tiredness Flashcards
what percentage of patients presenting with tiredness get a diagnosis?
66%
what percentage of patients with fatigue receive a diagnosis through blood tests?
less than 10%
what differentials are possible for fatigue?
anaemia (esp if heavy periods or pregnant)
sleep apnoea
hypothyroidism
coeliac disease
chronic fatigue syndrome
diabetes
glandular fever
depression
restless legs
anxiety
malignancy
vitamin D deficiency
heart failure
infection
lupus
what do the additional symptoms indicate?
weight gain, constipation, dry skin, feeling cold - hypothyroidism
family history - vitamin D deficiency, diabetes
CKD?
anaemia (vegetarian etc.) ?
infection?
haematological malignancy?
what can be excluded based on the history?
sleep apnoea
glandular fever - no feeling unwell
lupus
pregnancy
what blood tests would be ordered?
FBC
urea and electrolytes
vitamin D
thyroid function tests
HbA1c
what do the blood test results show?
TSH - 18 mU/L (0.2 - 5.5 mU/L) - high
fT4 - 1.2 pmol/L (10 - 24.5 pmol/L) - low
fT3 - 0.9 pmol/L (3.1 - 6.8 pmol/L) - low
what are the symptoms of hypothyroidism?
dry hair
loss of eyebrow hair
puffy face
enlarged thyroid
slow heartbeat
arthritis
cold intolerance
depression
dry skin
fatigue
forgetfulness
menstrual disorders
infertility
muscle aches
weight gain
constipation
brittle nails
hoarse voice
what is the mechanism by which fT4 and fT3 are low but TSH is high?
fT3 and 4 usually produce negative feedback to prevent pituitary from producing TRH and therefore TSH
low fT3 and 4, therefore increased TRH and TSH
(primary hypothyroidism)
what is the most common autoimmune reaction that causes hypothyroidism?
Hashimoto’s disease
what is the sequence of events that causes the immune system to attack the thyroid cells in Hashimoto’s disease?
thyroid usually produces TPO (thyroid peroxidase), used for production of thyroid hormones
MHC II and B7 proteins on APCs that are sensitive to TPO complement TCRs and CD28 proteins on T cells to activate it
TCRs and CD40s on T-cell interact with BCRs and CD40s on B-cells
B cells produce anti TPO antibodies
why don’t immune cells attack host cells?
PAMPs - pathogen associated molecular patterns, not found on human cells
- peptidoglycan, lipopolysaccharide, lipoteichoic acid, mannan, flagella proteins etc.
- allows eosinophils, basophils, neutrophils, macrophages and dendritic cells to recognise infected cells
normal healthy cells express MHC I receptors that mark it as ‘self’ - inhibitory receptors on surface of NK cells recognise MHC I, prevents it from killing
complementarity-determining regions (CDRs) are part of the variable chains in immunoglobulins (antibodies - generated by B-cells) and TCRs
how would a patient presenting with tiredness be approached?
75% of tiredness symptoms resolve within a month
67% of tiredness episodes triggered by life stresses
1 - must determine physical causes
- define type of tiredness (drowsiness, short of breath, weakness)
exertional tiredness - more likely to be physical
- tiredness gets worse as they do something = worrying
- tiredness gets better as they do something = not worrying
2 - why did patient present
- look for functional impairment (e.g. unable to make dinner for family)
3 - screen for red flags
- lymphadenopathy
- weight loss
- specific malignancy features, focus on lung, breast, colon, upper GI, gynae
- joint pains
- focal neurology
- infective symptoms - TB, glandular fever, Lyme
4 - explore psychosocial triggers
- work
- money
- family
- mood
- drugs and alcohol
5 - examine patient
- pulse
- blood pressure
- BMI
6 - plan
- initial bloods: FBC (anaemia, iron deficiency, haematological malignancy), TFT, ESR (erythrocyte sediment rate - quicker fall = greater levels of inflammation, diagnose arthritis, endocarditis, Crohn’s disease, giant cell arteritis, polymyalgia rheumatica), glucose
- even in non-anaemic menstruating women, treating low ferritin can improve tiredness symptoms
- lymphomas often have normal total white cell count with abnormal differential in early stages
7 - manage persisting unexplained tiredness with normal initial bloods
what are some questions that someone with an underactive thyroid may ask?
why did I get an underactive thyroid?
will I get better?
do I need treatment?
what’s the best treatment for me?
will I need to have treatment for the rest of my life?
what are the side effects of treatment? how can I cope with them?
should I change what I eat?
what are the chances that someone else in my family will get an underactive thyroid?
does it run in families?
how will my treatment be managed if I wish to get pregnant?
what are the causes of an underactive thyroid?
autoimmune thyroid disease (most common cause) - usually Hashimoto’s thyroiditis
radioactive iodine treatment/surgery to correct hyperthyroidism/treat thyroid cancer
anti-thyroid drugs if given for an overactive thyroid disorder in too large a dose
medicines such as lithium (some mental health problems) and amiodarone (some heart problems)
some cough medicines containing large amounts of iodine can interfere with
thyroid function
some health foods taken in excess, e.g. kelp (seaweed)
malfunction of the pituitary gland
radiation for head and neck cancers (not common in the UK)
(congenital)
how is hypothyroidism diagnosed?
thyroid function test
underactive thyroid - high TSH, low fT4
if antibodies present, autoimmune
what can alter the results of a thyroid function test?
common illnesses can temporarily alter blood
test readings - need to rule out
some medicines (prescribed and over-the-counter) - tell doctor about any medication you are taking
sometimes hypothyroidism can develop after pregnancy and giving birth (temporary)
what is subclinical hypothyroidism?
