Structure and Function of Thyroid Gland Flashcards
Where is the thyroid gland located?
In the neck, in front of the lower larynx and upper trachea
When is the thyroid gland visible and palpable?
When enlarged
What is the thyroid gland called when its enlarged?
A goitre
What lies in close proximity to the thyroid gland?
Two nerves
What nerves lie in close proximity to the thyroid gland?
The recurrent laryngeal and the external branch of the superior laryngeal
What is the problem with thyroid surgery?
During surgery, the close nerves are at risk, and must be avoided
What is the consequence of damage to the nerves close to the thyroid?
They supply the larynx, and are involved in speech
Describe the vascular supply to the thyroid
Very good, with three arteries supplying it and three veins draining it
What are the three arteries and veins supplying the thyroid gland called?
Superior, muddle and inferior thyroid arteries/veins
What shape is the thyroid gland?
Butterfly, with two lateral lobes joined by a central isthmus
How big is the thyroid gland?
Varies in size, but usually 2-3cm across, and weighs 15-20g
What are the the major cell types found in the thyroid gland?
- Follicular
- Parafollicular (C-cells)
How are the follicular cells of the thyroid gland arranged?
In numerous functional units called follicles, separated by connective tissue
Where are the parafollicular cells found?
ln the connective tissue
What shape are follicles?
Spherical
Describe the structure of follicles
Lined with epithelial (follicular) cells, surrounding a central lumen
What do the follicle lumens contain?
Colloid
What is colloid rich in?
The protein thyroglobulin
What does the thyroid gland produce?
3 hormones
What hormones are produced in the follicular cells?
NAME?
What hormone is produced in the parafollicular cells?
Calcitonin
What are T3 and T4?
Small molecules derived from the amino acid tyrosine
How are T3 and T4 derived from tyrosine?
With the addition of atoms of iodine
What is calcitonin?
A polypeptide hormone
What is calcitonin involved in?
Calcium metabolism
What are the basic steps of synthesis of T3 and T4 in the thyroid follicles?
- Transport of iodide into the epithelial cells against a concentration gradient
- Synthesis of a tyrosine rich protein (thyroglobulin) in epithelial cells
- Secretion (exocytosis) of thyroglobulin into the lumen of follicle
- Oxidation of iodide to produce an iodinating species
- Iodination of side chains of tyrosine residues in thyroglobulin to form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
- Coupling of DIT with MIT or DIT to form T3 and T4 respectively within the thyroglobulin.
What ratios are T3 and T4 produced in?
~1:10
How are T3 and T4 stored?
Extracellularly in the lumen of the follicles as part of the thyroglobulin molecules
How much T3 and T4 is stored?
Normally considerable- enough so would last for several months at normal rates of secretion
How is T3 and T4 secreted?
Thyroglobulin is taken into the epithelial cells from the lumen of the follicles by the process of endocytosis. Here, proteolytic cleavage of the thyroglobulin occurs to release T3 and T4, and these diffuse from the epithelial cells into the circulation
What is the synthesis and secretion of T3 and T4 under the control of?
The hypothalamus and the anterior pituitary gland
What is the hypothalamic factor for T3 and T4 secretion control?
Thyrotropin-releasing hormone (TRH)
What kind of molecule is TRH?
Tri-peptide
Where is TRH released from?
Cells in the dorsomedial nucleus of the hypothalamus
What is TRH release under the influence of?
NAME?
What do increased stress levels cause regarding TRH?
Increases release
What do increased temperatures cause regarding TRH?
Decreases releases
What does TRH do once released?
Travels in the hypothalamic/pituitary portal system to stimulate the secretion of Thyroid Stimulating Hormone (TSH)
Where is TSH secreted from?
The thyrotropes in the anterior pituitary
What does TSH do once secreted?
Travels in the blood to affect the follicular cells of the thyroid gland
What kind of molecule is TSH?
Glycoprotein hormone
What does TSH consist of?
Two covalently linked subunit s (α and ß subunit s)
In what manner is TSH released?
