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Endocrinology > Lec7 Thyroid hormone Physiology > Flashcards

Lec7 Thyroid hormone Physiology Flashcards

Anatomy of the thyroid Synthesis and actions of the thyroid hormones Drugs affecting thyroid gland function (84 cards)

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1
Q

Are the thyroid gland and its secretions essential for life?

A

No but they are essential for normal development and for physical and mental wellbeing of the individual

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2
Q

What is the thyroid gland composed of?

A

Follicles each consisting of a monolayer of epithelial cells enclosing a large core of viscous, homogeneous colloid

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3
Q

What is the function of the colloid?

A

It acts as a reservoir of thyroid hormone

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4
Q

What are the primary hormones secreted by the thyroid gland

A

T3 - triiodothyronine
T4 - thyroxine
Calcitonin –> concerned with calcium homeostasis and is secreted independently of the thyroid hormones

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5
Q

What makes T3 and T4 and where do they come from?

A

Tyrosine - from avocado & nuts

Iodine comes from meat

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6
Q

How are T3 and T4 made?

A

Tyrosine combines with iodine to form mono-iodotyrosince (MIT) or di-iodotyrosine (DIT)

MIT can combine with another MIT or a DIT to form
tri-iodothyronine (T3) or tetra-iodothyronine (T4)

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7
Q

What formations are biologically active?

A

3-monoiodotyrosine (MIT)
3,5-diiodotyrosine (DIT)
3,5,3’-triiodothyronine (T3)
3,5,3’,5’-tetraiodothyronine (T4)

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8
Q

Is reverse triiodothyronine biologically active?

A

No

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9
Q

Women who have iron deficiency can lead to what?

A

Dysfunction of the thyroid gland

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10
Q

How could indices of the thyroid hormone be improved?

A

By improving the iron status

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11
Q

Nuclear incidents can result in:

A

an increase of thyroid cancers and thyroid damage due to radioactive iodine

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12
Q

Thyroid function can be adversely effected by:

A

industrial contamination, pollution and nuclear incidents

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13
Q

How are MIT and DIT degraded?

A

By halogenases

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14
Q

Why are MIT and DIT degraded by halogenases?

A

To free the iodide which is reutilised by combination with THYROGLOBULIN

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15
Q

If industrial contamination gets into the food chain it can:

A

influence peoples thyroid function

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16
Q

What happens to the T3 and T4 once they are synthesised?

A

They leave the follicular cells and enter the blood stream for distribution to target cells

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17
Q

What percentage of thyroid hormone leaving the thyroid gland is in the form of T4?

A

95%

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18
Q

Where does the majority of conversion from T4 to T3 happen?

A

In the target tissues

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19
Q

What is required to convert T4 into T3?

A

Deiodinase enzymes

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20
Q

What percentage of T4 is converted into T3?

A

80%

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21
Q

What percentage of T4 is converted into reverse-T3?

A

20%

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22
Q

What is T3’s biological activity in comparison to T4?

A

T3 has biological activity 40 times greater than that of T4

Reverse T3 is biologically inactive

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23
Q

What percentage of biologically active thyroid hormone within the cell is in the form of T3?

A

90%

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24
Q

What is the plasma half life of T4?

