Thyroid Gland Flashcards by Anne-Marie Lacroix

What are the units of the thyroid gland?

thyroid follicles: epithelial cells in a single layer surrounding a colloid

parafollicular cells: C-cells are a source of calcitonin

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What are the functions of the thyroid gland?

-secrete thyroid hormone

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What regulates the blood flow to the thyroid gland?

sympathetic nerves

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What are the active forms of thyroid hormone?

T3 + T4

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What are the inactive forms of thyroid hormone?

rT3 (from T4) + T2 (from T3)

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What are the steps for the synthesis of T3 and T4?

TRAPPING
active transport of iodine into cell with Na/I symporter (NIS) => Na/K ATPase to lower [Na] intracellular concentration
binding of TSH on TSHR => activates IP3 (golgi = TG synthesis) + cAMP (activates NIS)
PDS throws iodine in colloid
Thyroglobulin synthesis and exocytosis in lumen of follicle
ORGANIFICATION + COUPLING
iodination of tyrosine residues in TG by TPO
linking pairs of iodotyrosines in TG to form T3 + T4
INTERNALIZATION
iodinated TG => proteolysis to release T3 + T4
DEIODINATION
recycling of I-

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What can inhibit iodine intake from thyroid cell?

perchlorate (ClO4-)
from diet
bromide (Br-)
nitrite (NO2-)

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What can protect from radioactive iodine in an emergency situation?

thyroid shield potassium iodide

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What drugs inhibit iodination and how do they work?

thiocarbamide inhibitors

they target TPO => low T3 and T4 = no -ve feedback = high TSH = hyperplasia and goiter

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How does the iodination of TG occur?

Need of hydrogen peroxide
O from blood and H from NADPH (pentose phosphate = high need for glu)
H2O2 formed by DUOX2

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What are the types of deiodinases?

Type I: T4 -> T3
Type II: T4 -> T3
Type III: T4 -> rT3 (when T3 in excess) and T3 -> T2

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How many thyroid hormones are formed within one TG?

maximum of 4
from the surface
to keep a steady-state of T3 and T4

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Where does type I deiodinase is present?

muscle, liver, kidney

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Where does type II deiodinase is present?

brain + pituitary = feedback on TRH and TSH

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What is the syndrome characterized by low T3 and higher rT3?

sick euthyroid syndrome

from cancer/anorexia

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What are the carrier proteins that allow transport of thyroid hormones?

TBG (thyroxine-binding protein)
transthyretin
albumin

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What drugs can cause hyperthyroidism?

epilepsy treatment = compete with carrier proteins = more free T3 and T4

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Which of the thyroid hormone forms has the longer half-life?

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Which form of thyroid hormone is more active?

What conditions increase the binding to proteins?

pregnancy and oral contraceptives

What conditions decrease the binding to proteins?

starvation and liver disease (thyroxine protein produced in liver)

What rare AA is part of deiodinases?

selenocysteine

Fill the blanks:

About __% of __ is metabolized by deiodination.

- T4

What is a positive aspect and a negative one about thyroid hormone storage?

storage is high
bad = if release triggered => hyperthyroidism
good = if iodine deficiency (can maintain for 50 days)

What are the thyroid hormone functions?

- growth and dev | - maintenance of basal metabolic rate

What type of receptor is THR and what does it activate?

``` Nuclear class II receptor (already bound to RE) Activates translation of 2 genes: THRA and THRB (2 receptor isoforms by alternative splicing) ```

How does T4 regulate metabolism?

it binds to integrins on the surface of cell membranes | and activates translation by MAPK pathway

What are the effects of TH in mitochondria?

T2 binds to cytochrome C for oxidative phosphorylation T3 binds to uncoupling proteins (UPC1) to increase heat production THR transcription in mitochondria

What are integrins?

proteins that link the cytoskeleton to the extracellular matrix = change shape inside cell

What is the calorigenic action of TH?

increases O2 consumption and heat production (except uterus, testes, brain, lymph nodes, spleen, and anterior pituitary) due to FAs mobilization + Na/K ATPase activity

What are effects secondary to calorigenesis of TH?

- increased N excretion (muscle wasting) - weight loss - increased erythropoiesis due to increased demand for O2 - positive N balance for children - hepatic conversion of carotene to vit A (by T4) = carotenemia

What are the consequences of a lack of T4?

myxedema | skin puffiness and bumps from no degradation of proteins, polysaccharides and hyaluronic acid accumulation

what is the effect of TH on the cardiovascular system?

- Myocytes triggered by T3: - activates a-myosin cells = increases ATPase activity = contraction - inhibits b-myosin = decreases ATPase activity - heat = vasodilatation => reabsorption of Na and water by kidneys = increased blood volume - catecholamines increase HR and BP

What are catecholamines?

effects similar to T3 and T4: increased metabolic rate, stimulation of nervous and cardiovascular system

What drugs can be used to reduce catecholamines activity?

beta-blockers

What is the effect of TH on nervous system?

increased T4 to T3 | increased response to catecholamines

What is the effects of TH on skeletal muscles?

increased protein turnover

What is the effects of TH on carbohydrates?

increased absorption in GI tract

What is the effects of TH on the reproductive system?

follicular dev and ovulation pregnancy spermatogenesis

What is the effects of TH on cholesterol metabolism?

decreases C levels by increasing hepatic LDL receptors

What is the effects of TH on growth?

- increased bone mass - epidermis, hair follicles and nails - increased rate + force of skeletal muscle contractions - degradation of mucopolysaccharides in subcutaneous tissues

What are the types of hypothyroidism?

- primary: thyroid gland failure - secondary: pituitary failure - tertiary: hypothalamic failure - peripheral resistance

What is the treatment for hypothyroidism?

T4 injections (bc longer 1/2 life)

What is Hashimoto's disease?

``` autoimmune disease against TPO or TG low TH with sufficient iodine => hypothyroid treatment with T4 goiter in children ```

What is Graves' disease?

hyperthyroidism | anti-TSH receptors anti-bodies that mimic TSH

What are the different types of THR?

- alpha-1 => widely distributed - alpha-2 => inhibitor - beta-1 => widely distributed - beta-2 => anterior pituitary specific