Lecture 11: Thyroid Disorders Flashcards
1
Q
What cells are responsible for thyroid hormone production?
A
- Thyroid follicular cells
2
Q
Why is iodine important in the diet
A
- To help in thyroid hormone synthesis
3
Q
What amino acid are thyroid hormones formed from?
A
- Tyrosine
4
Q
What active forms of the thyroid hormone are released into the bloodstream?
A
- Thyroxin (T4)
- Tri-iodothyronine (T3)
5
Q
What is the major secreted product from the thyroid gland?
A
- T4: thyroxin: serves as a precursor for T3 (active form)
6
Q
What is the process of thyroid hormone synthesis?
A
- Iodide Uptake (Iodide Trapping)
• Iodide (I⁻) is actively transported into thyroid follicular cells from the bloodstream via sodium-iodide symporter (NIS). - Iodide Oxidation and Organification
• Iodide is transported into the follicular lumen (colloid) by pendrin, where it is oxidized to iodine (I₂) by thyroid peroxidase (TPO).
• Iodine then binds to tyrosine residues on thyroglobulin (Tg), forming:
• Monoiodotyrosine (MIT) – one iodine attached.
• Diiodotyrosine (DIT) – two iodines attached. - Coupling of Iodotyrosines
• TPO catalyzes the coupling of iodotyrosines:
• MIT + DIT → T₃ (Triiodothyronine)
• DIT + DIT → T₄ (Thyroxine)
• These hormones remain stored in the colloid, bound to thyroglobulin
7
Q
What are the functions of the thyroid?
A
- Synthesis of T3 and T4 have effect on cardiovascular, metabolic, developmental
- Secretion of calcitonin
- Secrete PTH to maintain calcium and phosphate
8
Q
What is used to convert T4 to T3 at the liver, kidney and other tissues with high blood flow?
A
- 5’- deiodinase
9
Q
What features make the thyroid gland?
A
- Pyrimidal lobe: moves, different presentation and size in different people
- Right lobe
- Left lobe
- Isthmus: attaches R and L lobe
Also superior parathyroid gland and inferior parathyroid gland secreting parathyroid hormone
10
Q
What 4 things does the TSH released from the pituitary gland increase?
A
- increases iodine uptake
- increases thyroglobulin synthesis
- increases endocytosis and proteolysis of thyroglobulin
- increases blood flow through the thyroid gland
11
Q
How are thyroid hormones (T3 and T4) released?
A
- Hypothalamic nuclei releases Thyrotrophin releasing hormone (TRH)
- This stimulates the pituitary gland to release thyroid stimulating hormone (TSH)
- This then acts on the thyroid gland to release thyroid hormones (T3 & T4). T4:T3 -> 10:1
12
Q
A
13
Q
What is rT3?
A
- Inactive metabolite of T4
14
Q
what causes the negative feedback loop on the pituitary and hypothalamus when T3 and T4 have been released?
A
when the T3 levels are high, a negative feedback loop occurs to slow down/ stop their release
15
Q
what are the metabolic functions of thyroid hormones?
A
- Carbohydrate metabolism - increased glycolysis, increased insulin secretion etc
- Fat metabolism - reduced fat stores, increased fatty acid conc in plasma etc
- Protein metabolism - increased protein degradation, loss of muscle mass providing fuel for gluconeogenesis
16
Q
what is the effect of the thyroid hormone on the cardiovascular system?
A
- increased cardiac output
- increased heart rate
- increased ventilation rate
- increased sympathetic activity by potentiating catecholamine effects
17
Q
what occurs when there is a Thyroid deficiency during development?
A
cretinism (congenital hypothyroidism)
18
Q
what is the role of the thyroid hormone in growth?
A
Thyroid hormone is needed to allow bone, cartilage and other connective tissues to respond to growth hormone
19
Q
what is the effect of a lack of iodine in your diet and how does this cause enlarged thyroid glands?
A
- If iodine in diet is limited, little thyroid hormone can be synthesised
- Plasma levels of TSH will therefore rise since no negative feedback
- High levels of TSH will produce hypertrophy / hyperplasia of thyroid gland
- Increased mass of tissue will produce more thyroid hormone - thyromegaly
- In extreme cases – can lead to the development of a goitre
20
Q
What condition can cause high TSH secretion besides a lack of iodine in the diet?
A
- A pituitary tumour
21
Q
what is hyperthyroidism and what is the most common cause of hyperthyroidism?
