Hypothyroidism Flashcards

09.10.2019

1
Q

Draw the thyroid - hypothalamus - pituitary axis.

A

TRH, TSH, T3+T4

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2
Q

What is Myxoedema?

A

Primary hypoparathyroidism

  • high TSH
  • low T4
  • autoimmune damage to the thyroid
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3
Q

What are some symptoms of primary hypothyroidism?

A
  • Deepening voice
  • Depression
  • tiredness
  • Cold intolerance
  • Weight gain with reduced appetite
  • Constipation
  • Bradycardia
  • Eventual myxoedema coma
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4
Q

How are thyroid hormones made?

A
  • TSH binds to TSHR on follicular cells.
  • this has multiple effects
    a) I- enters cell via NIS and then colloid via pending pump
    b) TPO moves to the colloid
    c) TG moves to the colloid
    d) reaction 1: iodination (I- -> I* + TG -> TG bound to MIT and DIT)
    e) reaction 2: coupling reaction (DIT-TG-MIT -> TG bound to T3 and T4)

(both reactions via TPO and H2O2)

e) TG-T3-T4 packaged into a lysosome and then broken down into T3 and T4
g) packaged hormones are released into bloodstream
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5
Q

What are other names for T4?

A

Tetraiodothyronine, Thyroxine

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6
Q

Is T3 or T4 more active?

A
  • T3 is more active
  • T4 is a prohormone -> converted to T4 in the cell via deiodination
  • T3 provides almost all the thyroid hormone activity in target cells.
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7
Q

How much of circulating T3 is due to deiodination of T4?

A

80% (other 20% was produced as T3)

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8
Q

What does T3 do inside the cell?

A

It binds to TRE (thyroid response element) and alters gene expression.

(RXR (retinoid x receptor) and TR (thyroid hormone receptor) also bind to TRE to produce effects)

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9
Q

What is thyroid hormone replacement therapy?

A
  • Give oral thyroxine to replace the missing hormone
    other names: thyroxine sodium; thyroxine;
    Tetraiodothyronine; T4

Less commonly used: Liothyronine sodium
triiodothyronine; T3

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10
Q

Clinical use of levothyroxine sodium

A

Primary hypothyroidism:

  • eg autoimmune, iatrogenic - post-thyroidectomy, post-radioactive iodine
  • Oral administration
  • TSH used as guidance for thyroxine dose - aim to suppress TSH into the reference range

Secondary hypothyroidism:

  • eg pituitary tumour, post-pituitary surgery or radiotherapy
  • Oral administration.
  • TSH low due to anterior pituitary failure, so can’t use TSH as a guide to dose.
  • Aim for fT4 middle of reference range
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11
Q

Clinical use of triiodothyronine

A

Myxoedema coma - a VERY RARE complication of hypothyroidism
-> iv initially – as onset of action faster than T4, then oral when possible

=> no clinical evidence that T3 is better, but it is more expensive!

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12
Q

Combined Thyroid hormone replacement

A
  • Combination T4/T3 – some reported improvement in well-being
  • Complicated by symptoms of ‘toxicity’ – palpitations, tremor, anxiety - often combination treatment suppresses TSH
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13
Q

Pharmacokinetics of Thyroid hormone replacement therapy

A
  • orally active
  • long plasma half life: T3=2.5d; T4: 6d;
  • majority of hormone is ppb (tbg)
  • only free fraction of hormones is available to tissues
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14
Q

What is the half life of T3?

A

2.5d plasma half life

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15
Q

What is the half life of T4?

A

6d plasma half life

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16
Q

Plasma protein binding of thyroid hormones.

A
  • Approximately 99.97% of circulating T4 and 99.7% of circulating T3 are bound to plasma proteins, mainly thyroxine binding globulin (TBG)
  • only free hormone is available to tissues
  • plasma binding proteins increase in pregnancy and on prolonged treatment with oestrogens and phenothiazines
  • TBG falls with malnutrition, liver disease
  • certain co-administered drugs (e.g. phenytoin, salicylates) compete for protein binding sites.
17
Q

What fraction of T3 is plasma protein bound?

A

99.7%

18
Q

What fraction of T4 is plasma protein bound?

A

99.97%

19
Q

Which hormone provides almost all the thyroid hormone activity in target cells?

A

T3

there is ic deiodination of T4

20
Q

How would you treat myxoedema coma?

A
  • a very rare complication of hypothyroidism
  • i.v. T3 (trio-iodothyronine)
  • onset of action is faster than T4 and then given orally when possible.
21
Q

Deiodinase

A

converts T4 to T3

22
Q

which enzyme converts T4 to T3?

A

Deiodinase

23
Q

What happens in pregnancy in terms of PPB?

A
  • increase in PPB proteins

- in pregnancy and on treatment with oestrogens and phenothiazines (antipsychotics)

24
Q

What happens with TBG in malnutrition and liver disease?

A

TBG falls