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Year 2 - T2 Theme 1 > L7 - Thyroid hormone physiology > Flashcards

L7 - Thyroid hormone physiology Flashcards

1
Q

What is the thyroid gland composed of

A

The thyroid gland is composed of follicles, each consisting of a monolayer of epithelial cells enclosing a large core of viscous, homogeneous collioid

  • Colloid acts as a reservoir of thyroid hormone
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2
Q

What are the primary hormones secreted by the thyroid gland

A
  • Tri-iodothyronine(T3)
  • Tetraiodothyronine (T4, Thyroxine)
  • Calcitonin
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3
Q

What is calcitonin concerned with

A
  • Calcium homeostasis

- Is secreted independently of the other thyroid hormones

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4
Q

Iodine and tyrosine pathway

A
  • look up picture in notes
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5
Q

Link between iron status and thyroid hormones

A
  • Improvement of iron status was accompanied by an improvement in some indices of thyroid hormones
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6
Q

What are MIT and DIT rapidly degraded by

A
  • Halogenases to free the iodide, which is then re-utilised by combination with thyroglobulin
  • The T3 and T4 leave the follicular cells and enter the blood stream for distribution to the target tissues
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7
Q

Approximately what percentage of the thyroid hormone leaving the thyroid gland is in the form of T4(thyroxine)

A
  • 95%
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8
Q

What do deiodinase enzymes convert T4 into within target tissues

A

either T3 (80%) or reverse- T3(20%)

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9
Q

Biological activity levels of T3 and T4

A
  • T3 has a biological activity approximately 40 times greater than that of T4, whilst reverse-T3 is biologically inactive
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10
Q

What percentage of biologically active thyroid hormone within the cell is in the form of T3

A
  • 90%
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11
Q

Plasma half-life of T4 and T3

A

Plasma half-life of T4 is 6-8 days whilst that of T3 is one day

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12
Q

Transportation of thyroid hormones in blood

A
  • Thyroid hormones are insoluble in water, therefore transported in blood bound to plasma proteins
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13
Q

What is the majority of t4 bound to

A
  • Over 99% of the circulating thyroid hormones are protein-bound
  • The majority ( approximately 75%) of T4 binding is to thyronine-binding globulin (TBG), with a further 15-20% being bound to thyroxine-binding prealbumin (TBPA)
  • 5-10% being bound to albumin.
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14
Q

Features of thyroid hormone receptors

A
  • The receptors for the thyroid hormones are intracellular, more specifically nuclear.
    The effect of the interaction of the thyroid hormones with their receptors is to influence gene transcription and thus protein synthesis
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15
Q

Biological effects of thyroid hormones

A

The main effect of the thyroid hormones is to increase basal metabolic rate:
• increased in carbohydrate metabolism
○ increased in the synthesis, mobilisation and degradation of lipids
○ increased protein synthesis.
Thyroid hormones essential for the normal development of the CNS, especially myelination of nerve fibres.

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16
Q

Primary mechanism of thyroid hormone action

A

Primary mechanism is an increase in the number and size of mitochondria and an increased activity of metabolically important enzymes.
All aspects of carbohydrate metabolism are increased:
• glycogenesis and glucose uptake by muscle cells and adipose cells
- potentiation of the effects of insulin
- potentiation of the effects of the catecholamines
- increase in glucose absorption by the gastrointestinal tract

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17
Q

Effect of thyroid hormones on basal metabolic rate

A

Thyroid hormones increase basal metabolic rate, and therefore oxygen consumption, in nearly every organ except:

  • Brain
  • Uterus
  • Testes
  • Spleen
  • Thyroid gland
  • Anterior pituitary gland
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18
Q

What is levothyroxine used to treat

A
  • Levothyroxine is used to treat thyroid deficiency

- It can be used to suppress TSH secretion in the treatment of some thyroid tumours