A
it is an overactive thyroid gland in which excess thyroid hormone is released and it is most commonly caused by Graves disease.
22
Q
What happens in Graves’ disease to cause hyperthyroidism and what does it look like?
A
- B-lymphocytes secrete glycoproteins which activate the TSH receptors on the thyroid gland stimulating thyroid hormone release
- Buldging eyes, eyelids retract, redness
23
Q
What treatment is given for hyperthyroidism?
A
- Anti thyroid drugs (nasty): carbimazole or propylthiouracil (less used)
- Radioactive iodine
- Thyroidectomy
24
Q
How does Carbimazole work?
A
- Pro drug which undergoes metabolism by hepatic enzymes to active metabolite thiamazole/methimazole
- First line to quick thyroid hormone correction: 4-8 wks
- inhibits T3/T4 synthesis by inhibiting thyroid peroxidase
25
What are some counselling points for Carbimazole?
- TFTs checked every 6-8 weeks. Takes this to see observable effect
- Once thyroid hormone levels are in target: either choose block and replace or titration and continue for 12-18 months
- Need for additional meds (B blocker for symptom management)
- Urgent to report signs of blood and dyscrasias
- Pregnant potential se contraception
26
what is hypothyroidism and what is the most common cause of hypothyroidism?
it is an underactive thyroid gland in which little to no thyroid hormone is released and it is most commonly caused by cause Hashimoto thyroiditis – autoimmune destruction of thyroid follicular cells. A lack of thyroid hormone being released results in high TSH levels.
27
in which will TSH levels be raised: hypothyroidism or hyperthyroidism?
hypothyroidism
28
What are some causes of hypothyroidism?
- Autoimmune thyroiditis
- Iodine deficiency
- Post thyroidectomy or radioactive iodine treatment
- Drug treatment
- Congenital disease
29
what is used to treat hypothyroidism?
Levothyroxine - T4
30
what hormone is released by the parafollicular cells found in the thyroid gland?
calcitonin
31
What are the TSH and T4 levels like in Overt primary hypothyroidism, subclinical primary hypothyroidism, secondary hypothyroidism, peripheral hypothyroidism?
- TSH raises and free T4 low = overt primary hypothyroidism
- TSH slightly raised but FT4 within ref this is subclinical primary hypothyroidism
- TSH slightly raised= low and FT4 = low = secondary hypothyroidism
- TSH, FT4 and FT3 = all within range. Test rT3 of low = peripheral hypothyroidism
32
What are the different classifications of hypothyroidism?
- Primary: overt (definite), subclinical (mild) (severity)
- Secondary: Pituitary-hypothalamic dysfunction
- Peripheral hypothyroidism
33
what is primary hypothyroidism?
when the thyroid gland is unable to produce hormones because of iodine deficiency or abnormality of the gland itself.
34
what is secondary hypothyroidism?
the result of insufficient production of bioactive TSH due to a pituitary or hypothalamic disorder
35
which drug can commonly cause hypothyroidism?
amiodarone
36
what drugs reduce conversion of T4 to T3?
- b-blockers
- propylthiouracil
- amiodarone
- glucocorticoids
37
what drugs reduce T4 and T3 binding?
- furosemide
- salicylates
- NSAIDs
- heparin
38
what drugs increase thyroglobulin levels?
- oestrogen and tamoxifen
- opiates and methadone
39
what drugs alter T4 and T3 metabolism (increase hepatic metabolism)?
- Phenytoin
- Rifampicin
- Carbamazepine
40
before treating a patient suffering hypothyroidism with T4, what must you exclude? And why?
- you must exclude glucocorticoid deficiency
- to prevent precipitation of adrenal crisis
41
What are the signs of hypothyroidism?
- Fatigue, depression
- cold
- dry skin
- hair loss
- reduced appetite
- weight gain
- lower BP and HR
- swelling of eyelids
42
what instructions must be given to patients taking levothyroxine?
preferably taken at least 30 minutes before breakfast, caffeine-containing liquids (e.g. coffee, tea), or other medication (impaired absorption) milk, pois, calcium supplements IBD interact
- Imortance of compliance and life long
43
What are some thyroid antibody tests that can be done?
- Thyroid peroxydase antibodies
- Thyrogobulin antibodies
- Thyroid stimulating hormone receptor antibodies
44
What is monitoring like for hypothyroidism?
