Flashcards in Thyroid Physiology Deck (25):
Describe the main anatomy of the thyroid
Right and left lobes connected via isthmus with a pyramidal lobe at top in 50% adults
What is blood supply for thyroid?
Superior/inferior thyroid arteries
Superior/middle/inferior thyroid veins that drain into internal jugular
What are two main hormones made in thyroid? Where are they made? What is their precursor?
T4: exclusively made in thyroid
T3: 20% made in thyroid; 80% made by extra thyroidal conversion of T4 by deiodinases
Both are synthesized from tyrosine
Which thyroid hormone is biologically active? What is the role of the other?
T3 is the biologically active hormone as it has higher binding affinity for the thyroid hormone receptor.
T4 is more of a pro-hormone
What is calcitonin? Which cells synthesize it? What is its clinical significance?
Calcitonin is made by parafollicular C cells in response to changes in ionized calcium.
It's not important for physiology but is a marker in medullary thyroid cancer.
Describe the function of thyroid hormone in following areas:
Thyroid increases metabolic rate, helps control respiratory muscles and increases respiratory drive, increases the number of LDL-receptors, stimulates lipolysis and activates osteoclasts/osteoblasts
Describe the function of thyroid hormone in follow areas:
Increases number of ß-adrenergic receptors
Increases heart rate and contractility
Promotes increased oxygen dissociation from Hb into tissue
Promotes gut motility
Regulates ovulation and menses
Describe role of thyroid hormone in development. When does thyroid hormone synthesis begin?
Thyroid hormone starts by 11 weeks gestation. It is necessary for brain development and skeletal maturation
What occurs as a result of untreated congenital hypothyroidism? What is it called?
Congenital hypothyroidism, also known as cretinism causes Mental retardation and dwarfism.
Does thyroid hormone act via genomic or non-genomic actions?
Both. T3 acts on nuclear receptors to mediate transcriptional regulation
T3 and T4 interact with enzymes and mitochondrial proteins
When does thyroid receptor act as a transcriptional activator? As a repressor?
Depends on presence of thyroid hormone
In HPT axis, what is the mechanism for negative feedback
T3 from the thyroid and extra-thyroid conversion reduces TSH output from pituitary by down regulating TRH receptors on thyrotropes.
What are the elements of follicles? (4)
What are the recommended daily intake for iodine? Describe for kids, adults, preggers and lactating women
Lactating women: 290
What is thyroglobulin? Where is it stored?
Large glycoprotein stored in vesicles and exocytosed into colloid
Describe the first step of thyroid synthesis: Iodide transport
Iodide transport. Transported across basal membrane of follicular cells via Na/I symporters then transported across apical border into colloid surface via pendrin transporter (I/Cl transporter)
Describe the second step of thyroid hormone synthesis: oxidation and organification
Iodide is oxidized to iodine via thyroid peroxidase (TPO) enzyme. Then Iodine is combined with tyrosine residues of thyroglobulin via TPO to form either MIT or DIT
Describe the third step of thyroid hormone synthesis: Coupling
Two molecules of DIT combine to form T4 or one DIT and one MIT combine to form T3. Production of T4 is 10x faster. T4, T3 and DIT/MIT are stored in lumen as colloid. They remain bound to thyroglobulin.
How many iodines are in T3? T4?
T3: 3 iodines
T4: 4 iodines
Describe the fourth step of thyroid hormone synthesis: Proteolysis of thyroglobulin
When thyroid stimulated by TSH, colloid taken up in vesicles back into follicular cell
Vesicles fuse with lysosomes, which cleave T4,T3, inactive iodotyroines from thyroglobulin
Describe the fifth step of thyroid hormone synthesis: Secretion of thyroid hormone.
What happens to unused DIT/MIT?
T4/T3 are transported back across basal membrane into capillaries to enter circulation.
Thyroid deiodinase cleaves unused DIT/MIT. Iodines are aded to intracellular iodine pool and leftover tyrosine are used to synthesize new thyroglobulin molecules
How is T3 made from T4?
What is reverse T3 and how is it made?
Deiodinases cleave iodine from T4.
Cleavage from outer ring makes T3. Cleavage from inner ring makes reverse T3, which is biologically inactive
How are most thyroid hormones found in blood? In what state are thyroid hormones physiologically active?
Over 70% of both T4/G3 are bound to thyroxine-binding globulin (TBG)
Free hormones (less than 1%) are physiologically active.
What conditions increase TBG levels? (2) What conditions decrease TBG levels? (4)
TBG is increased by estrogen (OC, HRT, pregnancy) and increased hepatic release
TBG is decreased by decreased hepatic production, renal loss, congenital conditions and high levels of androgens.