Thyroid gland Flashcards
How many lobes form the thyroid gland?
2
Which structure does the thyroid gland wrap?
Trachea
Which structure connected the two thyroid lobes?
Isthmus
Which hormone is predominantly secreted from the thyroid gland?
Thyroxine
Which two arteries supply the thyroid gland?
Superior & inferior thyroid arteries
Which nerve supplies the thyroid gland and what major nerve does it branch off of?
Recurrent laryngeal nerve
Branch of Vagus nerve
Which cells form the epithelia of the thyroid gland?
Follicular cells
What is the mucous extracellular fluid that fills the thyroid follicles?
Colloid
Which cells secrete calcitonin?
Parafollicular cells
Describe the anatomical position of the parathyroid glands?
Bilateral structures (superior and inferior), are embedded within the thyroid
What is the purpose of the parathyroid gland?
Secretion of parathyroid hormone. PTH elevates Ca2+ levels by degrading bone and stimulating calcium release
What are the associated risks with thyroidectomy?
Parathyroid glands can be impacted, inadvertently interfering with calcium levels.
Which growth factor is involved with the development of the thyroid gland?
Fibroblast growth factor signalling pathways
Where does the thyroid gland originate from embrylogically?
Base of the tongue
Which hormone is released by thyrotroph cells and how does it activate thyroid hormone production?
Thyroid-stimulating hormone binds to target TSH receptors on cell-surface membrane of follicular cells
What action occurs during TSH receptor activation?
Active transport of iodide into the follicular cell via the sodium-iodide symporter
How is the sodium gradient maintained?
Sodium potassium ATPase
Which surface are the Sodium/iodide pumps located on thyroid follicular cells?
Basal membrane
Which protein pump, pumps iodide from the follicle into the colloid, via the apical membrane?
Pendrin pumps
Where is thyroglobulin made?
Within follicular ribosomes and stored into secretory vesicles
Which amino-acid residues are associated with thyroglobulin molecules?
Tyrosine residues
Where is thyroglobulin secreted into?
Secreted into the colloid
What is thyroglobulin?
Prohormone for thyroid hormone
How is iodide activated in the production of thyroid hormones?
Thyroid peroxidase
What is the single iodinated form of thyroglobulin?
3-monoiodothyronine (3-MIT)
Where does iodination occur on thyroglobulin molecules?
Tyrosine residues
Which molecule is formed upon the secondary iodination of MIT?
3,5-Diiodotyrosine (DIT)
How is T3 formed?
Coupling of MIT and DIT
How is T4 formed?
Coupling of two DIT molecules (thyroxine)
What is the fate of iodinated thyroglobulin?
Endocytosis by the apical membrane into the follicular cell, subjected to proteolysis
What is the purpose of cleavage of T3 and T4?
Removes thyroglobulin from t3/t4 to produce the actual hormones
Which hormone is the active thyroid hormone?
T3
Which thyroid hormone is the major product?
T4
Which enzyme deiodinates T4 into t3?
Iodothyronine deiodinases
What is reverse T3?
Biologically inactive molecule formed by the removal of the wrong Iodine group
Under starvation circumstances, what is the fate of t4?
Convered into rT3, rather then T3
What is the main thyroxine transportation hormone?
Thyroxine-binding globulin (TBG)
What are the other thyroxine transportation hormones(Apart from TBG)?
Albumin
Prealbumin
Describe the binding of albumin with T3/4?
Weak/loose
Which thyroxine hormone predominantly is associated with prealbumin?
T4
What is the circulating period for T3?
12 hours
What is the circulating time for t4?
72 hours
What are the sources of T3?
80% deiodination of T4
20% MIT+DIT coupling in thyroid
Why can iodothyronine enter cells?
Lipid soluble, thus can interact with intracellular receptors
Which thyroid hormone receptors bind onto iodothyronines?
T3 response elements (TREs)
Which receptors do heterodimer thyroid hormones receptors bind to?
Retinoid X receptor
What effect does iodotyronines have on cells?
Genomic action
What is the main action of iodothyronines?
Increases basal metabolic rate
Important in calorigeneis,
Temperature regulation
Increased protein, fat & carbohydrate metabolism.
How are thyroid levels measured?
Using a heel-prick test
What are the main actions of iodothyronines?
Enhances the effects of catecholamines,leading to tachycardia, glycogenolysis, and lipolysis
Interaction with endocrine systems
Have effects on the CNS
Increase Vitamin C synthesis
What effect does hypothyroidism have on retinal?
Retinal accumulation, leads to yellow skin
Which hormones increase iodothyronine production?
Thyroid releasing/stimulating hormones and oestrogen
What effect does elevated levels of T3/T4 have?
Negative feedback effect, directly acting on the adenohypophysis to inhibit the secretion of TRH, and indirectly on the hypothalamus
What effect does somatostatin have on the anterior pituitary?
Inhibits the release of growth hormone
What effects do glucocorticoids have on thyrotrophs?
Inhibitory effect-Decrease blood TSH conc
What is the Wolff-Chaikoff effect?
Inhibits the production of iodothyronines, through inhibition of TPO.
Due to increases inorganic iodide
What is primary hypothyroidism?
