L74: Thyroid & HPT Axis Flashcards
Anterior to cricoid cartilage
Location of thyroid gland
Two symmetrical lobes fused by
isthmus
blood supply by
sup and inf thyroid artery….forms a plexus
C-cells produce
calcitonin
2 precursors of thyroid hormone
- Iodide 2. Thyroglobulin
Very high doses of Iodide will
rapidly shut down thyroid hormone production in hyperhroid patients
Thyroid perixidase TPO
oxidizes iodide to iodine…
What inhibits TPO?
Carbimazole (among other drugs)….so you can’t oxidize I2 into I-…ultimately cant make thyroid hormone
DIT + DIT =
T4
MIT + DIT =
T3
Megalin
Endocytoses the TG-T3/4 complex from the colloid into the follicular cell.
Each step is under TSH control
?
What’s NIS?
Sodium iodide symporter
Diagnostic thyroid gland tests
?
>60% uptake
?
Graves disease
Antibodies stimulate TSH receptor
Elevated T4/T3
Goiter (symmetrical)
Tachycardia, opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting.
Organification defect
I- cannot be added to thyroglobulin in colloid.
Predominant in liver
Type I de-iodinase
Type II
?
Type III
?
Type IIi
Inner ring deiodinase (makes reverse T3)
Type II
mainly in brain and pituitary (this is the T3 being sensed by pit thyrotropes that is the negative feedback signal)….also in placenta
Which has highest affinity for T4?
TBG
Upon TSH stimulation, follicular cells (surrounding colloid) turn from
squamous to cuboidal
Inactivated follicles have flattened _____ epithelium
squamous
Parafollicular cells (C-cells) secrete
Calcitonin
5 cell types thyroid gland
Epithelial Fibroblasts Lymphocytes Adipocytes C-cells
Parafollicular cells dont touch
colloid
2 precursors for TH
Iodide
Thyroglobulin
Less than 20micrograms per day of Iodine
Iodine deficiency
“Increases in iodide intake decrease gland transport and hormone synthesis, and visa versa”
Wolf-Chaikoff Effect.
Note: this explains why excess Iodine will shut down hyperthyroidism….
What hypothalamic nucleus makes TRH?
PVN
What hypothalamic nucleus makes TSH?
Trick question! TRH is from hypothalamus
What blocks NIS?
Perchlorate
Lithium
Half life of T4
7-8 days because binds TBG
Binds receptor with LOW affinity
T4 to T3 via what enzyme?
De-iodinases (I, II, III)
Type 1 De-iodinase removes Iodide from
outer or inner ring
Type 2 De-iodinase
outer ring deiodinase
What deiodinase will make T4 into active T3?
Type II deiodinase because it removes outer ring iodine.
Found in brain, pituitary, placenta, and cardiac tissue.
Only deodinase in thyroid gland itself
Type I de-iodinase
Only way to get T3 into the blood via what de-iodinase?
Type I deiodinase (located in thyroid! think about it.)
Type ____ deodinase is the thyroid hormone “sensor” in the pituitary, thus INHIBITING IT.
Type II de-iodinase
Which deiodinase is protective so you dont make too much active T3?
Type 3 de-iodinase
EVEN THOUGH its a peptide hormone, TH needs to be
bound to TBG in the blood (99%)
How does it make sense that 70% of TH is bound to TBG, even though theres less TBG than albumin?
TBG has a higher affinity for TH than albumin!
What does estrogen and hepatitis do to TBG?
Increase TBG, thus increasing binding of T3/4 in circulation
Is TH receptor intracellular or extracellular?
Intracellular! Acts like a steroid hormone by affecting transcription
Cretinism
Iodine deficiency
Small body, mental retardation..
T3 effect on heart
Increased SV
Increased HR
Increased CO
Ab against TPO
Hashimotos. Autoimmune; can’t make I- from I2
GOITER
GOITER can be the result of
Hashimotos
Graves
Iodine deficiency
Thyroid storm
Hyperthyroid person with a severe illness. Inflammatory response and excessive T4/3 potentiates the cytokine response. Fever, tachycardia, altered mental status.
Note: excessive palpation of thyroid
Which DECREASES serum cholesterol levels: hypothyroid or hyperthyroid?
Hyperthyroid
What does hyperthyroidism do to Beta adrenergic receptors?
upregulates them. thats why you get arryhthmia
net cardiac effect of T3?
increased CO and HR
