Thyroid Physiology Flashcards
What comprises a thyroid follicle?
a capsule-enclosed layer of cuboidal epithelium (follicular cells) that surrounds colloid
What is the hypothalamus hormone here?
thyrotropin releasing hormone
What is the pituitary hormone here?
thyroid stimulating hormone
What are the two end product hormones?
T3 and T4 (thyroxine)
What are other negative regulators of this system?
somatostatin, dopamine and high levels of glucocorticoids
all will decreased TSH release to suppress this axis
How is thyrotropin releasin ghormone translated?
as a preprohormone,
the mature protein is a tripeptide
What is the important role for the thyroid axis?
regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation
How does TRH work?
binds to transmembrane TRH receptor on the thyrotrophs of the anterior pituitary gland
promotes release and synthesis of thyroid stimulating hormone TSH
(signals invved are G protein, PLC, IP3, etc)
Describe the structure of TSH
it’s a glcoprotein consisting of alpha and beta chains (the alpha is similar to those used in other pit hormones, but beta is specific)
Where is the receptor for TSH?
the plasmamembrane of thyroid follicular cells
it’s a GPCR
How does T3 and T4 get out of the follicular cell?
ther ear especific transporters for them
What does the 3 and 4 mean?
how many iodines are on the tyrosine
What is the first step in thyroid hormone synthesis?
dietary iodide is required and active transport of I- into the thyroid follicular cell occurs
What is the second step?
oxidize the iodide to iodine (organification)
third?
iodination of tyrosines attached to thyroglobuli protein backbone to make monoiodothyronin (MIT) and diiodothyronine (DIT)
WHat is the fourth step?
conjugation of MIT and DIT to make T3 and T3
What enzyme does that conjugation?
thyroid peroxidase
What then happends to the conjugates?
endocytosed into the follicular cell
What happens to the conjugate in the follicular cell?
Proteolysis into mature T3 and T4
THen what happens?
movement of T3 and T4 out of the cell
How does iodide get into the cell?
it’s an iodide/Na symporter - active transport
What’s the main drug target in this system?
the thyroid peroxidase
How are T3 and T4 related
T3 is more active than T4
T4 will be converted to T3 intracellularly so T3 has the action
T3 has a shorter circulating half life
So which one binds to thyroid hormone receptors?
trick question - both do
What binds up 75% of T4 and T3?
thyroxin binding globulin
What binds 20% of T4 and 5% of T3?
transthyrten
What binds the rest?
Albumin
Which ones has 1 bindin site? 2 binding site? multiple binding sites?
Thyroxine binding globulin has 1 binding site
Transthyretin has 2 binding sites
Albumin has several binding sites
MAJORITY OF T4 and T3 are bound
WHen will these carrier proteins icnrease?
pregnancy, estrogen/androgen treatment
When will these carrier proteins decrease?
hyperhtyroidism
malnutrition and nephritis syndrome (diseases that cause protein loss)
so focus on free hormone when measuring the axis
T4 to T3 activation in the cell requires activity of what enzyme?
deiodinase I and II
these can also convert to inactive state, but don’t woryr about it
Where is DI most prevalent?
Liver and kidney
What does Deiodinase I do?
converts the less active T4 to the more active T3 so increases T3 within the cells and in circulation
What will DI convert T4 into for disposal?
rT3
DI is the target for what drug?
prophylthiouracil
Where is deiodinase II?
brain, pituitary, skeletal and cardiac muscle
Where is deiodinase III?
brain, skin and placenta
but mainly only involved in deactivation of the hormones, not activation
What are the three ways TSH will promote production of new thyroid hormone?
