Thyroid Physiology and Pathophys (5/19) Flashcards
What is a goiter?
Enlarged thyroid gland…does not imply etiology
How do we describe goiter?
- Prevalence: endemic or non-endemic
- Structure: diffuse or nodular, solitary or multinodular
- Fxn (TH production): toxic or non-toxic
What is the most common cause of goiter world-wide?
Iodine def. Without iodine, can’t produce T3/T4, loss of neg feedback causes inc TSH, build up thyroglobulun and the gland hypertrophies
How do we define endemic goiter?
> 10% of a population has it
How many iodines do T3 and T4 have?
3 and 4 respectively…
What is iodine specifically req for?
Coupling of 2 iodotyrosines, catalyzed by TPO, does not occur unless they are iodinated
Describe TH synthesis
- I- is trapped via active transport across basement membrane of follicular cell (RLS)
- Oxidation and iodination of tyrosine residues on thyroglobulin (precursor for TH)
- Thyroglobulin’s tyrosine residues are iodinated to form MIT/DIT/thyroglobulin complex
- Coupling of iodotyrosine on thyroglobulin forms T3 and T4 via peroxidase transaminase
- Proteolysis of thyroglobulin allows for release of T3 and T4 and iodotyrosines (MIT/DIT=monoiodotyrosine and diiodotyrosine)
- Iodotyrosines are deiodinated in the follicular cell
Where is the hormone in the follicle stored?
Extracellular thyroid colloid in which the major material is thyroglobulin. This is entirely surrounded by thyroid follicular cells, which are responsible for the synth of thyroid hormones
Which has more neg feedback, T3 or T4?
T3
Describe the thyroid hormone axis
Hypothal–>THR–>ant pit–>TSH–>thyroid–>T3 and T4 production
How does T4 undergo deiodination?
Via extrathyroidal deiodinase enzymes in the liver and skeletal muscles
How much T3 is circulating vs in the thyroid?
80% circulating
20% in the thyroid
What decreases deiodinase activity?
Caloric restriction MAjor systemic illness Severe hepatic disease Fetal life Some drugs Selenium deficiency (cofactor for enzyme)
How are T3 and T4 transported?
Binding proteins (mainly TBG)
Why are THs carried by binding proteins?
Provides a large buffer pool of thyroid hormones in circ and prolongs the half life of T3 and T4
How are T3 and T4 levels affected by changes in TBG?
Inc TBG will cause dec in amt of free T3 and T4 initially, but there needs to be a set amt of free hormone so it will form a new steady state to replenish the free hormone levels.
What increases TBG levels?
- EStrogen (OCPs, HRT, pregnancy
- Inc hepatic release (hepatitis)
-note these raise TBG, but keep free thyroid hormone levels in a narrow range
What dec TBG levels?
- Androgens
- Dec hepatic production (liv disease, illness, malnut)
- Inc renal loss (nephrotic syndrome)
- Congenital causes
Where are type 1 deiodinases?
liver, kidney, thyroid (outer and inner ring)
ie can make reverse T3=inactive hormone and active T3
can also make inactive T2
What is the T4:T3 ratio sec by thyroid?
10:1
Where are type 2 deiodinases?
CNS, pituitary (outer ring) makes active T3 only
Where are type 3 deiodinases?
PLacenta (inner ring) –>makes reverse T3=inactive hormone
can also make inactive T2
What drugs can cause a dec in deiodinase activity?
PTU, propranolol, glucocorticoids, amiodarone
What family of receptors do thyroid receptors belong to?
Nuclear receptor family
What is the fxn of TR?
Gene expression by interacting through specific regions of DNA. TR acts as a transcriptional activator or repressor dep pn target gene and presence or absence of TH
In what tissues does T3 inc O2 consumptions?
All except spleen and testes
What does TH effect in the brain?
Mood
What does TH effect in the heart?
HR, contractility
What does TH effect in the liver?
Prot synthesis, lipid metab
What does TH effect in the GI
Inc gut motility
What does TH effect in the nerve?
Sympathetic tone, reflexes
What does TH effect in the bone?
inc bone turnover
What does TH effect in the bone marrow?
erythropoiesis