MNSR 42 - Thyroid Structure Hormones and Diseases Flashcards
describe where you can find thyroid gland
• Attached to the larynx
–Downgrowth from the floor of the pharynx
average weight of thyroid gland in adults
25 grams
describe the thyroid gland
highly vascularised - greater blood supply than kidney
Bi-lobed structure w/ one lobe on either side of the trachea (butterfly shaped)
what do thyroid glands consist of
follicles
what does each follicle consist of?
fluid filled space w/ jelly like substance from glycoprotein - thyroglobulin = colloid
surrounded by follicular cells
what does colloid consist of
thyroglobulin, - a precursor protein to the thyroid hormones
describe follicular cells
highly vascularized connective tissue with lightly stained follicular
cells
what holds follicular cells together
Held together by stroma - connective tissue supporting the follicles
thyroid gland regulation
Hypothalamus releases TRH Stimulates release of TSH from anterior pituitary Promotes release of thyroid hormones tri-iodothyronine (T3) and thyronine (T4)
effects of tri-iodothyronine (T3) and thyronine (T4) when released in the body
positive effects on target organs
negative feedback effects on
hypothalamus and pituitary
what substance is essential for production of thyroid hormones
iodine
what feature is found outside membrane of follicular cells
iodine pump
what controls iodine uptake
Uptake of iodine partially under the control of the pituitary hormone TSH
how much iodine needs to be ingested in the body daily?
How much iodine does iodine store
150µg/day is sufficient, the thyroid is very economical in its use and
recycles much iodine
• The thyroid stores about 4,000µg of iodine in a variety of forms
what does TSH stimulate
TSH stimulates follicular cells to increase uptake of iodide from the
bloodstream. Follicular cells then pump the iodide into the follicular
spaces
how is iodide oxidised
• Iodide (I- ) is oxidised by the thyroid peroxidase (TPO) enzyme to form
iodine (I2 )
production of tri-iodothyronine and thyroxine
- endoplasmic reticulum and golgi complex of the thyroid follicular cells produce tyrosine containing thyroglobulin(Tg) - this is transported by exocytosis to the colloid
- Iodide in the blood is sent into colloid symporters using active transporters (Na+ and I- enter the colloid)
- Iodide is oxidised by active form by thyroperoxidase (TPO) in luminal membrane and exits through luminal channel to center colloid.
- Active iodide attach to tyrosine within thyroglobulin catalysed by TPO to make monoiodotyrosine(MIT)
- When 2 iodides attach to tyrosine makes Di-iodotyrosine (DIT)
- 1 MIT + 1 DIT = Trio-iodothyronine
1DIT + 1DIT = thyroxine - thyroid follicular cells engulfed portion of thyrglobunlin (Tg) containing colloid by phagocytosis
- Lysosomes attack englufed vesicle and splite the iodine products
- T3 and 4 diffuse into blood
- MIT and DIT deiodinated and free iodide is recycled
Thyroglobulin (Tg)
Precursor to thyroid hormones
• Produced within the follicular cells
• Forms a homodimer (two Tg molecules bound together)
• Each thyroglobulin molecule contains 140 tyrosine amino acids
why does T4 thyroxine form more readily
Peroxidase is much more efficient at combining two DIT residues and thus generation of T4 occurs much more readily
1DIT + 1DIT = thyroxine/T4
The thyroid gland primarily
produces T4 rather than T3.
what must be stimulated for thyroglobulin to be moved back into follicle cells
Thyroglobulin remains within the colloid until TSH stimulates endocytosis of colloid back into the follicle cells
how can T3 and T4 be released into blood stream
A protease cleaves off T3 and T4, and the hormones can now be released into the bloodstream
which thyroid hormone is more potent
T3
half life of thyroxine/T4
6 days
half life of T3
1.3 days
what happens to thyroid hormone when it enters the cells
most of the thyroxine is de-iodinated to T3, (80%),
or reverse T3 (20%) which is
biologically inactive
thyroid hormone ratio released into blood stream
Hormones released into the bloodstream in a 10:1 ratio: 90% Thyroxine (T4) 10% Tri-iodothyronine (T3)
what proteins do T3 and T4 bind to
serum protein
globulin and albumin - becomes inactive and serve as reservoir
only free T4 and T3 can enter target cells
what type of proteins have a higher affinity for T3 and T4
carrier proteins
the proportion of T3 in the plasma in an unbound (or “free”) state is
about ten times greater than the amount of free T4.
