Thyroid Hormones Flashcards
Thyroid gland anatomy
follicles: thyroglobulin solution-filled lumen surrounded by thyroid cells; parathyroid cells b/w follicles synthesize calcitonin
What element is needed for thyroid hormone synthesis
IODIDE
Iodide transport
Stimulated by TSH= Actively transported into thyroid cells through NA/I symporter; I- is transported from the cell to the follicular lumen via pendrin
Na/I symporter
transports Na and I into thyroid cells (TSH stimulated)
Pendrin
causes I to move from the thyroid cell into the follicular lumen
Thiocyanate and perchlorate
BLOCK NIS transport of iodide
How would renal disease affect the thyroid gland?
affect the reabsorption of iodide
Production of T3 and T4
thyroglobulin produced by thyroid cells is excreted into lumen and iodine in lumen it reacts with the tyrosine’s (generating MIT) then sequentially DIT; coupling of MIT/DIT generates T3 and T4
MIT and DIT
are precursors to T3 and T4 and are biologically inactive
Thyroid peroxidase
Uses H2O2 to oxidize I-; also couples MIT and DIT molecules
Organification of the Iodide
menas the iodide is added to the tyrosine of the thyroglobulin molecule
T4 is formed by
2 DIT molecules
T3 is formed by
1 MIT and 1 DIT molecules
Propylthiouracil
inhibits the thyroperoxidases (TP); treatment for hyperthyroidism
Wolff-Chaikoff Effect
Excessive extracellular iodide is counteracted by an inhibition of organification (H2O2) of the iodide in the thyroid follicles, therefore inhibiting T3 and T4 production
Storage of Thyroid hormones
Large amounts stored in follicle attached to thyroglobulin
Body cannot store iodide so it stores
thyroid hormones in excess to circumvent a iodide shortage
Secretion of thyroid hormone
TSH-dependent megalin receptor causes endocytosis of thyroglobulin by thyroid cells; lysosomes fuse and cleave T3 and T4
Megalin
receptor that mobilizes the thyroglobulin colloid droplet from the lumen
Cathepsin
lysosomal enzyme that cleaves T3 and T4 from thyroglobulin
T4 is solely made by the
thyroid gland
T3 is made by
the thyroid gland and the liver cleaves T4 to T3
5’-deiodinase (D1, D2, D3 depending on location)
D1 in the liver; removes iodine from T4 to make T3
D1 deiodinase (removes iodide from outer ring)
liver and kidney and thyroid
D2 deiodinase (removes iodide from outer ring)
CNA and placenta
D3 deiodinase (removes iodide from inner ring)
peripheral tissue; reverses T3 producing inactive rT3
Deiodinases TYPE I that activate T3 are inhibited by
fasting, severe illness, high glucocorticoids, drugs, fetuses
Why doesn’t TSH stimulate more thyroid hormone production when fasting is inhibiting T3 production?
Because fasting only inhibits type I, type II deiodinase in the CNS is still active and therefore the pituitary still recognizes a higher level of T3 hormone
T3 and T4 are bound (except 1%) to transport proteins
only free hormone is active
Thyroid hormone transport proteins:
Thyroxine-binding globulin (TBG), albumin, thyroxine-binding pre-albumin
Production of TBG alters
the amount of free vs bound T3 and T4
Thyroid hormones effects
T3 (T4 little direct effect) increases O2 consumption, ATP synthesis, causes PM to become for permeable to solutes, enhances mito conversion of substrates to energy, and induces protein synthesis of mito enzymes
Thyroid hormone results in
thermogenesis and heat production, increased metabolism, and O2 consumption
Which tissues do not have effects of T3 and T4
brain, spleen, anterior pituitary, and gonads
A major contributor to the heat production is
Na/K ATPase which generates ADP, stimulates O2 consumption and heat production
Thermogenin
protein induced by T3 that uncouples OX PHOS and ATP generation to produce heat without generating ATP
Metabolic effects of thyroid hormones
increases Carb, Fat and protein metabolism
Thyroid hormones are permissive to
EPI, GH, and Insulin
Thyroid hormone effect son the heart
to increase HR, SV, and CO by increasing the adrenergic activity and increasing transcription of beta receptors, Ca-ATPases, G proteins, A.C.
Why would a beta blocker work to treat hyperthyroidism
to decrease HR, SV, and CO and MAP caused by increased T3
Thyroid hormone effect on respiration
increased rate of ventilation, increased RBC production
Thyroid hormone effect on brain
NO EFFECT on metabolism; but important for brian development
Thyroid hormone effect on growth
permissive to GH, necessary for normal growth and development in children
Metabolism of thyroid hormones
de-iodination and excretion through feces
TRH stimulates and SS inhibits
TSH release from the anterior pituitary; TSH enhances Iodine trapping, T3/T4 liberation, and thyroid tissue growth
T3 and T3 negative feedback
inhibits anterior pituitary and hypothalamus (reducing TRH and TRH receptor #) increases SS to inhibit TSH secretion
Why would you see a goiter in hyperthyroidism?
TSH is overstimulated, TSH is trophic meaning it causes growth of the thyroid gland
What would the labs look like for hypersecretion of T3 and T4
increased T3 and T4
What would the labs look like for hypersecretion of TSH or secondary hypersecretion of T3 and T4
increased TSH and T3 and T4
What would the labs look like for hypersecretion of TRH
increased TRH, TSH, and T3 and T4
What would the labs look like for inability of thyroid
increased TRH and TSH, decreased T3 and T4
Estrogens increase TBG, effect?
increased total serum concentration of T3 and T4 and also increases TRH sensitivity
Age effect thyroid function?
T4 serum levels remain constant, BUT T3 declines with age
GLUCOCORTICOIDS effect thyroid?
DEPRESS pituitary secretion of TSH (cortisol and dexamethasone)
Severe illness effects thyroid hormones
increases rT3 and peripheral metabolism of T4, generating inactive thyroid hormones to slow “sick hypothyroidism”
Acute iodine deficiency
T4 plasma levels decrease, TSH increases, and T3 is being generated in the thyroid at higher rates (T3 requires less I and is more potent)
Chronic iodine deficiency
T3 and T4 levels fall and TSH is chronically active causing hypertrophy of the thyroid gland (goiter)
Tumor in AP that secretes TSH
cause increased levels of T3 and T4 and TSH
Atrophy of AP
increased TRH, decreased TSH, T3, and T4
Abnormal stimulation of the thyroid gland
increased T3 and T4, decreased TSH
destruction of thyroud gland
decreased T3 and T4 despite high levels of TSH
Systemic illness
decreased T3, and NORMAL TSH and T4
acute iodine deficiency
Increased TSH, normal T3, low T4