Thyroid Flashcards
Thyroid anatomy; Thyroid hormones; Hypothalamo-pituitary-thyroid axis; Hypothyroidism; Hyperthyroidism
What is the general structure of the thyroid gland?
Two lobes + isthmus (sometimes pyramidal lobe above isthmus)
Parathyroid glands embedded in thyroid
Left reccurent larangeal nerve runs close (vocal cord supply)
sits above trachea
Contains follicles with a colloid centre
Lined by follicular cells
Surrounded by parafollicular receptors
What is the purpose of the parafollicular cells?
TSH receptors for TSH released from adenohypophysis to stimulate thyroid gland for thyroglobulin protein and iodide uptake
What is thyroglobulin?
Protein containing tyrosine residues to which iodine can be added
What are thyrotrophic cells?
Stimulated by thyrotrophin releasing hormone (from hypothalamus to anterior pituitary gland) to produce TSH and release to the bloodsteam
How does thyroid stimulating hormone stimulate synthesis of thyroglobulin and release of T3/4?
1) TSH binds to TSH receptor
2) Iodide taken up from blood into follicular cells via sodium-iodide symporter on basolateral membrane
3) Iodide pumped into colloid by Pendrin pump (iodide chloride antiporter)
4)Thyroglobulin is synthesised via transcription and translation and diffuses into colloid
5) Iodide oxidised via thyroid peroxidase (TPO) in the presence of H2O2
6) Iodine attaches to tyrosine on a molecule of thyroglobulin catalysed by TPO in the presence of H2O2
(one I = 3-mono-iodotyrosine, two I = 3,5-di-iodotyrosine)
7) Coupling of DIT and MIT to create T3 or DIT and DIT to create T4 using TPO and H2O2
8) In the cell, lysosome moves towards the apical membrane and T3/T4-TG are taken up into the cell via endocytosis, into the lysosome
9) Inside lysosome, proteolysis cleaves T3/T4 from TG
10) T3/T4 diffuse towards the basolateral membrane and then diffuse into the blood
Where does TSH take effect?
Follicular cells
Where do T3 and T4 have effect?
Action all around the body
How is the hypothalamo-pituitary-thyroid axis regulated?
Increased by: thyroid releasing hormone oestrogens Reduced by: somatostatin inorganic iodide thyrotropin Direct -ve feedback: -T3/T4 released from thyroid travels in blood to anterior pituitary where it inhibits TSH production Indirect -ve feedback: -T3/T4 can reduce levels of TRH production in the hypothalamus in order to reduce levels of TSH to reduce T3/T4 production
What causes hypothyroidism?
Reduced level of T4 so less negative feedback and high level of TSH produced
What is considered the major thyroid hormone?
T3 is more bioactive
BUT T4 major secretory product as it has higher concentration in bloodq
How is T4 converted to T3 and why?
Converted by deiodinases in target cells because T3 is more bioactive
Can also be converted to biologically inactive reverse T3 if deiondinated in different position (Iodine removal from ring closest to chiral carbon
How are T3 and T4 transported in the body?
Transported in the blood Mostly bound to plasma proteins: -70-80%Thyroid-binding globulin -10-15%Albumin -5%prealbumin/transthyretin 0.05-0.5%Very very small amounts unbound (bioactive components)
What is the general structure of a thyroid hormone?
tyrosine amino acids with 3 or 4 iodines attached
Describe the hypothalamo-pituitary-thyroid axis
Thyrotrophin releasing hormone released from hypothalamus to adenohypophysis, causes thyrotroph cells to produce Thyrotophin stimulating hormone which then stimulates the production of thyroglobulin and T3/T4
What are the actions of thyroid hormones?
Fetal growth and development
Increase basal metabolic rate
Protein, Carbohydrate and fat metabolism
Potentiate actions of catecholamines (e.g. tachycardia, lipolysis)
Effects on GI, CNS and reproductive system
