S11 Thyroid Gland Flashcards
Where is the thyroid gland?
- against and around front of larynx and trachea
- it is below the thyroid cartilage (Adam’s apple)
- isthmus extends from the 2nd to 3rd rings of the trachea
What is the structure of the thyroid gland?
- 2 lobes joined by isthmus
* “bow tie” shape and location
How does the thyroid develop in the embryo?
- At 3-4 weeks gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue
- Descends as diverticulitis through thyroglossal duct and migrates in front of hyoid bone
- During migration, remains connected to the tongue by the thyroglossal duct, which then degenerates
- Continues to final position once detached over 2 weeks
What does thyroid tissue look like under a microscope?
- follicular cells arranges in spheres called thyroid follicles
- the follicles are filled with colloid
What is colloid?
A deposit of thyroglobulin
Colloid is extracellular even though it’s inside the follicle
What do the thyroid follicular cells produce?
Thyroid hormone (uses thyroglobulin protein to help synthesis)
What do the thyroid parafollicular cells produce?
Calcitonin
What are thyroid hormones made up from?
2 tyrosines linked with iodine at 3/4 positions on the aromatic ring (can have 2 iodines)
Where do the tyrosine residues come from for making thyroid hormone?
Thyroglobulin protein (contains 134 tyrosines, but only a few are used to produce thyroid hormone
How do you make T3 (triiodiothyronine) hormone?
And T4 (tetraidodothyronine/thyroxine) hormone?
Monoiodotyrosine (MIT) + Diiodotyrosine (DIT)
DIT + DIT
What is thyroid peroxidase?
A membrane bound enzyme that regulates 3 separate reactions involving iodide
- Oxidation of iodide to iodine (needs hydrogen peroxide)
- Addition of iodine to tyrosine acceptor residues on protein thyroglobulin
- Coupling to MIT/DIT to generate thyroid hormones in thyroglobulin protein
Where is dietary iodine reduced to iodine?
Before absorption in the small intestine
What are the only molecules in the body that contain iodine?
Thyroid hormones and precursors
How is iodide taken up from the blood into thyroid glands?
By thyroid epithelial cells that have sodium iodide symporter or ‘iodine trap’
What are common sources of iodine?
- dairy products
- grains
- meat
- veg
- eggs
- iodised salt
What are the steps in thyroid hormone synthesis?
- Iodine enter thyroid follicle cells via ‘iodine trap’
- Iodine then moves into colloid where iodination occurs
- Coupling of MIT and DIT occurs
- The coupled MIT and DIT moves by pinocytosis into thyroid follicle cells attached to thyroglobulin
- Lysosome engulfs thyroglobulin forming a phagolysosome
- Enzymes in the lysosome break down the thyroglobulin, releasing the T3 and T4 hormones into the plasma
- Any MIT and DIT that didn’t couple is deiodinased and the iodine is recycled
Which hormone, T3 or T4 is mostly secreted? Which is it then converted into and where?
T4, however T4 is the less biologically active form
So most T4 is converted to T3 in the liver and kidneys
How are T3 and T4 transported in the blood? Why do they need to unbind?
Bound to protein thyroxine-binding globulin
To become biologically active
How is thyroid hormone secretion regulated?
By negative feedback
What is the negative feedback cycle for thyroid hormone secretion?
- Hypothalamus released TRH
- TRH stimulates anterior pituitary to release TSH
- TSH stimulates thyroid gland to produce thyroid hormone but also acts inhibiting the hypothalamus from releasing TRH
- Thyroid hormone acts on target tissues but also inhibits anterior pituitary from releasing TSH and the hypothalamus from releasing TRH
What effect does thyroid hormone have in the body?
It effects most cells and has two interconnected responses
- Effects cellular differentiation and development
- Effects metabolism
What is the structure of thyroid stimulating hormone (TSH)? What other hormones is it closer related to?
- glycoprotein hormone is composed of 2 non-covalently bound subunits (alpha and beta)
- the alpha subunit is the same subunit as in FSH and LH
- the beta subunit provides its unique biological activity
How does TSH trigger thyroid hormone release?
Binds to the TSH receptor (GPCR) on thyroid follicular cell membranes which activates T3 and T3 to be released
What type of GPCR is the TSH receptor?
Normally Gs but can also be Gq if there are higher concentrations of TSH
What does TSH stimulate?