In low-amplitude pulses following a diurnal rhythm
When are higher levels of TSH released?
At night
What does TSH interact with?
Receptors on the surface of the follicle cells
What does TSH do when it has interacted with the receptors on the follicle cells?
Stimulates all aspects of the synthesis and secretion of T3 and T4
What effects does TSH have?
Trophic effects on the thyroid gland
What are the trophic effects of TSH on the thyroid gland?
- Increased vascularity
- Increase in size
- Number of follicle cells
How can the trophic effects of TSH have negative consequences?
May result in an enlarged thyroid (goitre) that may or may not be overactive
Are T3 and T4 hydrophilic or hydrophobic?
Hydrophobic
How are T3 and T4 transported in the blood?
Bound to the proteins thyronine binding globulin, pre-albumin and albumin
How much T3 and T4 is free in solution?
What is important about the free T3 and T4?
It is biologically active
How do T3 and T4 differ in affinity?
T3 has a slightly lower affinity for transport proteins than T4
What is the result of T3 having a lower affinity to the receptor than T4?
A greater percentage is free, and it’s half-life in the circulation is shorter
What increases the synthesis of thyronine binding globulin (TBG)?
Oestrogen during pregnancy
What is the result in the increased TBG during pregnancy?
Fall in the amount of T3 and T4 in the blood, as more in bound
What is the result in the fall of free T3 and T4 in pregnancy?
Removes the inhibitory feedback on the pituitary and hypothalamus, and so more TRH and TSH are produced, so thyroid gland secretes more T3 and T4
What is the result in the increased T3 and T4 synthesis in pregnancy?
Amount of free T3 and T4 returns to normal, but total amount in the blood increases
Where do T3 and T4 exert their influences?
They have general effects on the metabolic activity of most tissues, and more specific effects on particular tissues
How long does the response of target tissues to T3 and T4 generally take?
Generally occurs slowly, taking day’s/weeks to manifest themselves
What are the effects of T3 and T4?
NAME?
Of what nature are the metabolic effects of T3 and T4?
Generally catabolic
What do the metabolic effects of T3 and T4 lead to?
- Increase in BMR
- Heat production
- Increased oxygen consumption
What is T3 and T4 important for?
Normal growth and development
What are their effects on physical growth related to?
In part, their metabolic effects on tissues
What specific effects do T3 and T4 have that affects growth?
- Affect bone mineralisation
- Increase synthesis of heart muscle protein
What is particularly sensitive to T3 and T4?
The nervous system
When is the nervous system particularly sensitive to T3 and T4?
During development
Why is the nervous system especially sensitive to T3 and T4 during development?
Because T3 and T4 are required for the development of the cellular processes of nerve cells, hyperplasia of cortical neurones and myelination of nerve fibres
What happens in the absence of thyroid hormones from birth to puberty?
The child remains mentally retarded (cretinism)
What happens if a thyroid hormone deficiency is not corrected within a few weeks of birth?
Irreversible damage occurs
What happens to newborns soon after birth?
They have their thyroid function assessed
What is lack of thyroid hormones characterised by in adults?
- Poor concentration
- Poor memory
- Lack of initiative
What is true of some of the actions of T3 and T4?
They are indirect
What are the indirect actions of T3 and T4 related to?
Important interactions with other hormones and neurotransmitters
What effects do T3 and T4 have on hormones and neurotransmitters?
They stimulate them
Where do T3 and T4 stimulate hormones and neurotransmitters?
In a variety of tissues, e.g. heart muscle, GI tract
What may the stimulation of hormones and neurotransmitters produce?
Increased responsiveness of these tissues to regulatory factors
What does T3 and T4 stimulation lead to in the heart muscle?
Tachycardia
What does T3 and T4 stimulation lead to in the GI tract?
Increased motility
What role does T3 and T4 have in the actions of hormones such as FSH and LH?
Permissive
What happens in the absence of thyroid hormones due to their permissive roles?
