Thyroid Flashcards by Shelby SK

What % of circulating T3 is bound to a protein? What % is free?

bound = 99.5%
free = 0.5%

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How does coupling of iodinated tyrosine residues to make T3 and T4 molecules happen while they are attached to thyroglobulin?

Coupling when the molecule forms a tertiary and quarternary structure

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Thyroid hormones can undergo conjugation in the _____

which increases their solubility and _____ excretion

liver

biliary

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Of the ~400ug of iodine that is taken in daily from the diet, how much is excreted, and how much is taken up by the thyroid from a plasma pool?

320ug is excreted

80 is taken up by the thyroid

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What effect does TSH have on the iodide channels anoctamin-1?

opening of anoctamin-1 iodide channels on the apical membrane facilitating the leak of iodide into the colloid

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What 4 things do T3 and T4 bind to in the plasma?

thyroxine-binding globulin (TBG)
albumin
transthyretin
lipoprotein

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The oxidation of iodide and also organification coupling of MIT and DIT are facilitated by the enzyme thyroid peroxidase. What is an inhibitor of Thyroid peroxidase?

Propylthiouracil

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Where is thyroglobulin (Tg) produced?

cytosol of the follicular cell

contained in a vesicle with TPO

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The uptake (trapping) of iodine from the blood stream into the thyroid cells first occurs by iodine entering the follicular cell through the __________ symporter on the __________ membrane

Na+-I- symporter on the basolateral membrane

2 Na+ and 1 I- flow through the symporter

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The follicular cell of the thyroid has a lumen filled with ______

colloid

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The Na+-iodide symporter on the basolateral membrane of the thyroid follicular cells is a ___________ in autoimmune disease

autoantigen

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Why does a goiter happen when there is LOW iodide due to diet-induced deficiency?

TSH goes unopposed due to no negative feedback (increased tropic hormone secretion)
TSH = uncontrolled growth of thyroid

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Deiodinase type 3 converts T3 into ____ by removing an iodine from the _____ position, making it (active/inactive)

T2
inner 5
inactive

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Hypothyroid and Hyperthyroid effect on:

perspiration

HYPO = decrease
HYPER = increase

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Which transporter that thyroid hormones use to enter the cell has a preference for T4?

Na+ independent organic anion transporting polypeptide (OATP)

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What is the “organification defect” in relation to the thyroid

does it lead to hyper or hypothyroidism

iodine cannot be incorporated into tyrosine

HYPOthyroidism

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What do minor levels of thyroglobulin (Tg) that leak into the plasma indicate?

What do high levels of thyroglobulin (Tg) that leak into the plasma indicate?

minor = normal

high = HYPERthyroidism

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At what time during gestation is the hypothalamus-pituitary-thyroid axis functional?

12 weeks

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After traveling through the blood stream and entering a cell, what is the first thing that happens to T4?

Deiodinated into T3 so that T4 and T3 levels are equal

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What is the difference in structure between T3 and rT3?

T3 = lacking a 5' outer ring (has a 5 inner)
rT3 = lacking a 5 inner ring (has a 5' outer) = INACTIVE

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What is the main NONGENOMIC effect of thyroid hormones (especially T3)

rapid effects on ion influxes esp. in cardiovascular system

Ca2+ ATPase at plasma membrane and SR
Na+/H+ antiporter in muscle
oxygen consumption

ION FLUXES ION FLUXES ION FLUXES

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What effects do thyroid hormones have on metabolism?

increase glucose absorption from gut
increases gluconeogenesis
increases lipolysis
increases protein synthesis and proteolysis (futile cycling)
net degradation of tissue protein (negative N balance)

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How much blood does the thyroid gland receive?

2% of total blood flow

HIGH VASCULARITY!

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Which is made more, T3 or T4?

