S7) The Thyroid Gland Flashcards
Briefly, describe the structure of the thyroid gland
2 lobes joined by isthmus
Describe the location of the thyroid gland
- Lies against and around front larynx and trachea
- Below thyroid cartilage
- Isthmus extends from 2nd to 3rd rings of the trachea
Thyroid is first endocrine gland to develop.
In 5 steps, describe the embryological development of the thyroid gland
⇒ Appears as an epithelial proliferation in floor of pharynx at base of tongue
⇒ Descends as diverticulum through thyroglossal duct
⇒ Migrates downwards in front of hyoid bone
⇒ Remains connected to tongue by thyroglossal duct
⇒ Duct degenerates and detached thyroid continues to final position
Describe the microscopic structure of the thyroid gland
- Follicular cells arranged in spheres called thyroid follicles
- Follicles filled with extracellular colloid, a deposit of thyroglobulin
The thyroid and parathyroid are distinct glands.
Describe how their cells vary in terms of hormone production
Describe how thyroid hormones are formed
2 tyrosine molecules are linked together with iodine at 3/4 positions on the aromatic rings
What is the role of thyroglobulin in thyroid hormone formation?
Thryoglobulin acts as a scaffold on which thyroid hormones are formed
What is thyroid peroxidase and what does it do?
Thyroid peroxidase is a membrane bound enzyme that regulates thyroid hormone synthesis
Thyroid peroxidase regulates 3 separate reactions involving iodide.
Identify these
- Oxidation of iodide to iodine (requires H2O2)
- Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
- Coupling of MIT/DIT to generate thyroid hormones within the thyroglobulin protein
How is dietary iodine absorbed in the thyroid gland?
- Iodine is oxidised to iodide before absorption in the small intestine
- Iodide (I-) is taken up from blood by thyroid epithelial cells via a sodium-iodide symport
Explain the following statement: most of T4 is converted to T3 outside of the thyroid
- 90% of thyroid hormone secreted is T4
- Most T4 is converted to T3 in the liver & kidneys
- 80% of circulating T3 is derived from T4
Which thyroid hormone is more biologically active?
Biological activity of T3 is 4x that of T4
How are the thyroid hormones transported in the blood?
T3 & T4 are transported in blood bound to the protein thyroxine-binding globulin
Thyroid hormones effect virtually every cell in the body and have two interconnected responses.
What are these?
- Effects on cellular differentiation and development
- Effects on metabolic pathways
Regulation of thyroid hormone secretion is via negative feedback.
Outline this
Describe the structure of thyroid stimulating hormone
Glycoprotein hormone composed of 2 non-covalently bound subunits:
- α subunit is also present in FSH and LH
- β subunit provides unique biological activity
TSH is a trigger for thyroid hormone release.
Identify the seven processes stimulated sequentially
⇒ Iodide uptake
⇒ Iodide oxidation (iodine)
⇒ Thyroglobulin synthesis
⇒ Thyroglobulin iodination
⇒ Colloid pinocytosis into cell
⇒ Proteolysis of thyroglobulin
⇒ Cell metabolism & growth
Describe the cellular mechanisms involved in the TSH induced signalling pathway for thyroid hormone secretion
Identify the three general effects of thyroid hormones on the body
- Increase in BMR and heat production
- Stimulation of metabolic pathways
- Sympathomimetic effects
How do thyroid hormones increase BMR and heat production?
- Increases number and size of mitochondria
- Stimulates synthesis of enzymes in respiratory chain
Describe two metabolic pathways stimulated by thyroid hormones
Catabolic pathways:
- Lipid metabolism – lipolysis and β-oxidation
- Carbohydrate metabolism – insulin-dependent entry of glucose into cells, gluconeogenesis and glycogenolysis
What are the sympathomimetic effects of thyroid hormones?
Sympathomimetic effects – increases target cell response to catecholamines by increasing receptor number
Identify the tissue specific effects of thyroid hormones in terms of the following:
- Cardiovascular system
- Nervous system
- CVS – increases heart’s responsiveness to catecholamines (increased cardiac output and peripheral vasodilation)
- Nervous system – myelination of nerves & development of neurones
Describe the function and action of thyroid hormone receptors
- Function as hormone-activated transcription factors
- Act by modulating gene expression
In four steps, outline the cell signalling pathway induced by thyroid hormones on intracellular receptors
Indicate the normal plasma levels of thyroid hormones as well as reasons for variations unrelated to thyroid disease
What is goitre?
- Goitre is the enlargement of the thyroid gland due to its overstimulation
- It may accompany either hypo- or hyperthyroidism
What is hypothyroidism?
Hypothyroidism is an endocrine disorder wherein the thyroid gland is underactive and produces an insufficient amount of T3/T4
How does a patient with hypothyroidism present?
- Obesity
- Lethargy
- Intolerance to cold
- Bradycardia
- Dry skin
- Alopecia
What are the thyroid function test results for a patient with hypothyroidism?
- Low T3
- Low T4
- Elevated TSH
Identify 6 possible causes of hypothyroidism
- Failure of thyroid gland
- Congenital (TSH/TRH deficiency)
- Inadequate dietary supply of iodine
- Autoimmunity
- Post surgery
- Anti-thyroid drugs
Severe hypothyroidism in infants is referred to as cretinism.
How does this present?
- Dwarfed stature
- Mental deficiency
- Poor bone development
- Slow pulse
- Muscle weakness
Severe hypothyroidism in adults is referred to as myxedema.
How does this present?
- Thick puffy skin
- Muscle weakness
- Slow speech
- Mental deterioration
- Intolerance to cold
What is Hashimoto’s disease?
- Hashimoto’s disease is an autoimmune disease resulting in destruction of thyroid follicles, leading to hypothyroidism
- Is is 5x more common in women and goitre may be present
What are the thyroid function test results for a patient with Hashimoto’s?
- Low T3
- Low T4
- Elevated TSH
How is Hashimoto’s disease treated?
Oral thyroid hormone (T4 – longer half-life)
What is hyperthyroidism?
Hyperthyroidism is an endocrine disorder wherein the thyroid gland is overactive and produces an excess amount of T3/T4
How does a patient with hyperthyroidism present?
- Weight loss
- Irritability
- Heat intolerance, sweating warm vasodilated hands
- Tachycardia
- Fatigue, weakness
Identify 6 possible causes of hyperthyroidism
- Autoimmune
- Toxic multinodular goitre
- Toxic adenoma / thyroid carcinoma
- Excessive T4/T3 therapy
- Drugs e.g. amiodarone
- Ectopic thyroid tissue
What is Graves’ disease?
- Graves’ disease is an autoimmune disease resulting in hyperthyroidism caused by the production of thyroid stimulating immunoglobulin (TSI)
- TSI continuously stimulates thyroid hormone secretion outside normal negative feedback control
How does Graves’ disease present?
- Increased BMR
- Excessive sweating
- Decrease in body weight
- Muscle weakness
- Heart palpitations
- Exopthalmos (not always)
What are the thyroid function test results for a patient with Graves’ disease?
- Increased T3
- Increased T4
- Very low TSH
How is Grave’s disease treated?
Antithyroid drugs are used to treat overactive thyroid
Carbimazole is the most commonly used antithyroid drug in the UK.
Describe the mechanism of its action
- Carbimazole block formation of thyroid hormone
- Carbimazole is a pro-drug and is converted to methimazole in body
- Prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin
Which imaging technique is used to visualise the thyroid gland and how is it performed?
Thyroid scintigraphy – technetium-99m (99mTc) used for isotope scanning of the thyroid with a gamma camera
