRE
Treg cells are responsible for suppressing this autoimmunity and destroying them
NK cells → Inhibitory receptor on the NK cell as well as a stimulatory receptor
The stimulatory receptor binds to the stimulatory ligand of the host/foreign cell
The inhibitory receptor binds to the self-MHC I which is present on all nucleated (host) cells
If both receptors are bound, then the NK cell does not react which should be good as all host cells have the MHC I
Foreign cells or abnormal host cells will not usually have self-MHC I and so the NK cell has nothing to inhibit it from killing the cell
What proportion of tiredness symptoms resolve within 4 weeks?
3/4
2/3 of tiredness episodes are triggered by what?
Life stresses
What are 3 types of tiredness?
Drowsiness
Shortness of breath
Weakness
Is exertional tiredness more likely to be physical or mental?
Physical - ‘I feel ok when I wake up, but it gets worse as I do things’ - this is worrying
What proportion of people who are tired will present to GP with tiredness?
1 in 400
After finding out the type of tiredness, what is the next approach?
To find out why this patient presented
E.g. functional impairment - not being able to make food for their family etc
What are some of the red flag symptoms associated with tiredness?
- Specific malignancy features - focus on lung, breast, colon, upper GI and gynae
- Weight loss - Thyroid, Coeliac disease
- Infective symptoms - TB, Glandular fever, Lyme
- Lymphadenopathy
- Focal neurology - stroke
- Joint pains - rheumatoid arthritis
What would you do after screening for red flag symptoms?
Explore any psychological triggers
Give 5 examples of psychological triggers
- Money
- Family
- Work
- Drugs and Alcohol
- Mood
What are the minimum requirements in the examination of a patient who presents with tiredness?
- Pulse
- Blood pressure
- BMI
What proportion of blood tests which are for tiredness, will give a physical cause for tiredness?
3%
What are the initial bloods taken for tiredness?
- FBC - not just for anaemia but also iron deficiency and haematological malignancy
- Lymphomas can have a normal Total WCC with an abnormal differential in early stage, later could be low RBC, WCC, platelets
- Thyroid function
- ESR
- Glucose: diabetes mellitus
Treating what for anaemic menstruating women can improve symptoms of tiredness for them?
Low ferritin
Why do patients get an under active thyroid?
- Autoimmune thyroid disease
- Radioactive iodine treatment
- Anti-thyroid drugs
- Medicines: lithium and amiodarone
- Health foods in excess
- Pituitary gland malfunction
- Radiation for head and neck cancers
- Congenital hypothyroidism
Explain how autoimmune thyroid disease causes an under-active thyroid?
Most common cause
Self destructive process in which the body’s immune system attacks the thyroid cells as though they were foreign cells and the most common cause of this is Hashimoto’s
What is radioactive iodine treatment?
Given during surgery to correct hyperthyroidism or to treat thyroid cancer
Explain how an anti thyroid drug can cause an under active thyroid
If given for an overactive thyroid disorder in too large a dose
What is lithium and amiodarone used for?
Used for certain mental health problems
Used for particular heart problems
Which foods can cause an under-active thyroid?
Seaweed (kelp)
How common is radiation for head and neck cancers?
Not common in the UK
How does congenital hypothyroidism work?
Failure of development of thyroid gland
Will a patient with an under active thyroid get better?
Yes by treating the underlying cause whether physically through drugs, surgical interventions but treatment usually lifelong
What is the best treatment for patients with an under active thyroid?
Usually depends on the cause but if there is a lack of thyroxine production, then levothyroxine is option to take
Would patients need to have treatment for the rest of their lives?
Usually unless surgery, then yes
What are the side effects of treatment and how can patients cope with them?
If too high dose - atrial fibrillation or bones may get too thin
Weight gain or loss, headache, vomiting, diarrhoea, changes in appetite, fever, changes in menstrual cycle, sensitivity to heat
Talk to GP to lower the dose
Should patients with an under active thyroid change what they eat?
Eat at least 5 portions of a variety of fruit and veg every day
Base meals on higher fibre starchy foods like potatoes, bread, rice or pasta
Have some dairy or dairy alternatives
Eat some beans, pulses, fish, eggs, meat and other protein
Does under active thyroid run in the family?
