Tiredness & Thyroid Disorders Flashcards

1
Q

What are the possible cardiac, respiratory and endocrine differentials for fatigue?

A

Cardiac:

  • heart failure
  • atrial fibrillation
  • myocardial infarction

Respiratory:

  • COPD
  • tuberculosis
  • obstructive sleep apnoea

Endocrine:

  • diabetes
  • hypothyroidism
  • Addison’s disease
  • Vitamin D deficiency
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2
Q

What are the neurological, infectious and GI differentials for fatigue?

A

Neurological:

  • stroke
  • multiple sclerosis
  • Parkinson’s disease

Infectious:

  • COVID-19
  • glandular fever
  • HIV

GI:

  • coeliac disease
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3
Q

What are the haematological, neoplastic and mental health possible differentials for fatigue?

A

Haematological:

  • anaemia

Neoplastic:

  • any cancer, including lymphoma and leukaemia

Mental health:

  • depression
  • anxiety
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4
Q

What are other possible differentials for fatigue?

A
  • poor sleep hygiene
  • drugs / alcohol
  • fibromyalgia
  • chronic fatigue syndrome
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5
Q

What bedside investigations would be performed in someone presenting with fatigue?

A
  • examination - resp / cardiac / GI / thyroid
  • urine dip to check for UTI
  • baseline observations
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6
Q

What blood tests might be performed in someone presenting with fatigue?

A
  • 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
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7
Q

What imaging / interventional tests may be considered in someone presenting with fatigue?

A

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
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8
Q

What is the main function of the thyroid gland?

What can high levels of thyroid hormones cause?

A
  • 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
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9
Q

What are the main metabolic processes that are increased by thyroid hormones?

A
  • basal metabolic rate
  • gluconeogenesis (making new glucose)
  • glycogenolysis (breaking down glycogen into glucose)
  • protein synthesis
  • lipogenesis
  • thermogenesis
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10
Q

In what ways can T3 and T4 increase the rates of metabolic processes?

A
  • 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
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11
Q

How is the thyroid involved in bone metabolism?

A
  • it secretes calcitonin in response to hypercalcaemia
  • this inhibits osteoclasts to slow down bone breakdown and decrease calcium levels
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12
Q

What are the 2 components of thyroid function tests and why are they tested for?

A
  • 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

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13
Q

What are the different components involved in the hypothalamic-pituitary-thyroid axis and what do they produce?

A
  • 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
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14
Q

What are the 2 stages in deciding what type of hyper/hypo thyroidism is present?

A
  • look at the T4 - is it high, low or normal?
  • look at the TSH - is it compensating for or causing the change in T4?
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15
Q

What are the levels of T4 and TSH like in secondary hyperthyroidism?

What usually causes this?

A

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
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16
Q

What are the levels of T4 and TSH like in primary hyperthyroidism?

What is the most common cause of this?

A

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
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17
Q

What are other less common causes of primary hyperthyroidism?

A
  • toxic multi-nodular goitre
  • toxic adenoma
  • iodine-induced
  • trophoblastic tumour
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18
Q

What are the levels of T4 and TSH in secondary hypothyroidism?

What are the causes of this?

A

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
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19
Q

What are the levels of TSH and T4 like in primary hypothyroidism?

What is the most common cause of this?

A

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
20
Q

What are other causes of primary hypothyroidism?

A
  • iodine deficiency
  • thyroidectomy
  • radiotherapy
21
Q

What is subclinical hyperthyroidism?

A

there are normal T4 levels but lowered TSH

22
Q

What is subclinical hypothyroidism?

What condition / situation is this commonly seen in?

A

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)

23
Q

What are all the possible causes of primary hypothyroidism?

A
  • 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
24
Q

What is the epidemiology of primary hypothyroidism like?

A
  • prevalence of 1-2% in the UK
  • 10x more common in women than men
  • 95% of hypothyroidism is primary
25
Q

What are the risk factors for primary hypothyroidism?

A
  • female gender
  • age >60
  • TPO autoantibodies
  • pregnancy
  • having other autoimmune diseases
26
Q

What are the symptoms of primary hypothyroidism?

