Thyroid Gland Flashcards

1
Q

Give a brief overview of thyroid function.

A
  • essential for normal development, especially the CNS and bone
  • essential for normal metabolism of many body tissues
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2
Q

What are the functions of the different cells in the thyroid?

A
  • Follicular cells synthesise and secrete thyroid hormone.
  • Colloid is where TH is stored.
  • C-cells secrete calcitonin - to reduce plasma Ca2+
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3
Q

Thyroid hormones are derived from two iodinated tyrosine molecules.
Describe two thyroid hormones learnt.

A

T4: major form released to blood, less active (prohormone)
T3: active form, converted in target cells

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4
Q

What are the steps to TH synthesis? PART 1

A
  • Active uptake of I- across the basolateral membrane, against the concentration gradient. Done by the Na/I symporter, and stimulated by TSH.
  • Iodide efflux (by diffusion) then occurs across the apical membrane via pendrin exchanger
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5
Q

What are the steps to TH synthesis? PART 2

A
  • At the extracellular apical membrane, iodide is oxidised to iodine and covalently bind to tyrosine residues within thyroglobulin (TG) macromolecules.
  • Requires TPO and H2O2.
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6
Q

What are the steps to TH synthesis? PART 3

A
  • Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or two (DIT) positions.
  • Coupling of iodotyrosine residues produces T4 (DIT-DIT) and a smaller amount of T3 (DIT-MIT). Catalysed by TPO
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7
Q

What are the steps to TH release? PART 1

A
  • Under influence of TSH, colloid droplets consisting of thyroid hormones within TG molecules are taken back up into the follicular cells by pinocytosis.
  • Fusion of the colloid droplets with the lysosomes causes hydrolysis of TG and release of T3 and T4.
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8
Q

How do thyroid hormones circulate?

A
  • Bound to plasma proteins.
  • Mainly TBG (~70%), transthyretin (10-20%) and albumin (10-20%).
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9
Q

How do thyroid hormones act on target tissues? PART 1

A
  • TH receptors (TRs).
  • Belong to the nuclear receptor superfamily - high affinity for T3
  • Ligand-activated transcription factors.
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10
Q

How do thyroid hormones act on target tissues? PART 2

A
  • Activation requires dimerisation with another TR or a retinoid X receptor (RXR).
  • TRs are encoded by two genes: TR α and TR β.
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11
Q

Describe the metabolic regulation of THs.

A
  • Done by selenodeiodinases, abbreviated to D1-3.
  • Used selenium as their trace element, so it is essential in the diet.
  • Regulate the amount of T3 available to bind with the receptor.
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12
Q

Outline the functions of the selenodeiodinases.

A
  • Activate by converting T4 to T3 (D2)
  • Inactivate by converting T3 to T2 (D3)
  • Inactivate by converting T4 to rT3 (D3).
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13
Q

What are some ways TH increases metabolic rate?

A
  • affects number and size of mitochondria, enzymes, Na/K ATPase activity, etc.
  • positive inotropic and chronotropic effects on the heart
  • synergises with the sympathetic nervous system
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14
Q

What are some ways TH is involved in energy metabolism?

A
  • antagonises insulin signalling
  • gluconeogenesis, lipolysis
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15
Q

Describe how TH moves across the membrane.

A
  • HYPOTHESIS: TH diffused across the cell membrane to work.
  • TRUTH: TH transporters are required to allow TH across membrane e.g MCT8.
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16
Q

What genetic mutation is MCT8 linked to?

A

Allan-Herndon-Dudley Syndrome

17
Q

Describe the role of the hypothalamic-pituitary-thyroid axis.

A
  • Negative feedback control of thyroid hormone synthesis and secretion
  • Hypothalamic neurosecretory cells release TRH into the portal capillaries.
  • TRH stimulates thyrotrophs of the anterior pituitary to secrete TSH.
18
Q

What happens with high levels of T4 and T3?

A
  • Release of TSH and TRH are turned down.
19
Q

Describe congenital hypothyroidism.

A
  • Inadequate thyroid hormone production in neonates.
  • Occur because of anatomic defects in gland, an inborn error of thyroid metabolism, or iodine deficiency.
20
Q

How is congenital hypothyroidism investigated and treated in neonates?

A
  • Preventable with a simple neonatal heel prick before testing for TSH levels.
  • Possible congenital hypothyroidism if the levels of TSH are high.
21
Q

Describe the TSH receptor and its actions.

A
  • G-protein coupled receptor
  • Done through Adenylate Cyclase (αGs and the cAMP-PKA cascade).
  • Leads to iodide uptake, the transcription of NIS (Na+/I- symporter), TG and TPO, etc.
22
Q

What are the actions of TSH?

A
  • increases iodine uptake
  • stimulates other reactions involved in TH synthesis (eg. TPO)
  • stimulates uptake of colloid
  • induces growth of the thyroid gland (which can lead to goitre)
23
Q

Define hyperthyroidism.

A
  • Occurs when there is TH excess.
  • Primary - problem with the thyroid gland
  • Secondary - problem with pituitary regulation
24
Q

Define hypothyroidism.

A

TH deficiency

25
Describe Grave’s Disease.
- Common cause of primary hyperthyroidism. - Autoimmune disease characterised by high levels of circulating TH/ low levels of TSH. - Antibodies are directed to the TSH receptor - work as pharmacological agonists, so we end up with unregulated overproduction of TH.
26
What are the symptoms of Grave's Disease?
- Weight loss (due to the increased metabolism) - Tachycardia - Fatigue - Diffuse goitre (due to TSH receptor stimulation) - Ophthalmopathy (an inflammatory disorder of the orbit and periorbital tissues).
27
Describe Hashimoto’s Disease.
- Cause of hypothyroidism. - Autoimmune disease characterised by low levels of circulating TH/high levels of TSH. - Antibodies cause thyroid destruction and dysfunction.
28
What are the symptoms of Hashimoto's Disease?
- Lethargy - Weight gain - Lack of growth and development - Diffuse goitre.
29
What are the 2 main branches that supply the thyroid?
- Inferior thyroid artery - subclavian - Superior thyroid artery - carotid
30
What is reverse T3?
- Iodinated on a different side - Inactive
31
What 2 factors stimulate the hypothalamus to produce TH?
- Stress - Cold
32
Why is high TSH and high TRH indicative of HYPOthyroidism?
→ If thyroid isn’t producing T3 or T4 → There is no negative feedback → TRH and TSH concentration are high
33
What is the diagnosis for low TRH and low TSH but high T4 and T3?
Primary hyperthyroidism
34
What is the diagnosis for high TRH & TSH but low T4 and T3?
Primary hypothyroidism
35
What is the diagnosis for low TRH, high TSH and high T4 and T3?
Secondary hyperthyroidism