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Met2 > Thyroid > Flashcards

Thyroid Flashcards

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?

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?

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?

A

Graves’ disease

- due to autoantibodies against TPO, thyroglobulin and TSHR

21
Q

What are the risk factors for Graves’ disease?

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

How can Graves’ disease affect the eyes?

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?

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?

A
  • nervousness
  • tremors
  • seizures
25
Q

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

A
  • disordered GnRH pulse
  • oligomenorrhoea/amenorrhoea
  • gynaecomastia (androgen –> oestrogen)
  • erectile dysfunction (androgen –> oestrogen)
  • miscarriage
26
Q

What is the effect of excess thyroid hormone on the metabolism?

A
  • 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
Q

What is the effect of excess thyroid hormone on the skin?

A
  • warm, moist, sweating - vasodilation
  • plummer’s nail - uneven, black lines
  • vitiligo - pigmentation lost
  • pretibial myxoedema
28
Q

What is the effect of excess thyroid hormone on the GIT?

A
  • increased appetite
  • reduced weight
  • increased motility (reduced fat absorption)
  • increased transaminase in serum
29
Q

What is the effect of excess thyroid hormone on the blood?

A
  • pernicious anaemia

- B12 deficiency

30
Q

What is the effect of excess thyroid hormone on the eyes?

A
  • exophthalmos/proptosis - eyes bulge out
  • eyelid retraction + inflammation of soft orbital tissue
  • lid lag
31
Q

What is the effect of excess thyroid hormone on the bones?

A
  • increased osteoclast activity (T3)

- hypercalcaemia - osteoporosis

32
Q

What are the other causes of thyrotoxicosis?

A
  • toxic multinodular goitre
  • toxic adenoma
  • excess iodine
  • amiodarone
  • HGC thyroiditis
  • TSHoma
  • Struma ovarii
  • Hamburger thyrotoxicosis
33
Q

How should hyperthyroid conditions be managed?

A
  • Technetium or iodine uptake scans
  • thyroidectomy
  • thionamide drugs (propylthio-uracil, carbimazole)
  • radioactive iodine
34
Q

Give an example of a condition causing hypothyroidism?

A

Hashimoto’s

  • due to antibodies to TPO
  • apoptotic follicular cell destruction
35
Q

What is the effect of hypothyroidism on the cardiovascular system?

A
  • reduced cutaneous circulation - (overdressed)
  • sinus bradycardia
  • increased LDL cholesterol - fatty plaques in arteries
  • J waves of hypothermia
36
Q

What is the effect of hypothyroidism on the renal and haematological system?

A
  • reduced GFR
  • hyponatraemia - water retention
  • reduced reabsorptive and secretory capacity
  • normochromic and normocytic anaemia
37
Q

What is the effect of hypothyroidism on the endocrine system and metabolism?

A
  • delayed puberty
  • reduced libido
  • erectile dysfunction
  • reduced BMR
  • reduced GLUT4 stimulation
38
Q

What is the effect of hypothyroidism on the GIT?

A
  • reduced appetite
  • reduced peristalsis –> constipation
  • increased weight - fluid retention
39
Q

What is the effect of hypothyroidism on the nerves, muscle and bone?

A
  • 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
Q

How does Hashimoto’s cause goitre (swelling of thyroid gland)?

A

TSH trophic effects

41
Q

Apart from Hashimoto’s, what are the causes of hypothyroidism?

A
  • endemic goitre - iodine deficiency
  • hypopituitarism
  • Pendred’s syndrome
  • infiltrate disease
  • lithium (inhibits TSH release)
42
Q

How are hyper and hypothyroidism diagnosed?

A

Hyper:

  • increased T3, T4
  • low TSH

Hypo:

  • high TSH
  • low T4
43
Q

How is hypothyroidism managed?

A

Levothyroxine and liothyronine

Met2 (26 decks)

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