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After traveling through the blood stream and entering a cell, what do T3 and T4 bind to? Which one has a higher affinity for binding?

thyroid hormone receptor T3 (10 fold!) (T3 ~90% of occupancy of TR)

Hypothyroid and Hyperthyroid effect on: | thermogenesis

``` HYPO = decrease HYPER = increase ```

Where does the iodine we need to make thyroid hormones come from? Where does the tyrosine we need to make thyroid hormones come from?

iodine = diet only tyrosine = endogenous

What is the effect of thyroid hormones on the sympathetic nervous system?

increased synthesis of B adrenergic receptors in cardiac/skeletal muscles and adipocytes

What is coupled to form T4?

DIT (diiodotyrosine) + DIT (diiodotyrosine)

Hypothyroid and Hyperthyroid effect on: | protein synthesis

``` HYPO = decrease HYPER = increase ```

What is the key hormone in inhibiting the release of TRH from the hypothalamus

free T3

When the _______ detects low levels of thyroid hormone in the blood, it is stimulated to release ______ which stimulates the release of _______ from the pituitary, which in turn stimulates the steps of thyroid hormone synthesis and release at the thyroid

hypothalamus TRH TSH

Calorigenic effect of thyroid hormones occurs in all tissues except:

brain gonads spleen

Can hypothyroidism at birth be reversed?

yes with treatment

What are the 4 transporters that thyroid hormones use to enter the cell

1. Na+ taurochlorate cotransporting peptide (NTCP) 2. Na+ independent organic anion transporting polypeptide (OATP) 3. L- and T- type amino acid transporters (LAT) 4. Monocarboxylate transporters (MCT)

Hypothyroid and Hyperthyroid effect on: | intestinal glucose absorption

``` HYPO = decrease HYPER = increase ```

In the cell, once T3 or T4 has bound to thyroid hormone receptor, what does the thyroid hormone receptor bind to?

nuclear DNA on the TRE in the promoter region of genes regulated by T3 and T4

If the follicular cell if stimulated by TSH, how does T3/T4 stored in the colloid get to the blood stream for secretion?

1. follicular cell engulfs (endocytosis) Tg molecule with T3 and T4 attached to it by MEGALIN 2. lysosomes enter vesicle, proteases split T3/T4 from Tg 3. T3/T4 diffuses out into the blood

How many Iodide transport defect-causing mutations of NIS gene have been identified?

Hypothyroid and Hyperthyroid effect on: | lipolysis

``` HYPO = decrease HYPER = increase ```

What is responsible for the deactivation of thyroid hormone? (T3 to T2)

deiondinases

Which is more active, T3 or T4?

T3 T4 is a PROhormone- converted to T3 to be active

Which transporter that thyroid hormones use to enter the cell has a preference for T3?

Monocarboxylate transporters (MCT)

What critical role does the hypothalamus-pituitary-thyroid axis play during gestation?

myelination of CNS neural sprouting growth of the fetus

When doing a radioactive iodine uptake test, normal conditions would be ____% uptake of iodine after 6 hours

15%

What stimulates the release of TSH from the pituitary? | What inhibits the release of TSH from the pituitary?

TRH (thyrotropin-releasing hormone) bind to a receptor on the thyrotrophs dopamine, somatostatin, peripheral T4 and T3

What is thyroglobulin? (Tg)

glycoprotein that contains ~132 tyrosine molecules contained in a vesicle in the colloid ***what iodine attaches to in the colloid before becoming T3 and T4

Hypothyroid and Hyperthyroid effect on: | sleep

``` HYPO = sleepiness, tiredness HYPER = insomnia ```

Hypothyroid and Hyperthyroid effect on: | lipogenesis

``` HYPO = decrease HYPER = increase ```

Hypothyroid and Hyperthyroid effect on: | catecholamine levels

``` HYPO = none HYPER = increase B adrenoceptors = increased sensitivity to catecholamines but serum level does not change ```

What do parafollicular cells of the thyroid do?

release calcitonin calcium and phosphate regulation

What % of thyroid hormones secreted are T4? What % of thyroid hormones secreted are T3? What % of thyroid hormones secreted are rT3?

