L07 - Thryroid Hormone Flashcards
Histology of the thyroid gland
Composed of follicles consisting of a monolayer of epithelial cells
these enclose a large core of viscous homogenous colloid
colloid acts as a reservoir
Synthesis and chemistry of thyroid hormones
what are the primary hormones secreted by thyroid
T3: tri-iodothyronine
T4, thyroxine: tetraiodothyronine
calcitonin
the map of how T3 and T4 are produced
iodine and tyrosine --> MIT --> DIT --> MIT+DIT or DIT+DIT --> T3 and T4 ---> T4 can convert to T3
What are MIT and DIT broken down by and why
What is the route T3 and T4 and travel through
what form is the thyroid hormone predominantly in leaving the gland?
MIT and DIT are rapidly degraded by halogenases to free the iodide,
which is then re-utilised by combination with thyroglobulin.
The T3 and T4 leave the follicular cells and enter the blood stream
for distribution to the target tissues.
Approximately 95% of the thyroid hormone leaving the thyroid gland
is in the form of T4 (thyroxine).
what happens to thyroid hormones within the tissues
what is the difference between T3, T4, reverse-T3
what is most of the active thyroid hormone present as
what is the half life T4
Within the target tissues deiodinase enzymes convert the T4 to either T 3 (80%)
or reverse-T3 (20%).
T 3 has a biological activity approximately 40 times greater than that of T4,
whilst reverse-T3 is biologically inactive.
Up to 90% of the biologically active thyroid hormone within the cell is in the
form of T 3.
The plasma half-life of T4 is 6 - 8 days whilst that of T3 is one day.
How are thyroid hormones transported in the blood
what is T4 bound to and what proportion
Thyroid hormones are insoluble in water, therefore transported in blood
bound to plasma proteins.
Over 99% of the circulating thyroid hormones are protein-bound,
the
majority (approximately 75%) of T4 binding is to thyronine-binding
globulin (TBG), with a further 15-20% being bound to thyroxine-binding
prealbumin (TBPA) and 5-10% being bound to albumin.
Receptors for thyroid hormones
what are they like
what is their effect once interaction with thyroid hormones
The receptors for the thyroid hormones are intracellular, more
specifically nuclear.
The effect of the interaction of the thyroid hormones with their
receptors is to influence gene transcription and thus protein synthesis;
BIOLOGICAL EFFECTS OF THYROID HORMONES
what is it involved with and what do they do
what are they essential for the development
The main effect of the thyroid hormones is to increase basal metabolic
rate:
increased in carbohydrate metabolism
increased in the synthesis, mobilisation and degradation of lipids
increased protein synthesis.
Thyroid hormones essential for the normal development of the CNS,
especially myelination of nerve fibres.
Thyroid hormones:
what is the primary mechanism – how does it perform it action
what type of metabolism is it involved with and what aspects does it effect?
Primary mechanism is an increase in the number and size of
mitochondria and an increased activity of metabolically important
enzymes.
All aspects of carbohydrate metabolism are increased:
–glycogenesis and glucose uptake by muscle cells and adipose cells
–potentiation of the effects of insulin
–potentiation of the effects of the catecholamines
—increase in glucose absorption by the gastrointestinal tract.
What organs do thyroid hormones not effect?
Thyroid hormones increase basal metabolic rate, and therefore oxygen
consumption, in nearly every organ except:
Brain Uterus Testes Spleen Thyroid gland Anterior pituitary gland
What hormones can have major effects on growth and development if not present?
Thyroid hormone and GH deficiency
LEVOTHYROXINE
what is it
what does it do
adverse effects
treats thyroid deficiency
suppress TSH secretion in treatment of some thyroid tumours
oral / IV
adverse: at XS doses - palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss
What are some antithyroid drugs
carbimazole and methimazole (inhibition of syn of thyroid hormones – by preventing incorporation of the iodine into the thyroglobulin
propylthiouricil (prevents peripheral of T4 –> T3)
potassium perchlorate —> competing with iodine for the active idodide pump
CARBIMAZOLE and METHIMAZOLE
how do they act
how does it work
adverse effects
inhibition of synthesis of thyroid hormones by preventing the iodide being incorporated into the thyroglobulin
CARBIMAZOLE
prodrug –> active form is methimazole –> prevents peroxidase iodinating the tyrosine residues on thyroglobulin –> this reduces the production of T3 and T4
Rashes and pruritus –> common, can be treated with antihistamines
Most serious side effect RARE –> neutropenia and agranulocytosis
teratogenic
PROPYLTHIOURACIL
how does it act
used when
drug of choice for what
adverse effects?
prevents the peripheral conversion of T4 to T3
hyperthyroidism — inhibits thyperoxidase (synthesis) and and tetraiodothyronine deiodinase (conversion)
drug of choice for use in 1st trimester
adverse - rashes and pruritus. also agronulocytosis and risk fo serious liver injury, including liver failure and death
