Thyroid and parathyroid gland 6,7,8 Flashcards
Briefly describe the thyroid
Endocrine gland
Secretes T3 and T4
Located in neck Two lobes united by a narrow isthmus
Containing follicles C cells- involved in control of serum calcium homeostasis, secrete calcitonin, inhibit osteoclasts from resorbing bone
Follicular endothelial cells- majority of thyroid cells, line follicular lumen filled with colloid, controlled by TSH, responsilbe for production of T3 and T4
Describe thyroid hormone synthesis
Thyroid hormones contain iodine (essential for thyroid hormone biosynthesis - sources include fish wheat)
Triiodothyronine (T3) has 3 iodine atoms
Thyroxine (T4) has 4 iodine atoms
Iodine transport from the blood to cell- first rate limiting step Active transport via Na-I symporter (NIS) located on the basolateral cell membrane mediates iodine uptake and can also let Na into the cell
Na conc gradient maintained by Na/K ATPase letting Na out and K in
Iodine transport into follicular lumen (out of the cell) via pendrin- passive
Thyroglobulin- most highly expressed protein in the thyroid gland serves as a scaffold for hormone synthesis
Thyroid peroxidase- located on apical membrane, catalyses oxidation of iodide, iodination of thyroglobulin tyrosine residues, and the coupling of the iodotyrosines to form thyroid hormone MIT +DIT➡ T3 DIT+DIT➡ T4
Describe thyroid hormone release
Stored in follicular lumen as colloid
When thyroid hormone is requied, the colloid is endocytosed from lumen into vesicles
Fusion of these vesicles with lysomes causes the digestion of thyroglobulin to release T3&T4 Secreted into bloodstream via MCT8 transporters
Describe thyroid hormone regulation
Hypothalamus- TRH➡ pituitary- TSH➡ thyroid- T3&T4➡ negative feedback (reduce levels of TSH and TRH)
Describe the TSH receptor
G-protein coupled receptor
Located in the basolateral membrane of the thyroid cells
Conformation change in TSHR G protein after TSH binding replaces GDP with GTP. Activating it
Intracellular effects (activation) mediated by cAMP➡ PKA➡ CREB+ CBP increase transcription of proteins such as Thyroglobulin and NIS
(PKA phosphoylates transcription factors such as CREB and CBP which activate gene expression)
Action of TSH
TSH binds to receptor and stimulates signalling cascade. Can increase NIS and NA/I symporter to increase iodie uptake, increased about of NIS on membrane. TSH can stimulate the amount of pendrin in plasma membrane where it mediates iodide crossing apical membrane, can express Tg protein and stimulate expression of TPO by stimulating the oxidaition, iodination and conjugation of thyroid hormones. TSH can stimulate endocytosis of colloid back into cell.
Describe the transport of thyroid hormones
T3 and T4 are Hydrophobic and so bound to thyroid new binding globulin (TBG) (70%), transthyretin (TTR)(15%-20%) and albumin (10%-15%)
Only free hormone enters the cell
Most of circulating thyroid hormones are T4, a prohormone, T3 is the active hormone
T3 is active hormone
Describe the conversion of T4 to T3
MCT8 take up T3 and T4 into the tissues. T4 Converted to T3 by deiodinases in peripheral tissues. T3 passes back into blood stream.
T4 = iodine redidues on inner and outer ring
T3 = one iodine on outer ring
As a further level of hormone regulation D1 works on both inner and outer rings- can activate and inactive thyroid hormones- found in liver and kidney
D2 works on the outer ring, removing iodine from outer ring- main activator of T3, in CNS, pituitary, skeletal muscle, placenta, heart
D3 works on the inner ring- inactivates thyroid hormones- CNS and placenta
Describe thyroid hormone action
Control growth and development- essential for early brain development,
Lack of hormone results in mental retardation and delayed skeletal maturation
Basic metabolic rate- increase heat produced through increases oxygen consumption and heat production- alters mitochondrial activity
Other- increase carbohydrate, fat metabolism, decreases circulating cholesterol and triglycerides by increasing cholesterol secretions in bile
Regulates cardiac contractility and heart rate
Acts on nuclear hormone receptors Ligand (T3)-activated transcription factors bind to thyroid hormone response elements (TRE)
TRE = 2 genes with 2 splice variants
- Alpha 1- heart and muscle
- Alpha 2- cannot bind T3 but can bind response element on gene- suppressive?
- Beta1- liver, kidney, Brain, pituitary
- Beta2- pituitary and CNS- involved in negative feedback
Non-genomic effects- cytoplasmic signals transduction pathways- MAPK, cAMP and PKA Modulate of PM ion pumps or channels Rapid uptake of glucose and amino acids
Describe hyperthyroidism
Decreased serum TSH, increased serum T3 and T4. Hypothyroidism is the opposite
Graves hyperthyroidism- autoimmunity- most common
Toxic nodular goitre
TSH-R antibodies can cross placenta and pass to baby. But baby will make antibodies against them so will eventually dissapear
Thyroiditis- inflammation
Symptoms- tachycardia, atrial fibrillation, shortness of breath, ankle swelling Weight loss, diarrhoea, increased appetite Tremor, myopathy, anxiety Sore gritty eyes, double vision, stating eyes, itching
Describe Graves disease
60-80% of hyperthyroidism
Most common autoimmune disease
Pathogenic stimulating auto-antibodues to TSH receptor on thyroid follicular cells. This causes TSH to be low so no negative feedback occurs, so overexpression of T3 and T4
Eye lid kag, conjunctival oedema, periorbital puffiness, bulging, weakness of eye muscles
Diagnosis by iodine uptake scan TPO abs and TSH abs
Describe treatment of hyperthyroidism
Anti thyroid drugs- thionamides- carbimazole, propylthiouracil- blocks iodine incorporation SE- rash, joint pain, sickness, no WBCs, liver disease- propulthiouracil Low cure rate
Surgical removal of thyroid- used for patients with large goitre, in pregnant women, and in severe eye swelling and protrusion
Radioactive iodine- 85% cure, may lead to hypothyroidism, not for pregnant women, (cancer and infertility?)
Treatment aims to relieve symptoms, restore T4/T3
Describe hypothyroidism
Hashimotos thyroiditis- autoimmune antibodies for TPO and thyroglobulin- genetic predisposition After treatment for hyperthyroidism,
iodine deficiency- major cause of hypothyroidism
Congential - cretinism Sympotoms- Bradycardia, heart failure, pericardial effusion Myxoedema, rash on kegs, weight gain, constipation, depression, psychosis T
reated using Levothyroxine to normalise T3 and T4 levels
Describe thyroid cancer
Rare Assessment of thyroid function- serum TSH, thyroid abs, calcitonin/thyroglobin measurement.
Goiture = swelling on neck due to swelling of thyroid gland
Assessment of thyroid size- X-ray thoracic inlet, CT or MRI of neck, respiratory loop
Assessment of thyroid pathology- radionuclide, ultrasound scanning Used to differentiate between benign cystic nodules and tumours, guidance for fine needle aspiration
Treatment- radiation, chemo, TK inhinbitor, surgery, levothyroxine
Describe calcium homeostasis
Bone- main reservoir for calcium
Bone turnover- calcitonin
Soluble calcium-
Kidneys, GI tract and bone all contribute to calcium in circulation
Functions of skeleton: support and muscle attachments, protection for vital organs and marrow, ion homeostasis for calcium and phosphate