A
  • fatigue / lethargy
  • cold intolerance
  • weight gain
  • constipation
  • non-specific weakness
  • menstrual abnormalities
  • dry skin / hair loss
  • hoarse voice
  • neck swelling
27
Q

What are the signs of primary hypothyroidism?

A
  • bradycardia
  • delayed reflexes
  • paraesthesia / peripheral neuropathy
28
Q

What are the investigations and treatments for primary hypothyroidism?

A

Investigations:

* thyroid function tests (TFTs)
 TPO autoantibodies (only done once)

Treatment:

  • regular TSH monitoring + replacement of T4 with levothyroxine
29
Q

What is the epidemiology of primary hyperthyroidism like?

A
  • prevalence of 0.5-2% in the UK
  • women are 10x more likely to have this than men
30
Q

What are the 3 most common causes of primary hyperthyroidism?

A
  • 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
31
Q

What are other possible but less common causes of primary hyperthyroidism?

A
  • medications - iodine & amiodarone
  • during pregnancy
  • thyroiditis can also cause hyperthyroidism as already made T4 is released
    • this is thyroid toxicosis rather than hyperthyroidism
32
Q

What are risk factors for primary hyperthyroidism?

A
  • female gender
  • smoking
  • having other autoimmune diseases
33
Q

What are the symptoms of primary hyperthyroidism?

A
  • agitation
  • emotional lability / irritability
  • insomnia
  • anxiety
  • palpitations
  • heat intolerance / increased sweating
  • increased appetite
  • diarrhoea
  • polyuria
34
Q

What are the signs of primary hyperthyroidism?

A
  • tremor
  • sinus tachycardia
  • atrial fibrillation
  • thyroid enlargement
  • hyperreflexia
  • in Graves’ disease there is eyelid retraction, lid lag & proptosis
35
Q

What investigations and treatments are there for primary hyperthyroidism?

A

Investigations:

  • TFTs
  • TSH-receptor antibodies
  • neck USS

Treatments:

  • carbimazole
  • radioactive iodine
  • surgery
36
Q

What mnemonic is used to remember the 6 steps involved in the synthesis of thyroid hormone?

A

ATE ICE:

  • A - active transport
  • T - thyroglobulin
  • E - exocytosis
  • I - iodination
  • C - coupling
  • E - endocytosis
37
Q

What is involved in the active transport phase of thyroid hormone synthesis?

A
  • 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
38
Q

What is involved in the thyroglobulin stage of thyroid hormone synthesis?

A
  • thyroglobulin (Tg) is a large protein that is rich in tyrosine
  • it is formed in follicular ribosomes and placed into secretory vesicles
39
Q

What is involved in the exocytosis stage of thyroid hormone synthesis?

A
  • exocytosis of thyroglobulin into the follicle lumen, where it is stored as colloid
  • thyroglobulin is the scaffold upon which thyroid hormone is synthesised
40
Q

What is involved in the iodination stage of thyroid hormone synthesis?

A
  • 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)
41
Q

What is involved in the coupling stage of thyroid hormone synthesis?

A
  • coupling of MIT and DIT gives triiodothyronine (T3) hormone
  • coupling of DIT and DIT gives tetraiodothyronine (T4) hormone, also known as thyroxine
42
Q

What is involved in the endocytosis stage of thyroid hormone synthesis?

A
  • 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
43
Q

How are T3 and T4 carried in the blood?

A

they are fat soluble and mostly carried by plasma proteins

these are Thyronine Binding Globulin and albumin

44
Q

What is the more potent form of thyroid hormone?

What is its half-life like relative to the other thyroid hormone?

A
  • 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
45
Q

How are T3 and T4 deactivated?

A
  • T3 and T4 are deactivated by removing iodine
  • this happens in the liver and kidney
46
Q

Which thyroid hormone is used in the treatment of hypothyroidism and why?

A
  • T4 is used as it has a longer half-life
  • its plasma concentrations are also easier to manage
47
Q
A