• Initially TFTs every 3 months until stable then annually
• Can take up to 6 months for TSH to normalise. Most adult patients will
stabilise on doses between 100-200micrograms daily
• Dose is titrated in steps of 25mcg until therapeutic effect is achieved
• If TSH is within normal limits and symptoms still present, test FT4 to
investigate for secondary hypothyroidism
45
what drug is used in severe hypothyroid states when a rapid response is desired?
Liothyronine sodium
- synthetic form of T3 - more potent but lack of evidence
46
What should happen to levothyroxine dose whilst pregnant?
- Insufficient thyroid hormone can have teratogenic effects
- Must consult with GP/ specialist
- Should increase dose by 25-50mch and TSH levels checked
Monitor every 4-6weeks (TSH)
47
What are some signs and symptoms of hyperthyroidism?
- Hyper excitable
- Hot
- Sweaty skin
- Soft hair
- Weight loss
- Diarrhoea
48
what is thyrotoxicosis?
clinical syndrome associated with prolonged exposure to raised thyroid hormone levels
49
What is nodular disease and thyroditis?
- Can be single or multinodular goiter on thyroid
- which actively releases T3/T4
- Thyroiditis: Inflammation of thyroid follicles caused by infection, trauma, drug induced
- T3 and 4 leak from inflamed cells
50
what is the preferred beta-blocker of choice for treating hyperthyroidism symptoms?
propranolol - tapered and stopped once patient is euthyroid and asymptomatic
51
What does low TSH levels and ft4 and 3 are raised mean?what about all are raised
- Hyperthyroidism
- Could be thyroiditis confirmed with TRANs
- Definitive diagnosis = 2 sets of TFTs at least 6 weeks apart
- Hyperthyroidism of extra thyroid origin (pituitary/ hypothalamic disease)
52
What is radioactive iodine uptake scanning and when is it used?
- is done to evaluate thyroid function and activity by measuring how much iodine the thyroid gland absorbs over time. It helps diagnose the cause of hyperthyroidism and assess thyroid nodules.
- Avoid Contact with preg women and children for 24 days post radiation exposure
53
What are the side effects of Carbimazole?
- Macropapular rash – can be treated with generic antihistamine
• Bone marrow suppression – some fatal cases of agranulocytosis have occurred
in patients treated with carbimazole
• On initiation patients need to be counselled on the signs and symptoms of blood
dyscrasias – sore throat, bruising, bleeding, mouth ulcers, fevers and malaise
• Full blood count to be checked as a baseline and 6 monthly during treatment
54
What are contraindications of Carbimazole and propylthiouracil?
• Severe hepatic impairment (unable to metabolise to active metabolite –
methimazole)
• Pre-existing blood disorders (risk of dyscrasias)
• History of pancreatitis (may exacerbate)
55
what are the 2 main problematic side effects of antithyroid drugs?
neutropenia and agranulocytosis
56
What are some counselling points for radioactive iodine therapy?
- Stop Carbimazole and propylthiouracil 1 week prior to receiving treatment to ensure adequate uptake of radiated iodine into damaged part of thyroid
- 2/3 weeks to see effect
- Measure TSH every 6 wks post treatment
57
What is thyroid crisis/ Thyrotoxic storm?
• Hyperthyroid crisis (thyroid storm) is a rare, extreme manifestation of
thyrotoxicosis due to overproduction of thyroid hormones.
• Although rare it quickly cause multiorgan failure and is often fatal
• Occurs in 1-2% of patients with hyperthyroidism
58
What are the causes of thyroid crisis?
• Can be precipitated by infection, trauma, medications (e.g.
amiodarone), radioiodine tx, sudden cessation of antithyroid medicines
and surgery
• Other causes may be:
• Over treatment of levothyroxine
• TSH secreting pituitary adenoma
• Pituitary resistance to thyroid hormones (loss of negative feedback)
59
What are the symptoms of thyroid crisis?
- Hyperthermia (over 41)
- Dehydration
- Tachycardia
- Atrial dysthymias
- Hypotension
- Sweating
- Jaundice and abdominal pain
- Confusion, agitation, delirium
60
What are the 4 mechanisms of treatment of thyroid crisis?
- inhibit thyroid hormone synthesis: Carbimazole/propylthiouracil
- Inhibit thyroid hormone release: release blocked by admintering iodine (Lugols solution) 1hr between antithyroid med and iodine for uptake
- inhibit peripheral action of excess thyroid hormone - propanalol. If asthma/COPD use metoprolol
- Supplementary management: paracetamol, cholestryamine
