Lec7 Thyroid hormone Physiology Flashcards
Anatomy of the thyroid Synthesis and actions of the thyroid hormones Drugs affecting thyroid gland function
Are the thyroid gland and its secretions essential for life?
No but they are essential for normal development and for physical and mental wellbeing of the individual
What is the thyroid gland composed of?
Follicles each consisting of a monolayer of epithelial cells enclosing a large core of viscous, homogeneous colloid
What is the function of the colloid?
It acts as a reservoir of thyroid hormone
What are the primary hormones secreted by the thyroid gland
T3 - triiodothyronine
T4 - thyroxine
Calcitonin –> concerned with calcium homeostasis and is secreted independently of the thyroid hormones
What makes T3 and T4 and where do they come from?
Tyrosine - from avocado & nuts
Iodine comes from meat
How are T3 and T4 made?
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)
What formations are biologically active?
3-monoiodotyrosine (MIT)
3,5-diiodotyrosine (DIT)
3,5,3’-triiodothyronine (T3)
3,5,3’,5’-tetraiodothyronine (T4)
Is reverse triiodothyronine biologically active?
No
Women who have iron deficiency can lead to what?
Dysfunction of the thyroid gland
How could indices of the thyroid hormone be improved?
By improving the iron status
Nuclear incidents can result in:
an increase of thyroid cancers and thyroid damage due to radioactive iodine
Thyroid function can be adversely effected by:
industrial contamination, pollution and nuclear incidents
How are MIT and DIT degraded?
By halogenases
Why are MIT and DIT degraded by halogenases?
To free the iodide which is reutilised by combination with THYROGLOBULIN
If industrial contamination gets into the food chain it can:
influence peoples thyroid function
What happens to the T3 and T4 once they are synthesised?
They leave the follicular cells and enter the blood stream for distribution to target cells
What percentage of thyroid hormone leaving the thyroid gland is in the form of T4?
95%
Where does the majority of conversion from T4 to T3 happen?
In the target tissues
What is required to convert T4 into T3?
Deiodinase enzymes
What percentage of T4 is converted into T3?
80%
What percentage of T4 is converted into reverse-T3?
20%
What is T3’s biological activity in comparison to T4?
T3 has biological activity 40 times greater than that of T4
Reverse T3 is biologically inactive
What percentage of biologically active thyroid hormone within the cell is in the form of T3?
90%
What is the plasma half life of T4?
6-8 days
What is the plasma half life of T3?
1 day
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
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
What percentage of T3 and T4 is protein bound?
99%
If you lose the negative feedback of T3 and T4 what happens?
Increased TSH secretion
What could be a consequence of iodine deficiency?
Increased TSH secretion and therefore the thyroid gland enlarges
What is the Derbyshire neck?
Goitre due to increased TSH
Are thyroid hormones soluble in water?
No
How do thyroid hormones travel in blood?
Bound to plasma proteins - over 99% of circulating thyroid hormones are bound to plasma proteins
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%
Where are the receptors for thyroid hormones?
Intracellular - specifically nuclear
What is the effect of the interaction of thyroid hormones with their receptors?
They influence gene transcription and thus protein synthesis
What is the main biological effect of thyroid hormones?
To increase basal metabolic rate
How do thyroid hormones increase basal metabolic rate?
By increasing carbohydrate metabolism
Increased synthesis, mobilisation and degradation of lipids
Increased protein synthesis
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
What effects does increased carb metabolism have?
Lose weight even when appetite is increased
Why does the appetite become increased?
Due to fat metabolism
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
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
Thyroid hormones are not essential for life but they are:
necessary for the normal development of the CNS - especially myelination of nerve fibres
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
Thyroid hormones are essential for:
Normal growth and development
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
What happens to growth hormone deficient individuals?
They stay short by undergo normal raging
Thyroid hormone deficient individuals
stay short and looking like a child
What happens to iodine deficient tadpoles?
They grow into big tadpoles but don’t change into frogs
What is levothyroxine used for?
To treat thyroid hormone deficiency
Suppress TSH secretion in the treatment of some thyroid tumours
How can levothyroxine be administered?
Orally or by injection
What is the oral bioavailability of levothyroxine?
100%
What percentage of levothyroxine is protein bound?
> 99%
How is levothyroxine metabolised?
By the liver - glucuronidation
What is the half life of levothyroxine
Approximately 7 days
How is levothyroxine excreted?
20-40% excreted in urine
What is the standard maintenance dose of levothyroxine?
50-100micrograms/day
What are the adverse effects of levothyroxine?
Over active metabolism leading to:
palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss
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
What is way of treating hyperthyroidism?
Carbimazole - inhibits synthesis of thyroid hormones
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
What is carbimazole?
It is used to treat hyperthyroidism
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
What is the oral bioavailability of carbimazole?
> 90%
How much of carbimazole is protein bound?
85%
What is the standard dose of carbimazole?
5-15mg/ day
How is carbimazole metabolised?
Rapidly metabolised to methimazole
What is the half-life of carbimazole?
6.4 hours as methimazole
How is carbimazole excreted?
90% excreted in urine as metabolites
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
What is propylthiouracil (PTU)?
It is used to treat hyperthyroidism including Grave’s disease
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
What is the drug of choice to treat hyperthyroidism in the first trimester of pregnancy?
Propylthiouracil
What is the oral bioavailability of propylthiouracil?
80-95%
What is the percentage of protein binding in propylthiouracil?
70%
How is propylthiouracil metabolised?
By hepatic glucoronidation
Half life of propylthiouracil?
2 hours
Excretion of propylthiouracil?
Renal
Standard dose of propylthiouracil?
50-100 mg/day
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
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
What is the risk of iodine administration?
Jod-Basedow phenomenon - precipitates hyperthyroidism
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
