The Thyroid Gland Flashcards
What is the thyroid gland called if it enlarged?
A goitre
Where is the thyroid gland located?
In the upper neck
In front of the larynx and upper trachea
Structure of thyroid?
Two lateral lobes joined by a central isthmus - butterfly shaped
2-3cm across and weighs ~20g
Follicular cells arranged in functional units called follicles.
Para follicular cells found in connective tissue.
Structure of follicles in thyroid gland?
Spherical follicle cells lined with epithelium surrounding a lumen containing the protein
Which hormones are produced in the thyroid and from which cells?
T3 (thyroxine) and T4 in the follicular cells
Calcitonin in the parafollicular cells
Synthesis of T3 and T4?
Transport of iodide ions into epithelial cells against a concentration gradient
Synthesis of a tyrosine rich protein, thyroglobulin in the epithelial cells
Secretion of thyroglobulin into the lumen
Oxidation of iodide to give an iodinating species
Iodination of tyrosine residues in thyroglobulin to form MIT and DIT
Coupling of DIT with MIT (T3) or with DIT (T4) in the thyroglobulin.
What are T3 and T4 produced in the ratio of?
1:10
Where are T3 and T4 stored?
Extracellularly in the lumen of the follicles as part of the thyroglobulin molecules.
How are T3 and T4 secreted?
Thyroglobulin is taken into epithelial cells from the lumen by endocytosis
Proteolytic cleavage to release T3&4
They diffuse from cells into the circulation
How is thyroid hormone secretion controlled?
TRH released from dorsomedial nucleus of hypothalamus under the influence of circulating T3&4 (negative feedback)
This stimulates release of TSH from thyrotrophs in the anterior pituitary
TSH travels in blood to affect follicular cells of the thyroid
What stimulates the release of TRH?
Low levels of T3&4
Low temperature
Stress
What does TSH do?
Interacts with receptors on the surface of follicle cells and stimulates synthesis and secretion of T3&4.
Has trophic effects on the thyroid causing increased vascularity, size and number of follicle cells.
Which has a lower affinity for binding to transport proteins in the blood? T3 or 4
T3 has a lower affinity so it has a greater percentage free in the blood (less T3 is produced that T4)
What happens during pregnancy to the levels of hormones concerning the thyroid gland?
Oestrogen increases the synthesis of Thyroid Binding Globulin
Fall in the amount of free T3&4 in circulation
Removed inhibitory feedback so more TRH and TSH are produced
More T3&4 secreted
Same amount of free T3&4 in blood but there is more T3&4 over all
What effect do the thyroid hormones have?
Increase metabolic rate
Stimulate glucose uptake
Stimulate mobilisation and oxidation of fatty acids
Stimulate protein metabolism
Increase in BMR, heat production and oxygen consumption
Affect bone mineralisation
Development of nervous system
How do T3&4 act on a cell
Pass through plasma membrane
Bind to high affinity receptors in the nucleus and mitochondria (higher affinity for T3 than T4)
Binding of T3 to hormone-binding domain unmasks the DNA binding domain
This increases the rate of transcription of specific genes
How can T4 be converted to T3 and what effect does this have?
Removal of 5’ iodide from T4 producing rT3
rT3 can bind to hormone receptors without having any effect - inactive
Blocks the effect of T3
This is important in regulating the amount of active hormone
What is the most common form of hypothyroidism and what does this disease do?
Hashimoto’s disease
Autoimmune destruction of the thyroid follicles or production of antibodies that block the TSH receptor.
How is hypothyroidism treated?
Oral thyroxine
What a some signs and symptoms of hypothyroidism?
Cold intolerance and reduced BMR Bradycardia Weight gain Tiredness and lethargy Dry and flaky skin Alopecia Deep and husky voice Affects neuromuscular system - weakness, muscle cramps, and cerebellar ataxia
What is the main form of hyperthyroidism and what does it do?
Grave’s disease
Antibodies produced which stimulate TSH receptors on the follicle cells, increasing synthesis and secretion of T3&4
How can hyperthyroidism be treated and how does this drug work?
Carbimazole
Inhibits the enzyme thyroid peroxidase, preventing coupling of iodidination of tyrosine residues on thyroglobulin
What are signs and symptoms of hyperthyroidism?
Weight loss
Tachycardia
Heat intolerance, increased oxygen consumption and BMR
Physical and mental hyperactivity
Intestinal hyper-mobility
Skeletal and cardiac myopathy causing tiredness, weakness and breathlessness
Osteoporosis due to increased bone turnover and preferential resorption
