Met2 > Thyroid > Flashcards

Thyroid Flashcards

(43 cards)

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1
Q

What type of receptor is the thyrotropin receptor (TSHR)?

A

GPCR

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2
Q

Where do TSHRs receive signals from?

A

Pituitary

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3
Q

How are thyroid hormones synthesised?

A
  1. thyroglobulin is synthesised in the RER, follows a secretory pathway and enters the colloid via exocytosis
  2. Simultaneously, Na+/I- symporter (NIS) pumps iodide actively into the cell
  3. iodide enters the follicular lumen (colloid) from the cytoplasm by the transporter pendrin
  4. Colloid: iodide – TPO –> iodine
    - TPO = thyroid peroxidase
  5. iodine iodinates the thyroglobulin (at tyrosyl residues)
  6. thyroglobulin reenters the follicular cell by endocytosis
  7. proteolysis liberates thyroxine and triiodothyronine
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4
Q

What ion inhibits T4 release? In what situation/condition might this occur? How is this treated?

A
  • T4 inhibited by iodide
  • can occur in thyrotoxicosis
  • use Lugol’s iodine or potassium iodide as treatment
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5
Q

What effect does TSH have on the thyroid?

A

increases NIS, TPO, thyroglobulin, H2O2 (oxidising agent), T4 and T3
- also increases thyroid blood flow and thyroid follicular cell hyperplasia

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6
Q

What are the different forms of deiodinase and what is their role?

A

D1, D2, D3 = iodothyronine deiodinase

Release iodine from thyronine hormones

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7
Q

Explain the control of thyroid function from the level fo the hypothalamus.

A

Hypothalamus – TRH –> pituitary – TSH –> Thyroid –> T3 and T4
- T4 —> T3 + rT3

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8
Q

What stimulates TRH release from the hypothalamus?

A
  • cold
  • acute psychosis
  • circadian rhythm
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9
Q

What inhibits TRH release from the hypothalamus?

A
  • somatostatin
  • stress
  • excess TRH
  • T3
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10
Q

What stimulates TSH release from the pituitary?

A
  • TRH
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11
Q

What inhibits TSH release from the pituitary?

A
  • corticosteroids
  • dopamine
  • excess TSH
  • T3
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12
Q

What stimulates thyronine hormone release from the thyroid?

A

TSH

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13
Q

What stimulates thyronine hormone release from the thyroid?

A
  • excess iodine
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14
Q

What hypothyroidism and how is it treated?

A

Lack of thyroid hormone

Treat with levothyroxine

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15
Q

Should the dose of levothyroxine change if a woman is pregnant? If so, why?

A

Dose should INCREASE

  • oestrogen binds to thyroid binding globulin which binds to free thyroid
  • this reduced free T4 (=hypothyroidism)
  • in pregnancy, there is more oestrogen therefore more levothyroxine is needed
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16
Q

Which transporters mediate the entry of T4 and T3 into cells?

A 
ATP-requiring
Transporters:
- MCT8
- MCT10
- OATP1c1
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17
Q

What changes occur once thyroid hormones enter cells?

A
  • can have a genomic effect –> means they can directly influence gene transcription and translation
  • thyroid hormone bind to the thyroid response element
  • T3 binds to the co-repressor, displacing it from the receptor/DNA complex
  • this causes the TRs to cleave
  • retinoid X receptor monomers bind on (new TR/RXR dimer)
  • this causes CoA to bind
  • transcription is activated
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18
Q

What are the effects of thyroid hormones on the body?

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A
  • increases BMR
  • increases O2 consumption
  • increases the rate of ATP hydrolysis
  • increases fat mobilisation
  • enhances fat oxidation
  • reduces/controls LDL cholesterol
  • increases gluconeogneeiss
  • increases glycogenolysis
  • increases glucose uptake
  • causes vasodilation –> enhances blood flow to organs
19
Q

What is the difference between hyperthyroidism and thyroidtoxicosis?

Study These Flashcards
A

Hyperthyroidism = due to excessive production of thyroid hormone by the thyroid gland

Thyrotoxicosis = excessive thyroid hormone of any cause - include hyperthyroid

20
Q

Give an example of a condition causing hyperthyroidism?

Study These Flashcards
A

Graves’ disease

- due to autoantibodies against TPO, thyroglobulin and TSHR

21
Q

What are the risk factors for Graves’ disease?

