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Endocrying > The thyroid gland > Flashcards

The thyroid gland Flashcards

1
Q

Where is the thyroid gland located?

What shape and size is it?

A

The thyroid gland lies across trachea at base of larynx

Butterfly shaped. One of the larger endocrine glands - but neither palpable or visible in health

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2
Q

What does the thyroid gland produce?

A

Synthesises the Thyroid hormones - of which there are 2 physiologically active forms

These are:

T3 - triiodothyronine

T4 - thyroxine

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3
Q

Describe the structure of the thyroid gland

A

Contains 2 main cell types:

  • C (clear) cells - secrete calcitonin (Ca2+ regulating hormone)
  • Follicular cells - support thyroid hormone synthesis and surround hollow follicles

Thyroid follicles:

  • Spherical structures lined by follicular cells
  • Centre is filled with colloid
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4
Q

Identify the different cells n shit in the thyroid gland

A
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5
Q

What is colloid?

A

Sticky glycoprotein matrix - which contains 2-3 months supply of Thyroid hormones

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6
Q

Describe the function of Follicular cells

A

Manufacture the enzymes that synthesize thyroid hormones and also thyroglobulin - a large protein, rich in tyrosine residues

The enzymes and thyroglobulin are packaged into vesicles and exported from the follicular cells into the colloid

It also moves iodine into the colloid from the blood through active transport

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7
Q

Where do we get our iodide and tyrosine

A

Diet

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8
Q

How is iodide moved into the colloid from the blood?

A

Iodide enters the follicular cells from the plasma via a Na+/I- transporter (symport). The coupling to Na+ enables the follicular cells to take up iodide against a concentration gradient

Iodide is then transported into the colloid via the pendrin transporter

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9
Q

What are the thyroid peroxidases?

A

These are the enzymes that follicular cells exocytose into the colloid along with thyroglobulin

Part of the thyroid hormone production pathway…

They catalyse:

  • the oxidation of Iodide to iodine
  • The addition of iodine^ to tyrosine residues on the thyroglobulin molecule
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10
Q

What molecules are produced through the addition of iodine in the colloid?

A

Addition of 1st iodine = MIT (monoiodotyrosine)

Addition of 2nd iodine = DIT (diiodotyrosine)

MIT & DIT can then undergo conjugation reactions:

  • MIT + DIT = T3 (triiodothyronine)
    • 3 iodines
  • DIT + DIT = T4 (thyroxine)
    • 4 iodines
    • aka tetraiodothyronine
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11
Q

Describe the thyroid hormones in terms of tyrosines and iodines

A

Triiodothyronine

  • 2 tyrosines + 3 iodines

Thyroxine

  • 2 tyrosines + 4 iodines
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12
Q

Once synthesised - thyroid hormones are stored in the colloid

How is there release triggered?

A

In response to Thyroid-stimulating hormone - there is uptake of colloid into follicular cells

Within the cells they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones.

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13
Q

How do T3 and T4 get into the blood?

A

Both T3 and T4 are lipid-soluble and so pass across the follicular cell membrane into the plasma

Once in plasma - they bind to plasma proteins, mainly thyroxine-binding globulin

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14
Q

Are there any transporters involved in the movement of thyroid hormones into the blood?

A

They are lipid soluble so dont need transporter proteins

however

Transporter proteins may also be involved in this process as rare mutations in this protein cause major disruption to TH balance

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15
Q

Movement of TH from colloid to plasma is under the influence of a)______________ released from the b)_________.

c)____________ stimulates the follicular cells to d)_________ colloidal thyroglobulin. When not stimulated, the thyroid hormones are stored in the colloid

A

Movement of TH from colloid to plasma is under the influence of TSH released from the pituitary. TSH stimulates the follicular cells to endocytose colloidal thyroglobulin. When not stimulated, the thyroid hormones are stored in the colloid

a) Thyroid-stimulating hormone
b) Pituitary gland
c) TSH
d) Endocytose

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16
Q

How do the thyroid hormones circulate?

A

99.8% of T3 and T4 circulates in plasma bound to plasma protein

Thyroxine Binding Globulin (TBG) has particularly high affinity for T4 releasing it only slowly into the plasma

Only free Thyroid hormones can do anything

17
Q

What is the inhibitory effect of thyroid hormones in the blood?

