What inhibits the iodine/sodium transporter into the follicular lumen?
Thiocyanate, perchlorate anions
What catalyzes oxidation of I- to I2?
What inhibits this enzyme?
Peroxidase enzyme
PTU (propylthiouracil)
What is the Wolff-Chaikoff effect?
High levels of I- inhibit organification (I2 combining with tyrosine on thryoglobulin), or formation of MIT and DIT –> inhibit thyroid hormone synthesis
(High doses of I- will only increase hormone synthesis initially)
How are T3 and T4 made?
DIT + DIT = T4
DIT + MIT = T3
thyroglobulin digested and T3, T4 released into circulation (mostly bound to thyroid binding globulin)
What converts T4 to T3?
5-iodinase
T3 3-4x as potent as T4
Most T4 and T3 in the blood is free. T4 is mostly bound to…
TBG (thyroid binding globulin)
Also to TBPA, albumin
- Very small changes in T4 will affect TSH
Iodide _____ regulates its uptake
negatively
What is the Jod-Basedow Effect?
Excessive iodine induced hyperthyroidism (opposite Wolff-Chaikoff)
- Seen in disease: Graves, toxic multinodular goiter, toxic adenoma
What increases in pregnancy?
TBG
hCG (increase intrinsic thyrotropic activity - activate TSH receptor)
Thyroid hormone increases…
Basal metabolic rate (and contractility/SV) via:
- Na/K ATPase
- beta-1 adrenergic receptors
Causes of hypothyroidism:
- I- deficiency
- Autoantibody destruction of thyroid
- Hypothalamic or pituitary disease (less TRH, TSH)
- Removal of thyroid
- Diseases that interfere with thyroid hormone production
**If problem in the thyroid gland, goiter will result (low T3 and T4 stimulate TSH)
What is myxedema?
Adult-onset hypothyroidism
- tiredness, lethargy, decreased metabolic rate
- slowing of mental fxn / motor activity
- cold intolerance
- weight gain
- goiter (stimulation of follicular cells and increased blood flow)
- hair loss, dry skin
maybe coma
Primary vs. secondary hypothyroidism:
Primary: thyroid can’t produce (is stimulated)
Secondary: thyroid isn’t being stimulated (TSH/TRH deficiency)
Treatment of hypothyroidism?
Levothyroxine
Graves’ Disease has ________ of adenyl cyclase
“locked” activation
IgG autoantibody stimulates TSH receptor
Symptoms of Graves’
- nervousness, irritability
- fatigue
- heat intolerance
- weight loss
- diffuse goiter
- atrial fibrillation (beta-1 adrenergic receptors)
- risk of osteoporosis, decreased muscle mass
Why do exophthalmos and dermopathy result from Graves’?
Fibroblasts in orbit and overlying shin express TSH receptor
- glycosaminoglycan buildup, inflammation, fibrosis, edema
Treatment of hyperthyroidism?
- Beta-blockers
- Surgery or radioactive iodine or PTU/methimazole
PTU blocks: peroxidase-mediated oxidation, organification, and coupling steps, as well as peripheral conversion of T4 to T3
Drugs that block iodine uptake?
- Pertechnetate
- Perchlorate
- Thiocyanate
- Nitrate
What does lithium do in the thyroid?
Inhibit iodination of thyroglobulin
What is a key differential point of subacute (granulomatous) thyroiditis?
IT REALLY HURTS
(DeQuervain’s)
- transient hyperthyroidism
- follows a viral illness
- self-limited (doesn’t progress to hypothyroidism)
What is Reidel’s fibrosing thyroiditis?
Extensive fibrosis, chronic inflammation (“hard as wood”)
- can extend to airway
