The Thyroid Gland Flashcards
Where is the parathyroid? What nerve runs close?
- Embedded in thyroid
- Left recurrent laryngeal nerve runs close (supplies vocal cords)
Describe the embryology of the thyroid gland?
- Midline outpouching from floor of pharynx (originates from base of tongue)
- Development of thyroglossal duct
- Divides into 2 lobes
- Duct disappears leaving foramen caecum
- Final position by week 7
- Thyroid gland then develops
What is T4 and T3?
- Thyroxine (T4) is the main hormone product of the thyroid gland
- Deiodinated to triiodothyronine (T3), its bioactive form, in target tissues
- Also deiodinated in a different position to produce reverse T3 (inactive)
What is tyrosine?
- Amino acid (part of thyroglobulin)
1. Iodine added to form 3-monoiodotyrosine
2. 2 iodine added to form 3,5 diiodotyrosine - If 1 and 2 combines get 3,5,3 triiodothyronine (T3)
- If 2 2’s combine get 3,5,3,5-tetrta-iodothyroinine (T4)
What is 3,5,3,5-tetrta-iodothyroinine (T4) also known as?
Thyroxine
What is the first step in thyroid hormone production?
- TSH secreted from anterior pituitary gland
- Arrives through bloodstream and binds to TSH-R receptor on follicular cell membrane
- Arrival of I- ions (presence of iodine is essential in making thyroid hormone)
- Iodide ions and through Na+ I- transporter crosses into cell and then enter colloid
- Then this is oxidised to make iodine
What is the second step in thyroid hormone production?
- TSH binding Starts production of thyroglobulin (prohormone) it has tyrosine (amino acid that can be iodinated so can stick iodine molecule to tyrosine) residues within its structure
What is the third step in thyroid hormone production?
- With TSH-R binding activate enzyme called throperoxidase which travels into colloid
- With hydrogen peroxide the throperpxodase catalyses the iodination reactions that occur in the colloid
What is the fourth step in thyroid hormone production?
- Thyroglobulin with residues, iodine sticks onto these residues (tyrosine and iodine) then mono-iodine thyronine and mono-iodine thyroxine formed
- These couple to form T3 and T4 which are bound to the thyroglobulin
- Then these move back into follicular cell where protein bonds are broken down and they are related from thyroglobulin and are related into the systemic circulation
Describe thyroglobulin
- Each protein has 100 tyrosine residues of which about 20 can be iodinated
- If add 3 (T3) - position of where bound can be changed from reverse T3
- If add 4 (T4)
How much T3 and T4 are secreted?
Circulating T3
•80% from deiodination of T4
•20% from direct thyroidal secretion
-T3 provides almost all the thyroid hormone activity in target cells.
What is the relation between T3 andT4?
- Healthy adult thyroid gland secretes both T3 and T4
- Tetraiodothyronine (Thyroxine, T4) is a prohormone converted by deiodinase enzyme into the more active metabolite triiodothyronine (T3)
How does thyroid hormone get around body?
Mostly bound to plasma proteins
a) thyroid-binding globulin: TBG (70-80%)
b) albumin (10-15%)
c) prealbumin (aka transthyretin)
- Only 0.05% T4 and 0.5% T3 is unbound (bioactive components)
What is the effect on the cell?
- T3 and T4 enter cell via receptors
- T4 activated by deoidiodinase enzymes (located in all target tissues)
- T3 enter nucleus and binds to thyroid hormone receptor
- Where alters gene expression
What actions of thyroid hormone in babies?
- Essential for fetal growth & development, in particular that of the central nervous system
- Need to monitor mothers as baby take thyroid
What is Untreated congenital hypothyroidism?
- Cretinism
- TSH measured in new-born infant’s heel-prick test
What is action of thyroid hormone?
- ↑Basal metabolic rate (how fast cells working
- Protein, carbohydrate & fat metabolism
- Potentiate actions of catecholamines (e.g. tachycardia, lipolysis)
- Effects on the GI, CNS, Reproductive systems
What is the half lives of T4 and T3?
Half lives:
T4: ~ 7-9 days
T3: ~ 2 days
What is action of thyroid hormone for CNS?
- Thyroid hormone binds to nucelar receptor
- Synthesis of new proteins
- maturation of CNS
What is action of thyroid hormone for growth?
- Thyroid hormone binds to nucelar receptor
- Synthesis of new proteins
- Growth formation and bone maturation
What is action of thyroid hormone for BMS?
- Thyroid hormone binds to nucelar receptor
- Synthesis of new proteins
- increase Na+/k+ ATPase increase oxygen consumption heat production and BME
What is action of thyroid hormone for metabolism?
