Endocrine 7: Thyroid and HPT Flashcards
Where is the thyroid gland located?
- anterior to the trachea and cricoid cartilage
What does the thyroid gland look like?
- 2 symmetrical lobes connected by an isthmus
Describe the blood supply of the thyroid gland.
- superior and inferior thyroid arteries (external carotid and thyrocervical trunk)
- venous plexus on anterior surface gives rise to superior, inferior, and middle thyroid veins => jugular vein drainage
What is a bruit and thrill?
In thyroid hypertrophy, the anterior venous plexus becomes vasodilated.
- bruit = you can hear the sound of blood through this area
- thrill = you can feel the blood moving through
How is the thyroid gland innervated?
middle and inferior cervical ganglia
- sympathetic
Describe the structure of the thyroid gland cells.
- colloid/lumen
- surrounded by follicular epithelial cells
- parafollicular cells
How are follicular epithelial cells activated?
- when inactivated, they are flat and squamous
- when activated by TSH, they become cuboidal
Define colloid.
lumen of thyroid cellular components
- large storage of TG
- surrounded by FECs
Define follicular epithelial cells.
- surround the colloid
- where TG is made and secreted into the colloid
- microvilli extend into the colloid to deliver iodide and TG
- close to fenestrated capillaries to deliver hormones directly to blood
Define parafollicular cells.
- C cells
- produce calcitonin
- do NOT line the colloid
- maintain the follicles
How is iodide intake and thyroid hormone production related?
- thyroid hormones are iodothyronines
- thyroid hormone production requires TG and iodide
- excess dietary iodide is mostly excreted
- thyroid keeps 3-4 months worth of iodide
- iodized salt is main dietary source
Describe the Wolf-Chaikoff effect.
- autoregulatory effect inside the thyroid to control iodide intake and maintain iodide storage
- low iodide dose = thyroid takes as much as it can
- high iodide dose = thyroid stops taking it in, and might even stop altogether
Describe the clinical use of the Wolf-Chaikoff effect.
- treat hyperthyroidism
- give high dose iodide to shock the thyroid gland to stop taking in iodide => prevent further production of thyroid hormones
Why is iodide intake important?
- need it to make thyroid hormones
- most common cause of mental retardation worldwide
- iodized salt
Define the HPT axis.
H - hypothalamus - PVN secretes TRH
P - pituitary - thyrotrophs respond to TRH and secrete TSH
T - thyroid - responds to TSH and makes T3/T4/rT3
What are the negative feedback mechanisms of the HPT?
- T4 goes to pituitary => converted to T3 inside thyrotrophs = stops TSH secretion
- T3/T4 negative feedback on PVN
- tonic inhibition by dopamine and SS
Define Thyroxin.
- T4
- long half-life
- VERY tightly bound to transport protein
- mostly inactive (low affinity binding to thyroid receptor inside cells)
- converted to T3 inside cells
Define Triiodothyronine.
- T3
- long half-life
- VERY tightly bound to transport protein
- primarily active thyroid hormone (high affinity, low capacity to thyroid receptors inside cell)
- most intracellular T3 source is converted from T4
Define rT3.
- reverse T3
- DIT on outer, MIT on inner
- inactive
- used to keep thyroid balance in check in fetus, brain, etc.
Why are follicular epithelial cells polarized?
- basolateral membrane = intake of I from the bloodstream; moves I against concentration gradient via NaI symporter; subsequent release of T3, T4 after hormone synthesis
- apical membrane = releases TG and I (NaI symporter) into colloid; reuptake of iodinated TG
List the mechanism of action of thyroid hormone synthesis.
- Iodide Trapping - TSH stimulates NaI symporter on the basolateral membrane to move Iodide into the FEC against its concentration gradient
- Transport - TG and iodide (via pendrin protein) are transported to colloid/lumen; thyroid peroxidase (TPO) converts iodide to iodine
- Iodination/Organification - tyrosine residues of TG are iodinated
- Conjugation - conjugation of iodinated tyrosines to form T3 or T4 (combining MIT and DIT)
- Endocytosis - T3/T4-TG are packaged into endosomes via megalin protein
- Proteolysis - cleavage of T3 and T4 from TG (TG, MIT, DIT are recycled)
- Secretion - T3 and T4 released from basolateral membrane
Describe conjugation of iodinated TG.
- if one Iodine is added = MIT
- if 2 iodine are added = DIT
T3 = MIT + DIT T4 = DIT + DIT rT3 = DIT + MIT (double I on outer ring)
How does lithium relate to thyroid hormone production?
- blocks NIS
- can’t make hormone b/c no iodide
Define carbimazole.
