Lecture 10 Flashcards by T I

Where is the thyroid located?

Front of the neck

How well did you know this?

Not at all

Perfectly

What is the structure of the thyroid gland?

Two lobes and an isthmus, in front of the trachea, with blood supply and surrounding tissues

How well did you know this?

Not at all

Perfectly

What types of cells are present in the thyroid?

Follicular cells, C-cells

How well did you know this?

Not at all

Perfectly

What do follicular cells do?

Absorb iodide and produce thyroxine (T4) and triiodothyronine (T3), T3 = active form, T4 = inactive form

How well did you know this?

Not at all

Perfectly

What do C cells do?

Produce calcitonin (calcium homeostasis)

How well did you know this?

Not at all

Perfectly

What are the 6 stages of T3 and T4 synthesis?

Thyroglobulin synthesis, 2. Uptake and concentration of iodide, 3. Oxidation of iodide to iodine, 4. Iodination of thyroglobulin, 5. Coupling of iodinated tyrosine molecules to T3/T4, 6. Secretion

How well did you know this?

Not at all

Perfectly

What is the difference between T3 and T4?

T3 has 3 iodines, T4 has 4 iodines

How well did you know this?

Not at all

Perfectly

What is MIT?

Monoiodotyrosine, 1 iodine on the 3’ position carbon of the ring

How well did you know this?

Not at all

Perfectly

What is DIT?

Diiodotyrosine, 2 iodines bound on the 3’ and 5’ carbons in the ring

How well did you know this?

Not at all

Perfectly

What is T3 produced from?

MIT + DIT, 3 iodines: 1 on the 3’ position of the left-hand ring, 2 on the 3’ and 5’ positions of the right-hand ring

How well did you know this?

Not at all

Perfectly

What is T4 produced from?

DIT + DIT, 4 iodines: 2 on each ring’s 3’ and 5’ positions

How well did you know this?

Not at all

Perfectly

Where does conversion of thyroglobulin to T4 occur? What happens?

In follicular cells: iodine pumped into cells, iodination occurs, T4 produced and may convert to T3, released into blood

How well did you know this?

Not at all

Perfectly

What is the HPT axis?

Hypothalamus, Pituitary gland, Thyroid gland

How well did you know this?

Not at all

Perfectly

What are the 3 main hormones involved in the HPT axis?

TRH (hypothalamus), TSH (pituitary), T3 and T4 (thyroid)

How well did you know this?

Not at all

Perfectly

What is the structure of TRH? Where is it produced?

Formed as large polypeptide (242 AAs), produced in paraventricular nucleus of hypothalamus

How well did you know this?

Not at all

Perfectly

What is the function of TRH?

Stimulates anterior pituitary to produce TSH

How well did you know this?

Not at all

Perfectly

What is the function of TSH?

Stimulates thyroid to produce T3 and T4 and promotes thyroglobulin transcription

How well did you know this?

Not at all

Perfectly

How does TSH stimulate thyroglobulin transcription?

TSH binds to receptors on follicular cells, activates adenylyl cyclase, PKA, upregulates thyroglobulin production

How well did you know this?

Not at all

Perfectly

Give some examples of conditions linked to problems in the TSH signaling pathway.

Thyroid adenoma, Follicular thyroid carcinoma

How well did you know this?

Not at all

Perfectly

How are T3 and T4 transported around the body? Why is this required?

They are lipophilic, require carrier proteins (e.g., thyroxin-binding globulin) for transport in blood

How well did you know this?

Not at all

Perfectly

Do we make more T3 or more T4? Why?

More T4 (inactive) is made to ensure stability and control hormone activity at the target site where it’s converted to T3

How well did you know this?

Not at all

Perfectly

What enzyme is required to convert between different forms of thyroid hormone?

Deiodinase

Which form of thyroid hormone can enter the cell?

Only free T3 and T4

How many types of deiodinase are there?

Three

What does Type I deiodinase (ID1) do?

Converts T4 to T3 and rT3, found on cell surface

How is rT3 different from T3?

rT3 is inactive, T3 is active (rT3 lacks iodine on the 5' position of the right-hand ring)

What does Type II deiodinase (ID2) do?

Converts T4 to T3, does not produce rT3, located intracellularly

What is the similarity between ID1 and ID2?

Both convert T4 to T3

What are the differences between ID1 and ID2?

ID1 is cell-surface-based, ID2 is intracellular; ID2 does not produce rT3

What does Type III deiodinase (ID3) do?

Converts T4 to rT3 and T3 to T2 (inactivates thyroid hormones)

What is the mechanism of ID3 function? What does it achieve?

Inhibits thyroid hormone activity by converting T4 to rT3 and T3 to T2, preventing formation of active hormones

What are the main basic functions of T3?

Upregulates glucose utilization, ATP production, increased cardiovascular and respiratory outputs

How does T3 affect Polymerase I and II?

Increases transcription of ATP pump and receptors, enhances ATP production

How does T3 affect production of Na/K ATPase pumps?

Increases production of Na/K ATPase pumps, enhancing glucose absorption and ATP production, speeding neuronal repolarization

How does T3 affect beta-adrenergic receptors?

Increases expression of beta-adrenergic receptors, enhancing adrenaline effects, increasing cardiac output, ventilation, glucose uptake, and ATP production

What are 4 key T3-associated disorders?

Cretinism, Hyperthyroidism, Hypothyroidism, Goitre

What is cretinism and what is it caused by?

Impaired physical and neurological development, caused by iodine deficiency or hypothyroidism during fetal development

What are the treatments for cretinism?

Iodine supplement (if detected early), irreversible if untreated after 2 years of life

How long does it take to develop a functional HPT axis?

12 weeks of gestation

What is hyperthyroidism and what is it caused by?

Overproduction of thyroid hormones, causing thyrotoxicosis and increased frequency of AP firing

Give an example of a condition that causes hyperthyroidism

Graves' disease, auto-antibody stimulates TSH receptor continuously

What are the signs and symptoms of hyperthyroidism?

Heat intolerance, weight and muscle loss, increased appetite, diarrhea, nervous irritability, goitre

How is hyperthyroidism diagnosed?

Analyse blood for serum TSH and free T3/T4, increased T3 or T4; increased TSH suggests pituitary issue, decreased TSH suggests thyroid issue

What is hypothyroidism and what is it caused by?

Too little thyroid hormones, caused by iodine deficiency, leading to myxoedema (polysaccharide deposition)

Give an example of a condition that causes hypothyroidism

Hashimoto's thyroiditis (autoimmune destruction of thyroid)

What are the signs and symptoms of hypothyroidism?

Slow, lethargic, overweight, alopecia, goitre

How is hypothyroidism diagnosed?

Analyse blood for serum TSH and free T3/T4, decreased T3 or T4, usually increased TSH, reduced neuronal firing

What is a goitre? When can it form?

Enlargement of the thyroid gland, can form in both hyper- and hypothyroidism

What are goitres caused by?

Low or high T4 expression

How are goitres caused by iodine deficiency?

Iodine deficiency causes low T4, which stimulates excessive TSH production, leading to gland growth

How are goitres caused by Graves' disease?

Graves' disease leads to high T4 levels, suppressing TSH, but autoantibodies mimic TSH, causing continuous thyroid stimulation and goitre formation

What else can cause goitres?

Benign or cancerous tumors

What are the treatments for goitres? What are the problems with one of these treatments?

Drugs, radioactive iodine (destroys gland), surgery (risks: vocal cord damage, bleeding, parathyroid damage)