Physiology of Thyroid Gland Flashcards
What does the follicular structure of the thyroid gland contain?
Colloid
What is colloid?
Proteinaceous material that is an extracellular storage form of thyroid hormone
What are follicles lined by?
Single layer of epithelial cells
What is the function of follicular cells?
Synthesise and secret thyroid hormones in response to anterior pituitary TSH
What cell is found in the intrafollicular region?
Parafollicular or C cells
What do parafollicular cells secrete?
Peptide hormone called calcitonin - plays a role in Ca2+ homeostasis
What are the two thyroid hormones?
T3 and T4
What does T3 and T4 synthesis require?
Iodine at C3 and C5 positions
What is the polarity of T3 and T4?
Moderately polar with limited solubility in plasma
What does the AIT apical transporter do?
Moves iodine into colloid area for T3 and T4 synthesis
What is T3 and T4 bound to for storage
Thyroglobulin
What does thyroid peroxidase use to oxidase I- to I/I+?
H2O2 generated by 2 other enzymes (DUOX1 and 2)
What does TSH promote?
Endocytosis
What does secretion of thyroid hormones require?
Endocytosis of colloid (containing thyroglobulin and bound hormones) back into follicular cells
Which thyroid hormone is secreted most?
T4 ~ 80mg/day (>90% of output)
Which thyroid hormone is more potent?
T3
Which thyroid hormone has a greater half life and why?
T4 as it binds more avidly to its binding proteins
What is the major plasma transport protein?
Thyroxine binding globulin > transthyretin > albumin
What enzyme converts T4 to T3 in target cells?
5’ monodeiodinase
When is 5’ monodeiodinase less active?
During fasting/starvation and cortisol excess
What does 5’ monodeiodinase inactivate?
T3 in liver and other tissues (inner C5 position)
What is rT3?
Competitive inhibitor of T3
What increases rT3 production and thus decreased T3?
Cortisol excess (euthyroid sick syndrome)
What are thyroid hormones MoA?
- Entry into cells
- Deiodination
- Non genomic actions
- Nuclear import
- Binding to TH receptor, formation of heterodimer with retinoic acid receptor and binding to TRE
- Recruitment of co-activator proteins
What is the Basal metabolic rate?
Metabolic rate of awake relaxed person 12-14 hrs after eating at comfortable temperature
What is BMR highly influenced by?
Thyroid hormone levels
High BMR = hyperthyroidism
Low BMR = hypothyroidism
What 6 things do thyroid hormones increase?
Size and number of mitochondria
Oxygen consumption
ATP production
Activity of key metabolic enzymes
Protein and lipid turnover
BMR
Why are thyroid hormones essential for normal growth?
Role in protein synthesis
Increases energy production and substrate availability
Permissive for anabolic actions of growth hormone
What role do thyroid hormones play in CNS development?
Promotes nerve growth
Growth of dendrite cells
Myelin formation
What is cretinism?
Thyroid hormone deficiency - Impaired CNS development, intellectual and development disability
What does maternal and/or fetal hypothyroidism cause?
Delayed CNS development and intellectual disability
What secrets thyroid stimulating hormone?
Anterior pituitary
What does TSH stimulate?
stimulates follicular cell growth, follicle formation and maintenance and growth of thyroid gland
What secrets TRH?
Hypothalamus
What does TRH regulate?
Secretion of pituitary TSH
What is goitre?
Thyroid overstimulation by TSH
Hypo and hyperthyroid states
What are symptoms of hypothyroidism?
Cutaneous edema - increased deposition of CT
Goitre
Decreased HR, CO and appetite
lethargy
Low BMR
cold intolerance
children - intellectual disability and dwarfism
What is hypothryoxinaemia?
Low levels of TH production leads to reduced -ve feedback -> increases TSH prod. -> generalized hypertrophy
What causes primary hypothyroidism?
Iodine deficiency
genetic mutations
Toxicity
cancers
autoimmune diseases
What is secondary hypothyroidism?
Abnormality of hypothalamus or pituitary
What is the treatment for hypothyroidism?
Replacement theary with levothyroxine
Dietry iodine supplementation
What are symptoms of hyperthyroidism?
Increased BMR and body temp.
Increased sympathetic nerve activity -> increased HR
Anxiety
Goitre
Bulging eyes
What is thyrotoxicosis?
Any cause of increased thyroid hormone leading to hypermetabolic rate
What can cause thyrotoxicosis?
Overdose of T4 in hypothyroidism
Germline or somatic gain of function mutations in TSH receptors
What causes hyperthyroidism?
Primary - autoimmune - antibodies to TSH receptor, T3/4 hypersecretion, thyroid adenoma
Secondary - excess TSH (pituitary) (adenomas), excess TRH in hypothalamus
How does Graves Disease cause goitre?
Autoantibodies directed against TSH receptor - stimulates TH production and hypertrophy of gland
Increased feedback inhibition of pituitary TSH production
How is hyperthyroidism treated?
Agents that interfere with production of T3 and T4
Destruction of thyroid gland
What is Thyroid Storm?
Hypermetabolic state characterized by extreme hyperthyroidism
What are symptoms of throid storm?
tachycardia, cardiac arrhythmias, congestive heart failure, pyrexia and dehydration
How can thyroid storm be treated?
Beta blockers - reduce sympathetic activation
Glucocorticoids (reduce T4 to T3 conversion)
Thionamides (inhibit new hormone synthesis)
