Thyroid B&B Flashcards
there is sometimes a third lobe of the thyroid called the ______ that sits above the isthmus
pyramidal lobe
what is the blood supply of the thyroid? (2)
- superior thyroid artery - 1st branch of external carotid artery
- inferior thyroid artery - branch of thyrocervical trunk, off the subclavian
as the embryonic thyroid descends into the neck, it initially maintains connection to the tongue called the ______
thyroglossal duct - disappears later in development, remnants in adult as foramen cecum (in tongue) and pyramidal lobe of thyroid
what is a thyroglossal duct cyst
persistent remnant of thyroglossal duct - presents as painless midline neck mass discovered in childhood
classically moves up with swallowing or tongue protrusion
where is the most common location of ectopic thyroid and why does this make sense?
base of tongue - recall embryonic thyroid descends from the mouth (remnant in adult at tongue foramen cecum)
present as a mass in the tongue, detected when there is increased demand for hormones (puberty, pregnancy)
Which cells of the thyroid synthesize thyroid hormone? Where are they found?
Follicular cells: single layer of epithelial cells lining each thyroid follicle
Thyroid follicles are filled with colloid
What needs to happen for iodide in our diet to be added to thyroid hormone? (4 steps)
- taken up by follicular cells.
- Undergo oxidation
- Undergo organification – added to organic/carbon structure (forms MIT or DIT)
- coupling of MIT/DIT into T3/T4 (MIT + DIT = T3, DIT x 2 = T4)
describe how iodine is taken up by follicular cells of the thyroid
via NIS (Na-Iodine symporter)
iodine (- charge) is taken up with sodium (+ charge), but NIS can also take up other negative charged molecules like perchlorate (ClO4-) or pertechnetate (TcO4-) … therefore, these molecules competitively inhibit iodine uptake
what enzyme is required for iodide oxidation and organification in follicular cells of the thyroid
thyroid peroxidase (TPO): oxidizes iodide, also adds iodine to tyrosine (found on thyroglobulin molecules) for organification and catalyzes coupling reactions to create T3/4
which enzyme is responsible for converting T4 (“pro hormone”) to T3 in peripheral tissues?
5’ deiodinase: removes iodine from 5’ position - drug target for hyperthyroidism
what is the mechanism of propylthiouracil (PTU), and what is it used to treat?
hyperthyroid medication
inhibits TPO (thyroid peroxidase) —> decreased T3/4 production from thyroid gland + inhibits 5’-deiodinase —> decreased T4 to T3 conversion in peripheral tissues
which enzyme does methimazole inhibit, and what is it used to treat?
inhibits TPO (thyroid peroxidase) to treat hyperthyroidism —> decreased T3/4 production
how can propranolol be used to treat hyperthyroidism?
propranolol: beta blocker and weak inhibitor of 5’-deiodinase (converts T4 to T3)
great drug in patients with thryotoxicosis (because it’s not super strong)
also blocks catecholamines produced in hyperthyroidism
Wolff-Chaikoff Effect
thyroid protects itself from hyperthyroidism induced by excessive iodide in the diet
high levels of iodide INHIBIT organification of iodide —> less synthesis of MIT/DIT, and thus less T3/4 production
explain how amiodarone can induce hypothyroidism (2 mechanisms)
amIODarone: class III antiarrhythmic used for atrial fibrillation, contains iodine
- can cause hypothyroidism via EXCESS iodine, due to Wolff-Chaikoff Effect - self protective measure, high levels of iodide INHIBIT organification of iodide
- drug mimics T4, and can competitively inhibit 5’-deiodinase in peripheral tissues
describe the two ways by which radioactive iodine can be used in clinical settings
radioactive iodine has extra neutrons – emits beta decay radiation, competes with elemental iodine for uptake in the thyroid gland
Small dose can be used for imaging, large dose destroys thyroid issue and can be used to therapy for hyperthyroidism
how is T4 transported in the plasma?
