Session7-Thyroid Gland Flashcards
Describe the location of the thyroid gland
- lies against and around front larynx and trachea
- below thyroid cartilage
- isthmus extends from 2nd to 3rd rings of trachea
What joins the two lobes of the thyroid gland?
Isthmus
True or false: thyroid gland is the first endocrine gland to develop
TRUE
How does the thyroid gland appear at 3-4 weeks of gestation?
As an epithelial proliferation in the floor of the pharynx at the base of the tongue
Complete the sentences:
The thyroid gland first descends as a ________________ through the ____________ duct and migrates downwards, passing in front of the hyoid bone. During migration, the gland remains connected to the tongue by the _____________ duct which subsequently ________________.
Diverticulum
Thyroglossal
Thyroglossal
Degenerates
What are thyroid follicles?
Follicular cells arranged in spheres
What are thyroid follicles filled with?
Colloid
What is colloid?
Deposit of thyroglobulin and is extracellular even though it is inside the follicle
What do thyroid follicular cells produce?
Thyroid hormone
What do thyroid parafollicular cells produce?
Calcitonin
What do parathyroid cells/chief cells produce?
Parathyroid hormone
What are the two thyroid hormones?
T3 = triiodothyronine T4 = tetraiodothyronine (thyroxine)
What forms thyroid hormone T3?
Monoiodotyrosine (MIT) + diiodotyrosine (DIT)
What forms thyroid hormone T4?
Diiodotyrosine (DIT) + diiodotyrosine (DIT)
How does thyroglobulin play a role in thyroid hormone formation?
Acts as a scaffold on which hormones are formed
Which three reactions does thyroid peroxidase regulate?
1) oxidation of iodide to iodine
2) iodination of tyrosine acceptor residues on thyroglobulin
3) coupling of MIT or DIT to generate thyroid hormones within thyroglobulin protein
What does the oxidation of iodide to iodine require?
Hydrogen peroxide
How is iodide taken up from the blood?
By thyroid epithelial cells which have a sodium-iodide symporter or “iodine trap”
What are some common sources of iodine?
- dairy products
- grains
- meat
- vegetables
- eggs
True or false: most T3 is converted to T4 outside the thyroid
FALSE - T4 converted to T3
Where is most T4 converted to T3?
In liver and kidneys
How are T3 and T4 transported in the blood?
Bound to protein thyroxine-binding globulin
Why do T3 and T4 need a protein in order to be transported in the blood?
They are lipid soluble
Complete the flow chart:
Hypothalamus -> ___________ _____________ hormone -> anterior pituitary -> ___________ ________________ hormone -> thyroid gland -> ____________ hormone -> target tissues
Thyrotropin releasing (TRH) Thyroid stimulating (TSH) Thyroid
What are the two interconnected responses of thyroid hormones in the body?
- effects on cellular differentiation and development
- effects on metabolic pathways
What type of hormone is thyroid stimulating hormone (TSH) and what is it composed of?
Glycoprotein hormone
Composed of 2 non-covalently bound subunits (alpha and beta)
Which subunit in TSH provides unique biological activity?
Beta
True or false: TSH is the trigger for thyroid hormone release
TRUE
What does TSH stimulate?
- iodide uptake
- iodide oxidation
- thyroglobulin synthesis
- thyroglobulin iodination
- colloid pinocytosis into cell
- proteolysis of thyroglobulin
- cell metabolism and growth
What type of receptor is TSH receptor?
GPCR
What are the general actions of thyroid hormone?
- increase in basal metabolic rate and heat production
- stimulation of metabolic pathways
- sympathomimetic effects
How do thyroid hormones stimulate metabolic rate?
- by increasing number and size of mitochondria
- by stimulating the synthesis of enzymes in the respiratory chain
Which metabolic pathway is stimulated more by thyroid hormone?
Catabolic
Which metabolic pathways do thyroid hormones stimulate?
- lipid metabolism: stimulates lipolysis and beta oxidation of fatty acids
- carbohydrate metabolism: stimulate insulin-dependent entry of glucose into cells and increase gluconeogenesis and glycogenolysis
How do thyroid hormones increase target cell response to catecholamines?
By increasing receptor number on target cells
What effect do thyroid hormones have on the cardiovascular system?
Increases heart’s responsiveness to catecholamines:
- increases cardiac output (increase chronotropy and inotropy)
- increased peripheral vasodilation to carry extra heat to body surface
What effect do thyroid hormones have on the nervous system?
Increased myelination of nerves and development of neurones
How do thyroid hormone receptors act as hormone-activated transcription factors?
By modulating gene expression - bind DNA in absence of hormone, leading to transcriptional repression
Where is the thyroid hormone receptor pre-bound to specific DNA sequences?
On DNA called hormone response elements (HRE) in the promoter region of thyroid hormone regulated genes
What is the normal level of plasma T4?
10-25 pM
What is the normal level of plasma T3?
3-8 pM
What is goitre?
Enlargement of thyroid gland
True or false: goitre accompanies hyperthyroidism only
FALSE - hyper or hypothyroidism
What are the causes of hypothyroidism?
1) failure of thyroid gland
2) TSH or TRH deficiency
3) inadequate iodine in diet
4) radioactive iodine
5) autoimmunity
6) post surgery
7) congenital
8) anti-thyroid drugs
What are the symptoms of hypothyroidism?
- obesity
- lethargy
- intolerance to cold
- bradycardia
- dry skin
- alopecia
- hoarse voice
- constipation
- slow reflexes
Describe the levels of: 1) T3 2) T4 3) TSH In hypothyroidism
1) low
2) low
3) elevated
What can hypothyroidism cause in infants?
Cretinism - dwarfed stature, mental deficiency, poor bone development, slow pulse, muscle weakness, GI disturbances
What can hypothyroidism cause in adults?
Myxedema - thick puffy skin, muscle weakness, slow speech, mental deterioration, intolerance to cold
What is Hashimoto’s disease?
Autoimmune disease resulting in destruction of thyroid follicles -> hypothyroidism
How can Hashimoto’s disease be treated?
-oral thyroid hormone: T4 usually used since longer half-life
What are the causes of hyperthyroidism?
- autoimmune Graves’ disease
- toxic multinodular goitre
- excessive T4 or T3 therapy
- drugs
- carcinoma
What are some symptoms of hyperthyroidism?
- weight loss
- irritability
- heat intolerance, sweaty hands
- tachycardia
- fatigue
- increased bowel movements
- possible tremor
- hyper-reflexive
- breathless
- loss of libido
What is Graves’ disease?
Autoimmune disease resulting in hyperthyroidism, caused by production of thyroid stimulating immunoglobulin (TSI)
What does thyroid stimulating immunoglobulin (TSI) do?
Continuously stimulates thyroid hormone secretion outside normal negative feedback control
Describe the levels of: 1) T3 2) T4 3) TSH In Graves' disease
1) elevated
2) elevated
3) low
Which radioisotope is used for isotope scanning of the thyroid with a gamma camera?
Technetium-99m
What are antithyroid drugs used to treat?
Overactive thyroid eg Graves’ disease
How do antithyroid drugs work?
Block formation of thyroid hormone
What is the most commonly used antithyroid drug in the UK?
Carbimazole
What is carbimazole and how does it work?
Pro-drug and is converted to methimazole in the body
Prevents thyroid peroxidase from coupling and iodination get tyrosines on thyroglobulin
What is a pro-drug?
Drugs converted to something else in the body which has activity in the body
Why does carbimazole have a delayed effect?
Because there is a store of thyroglobulin which takes 2-4 weeks to diminish
