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BIOL 135 > 5 - ENDOCRINE DISORDERS: THE THYROID GLAND > Flashcards

5 - ENDOCRINE DISORDERS: THE THYROID GLAND Flashcards

1
Q

TRH

A

thyrotropin releasing hormone

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2
Q

TSH

A

thyrotropin stimulating hormone

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3
Q

Why is thyroid peroxide needed?

A

to attach iodine to tyrosine

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4
Q

Thyroid hormones (T3 and T4)

A

Stimulates metabolic activity

INCREASING METABOLLIC RATE

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5
Q

Thyroidglobulin (TGB)

A

A protein stored T3 and T4 (thyroid hormones)

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6
Q

Where is thyroglobulin stored?

A

colloid

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7
Q

What happens when the thyroid hormones, T3 and T4, are required?

A

colloid is endocytosed into follicle cells.
T3/T4 released into blood.
Transported bound to protein.

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8
Q

Free T3/T4

A

not bound to protein and is the metabolically active form.

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9
Q

Thyroid Stimulating Hormone (TSH) function test

A

2 site ELISA

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10
Q

Free T4 and Total T4 function test

A

2 step competitive ELISA

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11
Q

Autoimmune antibody detection function tests

A
  • Anti TSH receptor – cell assay

* Anti thyroid peroxidase - ELISA

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12
Q

2-SITE ELISA: THYROID STIMULATING HORMONE (TSH)

A
  1. Antibody to β subunit of TSH bound to ELISA well
  2. Patient’s serum added.
  3. TSH β subunit binds to Antibody.
  4. Second antibody added, linked to HRP.
  5. Antibody binds α TSH subunit
  6. TMB substrate added.
  7. Colour produced.
  8. Absorbance at 450nm Measured.
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13
Q

2 STEP COMPETITIVE ELISA: FREE T4 (FT4)

A
  1. Antibody to T4 attached to well
  2. Patient’s serum added and Free T4 in serum binds Antibody.
  3. HRP-labelled T4 added. This binds to rest of antibodies
  4. HRP converts TMB to colour.
  5. Measure absorbance
  6. Antibody to T4 attached to well
  7. Patient’s serum added. There is a lot of free T4 this time, so Free T4 in serum binds antibody.
  8. Most antibody sites are now occupied.
  9. HRP-labelled T4 added. This binds to the few remaining unoccupied antibodies
  10. HRP converts TMB to colour. Much less HRP, therefore less TMB coloured.
    WEAK ABSORBANCE = HIGH PATIENT FT4
    HIGH ABSORBANCE = LOW PATIENT FT4
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14
Q

2 STEP COMPETITIVE ELISA TOTAL T4

A
  1. Antibody to T4 attached to well
  2. Patient’s serum added
  3. ALL T4 (free and bound) in serum binds antibody
  4. HRP-labelled T4 added. This binds to the few remaining unoccupied antibodies
  5. HRP converts TMB to colour. Measure Absorbance.
    WEAK ABSORBANCE = HIGH TOTAL T4
    HIGH ABSORBANCE = LOW TOTAL T4
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15
Q

AUTOIMMUNE ANTIBODY DETECTION

A 
•Anti TSH receptor antibody test (TRAb) 
•(Graves’ )
– cell assay
•Anti thyroid peroxidase antibody test (TPO)
•(Hashimoto’s thyroiditis)
- ELISA
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16
Q

ANTI TSH RECEPTOR ASSAY – POSITIVE RESULT

A
  • Cells expressing TSH receptor.
  • Cells contain luciferase gene + promoter activated by cAMP
  • Patient’s serum added to cells.
  • Autoantibody binds TSH receptor.
  • cAMP rises and activates luciferase gene.
  • Luciferase produced.
  • Luciferase + luciferin = LIGHT
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17
Q