- iodide uptake
- iodide oxidation
- thyroglobulin synthesis
- thyroglobulin iodination
- colloid pinocytosis into follicular cells
- proteolysis of thyroglobulin
- cell metabolism and growth
What is the second messenger pathway that TSH induces by binding to Gs receptor? And for Gq receptor?
- Adenylyl cyclase activated
- Which activates cAMP (from ATP)
- Which activates PKA
- Phosolipase C activates
- Which activates DAG and IP3 (from PIP2)
- Which activates Ca2+ release via the IP3 receptor and PKC activation
Both stimulate thyroid hormone synthesis and release
How does thyroid hormone increase the basal metabolic rate and heat production?
- increases the number and size of mitochondria
* stimulates the synthesis of enzymes in the respiratory chain
Which tissues don’t respond to thyroid hormone increasing the basal metabolic rate and heart production?
- brain
- spleen
- testis
How does thyroid hormone stimulate metabolic pathways?
- lipid metabolism - lipolysis and beta-oxidation of fatty acids
- carbohydrate metabolism - stimulates insulin-dependent entry of glucose into cells, gluconeogenesis and glycogenolysis
What are the sympathomimetics effects of thyroid hormone?
It increases target cell response to catecholamines by increasing receptor number on target cells
What effect does thyroid hormone have on the cardiovascular system?
Increase the heart’s responsiveness to catecholamines
- increases CO (increases HR and contractility)
- increases peripheral vasodilation to carry extra heat to body’s surface
What effect does thyroid hormone have on the nervous system?
Essential for both development and adult function
* increases myelination of nerves and development of neurones
What is cretinism?
Hypothyroidism in childhood - lack of development of nervous system
What type of receptor are thyroid hormone receptors? How does it work?
Nuclear receptor - modulate gene expression
When unbound to thyroid hormone, the receptor binds to DNA and usually results in transcriptional repression
When bound to hormone, a conformational change occurs in the receptor allowing it to function as a transcriptional activator
What are 5 examples of thyroid hormone activated genes?
- PEPCK (gluconeogenesis)
- Ca2+ ATPase
- Na+, K+ ATPase
- cytochrome oxidase (ETC)
- 6-phosogluconate dehydrogenase (pentose-phosphate pathway)
What is goitre?
Enlargement of the thyroid gland
Can be part of hypo- or hyper-thyroidism
Develops when thyroid gland is overstimulated
What can cause hypothyroidism?
- failure of gland
- TSH or TRH deficiency
- inadequate dietary iodine
- radioactive iodine
- autoimmunity
- post-surgery
- congenital
- anti-thyroid drugs
What are general symptoms and signs of hypothyroidism?
- obesity
- lethargy
- intolerance to cold
- bradycardia
- dry skin
- alopecia
- hoarse voice
- constipation
- slow reflexes
- low T3 and T4
- elevated TSH
What are two types of hypothyroidism found in adults and infants?
Infants - cretinism - dwarfed stature, mental deficiency, slow pulse, poor bone development, muscle weakness, GI disturbances
Adults - myxedema - thick puffy skin, muscle weakness, slow speech, mental deterioration, intolerance to cold
What is hashimoto’s disease?
Most common type of hypothyroidism
An autoimmune disease leading to destruction of thyroid follicles
More common in women
May have goitre, may not
Low T3 and T4, high TSH
How do you treat hashimoto’s disease?
Oral thyroid hormone - use T4 as it has a longer half life
What are some causes of hyperthyroidism?
- autoimmune (Grave’s disease)
- toxic multinodular goitre
- solitary toxic adenoma
- excessive T4/T3 therapy
- drugs e.g. amiodarone
- ectopic thyroid tissue
What are general symptoms of hyperthyroidism?
- weight loss
- irritability
- heat intolerance
- tachycardia
- fatigue and weakness
- increased bowel movements
- hyper-reflexive
- breathlessness
- loss of libido
- sweating and tremor
some also have goitre or bulging eyes
What is Graves’ disease?
An autoimmune disease resulting in hyperthyroidism
Caused by the production of thyroid stimulating immunoglobulin (TSI)
TSI continuously stimulates thyroid hormone secretions outside the normal negative feedback control
What is thyroid scintigraphy?
Using a radioisotope (Technetium-99m) to scan the thyroid with a gamma camera
Use this radioisotope as it has a short half life (less than a day) so low radiation exposure
What is a common antithyroid drug?
Carbimazole - a prodrug that is converted into methimazole in the body, it prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin
Used to treat hyperthyroidism
