Tiredness & Thyroid Disorders Flashcards
What are the possible cardiac, respiratory and endocrine differentials for fatigue?
Cardiac:
- heart failure
- atrial fibrillation
- myocardial infarction
Respiratory:
- COPD
- tuberculosis
- obstructive sleep apnoea
Endocrine:
- diabetes
- hypothyroidism
- Addison’s disease
- Vitamin D deficiency
What are the neurological, infectious and GI differentials for fatigue?
Neurological:
- stroke
- multiple sclerosis
- Parkinson’s disease
Infectious:
- COVID-19
- glandular fever
- HIV
GI:
- coeliac disease
What are the haematological, neoplastic and mental health possible differentials for fatigue?
Haematological:
- anaemia
Neoplastic:
- any cancer, including lymphoma and leukaemia
Mental health:
- depression
- anxiety
What are other possible differentials for fatigue?
- poor sleep hygiene
- drugs / alcohol
- fibromyalgia
- chronic fatigue syndrome
What bedside investigations would be performed in someone presenting with fatigue?
- examination - resp / cardiac / GI / thyroid
- urine dip to check for UTI
- baseline observations
What blood tests might be performed in someone presenting with fatigue?
- FBC to check for anaemia
- haematinics (iron, B12, folate) to assess for anaemia
- U&Es to check baseline kidney function for CKD
- LFTs to assess for underlying liver disease
- CRP / ESR to check for underlying inflammation
- TFTs to assess thyroid function
- HbA1c to assess for possible diabetes
- IgA tissue transglutaminase to assess for coeliac disease
- consider bone biochemistry / myeloma screen
- vitamin D
- HIV / hepatitis if at risk
- Monospot test for glandular fever
What imaging / interventional tests may be considered in someone presenting with fatigue?
Imaging:
- consider CXR to screen for malignancy / TB
- consider CT if high concerns for malignancy
Interventional:
- consider OGD / colonoscopy if evidence of anaemia with an unclear cause
What is the main function of the thyroid gland?
What can high levels of thyroid hormones cause?
- the thyroid gland is a regulator of metabolism
- T3 and T4 act via nuclear receptors in target tissues to initiate a variety of metabolic pathways
- high levels of T3 and T4 cause the processes to occur faster and more frequently
What are the main metabolic processes that are increased by thyroid hormones?
- basal metabolic rate
- gluconeogenesis (making new glucose)
- glycogenolysis (breaking down glycogen into glucose)
- protein synthesis
- lipogenesis
- thermogenesis
In what ways can T3 and T4 increase the rates of metabolic processes?
- increasing the size and number of mitochondria within cells
- increasing Na-K pump activity
- increasing the presence of B-adrenergic receptors in tissues such as cardiac muscle
How is the thyroid involved in bone metabolism?
- it secretes calcitonin in response to hypercalcaemia
- this inhibits osteoclasts to slow down bone breakdown and decrease calcium levels
What are the 2 components of thyroid function tests and why are they tested for?
- T4
this is a marker of what the thyroid function is actually doing (producing or not producing hormones) and what will produce the symptoms
- TSH
this is marker to work out if the problem is in the thyroid itself or higher up the HPT axis
What are the different components involved in the hypothalamic-pituitary-thyroid axis and what do they produce?
- the paraventricular nuclei in the hypothalamus release thyroid-releasing hormone (TRH)
- this causes thyrotrope cells in the anterior pituitary to release thyroid-stimulating hormone (TSH)
- the thyroid responds to TSH by releasing T3 and T4
-
T4 inhibits the pituitary and hypothalamus in a negative feedback loop
- this is the “brake system” which aims to maintain a state of homeostasis
What are the 2 stages in deciding what type of hyper/hypo thyroidism is present?
- look at the T4 - is it high, low or normal?
- look at the TSH - is it compensating for or causing the change in T4?
What are the levels of T4 and TSH like in secondary hyperthyroidism?
What usually causes this?
there is high T4 and high TSH (or normal TSH)
- normally due to a TSH secreting pituitary adenoma
- the tumour does not respond to the inhibiting effects of T4
- can also be caused by excessive pituitary stimulation from the hypothalamus
- this is sometimes called tertiary hyperthyroidism
What are the levels of T4 and TSH like in primary hyperthyroidism?
What is the most common cause of this?
high T4 and low TSH
- 75% of cases are Graves’ disease
- this is an autoimmune condition against the thyroid where the binding of IgG autoantibodies to activate TSH receptors causes overproduction of thyroid hormones
What are other less common causes of primary hyperthyroidism?
- toxic multi-nodular goitre
- toxic adenoma
- iodine-induced
- trophoblastic tumour
What are the levels of T4 and TSH in secondary hypothyroidism?
What are the causes of this?
low T4 and low TSH (or normal TSH)
- most common cause is a non-secreting pituitary adenoma
- can also be caused by pituitary surgery or damage
- can be caused by hypothalamic tumour or damage
- this is sometimes called tertiary hypothyroidism
What are the levels of TSH and T4 like in primary hypothyroidism?
What is the most common cause of this?
there is low T4 and high TSH
- 50% of cases are due to autoimmune thyroiditis (Hashimoto’s)
- this results in lymphocyte infiltration and fibrosis of the thyroid gland
What are other causes of primary hypothyroidism?
- iodine deficiency
- thyroidectomy
- radiotherapy
What is subclinical hyperthyroidism?
there are normal T4 levels but lowered TSH
What is subclinical hypothyroidism?
