Thyroid Hormones Flashcards
Which hormones are secreted by the Thyroid Gland?
T4
T3
Calcitonin
What is T4?
Prohormone
Why is T4 converted to T3?
To exert their action
T3 is more biologically active than T4
Compare T4 and T3
T3 is more biological active
T3 has greater affinity for thyroid hormone receptors
T3 has a shorter half-life
What is calcitonin?
Hormone responsible for calcium homeostasis
Where is calcitonin produced?
Parafollicular C cells
Where is reverse T3 (rT3) produced?
Made outside thyroid gland by removal of iodine atom from T4
Constitutes 1% of circulating throid hormone
What are the steps in thyroid hormone synthesis?
Step 1: Iodide uptake
Step 2: Oxidation
Step 3: Organification
Step 4: Generation of T3 and T4
Step 5: Release of T3 and T4 from thyroglobulin into circulation
Describe the stages of Step 2 (oxidation) of thyroid hormone synthesis
Thyroid Peroxidase (TPO) oxidises iodide to active form iodine
Describe the stages of Step 3 (organification) of thyroid hormone synthesis
Describe the stages of Step 4 (Generation of T3 and T4) of thyroid hormone synthesis
TPO combines MIT and DIT to form T3 or combine two DITs to form T4
Describe the stages of Step 5 (Release of T3 and T4 from thyroglobulin into circulation) of thyroid hormone synthesis
Tg is endocytosed from the lumen into the follicular cell
Tg is recycled for additional iodination
How does deiodination occur?
T4 is deiodinized by 5’-deiodinase in peripheral tissues
What are the products of deiodination?
T3
rT3
Inactive degradation products
What is rT3?
Modulates action of active T3 by competing for receptor binding
What is the role of rT3?
Prevents the body from reacting strongly to T3
What is the Wolff-Chaikoff effect?
Excess iodide can inhibit thyroid peroxidase and reduce the thyroid’s ability to produceT3 and T4
Iodide is the form in which iodine is transported
How is the Wolff-Chaikoff effect limited?
Excess iodide is excreted from the urine
How are thyroid hormones transported?
99% of T3 and T4 bind to thyroid-binding globulin (TBG) proteins
Remainder is free in blood stream and biologically active
What may cause an increase in TBG levels?
Pregnancy
Oral contraceptive use
Estrogen stimulate TBG production in liver
What are the effects of TBG levels increasing?
Bound and total thyroid hormones rise
Free T3 and T4 are constant
What may cause a decrease in TBG levels?
Hepatic failure (in patients using corticosteroid drugs)
What are the effects of TBG levels decreasing?
Bound and total thyroid hormones fall
Free T3 and T4 are constant
How do T3 and T4 cross the cell membrane?
Transmembrane thyroid hormone transporters
T3 and T3 are lipophilic yet cannot cross the plasma membrane
Where do thyroid hormones exert their effect?
Bind to nuclear receptors to modulate gene expression
How do thyroid hormones exert metabolic effects?
Upregulate Na+/K+-ATPase
Promotes cellular uptake of glucose
Increases formation and catabolism of proteins
What effect does upregulating Na+/K+-ATPase have?
Increases cellular oxygen consumption
Increase heat production
Increases basal metabolic rate
What effects do thyroid hormones have on the heart?
Rapid pulse
Increased Cardiac Output
Why can thyroid affect the heart?
Upregulate β1-adrenergic receptors in the heart which increases response to sympathetic stimulation
What role does thyroid have in fetal development?
Enhances brain and bone development
How does the thyroid hormone enhance bone development?
Enhances formation and growth of osteoblasts
Acts on growth plate chondrocytes
How does the thyroid hormone enhance brain development?
Stimulates synapse and myelin fromation
Stimulates growth of dendrites and axons on neurons
Regulates neural crest cell migration and differentiation
Describe the pathway of thyroid hormone secretion
What is Graves Disease?
Autoimmune condition resulting in hyperthyroidism
What causes Graves Disease?
Abnormal thyroid-stimulating antibodies (TSI) bind to TSH receptors on thyroid follicular cells
Causes persistent thyroid hormone synthesis
Symptoms of Graves Disease
High excitability
Heat Intolerance
Increased sweating
Weight loss
Muscle weakness
Diarrhea
Nervousness or other psychic disorders
Fatigue with inability to sleep
Tremor of the hands
Exophthalmos
What is myxedema?
Total lack of thyroid function in adults
Symptoms of myxedema
Swelling of face (due to hyaluronic acid and chondroitin sulfate causing interstitial fluid accumulation)
Husky and Slow voice
Blood cholesterol increases and atherosclerosis develops
How does iodine deficiency cause goiter development?
Thyroglobulin formed but no thyroid hormones
TSH secretion remains uninhibited enabling hyperplasia and growth of thyroid gland
What is Thyroiditis/Hashimoto disease?
Antibody develops against thyroglobin which destroys thyroid cells
Causes hypothyroidism
What is Cretinism?
Stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones
What causes cretinism?
Lack of thyroid hormone or iodine during prenatal, neonatal or childhood stages
Effects of cretinism
Sluggish movement
Retarded physical and mental growth
Obese, stocky, short appearance
Tongue becomes large
