7. Thyroid Flashcards
The parafollicular cells within the thyroid gland secrete which substance?
Calcitonin
What is thyroxine?
tetraiodothyronine
The release of thyroid hormone from the thyroid gland is triggered by which hormone?
TSH
Where is thyroid stimulating hormone released from?
Anterior pituitary gland
What type of receptor does thyroid hormone bind to?
Nuclear receptor - bound to bind DNA causing transcriptional repression. Hormone binding causes conformational changet to function as a transcriptional activator rather than a repressor.
Which form of thyroid hormone has the longest half-life?
T4
Which protein serves to transport thyroid hormone (T3 & T4) in plasma?
Thyroxin-binding globulin
Outline the structure of the thyroid gland.
2 lobes joined by an isthmus
Where is the thyroid gland located?
Anterior to trachea, Inferior to thyroid cartilage, superior to sternal notch.
When does thyroid development take place?
At 4-7 weeks
Briefly explain the development of the thyroid gland.
- Epithelial proliferation at the base of tongue, floor of pharynx.
- Descends down thyroglossal duct, attached to tongue.
- Thyroglossal duct generates
- Thyroid gland continues descending for 2 weeks to it’s final position.
Outline the histological structure of the thyroid gland.
Arranged in follicles, lined with follicular cells and filled with extracellular colloid.
Parafollicular cells between follicles.
What is the contents of colloid?
Thyroglobulin store
What do parafollicular/C-cells secrete?
Calcitonin
What cells in the parathyroid gland secrete PTH?
Chief cells/principal cells
By what transporter does iodine enter the thyroid follicle cells?
Sodium/iodide symporter
Once in the follicular cell, what happens to iodide?
Oxidised to iodine by thyroid peroxidase
What 3 reactions does the membrane-bound thyroid peroxidase catalyse?
- Oxidation of iodide
- Iodination of tyrosine residues on thryogloblin
- Coupling of iodinated residues to form bound T3 and T4
How are thyroid hormones excreted from the colloid when needed?
Pinocytosis into the follicular cell, fusion with lysosome which degrades the thyroglobin protein. T3 and T4 released into plasma.
What happens to uncoupled T3 and T4?
Recycled back to iodide by enzyme deiodinase
What cofactor is required for oxidation of iodide?
H202
90% of thyroid hormone secreted is ____.
T4
The most potent thyroid hormone is ____.
T3
Where is most of T4 converted to T3 in circulation?
Liver and kidneys
What is the structure of TSH?
Glycoprotein
2 subunits - alpha shared with LH and FSH
beta subunit provides biological activity.
What receptor does TSH bind to?
GPCR - alpha q and alpha s
What does TSH binding stimulate?
iodide uptake iodideoxidation thyroglobulin iodination colloid pinocytosis proteolysis of thyroglobulin
What are the 3 general actions of thyroid hormone?
- Increase BMR and heat production
- Stimulation of metabolic pathways
- Sympathomimetic
How does thyroid hormone increase BMR?
Increase size and number of mitochondria
Synthesis of enzymes in respiratory chain
Which metabolic pathways does thyroid hormone stimulate?
- Lipolysis and beta-oxidation of fatty acids
2. insulin-dependent entry of glucose into cells via GLUT4, glycogenolysis, gluconeogenesis.
How does thyroid hormone have sympathomimetic effects?
Increases cell response to catecholamines by increasing receptor number on target cells.
How does thyroid hormone affect the CVS?
Increase CO (HR and contractility) Peripheral vasodilation to carry heat to body surface
How does thyroid hormone affect the nervous system?
Myelination of nerves and development of neurones. Essential for both development and adult function.
Which genes are activated by thyroid hormone?
PEPCK
Ca2+ ATPase
Na+/K+ATPase
cytochrome oxidase (ETC)
What is a goitre?
Enlargement of thyroid gland - can be present in both hypo and hyper-thyroidism.
What might cause hypothyroidism?
- Iodine deficiency
- TSH or TRH deficiency
- Autoimmune destruction
- Congenital
- Anti-Thyroid drugs
- Radioactive iodine
What symptoms are associated with hypothyroidism?
Obesity Intolerance to cold Bradycardia Menorrhagia Pallor Dry skin Loss of lateral third of eyebrow
What condition is caused by hypothyroidism in children?
