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Y2S1CVSBIOCHEM > Thyroid Function Test > Flashcards

Thyroid Function Test Flashcards

1
Q

Define the steps of Thyroid hormone synthesis

Explain Thyroid hormone storage, secretion, and transport

Identify the characteristics of thyroid hormone receptors

Describe the effect of the thyroid hormones on gene transcription and metabolism

Interpret Thyroid function profile

Explain Parathyroid hormone structure and function

A
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2
Q

What hormones are released from the thyroid gland?

A

1) T3 (Tri-iodothyronine), T4 (Tetra-iodothyronine, amino acid derivative from tyrosine)

2) Calcitonin

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3
Q

What does the parathyroid gland secrete?

A

The para thyroid hormone (involved in calcium and phosphorus hemostasis)

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4
Q

What controls the release of Tri and Tetraiodothyronine?

A

The thyroid stimulating hormone (released from the anterior pituitary), which is controlled by TRH released from the hypothalamus

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5
Q

Describe the structure of the thyroid hormone

A

1) 2-tyrosine residues in the thyroglobulin

2) Iodine is trapped as iodide

  • In T3 it is called 3,5,3-triiodothyronine (T3), the active thyroid hormone
  • In T4 it is called 3,5,3,5-tetraiodothyronine (converted to T3 via deiodination)
  • rT3 (reverse T3 “biologically inactive”) is when the deionization pattern of T4 changes it to 3,3,5 instead of 3,5,3
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6
Q

Describe the general steps in the synthesis of thyroid hormone

A
  • Thyroglobulin is the precursor for T4 & T3, it is Iodinated and glycosylated
  • Rich in tyrosine residue which represents a binding site for iodine (iodination)
  • About 70% of the iodide in the thyroglobulin exists in the inactive precursors (Mono-iodotyrosine “MIT”, & Di-iodotyrosine “DIT”), while the remaining is present in T4 & T3
  • Once iodination takes place this prevents the leaving of the iodine and it is trapped
  • T4 results from joining 2 di-iodotyrosine, while T3 results from joining a di-iodotyrosine with a mono-iodotyrosine
  • The coupling of DIT and MIT requires an oxidation rxn which is done by the thyroperoxidase (TPO)
  • After thyroid hormones (T3 and T4) are synthesized, they remain attached as part of the thyroglobulin protein within the thyroid follicles, until the thyroglobulin protein is degraded. This degradation releases free T3 and T4, which are then secreted into the bloodstream
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7
Q

What is the first step in the synthesis of thyroid hormone?

A

Iodination, preventing the iodine from leaving the cell

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8
Q

How do we synthesize T4?

A

It is synthesized via an oxidation reaction, carried by thyroperoxidase (TPO) joining 2 di-iodotyrosine together

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9
Q

What is the difference between T3 and rT3?

A
  • T4 is the inactive form, while T3 is the active one

When T4 is deionated to T3 everything is normal but sometimes the iodine goes to position 3,3,5 instead of 3,5,3 and this is called rT3 (reversed T3)

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10
Q

How do we synthesize T3?

A

Via an oxidation reaction carried by the thyroperoxidase enzyme joining one mono-iodotyrosine and di-iodotyrosine

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11
Q

Where does the synthesis of the thyroid hormone occur?

A

In the luminal portion of the follicular cells, then it moves to the basal

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12
Q

What is the first step in thyroid hormone synthesis?

A
  • In the follicular cells

1) Uptake of iodine ion

  • Iodine ion is actively transported from the blood into the follicular cells, and then it diffuses through the cell and goes into the colloid via facilitated diffusion
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13
Q

What is the second step in thyroid hormone synthesis?

A
  • In the follicular cells:

2) Formation of iodine molecule

  • Two iodide ions (i-) are joined to form molecular iodine (I2), in the plasma membrane of the follicular cells
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14
Q

What is the third step in the synthesis of the thyroid hormone?

A

3) The synthesis of thyroglobulin (glycoprotein)

  • This includes the production of the protein within the rough ER, then shipping it to the Golgi apparatus to add carbohydrates to it, then it is incorporated into a vesicle and released into the colloid via exocytosis
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15
Q

What is the 4th step in thyroid hormone synthesis?

A
  • In the colloid

4) The formation of mono-iodotyrosine and di-iodotyrosine

  • I2 is attached to a tyrosine amino acid of thyroglobulin via peroxidase enzyme
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16
Q

What is the fifth step in the synthesis of the thyroid hormone?

A
  • In the colloid

The formation of T3 and T4, facilitated by the enzymes in the colloid, and both of them remain attached to the thyroglobulin

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17
Q

What is the sixth step in the formation of the thyroid hormone?

A
  • In the colloid

T3 and T4 are endocytosed into the follicular cells

18
Q

What is the seventh step in the synthesis of the thyroid hormone?

A
  • In the follicular cells

7) Release of T3 and T4 from the thyroglobulin

  • A vesicle containing the thyroglobulin with the attached T3 and T4 is fused with a lysosome cleaving the T3 & T4 from the hyroglobulin
19
Q

What is the Eighth step in the synthesis of the thyroid hormone?

A
  • In the follicular cells

8) The release of T3 and T4 into the blood

20
Q

Which organelle synthesizes thyroglobulin?

A

Ribosomes bound to the rough endoplasmic reticulum, then Golgi apparatus for carbohydrate addition, and then exocytosis to enter the colloid

21
Q

In which part of the thyroid gland are the iodine molecules formed?

