Thyroid Physiology and Pathophysiology Flashcards
How does the thyroid develop? What happens when this gets messed up?
Starts high, migrates down the foramen cecum. Failure to migrate -> ectopic thyroid…
3 ways to describe a goiter?
Prevalence - endemic or not.
Structure - diffuse or nodular
- if nodular, solitary or multi-nodular.
Function - toxic (T3/4 producing) or not.
Most common cause of goiter worldwide?
Iodine deficiency. (usually the cause when goiter is endemic)
Can thyroid hyperplasia progress to worse things?
Yes. Can progress to nodular non-toxic, then to toxic.
but it doesn’t always happen this way
What’s the active part of thyroglobulin?
Tyrosine residues - they get iodinated.
How do T3 and T4 get synthesized?
Uhh… roughly…
I- brought across basement membrane of follicular cell.
Tyrosine residues on thyroglobulin (Tg) get iodinized.
Then T3 and T4 get built on the iodotyrosine.
Proteolysis of Tg releases T4, T3, and iodotyrosines.
(then free iodotyrosines get deiodinated for reuse..)
What’s the rate-limiting step in thyroid hormone synthesis?
Active transport of I- across the basement membrane of follicular cells.
In what form is the majority of secreted thyroid hormone?
T4
Where is secreted T4 converted to T3?
Liver and skeletal muscle.
Why are free T3 and T4 serum levels low?
They bind to proteins: Thyroxine binding globulin (TBG), Thyroxine-binding pre-albumin (TBPA), and albumin.
What happens when thyroid hormone binding proteins increase?
Initial drop in free T3/T4, but levels will increase to reach new steady state due to increased production by thyroid.
What can cause increases in thyroid binding globulin (TBG)?
Estrogen
Hepatitis - increase hepatic release.
4 causes of decreased TBG?
Androgens
Decreased hepatic production (liver disease, malnutrition)
Increased renal loss.
Congenital
What enzymes convert T4 to T3? What are the 3 different types, and where are they found?
…this seems low yield.
Deiodinases
Type 1: hepatic, kidney, thryoid
Type 2: CNS, pituitary
Type 3: placenta (deactivating)
6 things that decrease T4 -> T3 conversion?
Caloric restriction. Major systemic illness. Severe hepatic disease. Fetal life (? being a fetus?). Drugs (PTU, glucocorticoids, etc.) Selenium deficiency (uncommon).
Effect of T3 in the cell?
Transcriptional changes.
What effect does T3 have on all tissues except spleen and testes?
Causes increased O2 consumption.
Effect of T3 on brain?
“Mood” - people without it get depressed.
Effect of T3 on heart?
Increased HR, contractility
Effect of T3 on liver?
Increased protein synth, lipid metabolism
Effect of T3 on GI?
Increased motility
Effect of T3 on nerves?
Increased sympathetic tone, reflexes
Effect of T3 on bone?
Increased bone turnover
Effect of T3 on bone marrow?
Increased erythropoeisis.
Effect of T3 on female reproductive system?
“Menstrual function” …it’s necessary for it.
Effect of T3 on kidney?
Increased free water secretion.
What’s the optimal test for screening for thyroid problems in healthy patients? What do different values mean?
TSH levels.
Low TSH indicates hyperthyroid.
High TSH indicates hypothyroid.
(usually. assuming problem is in the thyroid gland itself)
Different tests for T3 and T4?
Test for total and unbound levels…