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MEH * > S11 Thyroid Gland > Flashcards

S11 Thyroid Gland Flashcards

1
Q

Where is the thyroid gland?

A
  • against and around front of larynx and trachea
  • it is below the thyroid cartilage (Adam’s apple)
  • isthmus extends from the 2nd to 3rd rings of the trachea
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2
Q

What is the structure of the thyroid gland?

A
  • 2 lobes joined by isthmus

* “bow tie” shape and location

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3
Q

How does the thyroid develop in the embryo?

A
  1. At 3-4 weeks gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue
  2. Descends as diverticulitis through thyroglossal duct and migrates in front of hyoid bone
  3. During migration, remains connected to the tongue by the thyroglossal duct, which then degenerates
  4. Continues to final position once detached over 2 weeks
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4
Q

What does thyroid tissue look like under a microscope?

A
  • follicular cells arranges in spheres called thyroid follicles
  • the follicles are filled with colloid
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5
Q

What is colloid?

A

A deposit of thyroglobulin

Colloid is extracellular even though it’s inside the follicle

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6
Q

What do the thyroid follicular cells produce?

A

Thyroid hormone (uses thyroglobulin protein to help synthesis)

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7
Q

What do the thyroid parafollicular cells produce?

A

Calcitonin

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8
Q

What are thyroid hormones made up from?

A

2 tyrosines linked with iodine at 3/4 positions on the aromatic ring (can have 2 iodines)

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9
Q

Where do the tyrosine residues come from for making thyroid hormone?

A

Thyroglobulin protein (contains 134 tyrosines, but only a few are used to produce thyroid hormone

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10
Q

How do you make T3 (triiodiothyronine) hormone?

And T4 (tetraidodothyronine/thyroxine) hormone?

A

Monoiodotyrosine (MIT) + Diiodotyrosine (DIT)

DIT + DIT

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11
Q

What is thyroid peroxidase?

A

A membrane bound enzyme that regulates 3 separate reactions involving iodide

  1. Oxidation of iodide to iodine (needs hydrogen peroxide)
  2. Addition of iodine to tyrosine acceptor residues on protein thyroglobulin
  3. Coupling to MIT/DIT to generate thyroid hormones in thyroglobulin protein
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12
Q

Where is dietary iodine reduced to iodine?

A

Before absorption in the small intestine

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13
Q

What are the only molecules in the body that contain iodine?

A

Thyroid hormones and precursors

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14
Q

How is iodide taken up from the blood into thyroid glands?

A

By thyroid epithelial cells that have sodium iodide symporter or ‘iodine trap’

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15
Q

What are common sources of iodine?

A
  • dairy products
  • grains
  • meat
  • veg
  • eggs
  • iodised salt
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16
Q

What are the steps in thyroid hormone synthesis?

A
  1. Iodine enter thyroid follicle cells via ‘iodine trap’
  2. Iodine then moves into colloid where iodination occurs
  3. Coupling of MIT and DIT occurs
  4. The coupled MIT and DIT moves by pinocytosis into thyroid follicle cells attached to thyroglobulin
  5. Lysosome engulfs thyroglobulin forming a phagolysosome
  6. Enzymes in the lysosome break down the thyroglobulin, releasing the T3 and T4 hormones into the plasma
  7. Any MIT and DIT that didn’t couple is deiodinased and the iodine is recycled
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17
Q

Which hormone, T3 or T4 is mostly secreted? Which is it then converted into and where?

A

T4, however T4 is the less biologically active form

So most T4 is converted to T3 in the liver and kidneys

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18
Q

How are T3 and T4 transported in the blood? Why do they need to unbind?

A

Bound to protein thyroxine-binding globulin

To become biologically active

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19
Q

How is thyroid hormone secretion regulated?

A

By negative feedback

20
Q

What is the negative feedback cycle for thyroid hormone secretion?

A
  1. Hypothalamus released TRH
  2. TRH stimulates anterior pituitary to release TSH
  3. TSH stimulates thyroid gland to produce thyroid hormone but also acts inhibiting the hypothalamus from releasing TRH
  4. Thyroid hormone acts on target tissues but also inhibits anterior pituitary from releasing TSH and the hypothalamus from releasing TRH
21
Q

What effect does thyroid hormone have in the body?

A

It effects most cells and has two interconnected responses

  1. Effects cellular differentiation and development
  2. Effects metabolism
22
Q

What is the structure of thyroid stimulating hormone (TSH)? What other hormones is it closer related to?

A
  • glycoprotein hormone is composed of 2 non-covalently bound subunits (alpha and beta)
  • the alpha subunit is the same subunit as in FSH and LH
  • the beta subunit provides its unique biological activity
23
Q

How does TSH trigger thyroid hormone release?

A

Binds to the TSH receptor (GPCR) on thyroid follicular cell membranes which activates T3 and T3 to be released

24
Q

What type of GPCR is the TSH receptor?

A

Normally Gs but can also be Gq if there are higher concentrations of TSH

25
Q

What does TSH stimulate?