Yes, genetic causes account for 15-20% of congenital hypothyroidism and in general, thyroid conditions do run in the family
How will the treatment be managed if a female patient wished to get pregnant?
- Consult GP as soon as they know they are pregnant or wish to try and get pregnant
- Have a blood test before conceiving
- If already taking levothyroxine, it is recommended that the dosage is increased immediately by 25-50mcg daily
- Arrange to have TFT asap
- Even if TFT isn’t ideal at start of pregnancy, as long as levothyroxine has been increased, the chance of complications of pregnancy occurring are only slightly higher and a normal pregnancy is likely
Give some examples of the most common symptoms of hypothyroidism
After a few months or years untreated:
- dry, flaky skin
- hoarse voice
- low mood or depression
How is hypothyroidism diagnosed?
TFT: High TSH, low T4
Thyroid antibody screen
What factors may affect these tests unexpectedly?
Medications the patient is on
Common illnesses that can alter the blood test readings temporarily
What is mild thyroid failure or sub clinical hypothyroidism?
Slight hypothyroidism that no obvious symptoms are seen and can only be detected by blood tests
What would the levels of TSH and T4 be for mild thyroid failure or sub clinical hypothyroidism?
Slightly high TSH, normal T4
If a patient has this, what must be done?
Regular TFT and consult doctor if notice of any symptoms as they may benefit from treatment
What is the initial dose of Levothyroxine dependent on?
Patient’s weight and blood test results
What dose do most patients require?
100-150mcg per day
Can be lower than 75 or above 300mcg depending on needs
If the patient has heart problems or has severe hypothyroidism, what should be done to the dose?
Increased
During the period where the TFTs take a while to get back to normal, what is done?
Regular TFTs every 6-8 weeks and dose may be adjusted according to results of tests
When in the day should Levothyroxine be taken?
In the morning with water, on an empty stomach at least half hour before eating and drinking anything
How far from taking Ca2+, Fe2+, cholesterol-lowering drugs and multivitamin tablets should Levothyroxine be taken?
4 hours as these can reduce absorption
What increases absorption of levothyroxine and how?
Grapefruit as it increases acidity of the stomach
Why would a patient not notice a difference if they miss a tablet of Levothyroxine for one day?
The body has a big reservoir of thyroxine so no difference is detected
In extreme temperatures what happens to the levothyroxine tablet?
It deteriorates
Once stable, how often should a blood test be done to check thyroid hormone levels?
Once a year
Despite TSH in reference range if a patient treated with Levothyroxine still has persistent complaints, then what can be given?
LT3 can be given through combination therapy of Levothyroxine and tri-iodothyronine and it may be considered as an experimental approach under the supervision of an accredited endocrinologist
However LT3 is not always available on the NHS
Is Levothyroxine given when both symptomatic and asymptomatic under active thyroid is present?
Yes as long as low T4 is shown in TFT to stop symptoms appearing or progressing
If mild hypothyroidism → TFT until shows low T4 or until symptomatic
Is hypothyroidism after giving birth often temporary or permanent?
Often temporary
As hypothyroidism is established or where treatment of thyroxine is given, what happens to the thyroid antibodies?
They may diminish
Why might TSH be normal or even low when there is low T4?
Down-grading of the hypothalamic-pituitary axis due to a state of hypo-metabolism that the low thyroid function induces
The hypothalamus responds poorly to low T4 in blood and may not produce normal level of TRH which then does not produce the normal level of TSH
The TSH receptors on the thyroid gland may be damaged anyways so chain reaction of failure as T4 production cannot be initiated
Describe the mechanism occurring in Goitrous Autoimmune Thyroiditis?
Progressive infiltration of white cells enlarges thyroid and in the gland becomes a mass of fibrous tissue with the follicular cells disappearing so there is no place for T4 to be made
The gland becomes enlarged into a goitre and sometimes the fibrous tissue takes over completely
How does an increase in dietary iodine affect autoimmune thyroiditis?
It has a tendency to worsen autoimmune thyroiditis
What occurs in Atrophic Autoimmune Thyroiditis?
Results in thyroid gland shrinking with progressive loss of tissue
Antibodies block the TSH receptors in the thyroid and so the glandular tissue shrinks
