Thyroid and parathyroid gland 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
Describe thyroid hormone synthesis
Thyroid hormones contain iodine
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, Na conc gradient maintained by Na/K ATPase
Iodine transport into follicular lumen 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
The colloid is endocytosed from lumen into vesicles
Fusion of these vesicles with lysomes causes the digestion of thyroglobulin to release T3&4
Secreted into bloodstream via MCT8 transporters
Describe thyroid hormone regulation
Hypothalamus- TRH➡ pituitary- TSH➡ thyroid- T3&4➡ negative feedback
Describe the TSH receptor
G-protein coupled receptor
Located in the basolateral membrane of the thyroid cells
Conformation change in TSHR after TSH binding replaces GDP with GTP
Intracellular effects mediated by cAMP➡ PKA➡ CREB+ CBP increase transcription of proteins such as Thyroglobulin and NIS
Describe the transport of thyroid hormones
Hydrophobic and so bound to thyroid new binding globulin (TBG), transthyretin (TTR) and albumin
Only free hormone enters the cell
Most of circulating thyroid hormones are T4, a prohormone, T3 is the active hormone
Describe the conversion of T4 to T3
Converted by deiodinases in peripheral tissues 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- 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)
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
Describer hyperthyroidism
Graves hyperthyroidism- autoimmunity- most common
Toxic nodular goitre
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
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?)
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
Treated using Levothyroxine
Describe thyroid cancer
Rare
Assessment of thyroid function- serum TSH, thyroid abs, calcitonin/thyroglobin measurement
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
Describe calcium homeostasis
Bone- main reservoir for calcium
Bone turnover- calcitonin
Soluble calcium-
What is the importance of the parathyroid glands
Regulate calcium and phosphate levels
Secrete parathyroid hormone in response to low calcium and high phosphate
PTH increase calcium reabsorption in the DCT and absorption in the intestine amd increases calcium release from the bone via osteoclast activity
Decreases phosphate reabsorption