- increases thyroid peroxidase synthesis
- increases thyroglobulin transcription
- increases the Na+/I- transport activity to get more iodide into the follicular cell
The thyroid hormone transporters make sure that intracellualr levels of thyroid hormone are ____ than in the ECF or plasma.
higher
Again, what type of receptor pattern is the thyroid hormone receptor?
an RXR - heterodimerizes
What does thyroid hormone do for oxygen consumption?
promotes it
What does thyroid hormone do for heat produciton?
increases it
What does thyroid hormone do for free radical formation?
promotes it
What does thyroid hormone do in terms of glucose?
increased glucose utilization, uptake and synthesis
What does thyroid hormone do to the sympathetic nervous system?
it’s permissive - allows for increased heart rate and increased contractility
Why do most states mandate newborn testing ot thyroid function?
because you need to initiate thyroid hormone replacement if necessary within the first few days of life, otherwise they’ll fall behind in both growth and neurological development (cretinism)
In infants, what are the effects of hypothyroid?
profound mental retardation short delayed motor dev coarse hair protruberant abdomens respiratory difficulty cyanosis poor feeding jaunduce hoarse cry umbilical hernia
What is the maternal hypothyroidism etiologies?
- lack of iodine in maternal diet
- Hashimoto’s thyroiditis
- exposure to radioactive iodine or antithyroid drugs during pregnancy (makes it tricky to treat someone with hyperT in pregnancy)
What are the natural sources for iodine?
sea life - kelp, certain seafood, and platns grown on iodine-rich soil
How do we get most of our iodine now?
iodized salt
If you catch a congenital hypothyroidism later on, which will catch up with supplementation - grwoth or brains?
growth only. can’t get back the lost brain development unfortunately
What does excess thyroid hormone do to catecholamien post-receptor action?
amplifies it - the issue with thyroid storm
What does excess thyroid hormone do in terms of erythropoietin release and erythropoiesis?
the increased O2 demand from all the increased metabolism leads to increased production of erythropoietin and increases erythropoiesis
What does excess thryoid hormone do to the GI tract?
promtoes hyperdefacation
What does excess thyroid hormone do to bone?
pomotes bone turnover with net bone loss and hypercalciuria
What does excess throid hormone do to muscle?
increases protein turnover and net loss in skeletal muscle with myopathy
so muscle weakness, muscle degeneration, muscle fatigue, and heat intolerance
What does thyroid hormone do in terms of muscle contraction?
increases the speed of muscle contraction and relaxation (this is why they have increased deep tendon reflexes and clonus in severe cases)
What are the ways in which thyroid hormone increases glucose levels in the blood?
- increases hepatic gluconeogenesis
- increases hepatic glycogenolysis
- increases intestinal glucose absorption
What does TH do to cholesterol?
increasees the LDL receptor # and thus increases LDL clearance (so total LDL cholesterol levels are typically elevated with hypothyroidism)
What does hyperthyroidism cause in terms of puberty?
precocious puberty
Why can hyperthyroidism cause gynecomastia in men?
it promotes aromatization of androgens to estrogens and increased sex hormone binding globulins
Why can hyperthyroidism cause fertility issues?
impairs gonadotropin releasing hormone
What does thyrotoxicosis refer to?
thyroid hormone toxicity in the body (any cause of excessive thyroid hormone)
What are the drugs we use to avoid thyroid storm?
beta adrenergic blockers
thioamines (antithyroid)
corticosteroids - to cover for functional hypoadrenalism incuced by thyrotoxicosis
What is the incidence for thyroid storm?
10% of people hospitalized for thyrotoxicosis
What is the mortality rate for thyroid storm?
20-30%!
hard to control 0 better to prevetn
Where is the problem in primary hypothyroidism?
the thyroid gland isn’t making enough?
Why does goiter develop in the case of iodine deficiency?
if you have decreased iodine, you have low T3 and T4 being made.
this signals the hypothalmus to produce TRH, which signals the pituitary to make TSH
the TSH signals the thyroid gland to produce the T3 and T4 (but it can’t!), but also to GROW - it just keeps snowballing until you get a goiter
Why does goiter develop in Graves?
the thyroid-stimulating immunoglobulins act like TSH, which triggers the thalamus to make T3 and T4, but you also get the grwoth signal from the immunoglobulins