What condition / situation is this commonly seen in?
this is normal T4 levels with raised TSH
this is seen in hypothyroidism with poor adherence to levothyroxine
(i.e. people start taking their tablets in the week leading up to a TFT)
What are all the possible causes of primary hypothyroidism?
- iodine deficiency
-
autoimmune thyroiditis
- if this is with a goitre then it is Hashimoto’s thyroiditis
- if there is no goitre then it is atrophic thyroiditis
- can be caused by medication - such as carbimazole used to treat hyperthyroidism
- surgery / injury to the thyroid
- transiently can be caused secondary to viral infections or post-partum
What is the epidemiology of primary hypothyroidism like?
- prevalence of 1-2% in the UK
- 10x more common in women than men
- 95% of hypothyroidism is primary
What are the risk factors for primary hypothyroidism?
- female gender
- age >60
- TPO autoantibodies
- pregnancy
- having other autoimmune diseases
What are the symptoms of primary hypothyroidism?
- fatigue / lethargy
- cold intolerance
- weight gain
- constipation
- non-specific weakness
- menstrual abnormalities
- dry skin / hair loss
- hoarse voice
- neck swelling
What are the signs of primary hypothyroidism?
- bradycardia
- delayed reflexes
- paraesthesia / peripheral neuropathy
What are the investigations and treatments for primary hypothyroidism?
Investigations:
* thyroid function tests (TFTs) TPO autoantibodies (only done once)
Treatment:
- regular TSH monitoring + replacement of T4 with levothyroxine
What is the epidemiology of primary hyperthyroidism like?
- prevalence of 0.5-2% in the UK
- women are 10x more likely to have this than men
What are the 3 most common causes of primary hyperthyroidism?
- the most common is Graves’ disease (80%)
- then toxic multinodular goitre
- this involves at least 2 autonomously functioning thyroid nodules
- then toxic thyroid nodule
- this is a single nodule producing hormones autonomously
What are other possible but less common causes of primary hyperthyroidism?
- medications - iodine & amiodarone
- during pregnancy
-
thyroiditis can also cause hyperthyroidism as already made T4 is released
- this is thyroid toxicosis rather than hyperthyroidism
What are risk factors for primary hyperthyroidism?
- female gender
- smoking
- having other autoimmune diseases
What are the symptoms of primary hyperthyroidism?
- agitation
- emotional lability / irritability
- insomnia
- anxiety
- palpitations
- heat intolerance / increased sweating
- increased appetite
- diarrhoea
- polyuria
What are the signs of primary hyperthyroidism?
- tremor
- sinus tachycardia
- atrial fibrillation
- thyroid enlargement
- hyperreflexia
- in Graves’ disease there is eyelid retraction, lid lag & proptosis
What investigations and treatments are there for primary hyperthyroidism?
Investigations:
- TFTs
- TSH-receptor antibodies
- neck USS
Treatments:
- carbimazole
- radioactive iodine
- surgery
What mnemonic is used to remember the 6 steps involved in the synthesis of thyroid hormone?
ATE ICE:
- A - active transport
- T - thyroglobulin
- E - exocytosis
- I - iodination
- C - coupling
- E - endocytosis
What is involved in the active transport phase of thyroid hormone synthesis?
- active transport of iodide into the follicular cell via the sodium-iodide symporter (NIS)
- this is secondary active transport and the sodium gradient driving it is maintained by a sodium-potassium ATPase
What is involved in the thyroglobulin stage of thyroid hormone synthesis?
- thyroglobulin (Tg) is a large protein that is rich in tyrosine
- it is formed in follicular ribosomes and placed into secretory vesicles
What is involved in the exocytosis stage of thyroid hormone synthesis?
- exocytosis of thyroglobulin into the follicle lumen, where it is stored as colloid
- thyroglobulin is the scaffold upon which thyroid hormone is synthesised
What is involved in the iodination stage of thyroid hormone synthesis?
- iodination of thyroglobulin
- iodide is made reactive by the enzyme thyroid peroxidase
- iodide binds to the benzene ring on tyrosine residues of thyroglobulin, forming monoiodotyrosine (MIT) then diiodotyrosine (DIT)
What is involved in the coupling stage of thyroid hormone synthesis?
- coupling of MIT and DIT gives triiodothyronine (T3) hormone
- coupling of DIT and DIT gives tetraiodothyronine (T4) hormone, also known as thyroxine
What is involved in the endocytosis stage of thyroid hormone synthesis?
- endocytosis of iodinated thyroglobulin back into the follicular cell
- thyroglobulin undergoes proteolysis in lysosomes to cleave the iodinated tyrosine residues from the larger protein
- free T3 or T4 is then released and the thyroglobulin scaffold is recycled
How are T3 and T4 carried in the blood?
they are fat soluble and mostly carried by plasma proteins
these are Thyronine Binding Globulin and albumin
What is the more potent form of thyroid hormone?
What is its half-life like relative to the other thyroid hormone?
- T3 is the more potent form
- it has a shorter half-life due to its low affinity for the binding proteins
- less than 1% of T3 and T4 is unbound free hormone
- at the peripheries, T4 is deiodinated to the more active T3
How are T3 and T4 deactivated?
- T3 and T4 are deactivated by removing iodine
- this happens in the liver and kidney
Which thyroid hormone is used in the treatment of hypothyroidism and why?
- T4 is used as it has a longer half-life
- its plasma concentrations are also easier to manage