A
  • iodide uptake
  • iodide oxidation
  • thyroglobulin synthesis
  • thyroglobulin iodination
  • colloid pinocytosis into follicular cells
  • proteolysis of thyroglobulin
  • cell metabolism and growth
26
Q

What is the second messenger pathway that TSH induces by binding to Gs receptor? And for Gq receptor?

A
  1. Adenylyl cyclase activated
  2. Which activates cAMP (from ATP)
  3. Which activates PKA
  4. Phosolipase C activates
  5. Which activates DAG and IP3 (from PIP2)
  6. Which activates Ca2+ release via the IP3 receptor and PKC activation

Both stimulate thyroid hormone synthesis and release

27
Q

How does thyroid hormone increase the basal metabolic rate and heat production?

A
  • increases the number and size of mitochondria

* stimulates the synthesis of enzymes in the respiratory chain

28
Q

Which tissues don’t respond to thyroid hormone increasing the basal metabolic rate and heart production?

A
  • brain
  • spleen
  • testis
29
Q

How does thyroid hormone stimulate metabolic pathways?

A
  • lipid metabolism - lipolysis and beta-oxidation of fatty acids
  • carbohydrate metabolism - stimulates insulin-dependent entry of glucose into cells, gluconeogenesis and glycogenolysis
30
Q

What are the sympathomimetics effects of thyroid hormone?

A

It increases target cell response to catecholamines by increasing receptor number on target cells

31
Q

What effect does thyroid hormone have on the cardiovascular system?

A

Increase the heart’s responsiveness to catecholamines

  • increases CO (increases HR and contractility)
  • increases peripheral vasodilation to carry extra heat to body’s surface
32
Q

What effect does thyroid hormone have on the nervous system?

A

Essential for both development and adult function

* increases myelination of nerves and development of neurones

33
Q

What is cretinism?

A

Hypothyroidism in childhood - lack of development of nervous system

34
Q

What type of receptor are thyroid hormone receptors? How does it work?

A

Nuclear receptor - modulate gene expression

When unbound to thyroid hormone, the receptor binds to DNA and usually results in transcriptional repression

When bound to hormone, a conformational change occurs in the receptor allowing it to function as a transcriptional activator

35
Q

What are 5 examples of thyroid hormone activated genes?

A
  • PEPCK (gluconeogenesis)
  • Ca2+ ATPase
  • Na+, K+ ATPase
  • cytochrome oxidase (ETC)
  • 6-phosogluconate dehydrogenase (pentose-phosphate pathway)
36
Q

What is goitre?

A

Enlargement of the thyroid gland

Can be part of hypo- or hyper-thyroidism

Develops when thyroid gland is overstimulated

37
Q

What can cause hypothyroidism?

A
  • failure of gland
  • TSH or TRH deficiency
  • inadequate dietary iodine
  • radioactive iodine
  • autoimmunity
  • post-surgery
  • congenital
  • anti-thyroid drugs
38
Q

What are general symptoms and signs of hypothyroidism?

A
  • obesity
  • lethargy
  • intolerance to cold
  • bradycardia
  • dry skin
  • alopecia
  • hoarse voice
  • constipation
  • slow reflexes
  • low T3 and T4
  • elevated TSH
39
Q

What are two types of hypothyroidism found in adults and infants?

A

Infants - cretinism - dwarfed stature, mental deficiency, slow pulse, poor bone development, muscle weakness, GI disturbances

Adults - myxedema - thick puffy skin, muscle weakness, slow speech, mental deterioration, intolerance to cold

40
Q

What is hashimoto’s disease?

A

Most common type of hypothyroidism

An autoimmune disease leading to destruction of thyroid follicles

More common in women

May have goitre, may not

Low T3 and T4, high TSH

41
Q

How do you treat hashimoto’s disease?

A

Oral thyroid hormone - use T4 as it has a longer half life

42
Q

What are some causes of hyperthyroidism?

A
  • autoimmune (Grave’s disease)
  • toxic multinodular goitre
  • solitary toxic adenoma
  • excessive T4/T3 therapy
  • drugs e.g. amiodarone
  • ectopic thyroid tissue
43
Q

What are general symptoms of hyperthyroidism?

A
  • weight loss
  • irritability
  • heat intolerance
  • tachycardia
  • fatigue and weakness
  • increased bowel movements
  • hyper-reflexive
  • breathlessness
  • loss of libido
  • sweating and tremor

some also have goitre or bulging eyes

44
Q

What is Graves’ disease?

A

An autoimmune disease resulting in hyperthyroidism

Caused by the production of thyroid stimulating immunoglobulin (TSI)

TSI continuously stimulates thyroid hormone secretions outside the normal negative feedback control

45
Q

What is thyroid scintigraphy?

A

Using a radioisotope (Technetium-99m) to scan the thyroid with a gamma camera

Use this radioisotope as it has a short half life (less than a day) so low radiation exposure

46
Q

What is a common antithyroid drug?

A

Carbimazole - a prodrug that is converted into methimazole in the body, it prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin

Used to treat hyperthyroidism

MEH * (22 decks)

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