T3/4 are poorly water soluble
bound to thyroxine-binding globulin (TBG) in the plasma - present in small amounts but has high affinity
note that low TBG = low T3/4 availability to tissues
contrast the effects of estrogen and liver failure on the availability of thyroid hormone
Estrogen raises TBG levels (T4 carrier) —> increase in total T4 levels (via feedback to thyroid that there is less free T4) - pregnancy, oral contraceptive pills
TBG is made in liver, so liver failure lowers TBG levels —> less available T4
match:
hypothyroidism / hyperthyroidism
with
hyperglycemia / high cholesterol
thyroid hormone speeds up metabolism
hypothyroidism —> high cholesterol via less fatty acid metabolism
hyperthyroidism —> hyperglycemia via increased carbohydrate metabolism (glycogenolysis, gluconeogenesis)
how does thyroid hormone raise basal metabolic rate?
increases expression of Na/K/ATPase pumps —> more ATP consumed
this increases oxygen demand to replenish ATP —> increased respiratory rate and body temperature
how does thyroid hormone increase CO/HR/SV/contractility?
increases beta1 adrenergic receptors in the heart
iodine deficiency, thyroid dysgenesis, and dyshormonogenesis can all result in stunted growth and mental retardation in children, known as ______
cretinism: most common treatable cause of mental disability (via hormone replacement therapy)
most babies initially appear normal because maternal T3/4 crosses the placenta
intellectual disability, coarse facial features, short stature, umbilical hernia, and enlarged tongue (macroglossia) are classic findings of…
cretinism: childhood hypothyroidism, most common treatable cause of mental disability (via hormone replacement therapy)
describe how thyroid hormone synthesis is regulated by TSH
TSH (thyrotropin) released by anterior pituitary binds receptors on follicular cells —> activates cAMP/PKA signaling to increase T3/4 release
can increase rate of proteolysis of thyroglobulin (releasing T3/4), also stimulates thyroid cell growth (sustained increase in thyroid hormone release)
describe how the hypothalamus regulates thyroid hormone release
serum T4/T3 is sensed by hypothalamus, which releases thyroid releasing hormone (TRH) from the arcuate nucleus
TRH induces thyrotropes in the anterior pituitary to secrete thyroid stimulating hormone (TSH, aka thyrotropin), which acts directly on thyroid to increase T3/4 release
Describe the effects of pregnancy on the thyroid hormone production (2)
high estrogen —> increased TBG (carrier protein) —> rise in total plasma T3/4
hCG stimulates thyroid (in same way as TSH) —> increased free T4 (note this causes feedback decrease in TSH in the beginning of pregnancy)
thyrotropin releasing home on (TRH) is secreted from which nucleus of the hypothalamus?
arcuate nucleus
stimulates thryotropes in the anterior pituitary to secrete TSH (aka thyrotropin)
what are 2 physiological benefits of thyroid hormone traveling bound to TBG (TH binding globulin)?
- bound form increases the half life of TH
- TH is freed from binding slowly, “as needed” basis - T4 is considered “slow acting hormone”
which type of iodothyronine deiodinase is prominent in the placenta, and what is its function there?
type 3/ D3 iodothyronine deiodinase - modules amount of maternal bioactive thyroid hormone which reaches the fetus (remember TH is crucial for proper development)
contrast the effects of hyperthyroidism vs hypothyroidism on CV function
hyperthyroidism —> vasodilation, increased systolic BP (via increased CO), elevated SNS, sinus tachycardia, atrial fibrillation
hypothyroidism —> vasoconstriction, increased diastolic BP (via increased afterload), bradycardia (decreased CO), narrow pulse pressure
what is the effect of hyper- vs hypo- thyroidism on female reproductive function?
hypothyroidism —> menorrhagia or polymenorrhea
hyperthyroidism —> oligomenorrhea (infrequent or long menses)
what is the effect of hypothyroidism on male reproductive function?
hypothyroidism —> low sperm count, reduced testicular function, erectile dysfunction, loss in libido