MEH 19 - The Thyroid Gland Flashcards
Where is the thyroid gland?
Describe its anatomy
- Against + around front larynx and trachea, below thyroid cartilage (adams apple)
- 2 lobes (left + right) joined via the isthmus
Describe what a histological section of thyroid tissue would look like
- Follicular cells arranged around the outside of thyroid follicles.
- Follicles filled with colloid, which stores thyroglobulin (this is where thyroid hormone is made)
How is T3 (triiodothyronine) and T4 (tetraiodothyronine) made?
What is the structural differences between the two?
- T3 = combination of MIT + DIT (1 and 2 iodines on aromatic ring)
- T4 = combination of 2 x DIT’s.
- T3 has 3 iodines on 2 aromatic rings, T4 has 4 iodines on 2 aromatic rings.
Describe the process of of T3/T4 synthesis (2 key steps)
1) Thyroglobulin protein acts as backbone/scaffold
2) Tyrosine residues on thyroglobulin iodinated (into MIT or DIT)
3) Coupling of 2 x tyrosines together to produce T3 or T4
What are the 3 roles of thyroid peroxidase in the synthesis of thyroid hormone?
1) Oxidation of iodide to iodine
2) Addition of iodine to thyroglobulin
3) Coupling of MIT or DIT to produce T3/4
What happens to dietary iodine before absorption in the small intestine?
- Conversion/reduction to iodide
- Iodide taken up from blood by thyroid epithelial cells which have a sodium-iodide symporter.
How much of thyroid hormone secreted is T4?
What is the biological activity of T3 compared to T4?
What happens to majority of T4?
How are T3/4 carried in blood?
- 90% secreted is T4
- T3 is 4x more active than T4
- Most T4 converted into T3 in liver + kidneys
- T3 + T4 transported in blood bound to thyroxine-binding globulin
How is thyroid hormone secretion regulated?
- long loop negative feedback - T3/T4 inhibit TSH from ant pit and TRH from hypothalamus
- Short loop negative feedback - TSH inhibits TRH from hypothalamus.
Describe the structure of TSH
- Glycoprotein hormone composed of an alpha and beta subunit.
- Alpha subunit the same in FSH and LH, B-subunit provides unique biological activity.
What is the role of TSH + how does it achieve this?
- TSH stimulates release of T3/4 by activating its receptor on follicular cells (a GPCR either Gs or Gq), activation activates signal cascade which promotes T3/4 synthesis and those steps involved (e.g.: iodide uptake, oxidation, thyroglobulin iodination etc)
What are the 3 general actions of thyroid hormone?
1) Increase in BMR + heat production - by increasing number and size of mitochondria and synthesising enzymes in respiratory chain.
2) Stimulation of metabolic pathways - e.g.: lipolysis, B-oxidation of fatty acids, gluconeogenesis + glycogenolysis (entry of glucose into cells)
3) Sympathomimetic effects - increases target cell response to catecholamines by increasing receptor number on target cells.
How do thyroid hormone receptors exert their effects?
- Thyroid hormones are lipid soluble, binding to intracellular receptor
- Receptor pre-bound to hormone response elements (HRE’s) on DNA in promoter region of thyroid hormone regulated genes.
- Binding of hormone relieves repression of gene transcription and gene is now expressed, mediating effects of thyroid hormone.
What is a goitre?
When does it develop?
- Enlargement of thyroid gland
- May accompany hypo or hyperthyroidism, but develops when thyroid gland is overstimulated.
What is hypothyroidism caused by?
What are the general symptoms?
What are the biochemical findings?
- Failure of thyroid gland, TRH/TSH deficiency, poor dietary iodine, anti-thyroid drugs etc.
- Obesity, lethargy, intolerance to cold, bradycardia, dry skin etc.
- Low T3/4, high TSH (no neg feedback of T3/T4 on hypothalamus/ant pit)
What are the general terms of hypothyroidism in children + adults?
Children = cretinism (dwarfed stature, mental deficiency, slow pulse, muscle weakness)
Adults = myxoedema (thick puffy skin, muscle weakness, slow speech, intolerance to cold)
What is Hashimoto’s disease?
Who is it common in?
Whats the treatment?
- Autoimmune disease resulting in thyroid follicle destruction + hypothyroidism. Low T3/4, high TSH.
- 5:1 F>M
- Oral thyroid hormone (T4 since longer half life).
What is Graves’ disease?
What are the symptoms?
What are the biochemical findings
- Autoimmune disease resulting in hyperthyroidism, caused by production of thyroid stimulation immunoglobulin (TSI). TSI stimulates T3/4 outside of normal negative feedback.
- Weight loss, muscle weakness, bulging eyes, heart palpitation, sweating, fatigue/weakness, breathlessness, tachycardia etc.
- High T3/4, very low TSH
What radioisotope is used to scan the thyroid gland with a gamma camera?
- Technetium-99m, short half life (1 day).
What anti-thyroid drugs are used to treat hyperthyroidism?
How do they work?
- Carbimazole
- Pro-drug, converted into methimazole in the body, prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin (presents T3/4 synthesis)