Autoimmune stimulated damage to the thyroid gland subsequently reduced iodothyronine productions, hence thyroxine levels decline.
Why are TSH levels elevated due to hypothyroidism?
TSH levels elevate due to reduced inhibitory effect from T3/T4 (Negative feedback loop is disrupted); eventually TSH levels decline as resources are exhausted.
Which autoimmune thyroid disease is associated with hypothyroidism?
Hashimoto’s thyroiditis
What are the symptoms of primary hypothyroidism? (6)
Deepening voice, depression and tiredness
Cold intolerance (Calorigenesis effects of secondary heat production is reduced)
Weight gain
Constipation
Bradycardia
Eventual myxoedema coma
Why is there weight gain with primary hypothyroidism?
Reduced basal metabolic rate of tissues and reduced lipolysis
what effects does T3 and T4 have on cells (genomic action)?
T4 and T3 bind to thyroid receptor proteins (TREs, and RXRs) in the cell nucleus and cause metabolic effects through transcription activation Levothyroxine is a chiral molecule in the L-form. Thyroxine supplements primarily replace the reduced level of iodothyronines.
Which therapy is the most effective for hypothyroidism?
T4/T3 therapy
What are the implications of thyroxine supplements?
Tachycardia, potential heart attack; weight loss; headaches and hyperthyroidism.
What is hyperthyroidism?
An overactivity of the thyroid gland, resulting in an elevated production of thyroxine, and subsequently reducing TSH levels.
What are the main features of hyperthyroidism?
Overproduction of thyroxine; raised basal metabolic rate; raised temperature; burn up calories and weight loss; tachycardia.
What are the main causes of hyperthyroidism?
Graves’ disease – whole gland smoothly enlarged and whole gland overactive
Toxic multinodular goitre
Solitary toxic nodule
Describe the pathophysiology of Graves disease:
Whole gland smoothly enlarged and the entirely of the gland is overactive. Autoimmune condition attributed towards increased thyroid-stimulating immunoglobulin (TSIs) levels that encourages the thyroid gland to hypertrophy, and synthesising increased amounts of thyroid hormone than required.
TSIs bind to thyroid cell receptors, ’docking stations’ for thyroid-stimulating hormone. The TSI behaves as an agonist, stimulating follicular cells and thyroid follicles to synthesis iodothyronines.
(Type 2 hypersensitivity)
What is a toxic multinodular goitre?
Excess production of thyroid hormones from functionally autonomous thyroid nodules which do not require stimulation from TSH.
What is a solitary toxic nodule?
A toxic adenoma, whereby a single nodule undergoes hypertrophy and produces excess thyroid hormones.
What is an exophthalmos?
Immunoglobulins bind to muscles behind the eye, which project the eye forwards and cause proptosis.
What are the clinical features of hyperthyroidism?
Myopathy; mood swings; feeling hot; diarrhoea; increased appetite despite weight loss; tremor of hands; palpitations; sore eyes and goitre.
What are the symptoms of hyperthryroidism?
Neuro: Insomnia, nervousness, depression
CV:Tach, +BP
Hair:Broken hair/hair loss
Endo: Goitre
Gastro:Weight loss,
Fragile fingernails, shaking hands
What are the symptoms of hypothyroidism?
Neuro:Fatigue, Memory impairment
Gastro:Weight gain, constipation
Repro:Low libido, diminished fertility and potency
Skin: Dry and rough
Endo: Goitre
Swelling of face, eye socket and deep, rough voice
What molecule is produced when thyroid peroxidase activates iodine
H2O2(Hydrogen peroxide)
What are the functions of thyroid peroxidase?
Activation of iodine
Stimulation of coupling reactions
What are the half lives of T3 and T4?
T4: 7-9 days
T3: ~2 days
What duct forms alongside the thyroid gland and what foramen does it leave
The thyroglossal duct
leaving the foramen caecum in the mouth
By what time has the thyroid gland finished development
Week 7
What 5 congenital abnormalities can the thyroid develop?
Thyroid agenesis
Lingular thyroid
Retrosternal goitre
Thyroglossal cyst
Thyroglossal fistula
In thyroid:
Top>Bottom
Follicular cells
Colloid
How are iodothyronines transported in the blood and in what percentages?
Mostly bound to plasma proteins
a) thyroxine-binding globulin: TBG (70-80%)
b) albumin (10-15%)
c) prealbumin (aka transthyretin)
What is released by the follicular nucleus after TSH receptor activation and why does said molecule do?
Thyroglobulin, binds to activated iodine as well as assists in coupling reactions
Parafollicular cells
How are t3/t4 levels controlled?
Negative feedback into the anterior pituitary releasing TSH and hypothalamus releasing TRH
What are the effects of thyroid hormone?
**Effects on growth, CNS, GI, Reproductive systems
↑Basal metabolic rate
Protein, carbohydrate & fat metabolism
Potentiate actions of catecholamines (e.g. tachycardia, lipolysis)**
What occurs to T3 and T4 when entering a cell
T4 deiodinated into T3, T3 binds to receptor in nucleus causing altered gene expression
Whole thyroid T4/T3 production
Where are the Na+/I- pumps found on follicular cells?
Basolateral membrane