level of hypothyroidism is slight
no obvious symptoms, can
only be detected by blood test (for another autoimmune disorder or if there is FHx of thyroid disorder)
what are the results for a blood test showing subclinical hypothyroidism?
slightly raised TSH, normal fT4
how is subclinical hypothyroidism dealt with?
regular thyroid function
test
consult your doctor if you notice any symptoms, as you may benefit from treatment
how is hypothyroidism treated?
levothyroxine prescribed
regular thyroid function tests (every 6-8 weeks), dose may be adjusted according to results
taken for life
what do levothyroxine doses depend upon?
body weight
blood test results
how does levothyroxine dose change in cases with severe hypothyroidism or with high risk of heart problems?
start low, increase dose
when is levothyroxine taken?
in the morning, with water, on an empty stomach, at least half an hour
before eating and drinking anything
what drugs can decrease levothyroxine absorption?
calcium
iron
cholesterol-lowering drugs (cholestyramine, colestipol)
multivitamin tablets
other drugs - check with pharmacist or doctor
what should be done to counteract the effects of calcium, iron, cholesterol-lowering drugs and multivitamin tablets on levothyroxine absorption?
take levothyroxine at least 4 hrs apart from others
why does grapefruit help increase levothyroxine absorption?
increases stomach acidity
why does missing a dose of levothyroxine not matter very much?
reservoir of thyroxine
when may levothyroxine tablets deteriorate?
exposed to extreme temperatures
what is the correct dose of levothyroxine for a patient?
TSH in lower part of reference range
T4 towards the upper part or even slightly above reference
range
what are the effects of an incorrect dose of levothyroxine?
too much levothyroxine - causes symptoms of
overactive thyroid
too little levothyroxine - underactive
thyroid symptoms not completely resolved
what treatment should be given if complaints persist even with normal TSH levels?
combination therapy of levothyroxine and tri-iodothyronine (LT4 and LT3)
this is an experimental approach under the supervision of an accredited endocrinologist
(LT3 not always available on NHS)
once stable, how is hypothyroidism managed?
annual blood test to check thyroid hormone levels
take tablets consistently every day; failure to do this can affect
blood test results and health
what are the side effects of levothyroxine?
minimal
why may people feel some differences between different brands of levothyroxine? (rare)
might
relate to differences in fillers and bulking agents between various brands
discuss with doctor to prescribe consistent brand
what are the steps to take if planning a pregnancy while on levothyroxine?
let your doctor know, ideally have a blood test before
you conceive
increase dosage by 25-50mcg daily once pregnancy is confirmed to normalise thyroid function
have a thyroid function test
what are the complications of pregnancy when taking levothyroxine?
risk only slightly higher than
normal
good chance of a successful pregnancy outcome
how are thyroid problems associated with genetics?
thyroid problems often run in families
if family members are unwell they should be encouraged
to discuss with their own GP whether thyroid testing is warranted
what are the risks of taking too much thyroxine?
atrial fibrillation
bones may get too thin (osteoporosis)
(doctor prescribes lowest possible dose to prevent)
how does Hashimoto’s disease start to present?
thyroid gets infiltrated by white cells and slowly loses its function
usually enlarges but may not
may start with an over-active phase before becoming under-active
what are the similarities between Graves’ disease and Hashimoto’s disease?
both forms of autoimmune thyroiditis - body’s defence mechanisms overact or respond dysfunctionally and cause damage to target tissues
can be triggered by stress factors and pregnancy
genetic predisposition
both may involve infiltration by white cells (lymphocytic infiltration), increased immunoglobulins within the gland, and increased blood levels of thyroid antibodies
what is the relationship between Graves’ disease and Hashimoto’s disease?
each can change into the other
usually the over-active thyroid resulting from immune dysfunction that will revert to the under-active phase
when may antibody levels decrease in hypothyroidism?
may diminish as hypothyroidism becomes established
treatment with thyroxine is given
why may Hashimoto’s disease by missed?
undue reliance on blood tests
usually T4 (and maybe T3) is low, but may not be out of range - suggests poor thyroid hormone output
TSH normally rises in this situation, it may actually be normal, or even low
why may TSH be normal or even low in Hashimoto’s disease, even though it should rise in normal cases of Hashimoto’s disease?
down-grading of HPG axis due to hypo-metabolism induced by low thyroid function (also applies to adrenal function, which can also be damaged by autoimmune disease)
hypothalamus responds poorly to low thyroid blood levels - may not produce a normal level of TRH
hypo-metabolism also adversely affects pituitary - may not properly respond to TRH, and therefore not produce a normal level of TSH
thyroid itself may be less responsive to TSH anyway (damaged by white cell infiltration and with damaged TSH receptors)
causes chain reaction of failure, beginning with the hypothalamus and extending to the pituitary
if TSH is low (abnormal hypothyroid response, is usually high), what can confirm Hashimoto’s disease?
antibody test
usually quite conclusive
any level of thyroid antibodies suggests autoimmune processes at work
(note: as damage becomes chronic antibody levels may lessen)
what are the 2 ways that autoimmune hypothyroidism may present?
goitrous autoimmune thyroiditis
atrophic autoimmune thyroiditis
what are the features of goitrous autoimmune thyroiditis?
progressive infiltration of white cells enlarges thyroid
gland itself becomes a mass of fibrous tissue - follicular cells (where thyroid hormone is made) disappearing, enlarges into a goitre
what effect does an increase in dietary iodine have on autoimmune thyroiditis?
worsens autoimmune thyroiditis
what are the features of atrophic autoimmune thyroiditis?
(most common form)
results in thyroid gland shrinking with progressive loss of tissue
antibodies block thyroid TSH receptors so glandular tissue shrinks due to disuse