``` T4 = ~90% T3 = ~10 % rT3 = less than 1% ```

Once the tyrosine molecules of thyroglobulin (Tg) are iodinated, what is the next step?

coupling to form T3 and T4

What is coupled to form T3?

MIT (monoiodotyrosine) + DIT (diiodotyrosine)

What two physical findings are associated with Pendred Syndrome

Goiter in childhood hearing loss ***variability in the expression of the phenotype exists

Hypothyroid and Hyperthyroid effect on: | serum cholesterol

``` HYPO = increase HYPER = decrease ```

Thyroid hormones are synthesized in the colloid by _________

thyroglobulin

Hypothyroid and Hyperthyroid effect on: | Glycogenolysis

``` HYPO = decrease HYPER = increase ```

What is a way we can MEASURE the activity of the thyroid gland?

radioactive iodine uptake test tracer dose of 123-iodine and labeled iodine and uptake measured by gamma detection measuring Na+-iodide symporter activity

What is the role of the Na+-Iodide symporter in a lactating mammary gland?

concentrating iodide in milk to supply newborns with iodide for thyroid hormone synthesis

Of the ~132 tyrosine molecules on a thyroglobulin (Tg), how many of them become iodinated? How many will be coupled to become active thyroid hormones?

20% 5%

What is the storage site for hormones in the thyroid?

colloid

If you stopped iodine intake from the diet, for how long could your thyroid function normally based upon stores of iodine?

2 months

Monoiodotyrosine (MIT) is formed when an iodine is attached to a tyrosine within thyroglobulin (Tg) by thyroid peroxidase on carbon # ____

outer ring deiodination is done by deiodinase type:

1 and 2

mutations in the ________ causes hypothyroidism

Na+-iodide symporter ...on the basolateral membrane of the thyroid follicular cells

inner ring deiodination is done by deiodinase type:

Hypothyroid and Hyperthyroid effect on: | muscle wasting

``` HYPO = none HYPER = increase ```

What is the total idodine content of the thyroid in the form of idothyronine (or thyronines)

7500ug

What is the Wolff-Chaikoff effect?

Increased serum Iodide --> increased TSH ---> increased organification of iodide ---> increased T3 and T4 ****increased concentration of iodide in the thyroid*** decreases organification of iodide ---> decreased T3 and T4

What stimulates the steps of thyroid hormone synthesis and release at the thyroid

TSH

How does T4 and T3 inhibit the release of TSH

down-regulating the TRH receptor on thyrotrophs

Organification of iodide can be regulated independently of ____

TSH

In a LOW iodide diet, the activity of the Na+-iodide symporter on the basolateral membrane of the thyroid follicular cells is (increased/decreased)? What steps in to compensate for the low iodide? What physical manifestation can appear?

increased! kidneys compensate to reduce excretion goiter

What are surgical/pharmological options for HYPERthyroidism?

1. remove gland 2. radioactive I-131 to destroy gland 3. B-adgrenergic antagonists 4. Propylthiouracil

Other than the follicular cells of the thyroid, where else can you find the Na+-Iodide symporter? What is different about the NIS in these tissues versus the thyroid?

gastric mucosa placenta lactating mammary glands NOT under TSH regulation

What is responsible for converting T4 into T3 in the periphery?

deiodinase: Thyroid peroxidase TPO

What is the most common effect that thyroid hormones mediate

genomic effects transcription regulation of target genes

What increases or decreases the activity of the sodium-iodide symporter on the basolateral membrane of the thyroid follicular cells?

DIET!!!! or diseased state

TSH stimulates the release of thyroid hormones form the thyroid, but it also stimulates gene transcription of what specific things in the process of thyroid hormone synthesis?

1. Na+-Iodide symporter 2. Thyroglobulin 3. Thyroid peroxidase 4. T3 and T4

DIiodotyrosine (DIT) is formed when an iodine is attached to a tyrosine within thyroglobulin (Tg) by thyroid peroxidase on carbon # ____

5 There is already an iodine on carbon 3 (MIT)

Deiodinases type 1 and 2 convert rT3 into ____ by removing an iodine from the _____ position, making it (active/inactive)

T2 outer 5' inactive

Once iodide is in the follicular cell through the Na+-iodide symporter on the basolateral membrane, how does it get through the cell to the apical membrane

carried by PENDRIN

Where in the cell is iodide oxidized to iodine? | What oxidizes it?

apical luminal membrane thyroid peroxidase (TPO) peroxide is the oxidizing agent

Daily intake of iodine is roughly:

~400 ug

Once T3 and T4 have been cleaved from thyroglobulin (Tg) and secreted into the blood stream, how are the rest of the MIT and DIT handled in the follicular cell?

deiodinated by intrathyroidal deiodinase | free iodine recycled for de novo synthesis of T3 T4

Hypothyroid and Hyperthyroid effect on: | body weight

