Thyroid physiology Flashcards
What are the stages of thyroid hormone synthesis?
Active transport Thyroglobulin formation Exocytosis of Thyroglobulin Iodination of Thyroglobulin Coupling (of MIT and DIT) Endocytosis of Thyroglobulin
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What happens during the active transport phase of thyroid hormone synthesis?
Active transport of Iodide into follicular cell via Sodium-Iodide Symporter (secondary AT driven by sodium gradient maintained by Na+/K+ ATPase)
What happens during the Thyroglobulin phase of thyroid hormone synthesis?
Thyroglobulin (a protein rich in Tyrosine) formed in follicular cell and placed into secretory vesicles
What happens during the Exocytosis phase of thyroid hormone synthesis?
Exocytosis of thyroglobulin into follicle lumen where it is stored as Colloid
What happens during the Iodination phase of thyroid hormone synthesis?
Iodide made reactive (into Iodine) by Thyroid Peroxidase (enzyme) on the luminal membrane which then binds to Benzene ring on Tyrosine residues of Thyroglobulin to form Monoiodotyrosine and then Diiodotyrosine
What happens during the Coupling phase of thyroid hormone synthesis?
Coupling of MIT and DIT to form T3 (Triiodothyronine) and DIT with DIT to form T4 (Tetraiodothyronine/ Thyroxine)
What happens during the Endocytosis phase of thyroid hormone synthesis?
Endocytosis of Thyroglobulin back into follicular cell where it undergoes proteolysis in lysosomes to cleave iodinated Tyrosine residue from larger protein.
Free T3 and T4 then released and Thyroglobulin scaffold is recycled
What are T3 and T4?
Fat-soluble hormones carried by plasma proteins (mainly Thyronine Binding Globulin and Albumin)
T3 = triiodothyronine
T4 = tetraiodothyronine (Thyroxine)
Where are T3 and T4 deactivated?
Liver and Kidneys
What is the Hypothalamic-Pituitary-Thyroid Axis?
Process by which thyroid hormones are released:
- Thyrotropin-Releasing-Hormone (TRH) released by the Hypothalamus in response to detection of low blood concentrations of Thyroid hormones
- TRH binds to receptors on Thyrotrophic cells of the Anterior Pituitary Gland causing release of Thyroid Stimulating Hormone (TSH) into the systemic circulation
- TSH binds to TSH receptors on the basolateral membrane of Thyroid Follicular Cells and induces synthesis and release of thyroid hormones
What is a Goitre?
Enlarged thyroid gland caused by Hypo-/ Hyperthyroidism, Iodine deficiency or Thyroid tumour - enlarges to try to compensate
What autoimmune disease can cause hyperthyroidism?
Grave’s Disease - body produces antibodies that stimulate TSH receptors on follicular cells
What autoimmune disease can cause hypothyroidism?
Hashimoto’s Disease - causes destruction of thyroid follicles and production of antibodies that block the TSH receptors on follicle cells
What is the anatomical location of the thyroid?
Anterior neck between C5-T1
Sits inferior to the thyroid cartilage and anterolaterally to the trachea
What is the anatomical structure of the thyroid?
Two lobes connected by an isthmus
How does the thyroid gland move during development?
Initially formed in the floor of the pharynx near the base of the tongue and descends down the neck during development
What is the vascular supply of the thyroid gland?
Highly vascularised!
Superior and inferior thyroid arteries - paired arteries on left and right side
Superior thyroid artery arises from the external carotid
Inferior thyroid artery arises from the thyrocervical trunk (a branch of the subclavian)
Small amount of individuals also have a Thyroid Ima
What is the venous drainage of the thyroid gland?
Superior, middle and inferior thyroid veins form a venous plexus
Superior and middle drain into the internal jugular veins
Inferior drains into the braciocephalic vein
What is the nerve innervation of the thyroid gland?
Branches of the sympathetic trunk
[Nb. nerves do not control endocrine secretion - hormone release is regulated by the pituitary as part of the HPT axis]
What hormones does the thyroid gland secrete?
Tetraiodothyronine/ THYROXINE = T4
Triiodothyronine (T3)
Calcitonin (important in calcium homeostasis)
Which thyroid hormone is not able to have effect on cells in its free form?
T4 - must be deiodinased to T3 (by thyroid hormone deiodinase) intracellularly
How does T3 have its effect on cells?
- Free T3 transported into cell by carrier protein (MCT8)
- T3 binds to receptor (T3R alpha or beta) which enters nucleus of cell
- Binds to DNA changing protein synthesis and inducing thyroid hormone response
What physiological actions do thyroid hormones have?
Increased metabolic rate
Maturation and differentiation (in bone, lungs, brain etc.)
Neurological functions (synapse formation, myelinogenesis, neuronal outgrowth)
Growth (needs T3/T4 but regulated by growth hormones)
How can iodide/ thyroid hormone deficiencies impact foetuses/ babies?
Impaired physical and neurological development (Cretinism)
Cannot be reversed after 2 years old
Screened for in new born heel prick test in the UK
What blood test results would you see in someone with hyperthyroidism?
High T3/T4 Low TSH (if problem is in thyroid gland) High TSH (if problem is in hypothalamus or pituitary)
What blood test results would you see in someone with hypothyroidism?
Low T3/T4
High TSH
What are the common signs/ symptoms of hyperthyroidism?
Everything sped up!
E.g. heart rate, sweating, metabolism (so weight loss), nervousness, goitre, diarrhoea
What are the common signs/ symptoms of hypothyroidism?
Everything slows down so fatigue, constipation, low mood, obesity, goitre
What treatments can be used for hyperthyroidism?
Drugs (Carbimazole is 1st line)
Radioactive Iodine
Surgery
What treatments can be used for hypothyroidism?
Replacement hormones:
Levothyroxine (synthetic T4) - drug of choice for maintenance as longer half life and activated in body
Liothyronine (synthetic T3) - rapid action
What is the difference between bound and free thyroid hormones?
Bound = carried in blood bound to proteins (e.g. Albumin or Thyroid Binding Globulin) - not active (majority of thyroid hormones are in this state) Free = not bound to proteins - biologically active
