The Thyroid Gland Flashcards
Describe the shape and position of the thyroid gland
•2 lobes joined by isthmus •“Bow tie” shape and location
•Parathyroid and thyroid are distinct glands
• Lies against and around front larynx
and trachea
• Below thyroid cartilage (Adam’s apple)
• Isthmus joins lobes and extends from 2nd to 3rd rings of the trachea
Describe the embryological development og the thyroid gland
• Thyroid is first endocrine gland to develop.
• At ~3-4 weeks gestation, thyroid gland appears as an epithelial proliferation
in floor of pharynx at base of the
tongue and the takes several weeks to
migrate to final position.
• First descends as diverticulum through thyroglossal duct and migrates
downwards passing in front of hyoid
bone.
• During migration remains connected to tongue by thyroglossal duct which
subsequently degenerates
• Detached thyroid then continues to its final position over following two weeks.
Cysts can form higher up it if it doesn’t mover properly
Describe the histology of thyroid tissue
• Follicular cells arranged
in spheres called thyroid
follicles
• Follicles filled with colloid, a deposit of thyroglobulin
• Colloid is “extracellular” even though it is inside the follicle
What are the cells of the thyroid and parathyroid ad what do they produce
Thyroid follicular cells produce thyroid hormone
Thyroid parafollicular cells produce calcitonin.
Parathyroid principal cells also called chief cells produce Parathyroid hormone
Colloid stores thyroglobulin
Parathyroid principal cells also called chief cells produce Parathyroid hormone
Describe. Teh structure of thyroid hormones
2 tyrosines linked together with iodine at three or four positions on the aromatic rings
In the colloid tyrosines are iodinated
Eg monoiodotyrosine (1 iodine)
Diiodotyrosine (2 indies added)
These 2 added to make
Triiodothyronine
DIT+DIT = T4 = Tetraiodothryonine (thyroxine)
What is thyroglobulin
Thryoglobulin acts as a scaffold on which thyroid hormones are formed
Thyroglobulin protein contains 134 tyrosines, although only a handful of these are actually used to synthesize T4 and T3.
What is thyroid peroxidase
Membrane bound enzyme that regulates 3 separate reactions involving iodide
1) Oxidation of Iodide to Iodine so they can be added to tyrosine (requires the presence of H2O2)
2) Addition of Iodine to tyrosine acceptor residues on the protein throglobulin
3) Coupling of MIT or DIT to generate thyroid hormones within the thyroglobulin protein
How is iodine absorbers
- Dietary iodine reduced to iodide before absorption principally in the small intestine.
- Thyroid hormones and precursors are the only molecules in the human body that contain iodine
- Thyroid gland contains 90-95% of iodine in body
- Iodide (I-), is taken up from blood by thyroid epithelial cells, which have a sodium- iodide symporter or “iodine trap” - balanced by Na+/K+ ATPase
What are common sources of dietary iodine
Dairy products, grains, meat, vegetables, eggs, iodised salt
Give an overview of thyroid hormone synthesis
See slide
What are differences between T3 and 4
Most T4 is converted to T3 outside thyroid
• 90% of thyroid hormone secreted is T4
• Biological activity of T3 is 4 times that of T4
• Most T4 is converted to T3 in liver and kidney
• 80% of circulating T3 is derived from T4
T3 and 4 are transported in blood bound to the
&T protein thyroxine-binding globulin
What cells to thyroid hormones affect
Thyroid hormones effect virtually every cell in the body and have two interconnected responses:
•Effects on cellular differentiation and
development
•Effects on metabolic pathways
Describe the negative feedback loops of thyroidd hormone
Slide
Describe the composition of TSH
• Glycoprotein hormone (carbohydrate groups linked by Glycosylation) composed of 2 non-
covalently bound subunits ( α and β).
• The α subunit is also present in FSH and LH.
• β subunit provides unique biological activity.
What type of receptor does TSH bind to and what are teh pathways this activates
GPCR • Iodide uptake • Iodide oxidation • Thyroglobulin synthesis • Thyroglobulin iodination • Colloid pinocytosis into cell • Proteolysis of thyroglobulin • Cell metabolism & Growth
Describe the TSH induced second messenger pathways
See slide
What are the general actions of thyroid hormone
Increase in Basal metabolic rate and heat production
In most tissues (exceptions include brain, spleen and testis), thyroid hormones stimulate the metabolic rate by:
• Increasing the number and size of mitochondria
• Stimulating the synthesis of enzymes in the respiratory chain
Stimulation of metabolic pathways
Catabolic pathways are generally stimulated more than anabolic.