ANTI TSH RECEPTOR ASSAY – NEGATIVE RESULT

A
  • Cells expressing TSH receptor and contain luciferase gene + promoter activated by cAMP.
  • Patient’s serum added to cells but no anti TSH receptor antibodies present.
  • TSH receptor is not bound.
  • cAMP does not rise so luciferase gene is not activated.
  • Luciferase is not produced.
  • No light is produced.
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18
Q

ANTI-TPO ELISA

A
  1. Wells coated with TPO antigen
  2. Patient’s serum added.
  3. Any anti-TPO antibodies bind to TPO antigen
  4. HRP-labelled anti-human antibody added. This binds to any anti-TPO antibodies bound.
  5. HRP converts TMB to colour. Measure Absorbance.
    HIGH ABSORBANCE = ANTI-TPO antibodies present
19
Q

Hyperthyroidism symptoms

A

Feeling hot, sweating, weight loss, tachycardia, palpitations, anxiety

20
Q

Hyperthyroidism diagnosis

A

TSH low/absent, FT4/3 high

21
Q

Graves disease symptoms

A
  • Standard hyperthyroidism symptoms and staring eyes

* Thyroid large and soft (goitre)

22
Q

Graves disease biochemical findings

A
  • FT4/FT3 increased
  • TSH low or absent (negative feedback)
  • Anti TSH receptor autoantibodies
23
Q

GRAVES’ DISEASE HISTOLOGY

A

Thyrotoxic Hyperplasia (all follicles active)

24
Q

Thyroid adenoma

A

a benign tumour in thyroid gland.
Benign effect on follicular epithelium.
Sometimes produces thyroid hormone - if so, FT3/4 high, TSH low

25
Q

Multinodular goitre

A
  • Lumpy and irregular thyroid
  • Common in elderly
  • Occasionally excess T3/T4 produced (‘toxic multinodular goitre’)
26
Q

HYPERTHYROIDISM TREATMENT

A

Antithyroid drugs, sub-total thyroidectomy, radioactive iodine (131 I)

27
Q

Antithyroid drugs

A
  • Prevents iodine binding to tyrosine.

* Anti-inflammatory

28
Q

Sub-total thyroidectomy

A

• Problems – hypothyroidism

29
Q

Radioactive iodine (131 I)

A
  • Radiation damage to thyroid.

* 80% of patients become hypothyroid

30
Q

Hypothyroidism symptoms

A

Fatigue, weight gain, dry hair and skin, hair loss, bradycardia…(clinical syndrome = Myxedema in adults)

31
Q

Hypothyroidism diagnosis

A

Raised TSH, FT4 low

32
Q

hypothyroidism treatment

A

Replacement T4 given and constant monitoring of thyroid hormones and TSH levels.

33
Q

Hashimoto’s thyroiditis

A
  • Autoimmune destruction of the thyroid

* Cut surface is white

34
Q

Hashimoto’s thyroiditis biochemical findings

A
  • TSH increased
  • FT4 low
  • Detectable autoantibodies (often anti TPO antibodies)
  • May be other autoimmune diseases present
35
Q

Congenital hypothyroidism

A
  • Underdeveloped thyroid, wrong location or absent
  • If not treated within 3 months leads to irreversible brain damage
  • Clinical syndrome = cretinism
  • Symptoms:
  • Growth failure
  • Developmental delay
36
Q

Iodine deficiency hypothyroidism

A
  • Symmetrical diffuse enlargement of thyroid

* Symptoms: myxedema

37
Q

Normal total T4 levels

A
  • Total T4 60-160 nmol/

* Free T4 10-25 pmol/l

38
Q

Normal total T3 levels

A

1.2-2.3 nmol/l

Free T3 4.0-6.5 pmol/l

39
Q

Normal Thyroid stimulating hormone (TSH) levels

A

•0.2-3.5 mU/l

40
Q

Normal Thyroxine binding globulin (TBG) levels

A

20mg/l

41
Q

Euthyroid

A

normal thyroid function

TSH and T4 levels are normal

42
Q

High TSH, low T4

A

Hypothyroidism

43
Q

low TSH, high T3, T4

A

hyperthyroidism

BIOL 135 (10 decks)

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