The Thyroid Gland Flashcards
What is the thyroid gland?
An endocrine gland in the neck consisting of two lobes connected by an isthmus
Where is the thyroid located?
Lies against and around front larynx and trachea
Below thyroid cartilage
Where does the isthmus extend from and to?
From 2nd to 3rd rings of the trachea
True or False:
The thyroid is the last endocrine gland to develop
False
It’s the first
Describe the embryological development of the thyroid
At 3-4 weeks gestation - appears as epithelial proliferation in floor of pharynx at base of tounge
First descends as diverticulum through thyroglossal duct and migrates downwards passing in front of hyoid cartilage
During migration remains connected to tongue by thyroglossal duct which subsequently degenerates
Describe the histology of thyroid tissue
Follicular cells arranged in spheres called thyroid follicles, filled with colloid
True or False:
Colloid is considered extracellular even though it is inside the follicle
True
What is colloid a deposit of?
Thyroglobulin
What are the principal cells in the parathyroid gland?
Chief cells - produce parathyroid hormone
What do thyroid follicular cells produce?
Thyroid hormone
What do thyroid parafollicular cells produce?
Calcitonin
What are the thyroid hormones?
T3 and T4
2 tyrosines linked together with iodine at three or four positions on the aromatic rings
What acts as a scaffold on which thyroid hormones are formed?
Thyroglobulin
What happens to thyroglobulin for it to become thyroid hormone?
Iodination and then coupling
What 3 separate reactions does thyroid peroxidase regulate?
1) Oxidation of iodide to iodine
2) Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
3) Coupling of MIT or DIT to generate thyroid hormones within the thryroglobulin protein
How is iodide taken up from blood to thyroid epithelial cells?
Sodium-iodide symporter (iodine trap)
What is 90% of thyroid hormone secreted?
T4
How does the biological activity of T3 compare to that of T4?
Biological activity of T3 is 4 times that of T4
What happens to most of T4 after secretion?
Most is converted to T3 in liver and kidneys (80% of circulating T3 is derived from T4)
How are T3 and T4 transported in the blood?
Bound to thyroxine-binding globulin
Starting from the hypothalamus, how is thyroid hormone secreted?
Hypothalamus -> TRH -> Anterior pituitary -> TSH -> Thyroid gland -> Thyroid hormone -> Target tissues
What effects do thyroid hormones have on cells?
Effects on cellular differentiation and development and effects on metabolic pathways
What is thyroid stimulating hormone?
Glycoprotein hormone composed of 2 non covalently bound subunits (a and b)
What does TSH stimulate?
1) Iodine uptake and oxidation
2) Thyroglobulin synthesis and iodination
3) Colloid pinocytosis into cell
4) Proteolysis of thyroglobulin
5) Cell metabolism and growth
What G proteins are TSH receptors coupled to?
Either Gs or Gq
In which tissues is metabolic rate not increased by thyroid hormone?
Brain, spleen, testis
How does thyroid hormone increase metabolic rate?
1) Increasing the number and size of mitochondria
2) Stimulating the synthesis of enzymes in the respiratory chain
What metabolic pathways do thyroid hormones stimulate?
Lipolysis and b-oxidation of fatty acids
Insulin-dependent entry of glucose into cells and increases gluconeogenesis and glycogenolysis
(More GLUT4 - more glucose taken up)
What sympathomimetic effects do thyroid hormones have?
Increases target cell response to catecholamines by increasing receptor number on target cells
What effects do thyroid hormones have on the cardiovascular system?
Increases heart’s responsiveness to catecholamines - increases cardiac output
Peripheral vasodilation so that extra heart can be carried to body surface
What effects do thyroid hormones have on the nervous system?
Increased myelination of nerves and development of neurons
What type of receptors are thyroid hormone receptors?
Nuclear receptors
What do thyroid hormone receptors do in the absence of hormone?
Bind DNA - usually leading to transcriptional repression
What happens when a hormone binds to thyroid hormone receptors?
Conformational change so receptors acts as a transcriptional activator
How do thyroid hormones enter cells?
Lipid soluble - enters cell through thyroid hormone transporters
How do thyroid hormones cause a cellular response?
1) Enter cell through thyroid hormone transporters
2) Thyroid hormone receptors are already bound to a specific DNA sequence (HRE) in promoter region of thyroid hormone regulated genes
3) Thyroid hormone enters the nucleus and binds to thyroid hormone receptor on DNA
4) Binding relieves repression of gene transcription so the gene is now expressed
5) New mRNA -> new protein - cellular response
What are some examples of thyroid hormone activated genes?
PEPCK Ca2+ ATPase Na+, K+, ATPase Cyochrome oxidase 6-phosphogluconate dehydrogenase
What is goitre?
Enlargement of the thyroid gland
What are some causes of hypothyroidism?
Failure of thyroid gland
TSH or TRH deficiency
Iodine deficiency
Autoimmunity
What are some symptoms of hypothyroidism?
Obesity, lethargy, cold intolerance, hoarse voice, dry skin, alopecia
Describe the hormone levels in hypothyroidism
Low T3 and T4
Elevated TSH
How do infants with hypothyroidism appear?
Cretinism
- Dwarfed stature
- Mental deficiency
- Poor bone development
- Slow pulse
- Muscle weakness
- GI disturbances
How do adults with hypothyroidism appear?
Myxedema
- Thick puffy skin
- Muscle weakness
- Slow speech
- Mental deterioration
- Cold intolerance
What is Hashimoto’s disease?
Autoimmune disease resulting in destruction of thyroid follicles - leads to hypothyoidism
How is Hashimoto’s disease treated?
Oral thyroid hormone (T4 - longer half life)
What are some causes of hyperthyroidism?
Graves' disease Toxic multinodular goitre Solitary toxic adenoma Excessive T4 therapy Drugs - amiodarone Thyroid carcinoma Ectopic thyroid tissue
What are some symptoms of hyperthyroidism?
Weight loss, irritability, heat intolerance, tachycardia, fatigue, increased bowel movements and appetite, hyper-reflexive
What is Graves’ disease?
Autoimmune disease caused by production of thyroid stimulating immunoglobulin (TSI) - results in hyperthyroidism
Describe the hormone levels in hyperthyroidism
Increased T3 and T4
Low TSH
What isotope is used in scanning of the thyrid with a gamma camera?
Technetium-99m
What is the most commonly used antithyroid drug?
Carbimazole
What type of drug is carbimazole?
Pro-drug - converted into methimazole in body
What does carbimazole do?
Prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin