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19
Q

How is levothyroxine administered

A
  • It can be given by mouth or by injection
20
Q

Oral bioavailability of levothyroxine

A

100%

21
Q

Where is levothyroxine metabolised

A
  • Metabolised in liver by glucoronidation
22
Q

Half-life of levothyroxine

A
  • Approx. 7 days
23
Q

Excretion of levothyroxine

A
  • 20-40% excreted in urine
24
Q

Standard maintenance dose of levothyroxine

A
  • 50-100 micrograms/day
25
Q

Adverse effects of levothyroxine in excessove doses

A
  • Palpitations
  • Arrhythmias
  • Diarrhoea
  • Insomnia
  • Tremor
  • Weight loss
26
Q

Effects of carbimazole and methimazole on thyroid function

A

The anti-thyroid drugs carbimazole and methimazole act by inhibition of the synthesis of thyroid hormones by preventing the incorporation of the iodide into the thyroglobulin

27
Q

Effect of propylthiouricil on thyroid function

A
  • Prevents the peripheral conversion of T4 to T3
28
Q

Mechanism of potassium perchlorate

A
  • Acts by competing with iodide for the active iodide uptake pump
29
Q

Effect of radioactive (131 I) iodine on the thyroid gland

A
  • An alternative to surgery is the use of radioactive (131I) iodine.
  • This is selectively concentrated in the thyroid gland where it causes tissue damage and therefore reduced thyroid hormone secretion.
30
Q

What is carbimazole used to treat

A
  • Carbimazole is used to treat hyperthyroidism
31
Q

Mechanism of action - carbimazole

A
  • Carbimazole is a pro-drug, after absorption, it is converted to the active form, methimazole which prevents peroxidase iodinating the tyrosine residues on thyroxglobulin, hence reducing the production of the thyroid hormones T3 and T4
32
Q

Oral bioavailability of carbimazole

A

> 90%

33
Q

Metabolism of carbimazole

A
  • Rapidly metabolised to methimazole
34
Q

Half-life of carbimazole

A
  • 6.4 hours (methimazole)
35
Q

Excretion of carbimazole

A
  • 90% excreted in urine as metabolites
36
Q

Standard maintenance dose of carbimazole

A

5-15 mg/day

37
Q

Adverse effects of carbimazole

A
  • Rashes and pruritus are common which can often be treated with antihistamines
  • The most serious rare side effect is neutropenia and agranulocytosis
  • Teratogenic
38
Q

What is propylthiouracil used to treat

A
  • Propylthiouracil (PTU) is used to treat hyperthyroidism (including graves’ disease) by inhibiting thyroperoxidase, which normally acts in thyroid hormone synthesis
  • PTU also acts by inhibiting tetraiodothyronine deiodinase which converts T4 to T3
  • Drug of choice to treat hyperthyroidism in first trimester
39
Q

Oral bioavailability of Propylthiouracil

A

80-95%

40
Q

Metabolism of propylthiouracil

A

90% hepatic glucuronidation

41
Q

Half life of propylthiouracil

A
  • 2 hours
42
Q

Excretion of propylthiouracil

A
  • Renal
43
Q

Standard maintenance dose of propylthiouracil

A

50-150 mg/day

44
Q

Adverse effects of propylthiouracil

A
  • Rashes and pruritus are common which can be treated with antihistamines
  • Its notable side effects include a risk of agranulocytosis and risk of serious liver injury, including liver failure and death
45
Q

Significance of prophylactic administration of iodine either by injection or by incorporation into table salt or flour

A

Prophylactic administration of iodine either by injection or by incorporation into table salt or flour has markedly reduced the incidence of endemic goitre worldwide, although it carries with it the risk of Jod-Basedow phenomenon in which iodine administration precipitates hyperthyroidism

46
Q

Drugs which can induce goitre

A
  • Lithium which is used in the treatment of bipolar depression
  • Iodides which are contained in vitamin preparations and some cough remedies

These ions are selectively concentrated within the thyroid gland where they interfere with iodide incorporation and hormone release

Year 2 - T2 Theme 1 (20 decks)

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