S10: the thyroid gland

Question 1

Describe the location and structure of the thyroid gland

Answer 1

Lies against and around front larynx and trachea
Below thyroid cartilage
2 lobes joined by isthmus (isthmus extended from 2nd to 3rd rings of the trachea)

Question 2

Describe the different types of cells in the thyroid gland

Answer 2

Thyroid follicular cells = produce thyroid hormone
Thyroid parafollicular cells = produce calcitonin
Colloid (extracellular) = stores thyroglobulin

Question 3

Describe the chemical structure of the thyroid hormones

Answer 3

Monoiodotyrosine + diiodotyrosine = T3 (triodothyronine)
Diiodotyrosine + diiodotyrosine = T4 (tetraiodothyronine, otherwise known as thyroxine)
Thyroglobulin acts as a scaffold on which thyroid hormones are formed

Question 4

Describe the 3 reactions regulated by thyroid peroxidase

Answer 4

1) Oxidation of iodide to iodine
2) Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
3) Coupling of MIT/DIT to generate thyroid hormones within the thyroglobulin protein

Question 5

Explain the importance of iodine in thyroid gland & how it is absorbed

Answer 5

Thyroid hormones & precursors are the only molecules in the human body that contain iodine
Dietary iodine reduced to iodide before absorption
Iodide is taken up from blood by thyroid epithelial cells -> sodium-iodide symporter

Question 6

Describe the mechanisms of secretion of the thyroid hormones

Answer 6

90% of thyroid hormone secreted is T4
Biological activity of T3 is 4 times that of T4
Most T4 is converted to T3 in the liver & kidneys
T3 & T4 are transported in blood bound to the protein thyroxine-binding globulin

Question 7

Describe how the activity of the thyroid gland is controlled

Answer 7

Hypothalamus -> TRH -> anterior pituitary -> TSH -> thyroid gland -> thyroid hormone -> target tissues
Thyroid hormone negatively feedbacks to the anterior pituitary gland & hypothalamus
TSH negatively feedbacks to hypothalamus

Question 8

Describe thyroid stimulating hormone and its actions

Answer 8

Glycoprotein hormone composed of 2 non-covalently bound subunits
Trigger for thyroid hormone release
Stimulates: iodide uptake & oxidation, thyroglobulin synthesis & iodination, colloid pinocytosis into cell, proteolysis of thyroglobulin & cell metabolism and growth
TSH receptor can couple to either G-alphas or G-alphaq

Question 9

Describe thyroid hormone receptors

Answer 9

Nuclear receptors
Thyroid hormone receptors bind DNA in the absence of hormone, usually leading to transcriptional repression
Hormone binding associated with a conformational change in the receptor = causes it to function as a transcriptional activator

Question 10

Describe what happens when thyroid hormone binds to its receptor

Answer 10

Thyroid hormone receptor is pre-bound to specific DNA sequences = hormone response elements in promoter region of thyroid hormone regulated genes
Thyroid hormone enters nucleus & binds to thyroid hormone receptor on DNA
Binding relieves repression of gene transcription & gene is now expressed
Expression of new protein mediated the effects of thyroid hormone

Question 11

Describe the effects of thyroid hormone on the body

Answer 11

1) Increase in basal metabolic rate & heat production = increase the number and size of mitochondria & stimulate the synthesis of enzymes in the respiratory chain
2) Stimulation of metabolic pathways = lipid metabolism & carbohydrate metabolism
3) Sympathomimetic effects = increases receptor number on target cells

Question 12

Describe tissue specific effects of thyroid hormone

Answer 12

1) CVS = increases heart’s responsiveness to catecholamines -> increases cardiac output & increases peripheral vasodilation
2) Nervous system = increases myelination of nerves & development of neurons

Question 13

Describe goitre

Answer 13

Enlargement of the thyroid gland
May accompany either hypo- or hyperthyroidism (but not necessarily present in either)
Develops with thyroid gland is overstimulated

Question 14

Describe the causes, blood test results & general symptoms of hypothyroidism

Answer 14

Causes: failure of thyroid gland, TSH/TRH deficiency, iodine deficiency, radioactive iodine, autoimmunity & anti-thyroid drugs
General symptoms: obesity, lethargy, intolerance to cold, bradycardia & slow reflexes
Blood test results: low T3, low T4, elevated TSH
Infants – cretinism (dwarfed stature, mental deficiency), adults – myxedema (thick puffy skin, muscle weakness)

Question 15

What is Hashimoto’s disease?

Answer 15

Autoimmune disease resulting in destruction of thyroid follicles
Plasma: low T3, low T4, elevated TSH
Treatment: oral thyroid hormone, T4 used since it has a longer half-life

Question 16

Describe the causes & general symptoms of hyperthyroidism

Answer 16

Causes: Graves’ disease, toxic multinodular goitre, excessive T4/T3 therapy, medication
General symptoms: weight loss, irritability, heat intolerance, sweating warm vasodilated hands, tachycardia, fatigue & weakness, increased bowel movements – increased appetite

Question 17

What is Graves’ disease?

Answer 17

Autoimmune disease resulting in hyperthyroidism
Caused by production of thyroid stimulating immunoglobulin -> continuously stimulates thyroid hormone secretion outside normal negative feedback control
Symptoms: increase in BMR, excessive sweating, decrease in body weight, heart palpitations

Question 18

What drugs are used to treat hyperthyroidism?

Answer 18

Carbimazole = blocks formation of thyroid hormone
Pro-drug & converted to methimazole in body
Prevents thyroid peroxidase from coupling & iodinating tyrosines on thyroglobulin

Question 19

What is thyroid scintigraphy?

Answer 19

Technetium-99m used for isotope scanning of the thyroid with a gamma camera
Biological half-life of ~1 day = radiation exposure is low
Also used for: bone scan, myocardial perfusion imagining & brain imaging