4.3: The thyroid gland Flashcards
What glands are embedded in the thyroid
Parathyroid glands
What nerve, supplying the vocal cords, runs close to the thyroid gland
Left recurrent laryngeal nerve
Embryology of the thyroid gland
Midline outpouching from floor of pharynx
Development of thyroglobulin duct
Divided into 2 lobes
Duct disappears leaving for amen caecum
Final position by week 7
Thyroid gland then develops
5 congenital anomalies of the thyroid gland
Thyroid agenesis
Lingular thyroid
Retrosternal goitre
Thyroglossal cyst
Thyroglossal fistula
Role of the isthmus
Separates 2 lobes of thyroid
What is the pyramid of the thyroid
3rd lobe of the thyroid, found in 10-30% of population
Role of parafollicular cells
Secrete calcotonin used to produce calcium
What 2 glands are important in calcium metabolism
Superior and inferior parathyroid gland
What can happen if the superior or inferior parathyroid glands are damaged during surgery
Permanent under active hypoparathyroid glands - hypoparathyroidism
Where is the thyroid hormone made
Colloid
How does the thyroid hormone enter the circulation
Via capillaries surrounding the follicles
How is thyroid hormone made within the thyroid gland
1) TSH from the blood binds to the TSH-R receptor
2) this activates the Na+/I- transporter on the basolateral membrane, stimulating active transport of iodide ions into the follicular cell
3) I- within colloid, oxidases in iodisation to form iodine
4) TSH binding also activates production of thyroglobulin
5) activates thryoperoxidase (enzyme)within cell which enters the colloid with H2O2 and catalyses iodisation reactions
6) once thyroglobulin is iodinated MIT and DIT (mono and id -iodothyrosine) are produced
7)MIT AND DIT join together to form T3 and T4
8) T3 T4 in colloid bound to thyroglobulin,
9) transported out of follicular cell by lysosome
10) T3 T4 enter circulation
What is thyroglobulin and where is it produced
Prohormone -glycoprotein which can be iodinated
Produced in the nucleus of the follicular cell
T3 is
Active form of thyroid hormone
Provides almost all thyroid hormone activity in target cells
T4 is
Tetraiodothyronine
Prohormone converted by deiodinase enzyme into more active triiodothyronine (T3)
What is the main hormone product of the thyroid gland
Thyroxine (T4)
What happens to T4 in target tissues
Deiodinated to triiodothyronine (T3) - bio active form
Deiodinated in different position to produce reverse T3 (inactive)
Proportions of circulating T3
80% from deiodination of T4
20% from direct thyroidal secretion
Half life of T4
7-9 days
Half life of T3
2 days
How are thyroid hormones transported in the blood
Bound to plasma proteins
70-80% thyroid-binding globulin TBG
10-15% albumin
prealbumin - aka transthyretin
Only 0.05% T4 and 0.5% T3 is unbound
How do T3 and T4 affect gene expression
1) enters target tissue cells through respective receptors on cell membrane
2)T4 deiodinated into active T3
3) binds to thyroid hormone receptor - nuclear receptor
4) layers gene expression
Actions of thyroid hormone in early life
Fetal growth and development - CNS
Untreated congenital hypothyroidism: cretinism
How is TSH measured in new borns
Heel-prick test
Where do foetuses gain their thyroid hormone from whilst in utero
Mothers, via placenta
4 Actions of thyroid hormone in humans
Effects on growth, CNS, GI Reproductive systems
Increases basal metabolic rate
Protein, carb and fat metabolism
Potentiate actions of catecholamines
Control of thyroid hormone production
1) TRH released from hypothalamus to activate TSH in anterior pituitary gland
2) TSH into circulation and to thyroid gland, stimulates production of T3 and T4
3)Negative feedback at anterior pituitary level and hypothalamic level
4) Somatostatin (prod. In hypothalamus) negatively acts on anterior pituitary
5)large quantities of iodine can inhibit T3/4 production in thyroid
What can be used to urgently control thyroid levels
Potassium iodide
What happens during primary hypothyroidism
Thyroxine levels decline
TSH levels climb
2 commonest forms of autoimmune thyroid disease
Hashimoto’s thyroiditis
Graves’ disease
Presence of one autoimmune disease increases risk of others
7 symptoms and signs of hypothyroidism
Deepening voice
Depression and tiredness
Cold intolerance
Weight gain with reduced appetite
Constipation
Bradycardia
Eventual myxoedema coma
What drug is used to treat hypothyroidism
Levothyroxine
Proposed mechanism of levothyroxine
Same as thyroid action
T4 -> active T3
Indications of levothyroxine use
Hypothyroidism
Hyperthyroidism- blocking and replacement regimen
Dosing of levothyroxine
Adjusted according to TSH - aim to get normal range
Common dose 100 micro grams
Most commonly administered orally once daily
Potential minor complications of levothyroxine
Weight loss
Headache
Potential major complications of levothyroxine
Heart attack
Rapid HR
Alternative therapy for hypothyroidism
Combined thyroid hormone replacement
Benefits of combined thyroid hormone replacement
Combination of T3 and T4 - some improvement in wellbeing
Disadvantages of combined thyroid hormone replacement
T3 has a shorter half life, so needs to be administered multiple times a day
Complicated symptoms of “toxicity” - palpitations, tremor, anxiety
Often surpresses TSH
In hyperthyroidism
Thyroid makes too much thyroxine
Thyroxin levels rise
TSH levels drop
3 causes of hyperthyroidism
Graves’ disease - whole gland smoothly enlarged and whole gland overactive
Toxic multinodular goitre
Solitary toxic nodule
What kind of disease is Graves’ disease
Autoimmune disease
In Graves’ disease
Antibodies bind to and stimulate TSH receptor in thyroid
Other antibodies bind to muscles behind eye
Or antibodies stimulate growth of soft tissue of shins
In Graves’ disease the binding to and stimulation of TSH receptors in thyroid is called
Smooth goitre
In Graves’ disease binding of antibodies to muscles behind the eye is called
Exophthalamos
In Graves’ disease the stimulation of growth of soft tissue in the shins due to antibodies is called
Pretibial myxoedema
8 symptoms and signs of hyperthyroidism
Heat intolerance
Weight loss and increased appetite
Myopathy
Mood swings
Diarrhoea
Tremor of hands
Palpitations
Sore eyes, goitre