- blocks TPO
- can take in iodide, but can’t convert to iodine
- iodide trapped in colloid…can’t make hormone
- organification defect => hypothyroid
What is the ratio of T3:T4 in blood?
mostly T4
Define cold and hot spots.
- normal = bilateral uptake;
- cold spots = one section has no iodide uptake; more indicative of malignancy
- hot spots = much more uptake on one side, diffuse in the other;
How can radioactive iodide uptake scans help in making diagnoses?
- normal = 25% uptake after 24 hours
- hypothyroid = 60%
- hyperstimulation/Graves Disease = rapid rise, plateau; high turnover
- organification defect = normal rise in intake, but declines after
Define Type 1 Deiodinases.
- can act on either outer or inner ring
- makes T3 or rT3
- present in liver, kidney, thyroid, skeletal muscle
- primary source of circulatory T3
Define Type 2 Deiodinases.
- can only act on outer ring
- makes T3
- expressed in brain, pituitary, placenta, cardiac muscle
- in locations where T3 activity is needed, negative feedback
Define Type 3 Deiodinases.
- can only act on inner ring
- makes rT3
- expressed in brain, placenta, skin
- in locations where you need to protect from excess T3
How are thyroid hormones transported?
- mostly thyroid binding globulin (TBG)
- some on transthyretin (TTR)
- some on albumin
- rarely free
Describe the structure of TBG.
- same family as CBG
- tightly bound, high affinity
- surrounds the thyroid hormone
- synthesized in liver (hence, affected by liver function)
- stimulated by TSH and estrogen
- reversible (can bind more right away)
Describe the mechanism of action of thyroid hormones inside its target cells.
- TBG delivers T3/T4 to cell
- Type 1 and 2 deiodinases convert T4 to T3
- T3 goes to nucleus and binds to thyroid hormone receptor (THR)
- THR and retinoic acid receptor (RXR) form a heterodimer and act as TF
Describe the affinity of thyroid hormones to THR.
- high affinity, low capacity for T3
- very low affinity for T4 (must be converted)
What are the general physiological effects of thyroid hormone?
- maintain BMR by continuous futile cycle of energy storage and breakdown
- —> gluconeogenesis, lipolysis, proteolysis ==> increased energy consumption and thermogenesis
- promotes CNS maturation
- upregulation of B-adrenergic receptors in heart, skeletal muscle, adipose tissue
Describe the physiological effects of thyroid hormone on metabolism.
- T3 increases energy consumption, oxygen consumption, and thermogenesis by increasing mitochondrial activity
Describe metabolic effects of hypothyroidism.
- decreased BMR
- decreased gluconeogenesis, decreased glycolysis = no change
- decreased lipolysis, decreased lipogenesis = high cholesterol
- decreased proteolysis, decreased muscle mass formation = no change
- decreased thermogenesis = cold intolerance
Describe metabolic effects of hyperthyroidism.
- increased BMR
- increased gluconeogenesis, increased glycolysis = no change
- increased lipolysis, increased lipogenesis = low cholesterol
- increased proteolysis, increased protein synthesis = muscle wasting (weight loss)
- increased thermogenesis = hot intolerance
What are the CNS physiological effects of thyroid hormones?
- normal brain development
- neural cell migration
- neural cell differentiation
- myelination
- synaptic transmission
Define cretinism.
- iodide deficiency during development
- hypothyroidism
- short stature
- impaired bone formation
- mental retardation
- delayed motor development
Describe thyroid hormone physiological effects on the CVS.
- upregulation of beta adrenergic receptors
- increased CO
- increased RHR, SV
- increased contractility
- hyperthyroidism can cause arrhythmias
Define goiter.
- enlarged thyroid gland
- either hypo or hyper can cause
Define Graves Disease.
- hyperthyroidism
- symmetrical goiter
- autoimmune disorder
- LATS antibodies bind to and activate TSH receptors in the thyroid gland
- rapid overproduction of T3/T4
- constant stimulation of thyroid leads to hypertrophy
- Sx: goiter, tachycardia, bugged eyes, irritability, heat intolerance, muscle wasting, low TSH b/c excess T3/T4 negative feedback
Define Hashimoto’s Thyroiditis.
- hypothyroidism
- autoimmune destruction of thyroid follicles
- antibodies against TG and TPO (can’t make thyroid hormones)
- Sx: goiter, lethargy, fatigue, hair loss, brittle nails, cold intolerance, weight gain
Define Thyroid Storm.
- occurs in individuals who are already hyperthyroid
- in acute stress, surge of catecholamines combined with elevated T3/T4 baseline leads to rapid tachycardia and arrhythmias, N/V, fever
- life threatening
- Tx
- propylthiouracil (PTU) - blocks TPO, only acute
- carbimazole - blocks TPO
- beta blockers
