Thyroid hormone physiology Flashcards
State the primary hormones secreted by the thyroid
Triiodothyronine (T3)
Thyroxine (T4)
Calcitonin (concerned with Ca2+ homeostasis, secreted independently of the other thyroid hormones)
Outline the production of thyroid hormone
Iodine + Tyrosine –> MIT –> DIT
MIT & DIT are rapidly degraded by halogenases to free the iodide, which is then reutilised by combination with thyroglobulin
MIT + DIT = T3
DIT + DIT = T4
T4 can be converted to T3 (80%) by the action of iodothyronine deiodinase. The other 20% is reverse-T3 (in tissues)
What does pernicious anaemia have to do with thyroid function?
How else can thyroid function be disrupted?
Iron deficiency can lead to dysfunction of the thyroid gland as it leads to increased TSH –> goitre
e. g. The Chernobyl Nuclear accident led to thyroid damage which eventually caused cancers
- Others: pollution, contamination
Comment on the biological activity of thyroid hormone
T3 & T4 leave the follicular cells and enter the blood for distribution to target tissues. Most (95%) of circulating thyroid hormone is in the form of T4, however T3 is 40x more biologically active. Reverse-T3 is biologically inactive
Plasma half-life of T4 = 6-8 days
T3= 1 day
Outline how the secretion of thyroid hormone is controlled
Hypothalamus - Secretion of thyrotrophin releasing hormone (TRH)
This stimulates the secretion of thyroid stimulating hormone (TSH) by the anterior pituitary gland
This stimulates the secretion of T3 (5nmol/day) & T4 100nmol/day) by the thyroid gland
! Secretion of T3 and T4 has negative feedback effect on both the hypothalamus and the adenohypophysis
Outline the mechanism of thyroid hormone action
TH are insoluble and therefore bound to proteins (99%)
- 75% of T4 bound to thyronine-binding globulin (TBG)
- 15/20% bound to thyroxine-binding prealbumin (TBPA)
- 5/10% bound to albumin
TH receptors are intracellular (nuclear), therefore interaction –> gene transcription –> protein synthesis
State the biological effects of thyroid hormone
Increased basal metabolic rate (and O2 consumption)
- Increased carbohydrate metabolism
- Increased synthesis, mobilisation and degradation of lipids
- Increased protein synthesis
TH is essential for the normal development of the CNS, especially myelination of nerve fibres
The primary mechanism of action of TH is to increase the number/size of mitochondria and increase activity of metabolically important enzymes. What is the result of this?
- Glycogenolysis and glucose uptake by muscle and adipose cells
- Potentiation of the effects of insulin
- Potentiation of the effects of catecholamines
- Increase in glucose absorption by the GIT
State 3 organs unaffected by TH
- Brain
- Uterus
- Testes
- Spleen
- Thyroid gland
- Anterior pituitary gland
How will a TH deficiency affect the growth of a pre-pubescent child?
How will a GH deficiency affect the growth of a pre-pubescent child?
- Child will not undergo puberty. (Can be replaced easily)
- Child will remain short but will age/undergo other aspects of puberty
CLINICAL APPLICATION
What drugs could be prescribe to treat hyperthyroidism?
Other treatment?
Potassium perchlorate acts by competing with Iodide for the active iodide uptake pump
Propylthiourcil- prevents the peripheral conversion of T4 to T3
Surgery using radioactive (131I) Iodide. This is selectively concentrated in the thyroid gland –> tissue damage–> reduced TH secretion
CLINICAL APPLICATION
What prophylactic treatment is available for hyperthyroidism?
Risk?
Prophylactic administeration of iodine (injection, fortification)
- Carries risk of Jod-Basedow phenomenon in which iodine administeration precipitates hypertension
CLINICAL APPLICATION
Which drugs can induce goitre?
Why?
Lithium - used in bipolar disorder
Iodide- contained in vitamin prep and some cough remedies
These ions are selectively concentrated within the thyroid gland where they interfere with iodide incorporation and hormone release
CLINICAL APPLICATION
How do carbimazole and methimazole work?
Indication?
Both anti-thyroid drugs that act by inhibiting the synthesis of TH by preventing the incorporation of the iodide into the thyroglobulin
Hyperthyroidism