Cretinism
What condition is caused by hypothyroidism in adults?
Myxedema
What autoimmune condition causes hypothyroidism?
Hashimoto’s disease
What antibodies are produces in hashimoto’s?
Against thyroglobulin and thyroid peroxidase
What is the treatment for hashimoto’s disease?
Oral T4 (longer half life)
What symptoms and signs are associated with myxoedema?
Thick puffy skin - around eyes Intolerance to cold Mental deterioration Slow speech Muscle weakness
What is the effect of cretinism in children?
Dwarfed stature Mental deficiency Poor bone development Muscle weakness Slow pulse
What can cause hyperthyroidism?
Autoimmune - Graves' disease Toxic multinodular goitre Toxic adenoma Excessive T4 therapy Thyroid carcinoma Ectopic thyroid tissue
What ar the symptoms associated with hyperthyroidism?
Weight loss Intolerance to heat Irritability Fatigue Sweating Tremor Anxiety May have - goitre, bulging eyes, bounding pulse
What autoantibodies are produced in Graves’ disease?
Thyroid stimulating immunoglobulin (TSI) which binds to TSH receptor and constantly stimulates thyroid hormone secretion.
What would you expect plasma T3, T4 and TSH levels to be in hyperthyroidism?
Elevated T3 and T4
Very low TSH
What would you expect plasma T3, T4 and TSH levels to be in hypothyroidism?
TSH elevated
Low T3 and T4
Which two signs would be indicative of Graves’ disease over other types of hyperthyroidism?
Exopthalmos - eye bulging
Pre-tibial myxoedema
Related to auto-immunity rather than thyroid levels.
What isotope is used in thyroid scintigraphy?
Technetium-99m
What anti-thyroid drug can be used in hyperthyroidism and Graves’ disease?
Carbimazole
How does carbimazole work?
Pro-drug, converted to methimazole which inhibits thyroid peroxidase from iodinating and coupling tyrosine on thyroglobulin.
Why does carbimazole have a delayed affect (2-4 weeks)?
There is a considerable store of thyroglobulin which takes 2-4 weeks to diminish.
What happens to the thyroid upon swallowing, what fascia explains this?
moves upwards upon swallowing as the pre-trachial fascia attaches the thyroid gland to the trachea and larynx.
What is lingual thyroid?
Developmental problem leaving thyroid gland tissue on the tongue.
What is a thyroglossal cyst, where is it located?
Remnants of the thyroglossal duct epithelium.
Always in the mid-line
When does a thyroglossal cyst move upwards?
Upon tongue protrusion
Why is the normal range for TSH so wide?
Hypothalamus is constantly responding to environmental changes so levels change accordingly.
When are physiological goitres most likely to occur?
Menarche
Pregnancy
Menopause
What is the commonest cause of a goitre globally?
Iodine deficiency
What is the commonest cause of a goitre in the UK?
Multinodular goitre
Does a multi-nodular goitre affect thyroid function?
No, only if it becomes toxic after many years and the patient may develop hyperthyroidism.
Which geographical areas are at a higher risk of goitre?
Mountainous areas - greater iodine deficiency
Why does iodine deficiency lead to goitre formation?
Decreased thyroxine levels lead to increased TSH secretion leading to stimulation and enlargement of the thyroid gland.
Why is iodine deficiency a particular concern during pregnancy?
If foetus is iodine deficient, can lead to cretinism.
What is a retrosternal multi nodular goitre and it’s main complication?
Multinodular goitre can enlrge inferiorly behind the sternum.
Can cause tracheal compression.
What proportion of plasma thyroid hormone is “free” in plasma?
1% - this is the only biological active hormone
What is subclinical hyperthyroidism characterised by?
Low or undetectable concentration of TSH with free T3 and T4 within laboratory reference ranges.
Which condition always results in goitre formation?
Dietary iodine deficiency
Which anti-arrythmic drug is commonly associated with side effects that disrupt thyroid function?
Amiodarone - similar structure to thyroxine so can disrupt thyroid function - both hypo and hyper reported.
Why does the thyroid gland move up on swallowing?
It is invested by the pre-tracheal fascia.
How can feeling a patients hands help to differentiate between possible hyperthyroidism and anxiety?
Warm and sweaty - hyperthyroid
Cold and clammy - anxiety