A

Free T4 & T3 exerts an inhibitor effect of TSH and TRH

18
Q

Compare the levels of T3 and T4 in the blood

A

Most TH circulates in the form of protein bound T4 ~100nmoles/l, while T3 is only ~2.3nmoles/l

This means about 50x more Thyroxine exists in the blood than T3

However - 90% of TH binding to TH receptors inside cells is T3

19
Q

Why is T3 more physiologically active than T4?

A

TH receptor has a much higher affinity for T3 than T4

20
Q

What is the fate of Thyroxine T4?

A

T4 is deiodinated to T3 by deiodinase enzymes.

Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells

The level of deiodinase activity can be altered at different times in different tissues to suit demand

21
Q

We know free TH has an inhibitory effect on TRH and TSH

What stimulates production of TRH in the hypothalamus?

A

There is a continuous secretion of TRH from the hypothalamus to keep stable hormone levels

However - Cold, exercise and pregnancy stimulate TRH production

22
Q

What hormones inhibit TSH?

A

Somatostatin (GHIH) - inhibits TSH

Glucocorticoids - inhibits TSH & conversion of T4 to T3

23
Q

Describe the effect of thyroid hormone action on target cells

A

TH bind to nuclear receptors in target cells, where they change transcription and translation to alter protein synthesis.

General actions of Thyroid hormones:

  • Increase metabolic rate & thermogenesis
  • Increase hepatic gluconeogenesis
  • net increase in proteolysis
  • net increase in lipolysis
  • stimulates GH receptor expression
  • brain development in utero
24
Q

How do thyroid hormones alter metabolic rate?

A

Increase metabolic rate & thermogenesis

They do so typically through promoting futile cycles of simultaneous catabolism and anabolism.

25
Q

One of the effects of thyroid hormones is to increase hepatic gluconeogenesis

What is the effect of this on blood glucose?

A

no effect on BG providing pancreas is releasing adequate insulin

(therefore not a counter-regulatory hormone)

26
Q

What is the importance of thyroid hormones in growth?

A

critical for growth (lack of TH results in retarded growth)

stimulates GH receptor expression

27
Q

Why risk is associated with low maternal iodine levels?

A

Low iodine levels impact thyroid production

Iodine essential for brain development in utero

Maternal iodine deficiency can cause congenital hypothyroidism

28
Q

What are the causes of hyperthyroidism?

A

Graves disease (common)

Thyroid adenoma (rare)

29
Q

What happens in graves disease?

A

Antibodies produced that bind mimic TSH and continually activate the thyroid gland.

Increased release of TH switches off TSH release from anterior pituitary so [TSH]plasma very low.

Thyroid gland may be 2-3x normal size due to hyperplasia. Hyperactivity of cells also apparent.

30
Q

What are the symptoms of Hyperthyroidism?

A

Weight loss

  • Increased metabolic rate
  • Increased protein catabolism

Heat intolerance

Muscle weakness/loss

Hyperexcitable reflexes

Psychological disturbances

31
Q

What are the signs of hyperthyroidism?

A

Neck swelling (goitre)

Hyperexcitable reflexes

Tachycardia (elevated cardio function)

Psychological disturbance

32
Q

What are the causes of hypothyroidism?

A

Hashimoto’s disease - autoimmune attack of thyroid gland

Dietary iodine deficiency

Idiopathic - may have links to thyroiditis

33
Q

What are the symptoms of hypothyroidism?

A

Weight gain

Cold intolerance

Fatigued state with slow speech/reflexes

Dry hair/hair loss

Puffiness appearing on face

34
Q

What are the signs of hypothyroidism?

A

Neck swelling (goitre)

Brittle nails

Thin skin

Dry hair

Puffy face (facies)

Bradycardia / weak pulse

35
Q

What is Goitre?

A

Thyroid gland swelling which can happen with either hypo or hyperthyroidism

caused by increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves Disease)

36
Q

What would be the difference between hypothyroidism caused by a thyroid lesion or caused by pituitary lesion?

A

Thyroid lesion - High [TSH] but low [TH]

Pituitary (2ndary) lesion - Low [TSH], low [TH]

37
Q
A

Endocrying (21 decks)

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