how many micro grams of T3 and T4 are delivered to tissue each day and explain
in circulation some of the thyroxine (T4) is de-iodinated to T3, so the
final tissue delivery is about 90 µgrams/day of thyroxine, to 40-60
µgrams/day of T3
effects of thyroid hormone in the body
. Increase Basal metabolic rate
- Promote growth and maturation
- Specific physiological effects
effects of thyroid hormone on metabolic rate
increase metabolic rate
what specifically in metabolism does thyroid hormone effect
• Increased O2 consumption
• Increase in protein synthesis:
RNA synthesis increases leading to greater production of ribosomes and mRNA
The levels of metabolically important enzymes increase
Mitochondria increase in numbers resulting in greater
ATP levels
how does thyroid impact growth and maturation in children
have a synergistic effect
with IGF-1 (insulin-like growth factor) on the growth of bone
how can low levels of thyroid hormone affect children
– Low levels of hormone cause poor growth and retarded sexual
development at puberty
how can high levels of thyroid hormone affect children
Paradoxically high levels in a young person will cause rapid
precocious growth at first, but this will stop at a younger age
because of early closure of the epiphyses
physiological effect of thyroid hormone
Stimulates carbohydrate and fat metabolism - higher levels of lipids in the liver and higher blood cardiac output to keep pace with the raised metabolic
rate resulting in increased systolic pulse pressure
• Increased IT secretion and motility -> diarrhoea
• CNS effects include nervousness, irritability and muscle tremor –> tiredness and inability to sleep
hypothyroidism
This is the state where the thyroid is underactive and producing insufficient levels of
hormone
– This will affect children and adults differently
– Often caused by low iodine in the diet
symptoms of hypothyroidism in children
if left untreated it leads to Cretinism
– Poor growth, dwarf stature, mental
retardation, general adult effects.
decreased thyroid activity before and after birth can risk what
risks severe mental retardation due to the failure of development of the CNS
prevalance of hypothyroidism
1: 4,000 births
give another name for hypothyroidism as an adult
Myxedema
symptoms of myxedema
Thickened dry skin • Hair loss Decreased mental ability Goitre muscle stiffness
treatment of hypothyroidism
Primary:
• Thyroid hormone
– Secondary:
• Alleviate symptoms
prevalence of hypothyroidism in adults
0.01 - 0.08% population
– 80% of sufferers are female, commonly between 30 to 60 years
causes of hypothyroidism in adults
Iodine deficiency
• Hashimoto’s thyroiditis
– Autoimmune
• Antibodies to thyroid peroxidase and/or thyroglobulin
• Self-destruction of cells of the thyroid
• Yo-Yo dieting
• Overactive adrenal gland
hyperthyroidism
Thyroid hormone levels may be 5 to 15 times higher than normal values
symptoms of hyperthyroidism
Hypertension, raised body temperature,
weight loss, hyperactivity, goitre.
– May be accompanied by a protrusion of
the eyeballs called exophthalmos
major causes of hyperthyroidism
Results from an overactive thyroid
– Graves’ Disease (70-80% etiology)
– Toxic multi-nodular goitre (enlarged and contains multiple thyroid nodules)
– Toxic thyroid adenoma (hyper-functioning follicle due to adenoma)
prevalence of graves disease
1.0% population
– Found more frequently in
women
– Female:male ratio 10:1
causes of grave’s disease
– Autoantibodies to TSH
receptors on the thyroid gland
– Antibodies stimulate receptor - interfere with stimulation of thyroid gland by TSH - only stimulated by Thyroid stimulating immunoglobulin
– Increase secretion of T3 and T4
goitre
Enlargement of the thyroid gland
when can goitre occur
Hypothyroidism
Hyperthyrooidism
Normal Thyroid
describe the condition exopthalmos
Bulging of the eye anteriorly out of the orbit
Retro-orbital oedema and fat deposition
what is exopthalmos a symptom of
symptom of grave’s disease not hyperthyroidism
how to diagnose hyperthyroidism
Blood tests Measuring the level of TSH in the blood Measuring specific antibodies Anti-TSH-receptor antibodies Iodine 123 uptake
treatment of hyperthyroidism - radioiodine
Radioiodine (131 I) treatment
Thyroid’s natural ability to concentrate iodine
131I decays to 131Xe
Releases radioactive β-particles which kill colloid tissue
treatment of hyperthyroidism surgery
Partial or full thyroidectomy
treatment of - thyrostatics
Pharmacological agents
Prevent generation of iodinated thyroglobulin
Prevent release of T3 and T4
