Thyroid hormones and physiology Flashcards
T3 and T4 synthesis
- Iodine + Tyrosine
- Forms monoiodotyrosine [MIT] or di-iodotyrosine [DIT] - MIT+DIT= Triiodothyronine [T3]
or
DIT+DIT= Tetraiodothyronine/ Thyroxine [T4]
Source of iodine
Plants grown in rich iodine environment.
Meat which were fed plants grown in rich iodine environment.
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
Halogenase
Enzyme that degrades MIT and DIT
- Releases free iodide ions.
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.
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.
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
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.
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.
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.
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%]
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.
Metabolic effects of thyroid hormones [3]
Increases lipid turnover
- Increased rate of synthesis, mobilisation and degradation.
Increased protein synthesis.
Increased carbohydrate metabolism.
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.
Organs thyroid hormones ineffective on [6]
Thyroid
Anterior pituitary
Brain
Testes, Uterus
Spleen
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+]
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
Levothyroxine
- Adverse effects
Similar to symptoms of hyperthyroidism
- Insomnia
- Weight loss
- Tremors
- Palpitations, arrhythmias
- Diarrhoea
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
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
Carbimazole
- Adverse effects
Rashes and pruritus
Neutropenia
Agranulocytosis
Teratogenicity
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
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]
Propylthiouracil
- Adverse effects
Similar to carbimazole + liver problems:
- Pruritus
- Rashes
- Agranulocytosis
- Liver injury
Potassium perchlorate
as a drug
Anti-thyroid drug
- Competes with iodide for the iodide uptake pump
Radioactive iodine
Used to treat hyperthyroidism
Inhibits T3+T4 secretion by suppressing the thyroid
Jod-Basedow phenomenon
Hyperthyroidism triggered by excess iodine consumption.
Iodine can be consumed via diet [vitamins, cough remedies] or via injections.
Lithium on the thyroid
Lithium can trigger hypothyroidism.
Induces goitre
- Decreases T4 production
