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
What is congenital hypothyroidism, how is it tested and treated and what happens if it isn’t treated?
High level of TSH in heel prick test at birth shows no negative feedback and therefore no T4
Given thyroxine immediately if this is found
If left untreated child develops into a cretin - irrevocable brain damage, low IQ, stunted growth
What are the chemical names of T3 and T4?
T3 - triioidothyronine
T4 - thyroxine
What are 4 problems with development of the thyroid gland?
Agenesis - lack of development
Incomplete descent - does not fully descend from base of tongue to trachea
Thyroglossal cyst - segment of duct persists and presents as a lump years later
Lingual thyroid - no descent at all, remains close to back of tongue and grows
What are the main roles of the thyroid gland?
synthesise, store and secrete thyroid hormones that regulate growth, development and metabolic rate
What is primary hypothyroidism and what causes it?
Failure of the thyroid gland caused by autoimmune damage or as a result of thyroidectomy
Causes decline in thyroxine levels and rise in TSH, eventually exhausting anterior pituitary and causes TSH levels to fall
What are features associated with primary hypothyroidism?
Everthing slows down i.e.: Deepening of voice Depression Tiredness Cold intolerance Weight gain with reduced appetite Constipation Bradycardia Eventual myxedema coma
How is primary hypothyroidism treated?
Replacement of thyroxine daily and monitoring of TSH levels, otherwise death due to xs cholesterol increases risk of myocardial infarction/stroke
What is primary hypothyroidism also known as?
Myxoedema
What is hyperthyroidism/thyrotoxicosis?
Too much thyroxine
means TSH falls to 0 as there is no need to stimulate
Causes increased basal metabolic rate with raised temperature, raised HR
What are features associated with hyperthyroidism?
Everything speeds up i.e. Increased appetite burning of calories and weight loss Myopathy Mood swings Feeling hot all the time Diarrhoea Tremor of hands Palpitations Sore eyes Goitre (swelling of thyroid in the neck)
How is hyperthyroidism treated?
Thionamides and surgery
What is Grave’s disease and its features?
A cause of hyperthyroidism
Autoimmune disease
Antibodies bind to TSH receptor and stimulate it
Causes smooth thyroid enlargement and hyperthyroidism
Antibodies also bind to eye muscles to cause exopthalamos
Stimulate growth of soft tissue on the shin - pre-tibial myxoedema
What are potential complications of a thyroidectomy?
Recurrent larangeal nerve injury Hypocalacaemia Infection Bleeding Hypothyroidism
