Thyroid and Parathyroid

Question 1

Structure of thyroid gland

Answer 1

• thyroid cartilage is just superior to it
• wraps around trachea
• very close to carotid aa.s and jugular vv.s
• follicular gland - follicles lined by simple cuboidal epithelium
• center of the follicles = colloid where protein is stored

Question 2

dietary requirement of iodine

Answer 2

150 mcg/day

-iodine is incorporated into T3/T4

Question 3

iodide trapping

Answer 3

• ingested iodine is converted to iodide and absorbed from gut –> some excreted and some taken up and concentrated in thyroid gland
• thyroid follicular cells actively transport iodide from circulation into cell by NIS (sodium/iodide symporter)

Question 4

Oxidation of iodide

Answer 4

-once inside thyroid gland, iodide is oxides to iodine by thyroid peroxidase (occurs on apical membrane)

Question 5

Synthesis of thyroglobulin

Answer 5

-synthesized by follicular cells and secreted into colloid

Question 6

Binding of iodine to tyrosine

Answer 6

• once iodides is oxidized to iodines, they attach to the tyrosine molecules of thyroglobulin to generate MITs and DITs.
• Two DIT molecules are coupled to form thyroxine (T4)
• one MIT and one DIT are coupled to form triiodothyronine (T3)

Question 7

Storage of T3/T4 in thyroid

Answer 7

• stored within the colloid

- it is unclear whether the production takes place within the cells of the follicle or within the colloid

Question 8

thyroglonulin formation

Answer 8

• elemental iodide is in circulatory system and sodium symporter takes it in
• TSH facilitates presence of transporters
• once within cell, thyroid peroxidase oxidizes molecule and forms I2 molecule
• from there, binding to tyrosine gives you MIT or DIT (mono or di iodinated tyrosine)

Question 9

MOA of thyroid hormones

Answer 9

• enters cell through surface receptor (not a steroid hormone, but sometimes acts like one)
• different receptor systems, some require ATP
• hormone receptor complex acts as a transcription factor (this is how it acts like a steroid)
• Receptor inhibits transcription when unbound and promotes transcription when bound

Question 10

Effects of Thyroid hormone (T4 or T3)

Answer 10

• effects probably all cells
• increases metabolic activity (i.e. thermogenesis, sweating, increased rate and depth of resp, increased CO, increase pulse pressure, increased utilization of substrates for energy)
• maintains growth
• maintains gut motility
• maintains cerebration (enhances wakefulness, alertness, responsiveness to various stimuli, memory, learning)
• muscle
• sleep
• sex

Question 11

regulation of thyroid hormone

Answer 11

• TSH from anterior pituitary acts through cAMP
• proteolysis of thyroglobulin
• iodide pumping
• iodination of tyrosine
• increase size and secretory activity of thyroid gland
• TSH is controlled by TRH from hypothalamus

Question 12

Thyroid disorders presentation and dx

Answer 12

• presentation: hot or cold all the time, constipation in hypo or diarrhea in hyper, mentation or cerebration (hypo = slow, hyper = overactivated)
• diagnosis: diagnose on presentation and blood work (particularly TSH and T3/T4 levels)
• according to derosa, “low normal” IS NOT A THING

Question 13

Calcium/Phosphate regulation

Answer 13

• narrow range
• most of both ions in bone (we also have a large amount of phosphate in cells)
• Calcium effects are dramatic (changes the excitability of the muscle cell membrane so this could lead to fasciculations or spasms)

Question 14

Balance of intake/excretion of calcium and phosphate

Answer 14

• 1000mg/day
• 35% absorbed (calcium, almost 100% phosphate is absorbed)
• 250mg added to GI tract and excreted (leaves through stool)
• 900mg (calcium) lost, phsophate excreted renally as part of buffering system
• out of the 1000mg we intake, we conserve only about 100mg

Question 15

Bone

Answer 15

• composed of matrix strengthened by deposits of calcium salts
• matrix = extracellular part of the bone (Ca/Phos salt)
• formed by osteoblasts (living within pockets of the matrix)
• bone is constantly being broken down (osteoclasts) and rebuilt (osteoblasts)
• amorphous salts vs. hydroxyapatite
• osteoclasts are one of the few multinucleated cells of the body, releases acid that breaks down the bone

Question 16

VitD and pathway of formation

Answer 16

• active form is hydroxylated by the liver and kidney
• pathway: 7-dehydrocholesterol –> cholecalciferol (via UV light) –> 25 hydroxycalciferol (via liver) –> 1,25 hydroxycalciferol (via kidney/PTH)
• vitD promotes Ca absorption and is regulated by calcium levels

Question 17

PTH

Answer 17

• comes from parathyroid glands –> “chief” cells release PTH
• prohormone 110aa, active hormone 84aa (calcium sparing hormone)
• people with rickets may have very big parathyroid glands because they are trying to compensate for the low level of calcium

Question 18

calcitonin

Answer 18

• thyroid product made by C cells
• peptide hormone
• primary stimulus is increase in Ca content –> OPPOSES PTH
• shifts dynamic toward deposition of Ca, inhibits formation of new osteoclasts
• effects are weak (initial reduction stimulates PTH, rate of absorption is low anyway - effect greater in kids or disease of osteoclast activity) –> not as powerful as PTH

Question 19

supersaturation of ions

Answer 19

the concentration of Ca and Phos is high enough in extracellular fluid to precipitate to form hydroxyapatite, but there are inhibitory factors that prevent that precipitation

Question 20

amorphous salts vs. hydroxyapatite

Answer 20

• hydroxyapatite = major crystalline salt in bones
• initial calcium salts deposited are not immediately hydroxyapatite crystals, but amorphous compounds which are a mixture of salts (Ca with other ions). These amorphous salts may eventually be broken down to form hydroxyapatite. they are also important because its easier to break down the amorpous salts to liberate calcium.