Thyroid Gland Flashcards
The thyroid gland weighs ~X-Y grams and is slightly heavier in males/females
15-25
Females
What vertebral levels is the thyroid gland found at?
C5/6 - T1
Which tracheal rings does the thyroid isthmus lie anterior to?
2nd and 3rd
Describe embryological development of the thyroid gland
- Begins ~week 4 as a midline epithelial proliferation at the back of the tongue, where the foraemen caecum is found in adults
- Migrates inferiorly through the thyroglossal duct while still attached to the tongue
- Travels anterior to the larynx
- Reaches its final position below the larynx in the anterior neck in week 7
What is meant by the pyramidal lobe of the thyroid?
A normal anatomical variant of the thyroid caused by a persistent remnant of the thyroglossal duct
List 4 possible defects in embryological development of the thyroid gland
- Failure of development (congenital hypothyroidism)
- Undermigration (lingual thyroid - closer to tongue)
- Overmigration (retrosternal thyroid - down in mediastinum)
- Remnants of the thyroglossal duct -> thyroglossal cysts
Where is the foraemen caecum found in adults?
At the junction between the anterior 2/3rds and the posterior 1/3rd of the tongue
What 3 hormones are secreted by the thyroid gland?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
What hormone is secreted by the 4 parathyroid glands?
Parathyroid hormone (PTH)
The thyroid gland is under autonomic nerve supply. Which nerves provide sympathetic and parasympathetic supply?
Parasympathetic: vagus nerve
Sympathetic:
Superior, middle and inferior ganglia of the sympathetic trunk
What nerve can potentially by damaged during thyroid surgery?
Recurrent laryngeal nerve
State the blood supply and venous drainage of the thyroid gland
Blood supply: superior and inferior thyroid arteries (+/- thyroidea ima)
Venous drainage: superior, middle and inferior thyroid veins
What is the basic functional unit of thyroid tissue?
Follicles
Describe the structure of follicles
- Circular border made up of flat to cuboidal follicular epithelial cells
- Pink colloid centre containing thyroglobulin
Thyroglobulin is produced by…
The follicular epithelial cells
What is the function of thyroglobulin?
To produce T3 and T4 and store them until they are required to be released
What are C cells and what do they do?
Parafollicular cells found surrounding the follicles
They secrete calcitonin
What does the secretion of calcitonin do?
Lowers serum Ca2+ levels
Describe the histological appearance of thyroid tissue
- Majority of the space taken up by the amorphous, pink thyroglobulin centres of the follicles
- C cells are large pale cells found between the follicles (large for cells but not larger than the follicles themselves)
Describe the steps involved in thyroid hormone release
- Hypothalamus releases thyrotropin releasing hormone (TRH)
- This stimulates the anterior pituitary to release thyroid stimulating hormone (TSH)
- TSH binds to TSH receptor on thyroid epithelial cells
- T3 and T4 are released from the thyroid
How does TSH binding lead to release of thyroid hormones from thyroid epithelial cells?
The TSH receptor is G-protein coupled
G protein activation leads to production of cAMP
cAMP increases production and release of T3 and T4
Once released, what is the fate of T3 and T4?
They circulate in the bloodstream in bound and free forms until they reach target cells
How do T3 and T4 act on target cells?
- Bind to nuclear receptors in the cytoplasm
- Translocate to the nucleus
- Bind to thyroid response elements on target genes
- Stimulate transcription of genes leading to increased basal metabolic rate
How is thyroid hormone release a -ve feedback loop?
T3 (mainly) and T4 suppress…
- Production of TRH from the hypothalamus
- Production of TSH from the anterior pituitary
… to regulate their own production
The thyroid is the only endocrine gland which requires substances from the environment to synthesise hormones. What is this substance?
Iodine
What are the 6 steps of thyroid hormone synthesis?
- Thyroglobulin synthesis in follicular cells
- Uptake and concentration of iodide (I-) in the colloid
- Oxidation of iodide to iodine (I2)
- Iodination of thyroglobulin (i.e., thyroglobulin and iodine combine in the colloid)
- Formation of intermediates MIT and DIT
- Linking of intermediates to form T3 or T4
What is the role of the enzyme thyroid peroxidase (TPO)?
Oxidises iodide to form iodine
Iodine is then combined with thyroglobulin to make T3 and T4
How is MIT formed?
When 1 iodine is attached to a tyrosine residue on thyroglobulin
(MIT = mono-iodotyrosine unit)
How is DIT formed?
When 2 iodines each join to a different tyrosine residue on the same thyroglobulin
(DIT = di-iodotyrosine unit)
The linking of X and Y intermediates forms the thyroid hormone T3
MIT and DIT
The linking of X and Y intermediates forms the thyroid hormone T4
DIT + DIT
Where are T3 and T4 stored until they are required?
The colloid thyroglobulin
The majority of secreted thyroid hormones are T3. T/F
False
~90% T4
~10% T3
T4 is the major biologically active thyroid hormone. T/F?
False
T3 is the major biologically active thyroid hormone
(~4x more potent than T4)
T4 is converted to the more biologically active T3 by the…
Liver and kidneys
The majority of thyroid hormones travel through the bloodstream bound to serum proteins. T/F
True
What 3 serum proteins can thyroid hormones bind to?
Which is most common?
Thyroxine binding globulin (TBG) 70%
Thyroxine binding pre-albumin (TBPA) 20%
Albumin 5%
Only bound thyroid hormones can enter target cells. T/F
False
Only unbound ‘free’ thyroid hormones can enter cells
Why is T3 so much more active than T4?
T4 is bound to TBG 10-20x stronger than T3, so more T3 will be free than T4
List 3 factors that increase TBG and 3 that decrease it
Increase TBG: pregnancy, OCP, hepatitis A
Decrease TBG: excess steroids, Cushings syndrome, chronic liver disease
Which tissues do thyroid hormones act on and how?
They act on nearly all cells and tissues (esp. neurones) via nuclear receptors which alter gene transcription
What is the main function of the thyroid hormones?
Increasing basal metabolic rate
How do thyroid hormones increase basal metabolic rate? (3)
- Increase no. and size of mitochondria
- Increase O2 use and rate of ATP hydrolysis
- Increase synthesis of respiratory chain enzymes
What other functions do the thyroid hormones have besides increasing basal metabolic rate? (5)
- Thermogenesis (responsible for ~30% of temperature regulation)
- Carbohydrate/ protein/lipid metabolism
- Growth (stimulates the hypothalamus to stimulate growth hormones)
- Development of the foetal brain
- Normal CNS activity
What is meant by the ‘permissive sympathomimetic action’ of thyroid hormones?
They increase responsiveness to adrenaline and noradrenaline by increasing numbers of receptors
Why are beta blockers required to treat initial stages of hyperthyroidism?
Permissive sympathomimetic action (increased responsiveness to adrenaline and noradrenaline) means that heart rate and force are increased
What are de-iodinases?
Enzymes which degrade T3 and T4
Where are the 3 types of de-iodinases found?
D1 - liver and kidney
D2 - thyroid, pituitary, cardiac & skeletal muscle, fat, CNS
D3 - brain (except pituitary), placenta, foetal tissue
Which de-iodinase carries out the majority of T3 and T4 breakdown?
D3
Summarise the degradation of T4
- 45% broken down by D3 to inactive reverse T3
- 40% broken down by D1 to T3
- 15% broken down by minor pathways
Summarise the degradation of T3
- Predominantly broken down by D3 into inactive T2
- Minor pathways responsible for breakdown of the remainder