``` HYPO = increase (weight gain) HYPER = decrease (weight loss) ```

Deiodinases type 1 and 2 convert T4 into ____ by removing an iodine from the _____ position, making it (active/inactive)

T3 outer 5' active

What % of circulating T4 is bound to a protein? What % is free?

``` bound = 99.98% free = 0.02% ```

What is thyroid peroxidase?

The enzyme involved in the oxidation of iodide and its incorporation into tyrosine residue

Mutations to which transporter that thyroid hormones use to enter the cell are associated with psychomotor retardation and thyroid hormone resistance?

Monocarboxylate transporters (MCT) (MCT8 gene)

Where does the process of T4 and T3 synthesis occur?

within the cytosol of the follicular cell AND the colloid *****synthesis is INTRAcellular and EXTRAcellular

Pendrin is a secretes iodide into the follicular lumen of the thyroid cells, but where else in the body can pendrine be found? What is its role?

Innear ear | endocochlear potential and structural development

What is thyroglobulin? | Where do you find it?

the glycoprotein that serves as a scaffold for tyrosine iodination as well as storage of the thyroid hormone Colloid of the follicular cell of the thyroid

What is the condition called when there is a deficiency oh the hypothalamus-pituitary-thyroid axis during gestation?

Cretinism

What effects do thyroid hormones have on the cardiovascular system?

T3 increases cardiac output and ventilation T3 is chronotropic and inotropic T3 reduces vascular resistance

Thyroid hormones act synergistically with GH and growth factors to promote ___________ in fetal development

bone formation

Hypothyroid and Hyperthyroid effect on: | Basal metabolic rate

``` HYPO = decrease HYPER = increase ```

In Grave's disease, what stimulates the release of T3 and T4 causing hyperthyroidism?

autoantibodies that IMITATE TSH bind to the TSH receptor and stimulate thyroid

What are the calorigenic actions of thyroid hormones?

increased oxygen consumption resulting in increased BMR and temperature by increasing the activity of the Na-K-ATPase pump

After iodide has entered the follicular cell, how does it get into the colloid?

iodide channel anoctamin-1 on the apical membrane

Having low iodide in the diet can lead to hypothyroidism goiter for anyone, but for what group of people is this particularly overt

Those with Pendred syndrome

Hypothyroid and Hyperthyroid effect on: | Proteolysis

``` HYPO = decrease HYPER = increase ```

Hypothyroid and Hyperthyroid effect on: | gluconeogenesis

``` HYPO = decrease HYPER = increase ```

Deiodinase type 3 converts T4 into ____ by removing an iodine from the _____ position, making it (active/inactive)

rT3 inner 5 inactive

What helps endocytosis of thyroglobulin (Tg) with iodinated tyrosine residues back into the follicular cell from the colloid

megalin

Iodide transport defect is a mutation in the ______ gene that causes:

``` NIS gene (Na+-Iodide-symporter) HYPOthyroidism, goiter, reduced uptake of radio-iodide ```

In the _____, iodine attaches to a tyrosine on a thyroglobulin molecule contained in a vesicle with TPO

colloid