Ovulation fails to occur
How do T3 and T4 exert their actions?
The cross the plasma membrane of target cells, and interact with specific high affinity receptors
Where are the T3 and T4 receptors found?
In the nucleus and possibly the mitochondria
What are the receptors made up of?
Protein
How does receptor affinity for T3 differ from that of T4?
The affinity for T3 is 10-fold that of T4
What do the receptors have?
A number of domains
What happens when T3 binds to the hormone-binding domain of it’s receptor?
It is thought it produces a conformational change in the receptor that unmasks the DNA binding domina
What happens on interaction of the hormone-receptor complex with DNA?
It increases the rate of transcription of specific genes, that are then translated into proteins
What DNA does the T3 hormone-receptor complex interact with?
Nuclear or mitochondrial
What does the increased rate of protein synthesis due to the action of T3 stimulate?
Oxidative energy metabolism in the target cells
What is the purpose of T3 stimulation of oxidative energy metabolism in the cells?
Provides the extra energy required for protein synthesis
What does increased protein synthesis by T3 produce?
Increased amounts of specific functional proteins
What does increased amounts of functional proteins result in?
- Increased cell activity
- Increased demand for energy
How can T4 be converted to T3 in tissues?
By removal of the 5’-iodine
Where is T4 to T3 an important mechanism?
In regulating the amount of active hormone in cells
Why is T4 to T3 conversion an important regulatory mechanism?
T3 has 10 times the activity of T4
What does the removal of the 3’-iodide produce?
Inactive reverse T3 (rT3)
What can rT2 do?
Bind to thyroid hormone receptors without stimulating them, but blocks the effect of T3
What is hyperthyroidism?
When there is too much physiological active thyroid hormones
What is hypothyroidism?
When there is too little physiologically active thyroid hormone
What is the most common form of hypothyroidism?
Hashimotos’ disease
How much of the population does Hasimotos’ disease affect?
1%, mostly women
What is Hashimotos’ disease?
An autoimmune disease, that results either in the destruction of thyroid follicles, or production of an antibody that blocks the TSH receptor on follicle cells, preventing them from responding to TSH
How are patients with Hashimotos’ disease generally treated?
With oral thyroxine
What does the dosage of thyroxine in treatment of Hashimotos disease depend on?
Patient’s signs and symptoms, and TSH levels
What is the most common form of hyperthyroidism?
Graves disease
How many people does Graves disease affect?
~1% of population, mostly women
What is Grave’s disease?
An autoimmune disease in which antibodies (thyroid stimulating immunoglobulin (TSI)) are produced that stimulate the TSH receptors on follicle cells, resulting in increased production and release of T3 and T4
Why do TSH levels fall in Grave’s disease?
Due to the negative feedback exerted by T3 and T4 on the anterior pituitary gland
Does the fall in TSH affect thyroid hormone secretion?
No
Why does the fall in TSH secretion not affect thyroid hormone secretion?
The stimulus for thyroid hormone release is TSI, rather than TSH
How are patients with Graves disease treated?
With carbimazole
What is carbimazole?
A drug that inhibits the incorporation of iodine into thyroglobulin
How does carbimazole work?
It inhibits the enzyme thyroid peroxidase, and therefore prevents coupling and iodination of tyrosine residues on thyroglobulin
What are the signs and symptoms of hypothyroidism in adults?
- Cold intolerance and reduced BMR
- Weight gain tiredness and lethargy
- Bradycardia
- Neuromuscular system signs
- Weakness
- Muscle cramps
- Cerebellar ataxia
- Dry and flaky skin
- Alopecia
- Deep, husky voice
What are the signs and symptoms of hyperthyroidism?
- Heat intolerance, increased oxygen consumption and increased BMR
- Weight loss
- Physical and mental hyperactivity
- Tachycardia
- Intestinal hyper-mobility
- Skeletal and cardiac myopathy giving rise to tiredness, weakness and breathlessness
- Osteoporosis due to increased bone turnover and preferential resorption