- Thyroid hormone binds to nucelar receptor
- Synthesis of new proteins
- increase glucose absorption, gylcogenolysis gluconeogensis lipolysis and protein synthesis and degradation
What is action of thyroid hormone for growth?
- Thyroid hormone binds to nucelar receptor
- Synthesis of new proteins
- Increase cardiac output
What is the control of thyroid hormone production
- TSH and thyrotrophin are same thing, and TRH produced in hypothalamus via circulation and enters anterior pituitary where stimulates thyrotroph cells to relate TSH
- Then enter systemic circulation where arrives at thyroid (production of T3 and T4)
- Negative feedback, and so tells anterior piutary and hypothalamus to switch off TRH and TSH to stop production
What is somatostatin?
Negatively inhibits TSH production from AP
What happens if a lot of iodide?
- Inhibits production of T3 and T4
- Wolff Chalkoff effect?
Are thyroid hormones more common in med or women?
- Women 4:1 ratio
- To do with autoimmunity
Is an overactive or underachieve thyroid more common?
Same
What can cause primary hypothyroidism?
Autoimmune damage to the thyroid (or surgery)
•Thyroxine levels decline
•TSH levels climb
What are the common forms of autoimmune thyroid disease?
- Commonest forms of autoimmune thyroid disease are Hashimoto’s thyroiditis and Graves’ disease.
- Hashimoto’s is usually associated with hypothyroidism
- The presence of one autoimmune disease increases risk of others.
What are the symptoms and signs with patents presenting with hypothyroidism?
- Deepening voice
- Depression and tiredness
- Cold intolerance
- Weight gain with reduced appetite
- Constipation
- Bradycaria
- Eventual myxoedema coma
- Enlarged thyroid gland
What is levothyroxine?
-T4 to T3
When give levothyroxine?
- Hypothyroidism
- Hyperthyroidism (blocking and replacement regimen)
What is dosing of levothyroxine?
- Adjusted according to TSH (aim to get into normal range)
- Common dose 100 micro grams
- Most commonly administered orally
Complication of levothyroxine?
If too much - heart attack or weight loss headache or rapid HR
Why not just give T3 as it is the active hormone?
-Have enzymes already
-Expensive
-• T4 = prohormone, converted by deiodinase action to T
• Combination T4 / T3 – some reported improvement in wellbeing
• Complicated by symptoms of ‘toxicity’ – palpitations, tremor, anxiety - often combination treatment suppresses TSH
What happens in hyperthyroidism?
Thyroid makes too much thyroxine
•Thyroxine levels rise
•TSH levels drop
What are the causes of hyperthyroidism?
- Graves’ disease – whole gland smoothly enlarged and whole gland overactive
- Toxic multinodular goitre
- Solitary toxic nodule
What happens in Graves disease?
-Autoimmune disease
-Antibodies bind to and stimulate TSH receptor in the thyroid (disrupt negative feedback leave)
•Smooth goitre
-Other antibodies bind to muscles behind eye
•Exophthalmos
-Other antibodies stimulate growth of soft tissue of shins
•Pretibial myxoedema
What are the symptoms and signs with patient presenting with hyperthyroidism?
- Heat intolerance
- Weight loss and increase dappetitie
- myopathy
- Mood swings, irritability
- Diarrhoea
- Tremor of hands
- Palpations
- Sore eyes. goitre
- Enlarged thyroids
- Broken hair, hair loss
What is the anatomy of the thyroid gland?
- An endocrine gland located in the neck
- Usually consists of two lobes connected by the isthmus
- Embryological origin is from floor of pharynx
- Cellular structure contains follicles
- Follicles are well perfused and surround the colloid ECF
Describe thyroid hormones
- Thyroxine (T4) = inert
- Triiodothyronine (T3) = active
- Thyroglobulin produced by follicular cells combined with iodine from blood to create T3 and T4 in presence of thyroperoxidase
- T4 -> T3 in presence of deiodinase
How is secretion control?
- TRH from hypothalamus travels to anterior pituitary
- TRH stimulates thyrotroph cells to secrete TSH into blood
- TSH binds to TSH receptors on follicular cells to stimulate T3/T4 synthesis pathways
- Circulating T3/T4 provide negative feedback to downregulate hypothalamus and anterior pituitary
What is hypothyroidism summary?
- Typically an autoimmune disorder
* Treatment includes thyroxine supplementation
What is hyperthyroidism summary?
- May be autoimmune (Graves’ disease) or nodule-related
* Graves’ disease associated with smooth goitre, eye disease and skin disease