Study These Flashcards
A
  • HLA status (esp DR3)
  • Infection
  • Female
  • Stress (cortisol + CRF)
22
Q

How can Graves’ disease affect the eyes?

Study These Flashcards
A
  • lymphocytes release IFN-gamma
  • fibroblasts secrete glycosaminoglycans
  • eyes become fibrotic
  • local hypoxia and increase inflammation (if smoking)
    result = exophthalmos and lid lag mostly
23
Q

What is the effect of excess thyroid hormone on the cardiovascular system?

Study These Flashcards
A
  • need to dissipate excess heat (underdress)
  • increases alpha:beta myosin = increased inotropy
  • increased nitric oxide = reduced peripheral resistance
  • widened pulse pressure = palpitations
  • AF
24
Q

What is the effect of excess thyroid hormone on the nervous system?

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A
  • nervousness
  • tremors
  • seizures
25
What is the effect of excess thyroid hormone on the reproductive system?
- disordered GnRH pulse - oligomenorrhoea/amenorrhoea - gynaecomastia (androgen --> oestrogen) - erectile dysfunction (androgen --> oestrogen) - miscarriage
26
What is the effect of excess thyroid hormone on the metabolism?
- increased BMR - increased appetite - heat intolerant - increased protein and lipid degradation = weight loss and myopathy - increased insulin turnover = hyperglycaemia - reduced gluconeogenesis - reduced insulin secretion
27
What is the effect of excess thyroid hormone on the skin?
- warm, moist, sweating - vasodilation - plummer's nail - uneven, black lines - vitiligo - pigmentation lost - pretibial myxoedema
28
What is the effect of excess thyroid hormone on the GIT?
- increased appetite - reduced weight - increased motility (reduced fat absorption) - increased transaminase in serum
29
What is the effect of excess thyroid hormone on the blood?
- pernicious anaemia | - B12 deficiency
30
What is the effect of excess thyroid hormone on the eyes?
- exophthalmos/proptosis - eyes bulge out - eyelid retraction + inflammation of soft orbital tissue - lid lag
31
What is the effect of excess thyroid hormone on the bones?
- increased osteoclast activity (T3) | - hypercalcaemia - osteoporosis
32
What are the other causes of thyrotoxicosis?
- toxic multinodular goitre - toxic adenoma - excess iodine - amiodarone - HGC thyroiditis - TSHoma - Struma ovarii - Hamburger thyrotoxicosis
33
How should hyperthyroid conditions be managed?
- Technetium or iodine uptake scans - thyroidectomy - thionamide drugs (propylthio-uracil, carbimazole) - radioactive iodine
34
Give an example of a condition causing hypothyroidism?
Hashimoto's - due to antibodies to TPO - apoptotic follicular cell destruction
35
What is the effect of hypothyroidism on the cardiovascular system?
- reduced cutaneous circulation - (overdressed) - sinus bradycardia - increased LDL cholesterol - fatty plaques in arteries - J waves of hypothermia
36
What is the effect of hypothyroidism on the renal and haematological system?
- reduced GFR - hyponatraemia - water retention - reduced reabsorptive and secretory capacity - normochromic and normocytic anaemia
37
What is the effect of hypothyroidism on the endocrine system and metabolism?
- delayed puberty - reduced libido - erectile dysfunction - reduced BMR - reduced GLUT4 stimulation
38
What is the effect of hypothyroidism on the GIT?
- reduced appetite - reduced peristalsis --> constipation - increased weight - fluid retention
39
What is the effect of hypothyroidism on the nerves, muscle and bone?
- impaired foetal brain development - dementia - slow relaxing reflexes - may be jittery - growth retardation - loss of initiative and memory - stiffness and muscle aches (worse in the cold) - epiphyseal dysgenesis - impaired linear growth (dwarfism)
40
How does Hashimoto's cause goitre (swelling of thyroid gland)?
TSH trophic effects
41
Apart from Hashimoto's, what are the causes of hypothyroidism?
- endemic goitre - iodine deficiency - hypopituitarism - Pendred's syndrome - infiltrate disease - lithium (inhibits TSH release)
42
How are hyper and hypothyroidism diagnosed?
Hyper: - increased T3, T4 - low TSH Hypo: - high TSH - low T4
43
How is hypothyroidism managed?
Levothyroxine and liothyronine
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