A

The plasma membrane of the follicular cells

22
Q

What happens after the liberation of T3 and T4 from the thyroglobulin?

A

They are deionated via deiodinase, and the tyrosine and iodide are returned for further utilization

23
Q

How to detect endogenous thyroid secretion?

A

By measuring the serum concentration of thyroglobulin

24
Q

How is iodine transported?

A

1) In the thyroid follicular cells Na+/Iodide symporter (NIS “secondary pump”) will take an iodide from the blood, using the concentration gradient of the Na+ created by the Na+/K+ pump “primary pump”, transporting them together, however iodide is transported against its concentration and electrical gradient

  • This involves an energy-requiring (ATPase-dependent) transport mechanism
  • Stimulated via TSH binding to the G-protein producing cAMP, this enables the thyroid gland to concentrate iodide 30-50 times compared to the ones in the circulation
25
Q

What controls the activity of the sodium/iodide symporter?

A

Thyroid-stimulating hormone

26
Q

What are the functions of the thyroid hormone?

A

1) Normal growth

2) Differentiation

3) Sex and Mental development

4) Regulates the speed of metabolism

27
Q

What is the effect of the thyroid hormone on gene transcription?

A
  • Thyroid hormone action is mediated by their binding to the nuclear receptors as they are lipid soluble hormones
  • Thyroid hormone receptors are attached to the DNA, which will activate gene transcription upon binding which will bind to the promoter region triggering the production of mRNA
28
Q

How does the thyroid hormone affect the metabolic RATE?

A
  • Except in the brain, spleen, and testis

1) It increases the number and size of the mitochondria

2) It stimulates the synthesis of enzymes in the respiratory chain

3) It increases the Na+/K+ ATPase activity, increasing the resting metabolic rate

4) It increases the synthesis of cytochrome c oxidase, increasing the synthesis of ATP due to the increase in oxidative phosphorylation (increasing the consumption of ATP)

  • The resting metabolic rate might increase by 100% in the presence of excess of the hormone or decrease by 50% in a deficiency
29
Q

What is the effect of the thyroid hormone on protein metabolism?

A
  • Hypothyroidism will stimulates the synthesis of proteins and nucleic acids
  • Hyperthyroidism will activate the decomposition of protein
30
Q

What is the effect of the thyroid hormone on lipid metabolism?

A

It will activate the decomposition and oxidation of lipids

31
Q

What is the effect of the thyroid hormone on carbohydrate metabolism?

A

1) Accelerate its absorption in the intestine

2) Activates the decomposition of glycogen

32
Q

What are the investigations of the thyroid hormone?

A

1) TSH

2) Total thyroxine & T3

  • More than 99% of T4 and T3 circulate bound to proteins in the plasma

3) Free T4 & T3

  • Free thyroid hormone concentrations are independent of thyroid hormone concentration changes, which makes them more reliable for thyroid dysfunction diagnosis
33
Q

When are the investigations for TSH done?

A

Plasma TSH is screened using ELISA for congenital hypothyroidism in neonates (1/4K live births)

34
Q

Which measure is more reliable the free to total T4 & T3?

A

The free form is more reliable as it represents the active hormone which is capable of exerting its effect by binding to the nuclear receptors

35
Q

What are the main causes of thyrotoxicosis?

A

1) Primary hyperthyroidism

  • Like in graves disease, where we have an increased FT4 & FT3, and decreased TSH due to the negative feedback inhibition

2) Secondary hyperthyroidism

  • We have an increased TSH and FT3 & FT4, like in:

1) TSH-producing pituitary adenoma

2) Thyroid hormone resistance

3) Gestational thyrotoxicosis

36
Q

What are the causes of hypothyroidism?

A

1) Primary hypothyroidism (more common), where there is an increased TSH and decreased T4, T3

2) Secondary hypothyroidism (less common), there is a decreased IN TSH and T4, T3

37
Q

What are the causes of hypothyroidism?

A

1) In 90% of the cases it is due to:

  • Autoimmune destruction of the thyroid gland (Hashimoto’s disease)
  • Radioiodine/Surgical treatment of hyperthyroidism

2) It is due to TSH deficiency like in the case of hypopituitarism (secondary)

38
Q

What is the main cause of goiter?

A
  • Iodine deficiency, requiring the thyroid to work extra hard
  • High TSH will also induce Goiter
39
Q

What is calcitonin?

A

It is a 32-amino-acid polypeptide hormone that is secreted by C-cells of the thyroid participating in the homeostasis of calcium along with the parathyroid hormone

40
Q

What is the parathyroid hormone?

A
  • A polypeptide hormone consisting of 84 amino acids
  • It is initially synthesized as a large precursor PreProPTH (115 AA), then in the rough ER of the parathyroid cells, 25 AA are cleaved to produce a ProPTH, further processing in the Golgi apparatus results in the cleavage of 6-amino acids to finally produce PTH, which is stored in secretory vesicles until needed
  • PTH has a half-life of 5-10 minutes, before being rapidly metabolized by the liver and kidney
  • Secreted from the chief-cells of the parathyroid gland
41
Q

What is the function of the PTH?

A

Increases calcium levels in the blood

1) Increases ita absorption in the GIT

2) Releases calcium and phosphorus from the bone

  • It does that by binding to the parathyroid hormone receptor (PTHR1) in the bones and kidney cells

Y2S1CVSBIOCHEM (6 decks)

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