Thyroid Hormone and Alterations in Thyroid Function Flashcards
What are the three types of thyroid follicles and their function?
- parafollicular cells = release of calcatonin
- follicular cells = secrete thyroid hormones
- colloid-filled follicles = stores inactive thyroid hormone until needed
Thyroid hormones are formed by?
adding iodine to two linked tyrosine amino acids
What is the difference between T4 and T3?
T4 is the predominant thyroid hormone produced by the thyroid gland (90%) and contains 4 iodines.
T3 is more biologically active. Most T3 produced at the target tissue by removal of an iodine.
Sources of iodine for thyroid hormones?
Has to be ingested.
Describe TH synthesis.
- Iodide enters follicular cells via Na/I symporter.
- Thyroglobulin (TGB - a tyrosine rich glycoprotein) is synthesized by follicular cells and released into colloid cells.
- Iodide is moved into colloid cells and converted to iodine (I2).
- Tyrosine residues of TGB form T1 or T2.
- Coupling with I2 forms T3 or T4 - stored attached to TGB in the colloid.
NOTE: colloid can store a 2-month supply of TH.
Describe the process of TH release.
- TSH (thyroid stimulating hormone) causes pinocytosis which moves colloid into follicular cells.
- lysosomes facilitate TGB breakdown and release of T3 and T4.
- Secretion of TH and transport in the blood (bound to a carrier protein).
How do lipid-soluble hormones such as TH enter cells.
Cross the plasma membrane and bind to intracellular receptors.
Describe the regulation of thyroid hormone.
- TRH (thyrotropin releasing hormone) from the hypothalamus travels in the blood to the anterior pituitary gland. NOTE: TRH increases in response to cold, stress and low T4.
- TRH stimulates the anterior pituitary gland to secrete TSH.
- TSH binds to TSH receptors on follicular cells and stimulates the release of T3 and T4
- Blood T3 and T4 levels rise.
- Elevated T3 and T4 inhibit release of TRH.
What are the effects of TSH other than the immediate release of stored T3 and T4?
- increases the activity of Na/I symporter.
- stimulates TH synthesis (restocking)
- increases number and size of follicular cells.
What are the intercellular effects of TH?
T4 inactive - converted to T3 at target cell. Pass through the membrane and attach to intracellular receptor where they alter gene expression and protein synthesis.
What does TH do?
- increases basal metabolic rate (the rate of o2 consumption at rest) by activating genes involved in metabolism
- increase body temperature as a result of increased metabolism and energy production.
stimulates skeletal and nervous system development and growth
increases HR and contractility (stimulates B1-adrenergic receptors and contractile proteins)
Stimulates GI motility and glucose absorption.
promotes normal body functions.
What is thyrotoxicosis?
A clinical state resulting from any condition that causes an increase in TH levels and action in tissues.
e.g:
- excessive exogeneous TH replacement
- subacute thyroiditis (inflammation d/t infection)
- postpartum thyroiditis (autoimmune mechanism caused through transient thyrotoxicosis and/or hypothyroidism).
What is hyperthyroidism?
A specific type of thyrotoxicosis caused by excessive synthesis and secretion of TH.
What is the difference between primary and secondary hyperthyroidism?
Primary = dysfunction of the thyroid gland. e.g. Graves disease and toxic multinodular goitre (hyperfunctioning thyroid nodules).
Secondary = disorders affecting the release of TSH from the pituitary gland. e.g a TSH-secreting pituitary adenoma.
What is Graves disease?
A type of hyperthyroidism involving dysfunction of the thyroid gland.
It is an autoimmune disease that involves thyroid stimulating autoantibodies.
How do autoantibodies contribute to the development of hyperthyroidism?
The autoantibodies thryotropin recepter antibodies (TRAb) or thyroid-stimulating immunoglobulins (TSI) bind to TSH receptors on follicular cells resulting in increased TH production and release with no negative feedback as neg feedback goes back to hypothalamus and pituitary gland.
What is Graves orbitopathy?
Swelling of the eye orbit tissue causing the eye to bulge.
Fibroblasts in orbital tissues are stimulated by TSH receptor autoantibodies to produce GAGs (particularly hyaluronic acid). Accumulation, inflammation and adipogenesis results in swelling.
Mild (won’t affect vision) to severe (sight-threatening).
What is the difference between primary and secondary hypothyroidism?
Primary involves the loss of functional thyroid tissue, a defect thyroid hormone synthesis, or congenital causes resulting in decreased production of TH. Accounts for 99% of all cases.
Secondary involves pituitary (secondary/TSH deficiency) or hypothalmic (tertiary/TRH deficiency).
What is Hashimoto’s disease?
The most common type of primary hypothyroidism and an autoimmune disease.
Marked infiltration of thyroid gland by autoreactive helper T cells, cytotoxic T cells as well as B cells (= lymphocytic infiltration).
The B cells are activated and produce autoantibodies against components of the thyroid follicle.
Follicular cells gradually destroyed by cytotoxic T cells.
NOTE: the destruction of folliclular glands initially causes an increase in TH levels as stored TH is released.
What is responsible for the enlargement of the thyroid gland in Hashimoto’s?
Inflammation caused by the autoimmune response.
Infiltration of the thyroid by t and b cells.