A

6-8 days

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25
What is the plasma half life of T3?
1 day
26
T3 is expensive to buy/prescribe because of pharma companies - what can you do instead?
Prescribe T4 - cheaper - the target tissues will convert it to T3 anyway
27
What is the control of thyroid hormone secretion?
The hypothalamus secretes thyrotrophin releasing hormone (TRH) TRH - stimulates secretion of TSH from the anterior pituitary gland This stimulates secretion of T3 of T4 by thyroid gland T3 and T4 causes negative feedback on TRH and TSH secretion
28
What percentage of T3 and T4 is protein bound?
99%
29
If you lose the negative feedback of T3 and T4 what happens?
Increased TSH secretion
30
What could be a consequence of iodine deficiency?
Increased TSH secretion and therefore the thyroid gland enlarges
31
What is the Derbyshire neck?
Goitre due to increased TSH
32
Are thyroid hormones soluble in water?
No
33
How do thyroid hormones travel in blood?
Bound to plasma proteins - over 99% of circulating thyroid hormones are bound to plasma proteins
34
What are the plasma proteins that T4 is bound to?
Thyronine binding globulin (TBG) - 75% Thyroxine-binding pre albumin (TBPA) - 15-20% Albumin - 5-10%
35
Where are the receptors for thyroid hormones?
Intracellular - specifically nuclear
36
What is the effect of the interaction of thyroid hormones with their receptors?
They influence gene transcription and thus protein synthesis
37
What is the main biological effect of thyroid hormones?
To increase basal metabolic rate
38
How do thyroid hormones increase basal metabolic rate?
By increasing carbohydrate metabolism Increased synthesis, mobilisation and degradation of lipids Increased protein synthesis
39
How are aspects of carbohydrate metabolism increased to increase basal metabolic rate?
Potentiating the effects of insulin Potentiating effects of catecholamines Increasing glucose absorption in the GI tract Glycogenolysis and glucose uptake by muscle cells and adipose cells
40
What effects does increased carb metabolism have?
Lose weight even when appetite is increased
41
Why does the appetite become increased?
Due to fat metabolism
42
Why is it not a good idea to take thyroid hormone to lose weight?
Excess T3 and T4 suppress TSH secretion Atrophy of thyroid gland So when you come off them - there is no thyroid hormone and become thyroid hormone deficient - feel the cold and gain weight Interferes with entire endocrine balance
43
Increased basal metabolic rate means that there is increased oxygen consumption in nearly every organ except:
``` Brain Uterus Testes Spleen Thyroid gland Anterior pituitary gland ```
44
Thyroid hormones are not essential for life but they are:
necessary for the normal development of the CNS - especially myelination of nerve fibres
45
What is the primary mechanism of increased basal metabolic rate?
An increase in the number and size of mitochondria and an increased activity of metabolically important enzymes
46
Thyroid hormones are essential for:
Normal growth and development
47
What does a lack of iodine translate to in puberty?
There is a great deal of change in puberty and pre-pubertal girls and boys will not undergo the change in puberty if they are iodine deficient and therefore thyroid hormone deficient
48
What happens to growth hormone deficient individuals?
They stay short by undergo normal raging
49
Thyroid hormone deficient individuals
stay short and looking like a child
50
What happens to iodine deficient tadpoles?
They grow into big tadpoles but don't change into frogs
51
What is levothyroxine used for?
To treat thyroid hormone deficiency | Suppress TSH secretion in the treatment of some thyroid tumours
52
How can levothyroxine be administered?
Orally or by injection
53
What is the oral bioavailability of levothyroxine?
100%
54
What percentage of levothyroxine is protein bound?
>99%
55
How is levothyroxine metabolised?
By the liver - glucuronidation
56
What is the half life of levothyroxine
Approximately 7 days
57
How is levothyroxine excreted?
20-40% excreted in urine
58
What is the standard maintenance dose of levothyroxine?
50-100micrograms/day
59
What are the adverse effects of levothyroxine?
Over active metabolism leading to: | palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss
60
Name the drugs affecting thyroid function:
Levothyroxine - treats thyroid deficiency Carbimazole and methimazole - inhibit synthesis of thyroid hormones Propylthiouracil - prevents peripheral conversion of T4 to T3 Potassium perchlorate - acts by competing with iodide for the active iodide uptake pump
61
What is way of treating hyperthyroidism?
Carbimazole - inhibits synthesis of thyroid hormones
62
What is an alternative to thyroidectomy to treat hyperthyroidism?
Use radioactive (I131) iodine - selectively concentrated in the thyroid gland where it causes tissue damage and therefore reduces thyroid hormone secretions
63
What is carbimazole?
It is used to treat hyperthyroidism
64
Carbimazole is a pro drug, what is the name of the active form and when/ how is it converted to the active form?
Carbimazole is converted to the active form methimazole after absorption Methimazole prevents peroxidase iodinating the tyrosine residues on thyroglobulin - hence reducing production of thyroid hormones T3 and T4
65
What is the oral bioavailability of carbimazole?
>90%
66
How much of carbimazole is protein bound?
85%
67
What is the standard dose of carbimazole?
5-15mg/ day
68
How is carbimazole metabolised?
Rapidly metabolised to methimazole
69
What is the half-life of carbimazole?
6.4 hours as methimazole
70
How is carbimazole excreted?
90% excreted in urine as metabolites
71
What are the adverse effects of carbimazole?
Rashes and pruritus are common - treatable with antihistamines Neutropenia and agranulocytosis (most serious rare side effect) --> teratogenic Neutropenia can be fatal - can't respond to minor infections which leads to sepsis
72
What is propylthiouracil (PTU)?
It is used to treat hyperthyroidism including Grave's disease
73
How does propylthiouracil work?
By inhibiting THYROPEROXIDASE which normally acts in thyroid hormone synthesis PTU also works by inhibiting tetra-iodothyronine deiodinase which converts T4 to T3
74
What is the drug of choice to treat hyperthyroidism in the first trimester of pregnancy?
Propylthiouracil
75
What is the oral bioavailability of propylthiouracil?
80-95%
76
What is the percentage of protein binding in propylthiouracil?
70%
77
How is propylthiouracil metabolised?
By hepatic glucoronidation
78
Half life of propylthiouracil?
2 hours
79
Excretion of propylthiouracil?
Renal
80
Standard dose of propylthiouracil?
50-100 mg/day
81
Adverse effects of propylthiouracil:
Rashes and pruritus - common and treatable with antihistamines Notable side effects = risk of agranulocytosis and risk of serious liver injury, including liver failure and death
82
Name the ways in which incidence of endemic goitre has been reduced worldwide
Prophylactic administration of iodine Either by injection OR Incorporation into table salt or flour
83
What is the risk of iodine administration?
Jod-Basedow phenomenon - precipitates hyperthyroidism
84
Name drugs that can induce goitre:
Lithium - used to treat bipolar depression - inhibits TH Iodides contained in some vitamin preparations and cough remedies - interfere with iodide incorporation and hormone release

Endocrinology (11 decks)

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