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203: The endocrine system > Thyroid hormones and physiology > Flashcards

Flashcards in Thyroid hormones and physiology Deck (28)
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1

T3 and T4 synthesis

1. Iodine + Tyrosine
- Forms monoiodotyrosine [MIT] or di-iodotyrosine [DIT]

2. MIT+DIT= Triiodothyronine [T3]
or

DIT+DIT= Tetraiodothyronine/ Thyroxine [T4]

2

Source of iodine

Plants grown in rich iodine environment.

Meat which were fed plants grown in rich iodine environment.

3

Iodothyronine deiodinase

Enzyme that converts T4 into T3 or rT3 in target tissues.

When thyroid hormones are synthesised in the thyroid, 95% are released as T4.

T3 is more biologically active than T4 [40x more]
- 80% of conversion

rT3 is biologically inactive
- 20% of conversion

4

Halogenase

Enzyme that degrades MIT and DIT
- Releases free iodide ions.

5

Thyroglobulin

Protein that combines with iodide released from MIT and DIT breakdown.
- Combination forms precursor of thyroid hormones T3 and T4.
- Source of iodine that combines with tyrosine.

6

T4
- Name
- Synthesis
- Action
- Half life

Tetraiodothyronine/ Thyroxine

Formed from 2 DIT molecules.

Main hormone produced and secreted by the thyroid.

Converted into T3 in target tissues using iodothyronine deiodinase.

Half life= 6-8 days.

7

T3
- Name
- Synthesis
- Half life

Triiodothyronine

Formed from MIT+DIT

Made in thyroid [5% of secreted thyroid hormones].

Converted from T4 in target tissue.
- Using iodothyronine deiodinase.

More biologically active that T4.

Half life= 1 day

8

Iron and thyroid activity

Iron concentration has an effect on thyroid activity
- Iron improves thyroid hormone indices

Iron deficiency can see a decrease in T4 and T3---> Hypothyroidism.

9

Role of radioactive iodine on thyroid function.

Radioactive iodine damages thyroid glands and can trigger the formation of neoplasms.
- Chronic exposure to digoxins= decrease in thyroid function.

Example
- Chernobyl incident = high incidence of thyroid cancer decades later.

10

Control of thyroid hormone secretion.

Hypothalamus secretes TRH
- Triggers anterior pituitary to release TSH.

TSH travels in systemic circulation and triggers release of Thyroid hormones from the thyroid.

Feedback regulation
- T3 and T4 negatively inhibit the release of TSH and TRH.

11

Transport of thyroid hormones.

Thyroid hormones are not water soluble.
- Mainly bound to plasma protein [99%]

T4
- TBG: Thyronine binding globulin [75%]
- TBPA: Thyroxine binding prealbumin [15-20%]
- Albumin [5-10%]

12

Overall biological effects of thyroid hormones

Increase basal metabolic rate by increasing the size and number of mitochondria.

Also important in the normal development and growth of prepubescent children.
- Important in the development of the CNS[ myelination of nerve fibres]

Increases activity of metabolically important enzymes.



13

Metabolic effects of thyroid hormones [3]

Increases lipid turnover
- Increased rate of synthesis, mobilisation and degradation.

Increased protein synthesis.

Increased carbohydrate metabolism.

14

Thyroid hormones on carbohydrate metabolism. [4]

Increases glycogenesis.

Increases glucose uptake in muscles and adipose tissue.

Potentiates the effects of insulin and catecholamines.

Increases glucose absorption in the gastrointestinal tract.

15

Organs thyroid hormones ineffective on [6]

Thyroid

Anterior pituitary

Brain

Testes, Uterus

Spleen

16

Levothyroxine
- Drug type
- Indication
- Route of administration
- Dose

Manufactured thyroxine [T4]

Indication
- Hypothyroidism
- Can treat goitre by inhibiting TSH.

Administration
- Oral
- IV

Dose
- 50-100 micrograms/day
- 25 micrograms/daily, titrated in older people [50+]

17

Levothyroxine
- Oral bioavailability
- Protein binding
- Metabolism
- Excretion
- Half life

Oral bioavailability= 100%
- Orally inactive

Protein binding= 99%
- Not soluble in water.

Metabolism
- Liver [glucorodination]

Half life
- 7 days

Excretion
- Urine

18

Levothyroxine
- Adverse effects

Similar to symptoms of hyperthyroidism

- Insomnia
- Weight loss
- Tremors
- Palpitations, arrhythmias
- Diarrhoea


19

Carbimazole
- Drug type
- Mechanism
- Indications
- Dose
- Administration route

Anti-thyroid pro-drug
- Inhibits the incorporation of iodide into thyroglobulin= inhibits the production of T3 and T4
- Inhibits peroxidase enzyme

Indications
- Hyperthyroidism

Dose
- 5-15mg/day

Administration
- Oral

20

Carbimazole
- Oral availability
- Protein binding
- Metabolism
- Half life
- Excretion

Oral availability = 90%

Protein binding =85%

Metabolism
- After absorption, converted into methimazole [active form]

Half life
- 6.4 hrs

Excretion
- Urine

21

Carbimazole
- Adverse effects

Rashes and pruritus

Neutropenia
Agranulocytosis

Teratogenicity

22

Propylthiouracil
- Drug type
- Mechanism
- Indications
- Dose

Anti-thyroid drug
- Inhibits thyroperoxidase and tetroiodothyronine deiodinase
- Prevents iodide + thyroglobulin incorporation
- Inhibits the conversion of T4 to T3.

Indications
- Hyperthyroidism [inc. Graves' disease]
- Hyperthyroidism in pregnancy

Dose
- 50-150mg/day

23

Propylthiouracil
- Oral bioavailability
- Protein binding
- Metabolism
- Half life
- Excretion

Oral bioavailability =80-95%

Protein binding= 70%

Metabolism
- Hepatic

Half life
- 2 hrs [good for breastfeeding]

Excretion
- Renal [urine]

24

Propylthiouracil
- Adverse effects

Similar to carbimazole + liver problems:
- Pruritus
- Rashes
- Agranulocytosis
- Liver injury

25

Potassium perchlorate
as a drug

Anti-thyroid drug
- Competes with iodide for the iodide uptake pump

26

Radioactive iodine

Used to treat hyperthyroidism

Inhibits T3+T4 secretion by suppressing the thyroid

27

Jod-Basedow phenomenon

Hyperthyroidism triggered by excess iodine consumption.

Iodine can be consumed via diet [vitamins, cough remedies] or via injections.

28

Lithium on the thyroid

Lithium can trigger hypothyroidism.

Induces goitre
- Decreases T4 production