• Lipid metabolism: Stimulates lipolysis and β-oxidation of fatty acids
Promoted glut4 to membrane - promoting entry of glucose
• Carbohydrate metabolism: Stimulate insulin-dependent entry of glucose
into cells and increase gluconeogenesis and glycogenolysis
Sympathomimetic effects
Increases target cell response to catecholamines by increasing receptor number on target cells
What are the tissue specific effects of thyroid hormone
Cardiovascular system:
Increases heart’s responsiveness to catecholamines
Increase cardiac output
(Increase in heart rate and increase in force of contraction)
Increase Peripheral vasodilation to carry extra heat to body surface
Nervous system:
Essential for both development and adult function
Increase Myelination of nerves & development of neurons.
Cretinism results from a lac of thyroid hormone
Describe thyroid hormone receptors
• Members of the large family of nuclear receptors
Generally act by turning genes on
• Function as hormone-activated transcription factors
• Act by modulating gene expression
• Thyroid hormone receptors bind DNA in the absence of hormone, usually leading to transcriptional repression.
• Hormone binding is associated with a conformational change in the receptor that causes it to function as a transcriptional activator.
Explain the action of thyroid hormone on its receptor
Thyroid hormone is Lipid soluble and enters cell through thyroid hormone transporters
Thyroid hormone receptor is pre- bound to specific DNA sequences on DNA called a hormone response elements (HRE) (TRE= thyroid hormone HRE) in promoter region of thyroid hormone regulated genes
Thyroid hormone enters nucleus and binds to thyroid hormone receptor on DNA. Changing conformation of receptor. Binding relieves repression of gene transcription and the gene is now expressed
Expression of new protein mediates the effects of thyroid hormone
New protein
Give examples of thyroid hormone activated genes
Examples of thyroid hormone activated genes: • Phosphoenolpyruvate carboxy kinase (PEPCK) • Ca2+ ATPase • Na+, K+ ATPase • Cytochrome oxidase • 6-phosphogluconate dehydrogenase
Wha are the normal plasma levels fo thyroid hormoend
Free T4 - 10-25 pM
Free T3 - 3-8 pM
TSH - 1-15pM
(Dont need to know actual numbers but know it’s in the pM range)
What is goitre
Enlargement of the thyroid gland
• May accompany either hypo- or hyperthyroidism
(but not necessarily present in either)
• Develops when the thyroid gland is overstimulated
What are the causes of hypothyroidism
Causes • Failure of thyroid gland • TSH or TRH deficiency • Inadequate dietary supply of iodine • Radioactive iodine • Autoimmunity • Post surgery • Congenital • Anti-thyroid drugs
What are the symptoms of hypothyroidism
General symptoms • Obesity • Lethargy • Intolerance to cold • Bradycardia • Dry skin • Alopecia • Low T3 • Low T4 • Elevated TSH
Infants – cretinism
• Hoarse voice
• Constipation
• Slow reflexes
Adults - myxedema • Thick puffy skin • Muscle weakness • Slow speech • Mental deterioration • Intolerance to cold
What is hashimotos disease?
• Autoimmune disease resulting in destruction of
thyroid follicles. Leads to hypothyroidism
• Most common disease of the thyroid gland
• 5 times more common in women than in men
• Goitre may or may not be present
Treatment: • Oral Thyroid hormone. • T4 used since longer half-life • Normally ~50-200 µg/day in single dose.
Plasma • Low T • Low T • Elevated TSH
3 4
What are the causes of hyperthyroidism
Causes • Autoimmune Graves' disease • To x i c multinodular goitre • Solitary toxic adenoma • Excessive T4 (or T3) therapy • Drugs - amiodarone • Thyroid carcinoma • Ectopic thyroid tissue
What are the general symptoms of hyperthyroidism
General symptoms • Weight loss • Irritability • Heat intolerance, sweating warm vasodilated hands • Tachycardia (noticeable heart beat) often irregular • Fatigue, weakness • Increased bowel movements - increased appetite • Possible tremor of outstretched hands • Hyper-reflexive • Breathlessness • Loss of libido • Sweating and tremor
What is Graves’ disease
• Autoimmune disease resulting in hyperthyroidism
• Caused by production o thyroid stimulating immunoglobulin (TSI)
• TSI continuously stimulates thyroid hormone secretion outside normal negative feedback control
Outside normal negative feedback loop - lots of thyroid produced - feedback to ant pituitary gland - Lowers TSH - but not having effect of production o thyroid hormone bc stimulus is from TSI
What are the symptoms of Graves’ disease
• Increase In BMR • Excessive sweating • Decrease in body weight • Muscle weakness • Heart palpitations • Bulging eyes
(not in every case)
Wat is thyroid scintigraphy
Technetium-99m used for isotope scanning of the thyroid with a gamma camera. • Most commonly used medical radioisotope • Biological half-life of ~1 day • Radiation exposure therefore low • Also used for: • Bone scan • Myocardial perfusion imaging • Brain imaging
What is a common antithyroid drug
- Used to treat overactive thyroid (hyperthyroidism) e.g. Graves’ disease
- Block formation of thyroid hormone
- Carbimazole most commonly used in UK
- Carbimazole is a pro-drug and is converted to methimazole in body
- Prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin
