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…
Is there much variability in T4/TSH setpoints?
Yep.
3 etiologies of hypothyroidism?
Primary.
Central (secondary) - in the pituitary/hypothalamus.
Transient.
5 causes of primary hypothyroidism? (2 are iatrogenic)
Autoimmune destruction. Damage by radioablation. Thyroidectomy Dysgenesis/agenesis of thyroid. Defects in biosynthesis.
What can cause transient hypothyroidism?
Thyroiditis..
Histology of Hashimoto’s (autoimmune) thyroiditis?
Lymphocytosis, destruction of follicules.
Speed of progression of autoimmune thyroiditis?
Slow - often takes years.
Sex difference in hypothyroidism (at age 55)?
Women have more, especially subclinical hypothyroidism.
Might there be ethnicity-based differences in thyroid setpoints?
Yes… which might make “normal” values of TSH etc. misleading.
Signs of hypothyroidism on face?
Periorbital edema
Laterally truncated eyebrows (not specific)
3 definitely bad, and probably real consequences of hypothyroidism?
Elevated cholesterol
Fetal death
Atherosclerosis
How does T3 lower cholesterol?
May work by increasing LDL receptor in liver, lowering LDL.
Does hypothyroidism have a clear effect on IQ?
No.
What’s myxedema coma?
Severe, life-threatening hypothyroid.
Hypothermia, coma.
Treatment for hypothyroidism?
Give T4, try to get TSH levels in normal range.
Common causes of hyperthyroidism?
Grave’s disease
Toxic nodules
Leakage in thyroiditis
3 causes of damage to thyroid?
Autoimmune, infections, toxins
How long does thyroiditis-induced leakage of thyroid hormones last?
Hormones depleted in 6-8 weeks.
Then normalizes or swings to hypothyroid.
What is Grave’s disease?
What will TSH levels be?
Antibodies agonize TSH receptor -> thyroid cranks out T4, T3.
TSH will be low (due to negative feedback)
What does Grave’s disease histology of the thyroid gland look like?
Overactive endocytosis of colloid results in lots of scalloping.
Notable symptoms of hyperthyroidism?
There are a lot… heat intolerance and palpitations are particularly noticable…
Some signs of hyperthyroidism?
Lots. Many have to do with metabolism just being ramped up. Focusing on the specific ones mentioned.
What happens to the eyes in hyperthyroidism and Grave’s?
Hyperthyroidism -> lid retraction and stare (wide-eyed look)
Graves - lid retraction + proptosis (eyes bulge out) and inflammation, diplopia
Very noticeable skin change in Graves’?
dermopathy with hemocitarin deposition.
If really severe, orange-tinged palm, nails coming off.
How do you differentiate between Graves’ diseease, toxic nodules, and thyroiditis?
Radioiodine uptake
What does thyroid radioiodine uptake look like when there’s a toxic nodule?
Only nodule lights up - rest of gland is suppressed.
What does thyroid radioiodine uptake look like when there’s a multinodular goiter?
Nodules light up..
What does thyroid radioiodine uptake look like when there’s subacute thyroiditis?
Damaged thyroid doesn’t take up radioiodine.
What does a diffuse increase in radioiodine uptake suggest?
Graves’ disease
3 therapeutic options for Graves’?
Which is first done, if possible?
Radioiodine (I-131) ablation - destroys thyroid.
Antithyroid drugs <- done first.
Surgery
When can’t you give antithyroid drugs?
Pregnancy
What 2 drugs are used for hyperthyroidism?
Remission rate?
Methimazole
Propylthiouracil (PTU)
60% remission rate
When is surgery for Graves’ recommended?
What surgery is done?
Thyroid so big it’s compressing things, Pregnancy, bad reaction to drugs.
Surgery: complete removal of thyroid.
What’s a thyroid storm? Signs?
Severe, life-threatening hyperthyroidism.
High fever, profound tachycardia, sweating, restlessness, altered mental status.
Are thyroid nodules necessarily cancer?
Nope.
Is palpation a good way to detect nodules? What’s a better way?
Nope. Ultrasound works better.
and autopsy…
What percentage of thyroid nodules are malignant?
5-10%
Risk factors of thyroid nodules?
Hx of neck irradiation.
Family Hx.
Age (60)
Being male
When does radiation seem to increase risk for thyroid nodules?
When it happens before 16-18 years, and not afterward.
What did Chernobyl teach us about radiation causing thyroid cancer?
It’s pretty nefarious:
I-131 on grass. Cows eat grass. Kids drink milk. People get more thyroid cancer than normal.
How do you work up a palpable thyroid nodules?
Do ultrasound.
Check TSH
-if normal or high -> fine needle aspiration
-if low, do “scan”
If a nodule is “hot” i.e. takes up lots of radioiodine, what does that tell you about malignancy?
Likely not carcinogenic. Don’t need to do fine needle aspiration.
(cold nodules must have FNA)
What system is used to determine malignancy based on FNA cytopathology?
Bethesda system…
What new technology might help us manage thyroid nodules of uncertain malignancy?
Genetic /molecular profiling to get a better sense of malignant potential,
