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105 Cards in this Set
- Front
- Back
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What are the hormones secreted by the thyroid?
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-Thyroxin T4
-Triiodothyronine T3 -Calcitonin |
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What cells secrete T3/T4? How much of each?
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Follicle cells
93% T4 7% T3 |
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What cells secrete calcitonin?
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Parafollicular cells
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Which thyroid hormone is more physiologically active?
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T3
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What is colloid made of?
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Thyroglobulin
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What ingredient is absolutely essential for Thyroxine formation?
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Iodine in the form of iodide
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Where do we get our iodized iodine?
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Table salt
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Where is iodine absorbed?
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In the GI tract
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What is the first step in forming thyroid hormones?
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Iodide trapping
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What is responsible for Iodide trapping?
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A specific active transporter on the basal membrane of thyroid follicle epithelial cells.
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What does the pump do to intracellular iodide conc
-At normal activity -At maximal activity |
Normal: increases the [I] to 30x the blood concentration
Max Activity: to 250X it! |
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What is responsible for stimulating the iodide pump?
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TSH
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What do the ER and golgi apparatus of thyroid epithelial cells secrete?
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The glycoprotein Thyroglobulin
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What does thyroglobulin consist of?
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~70 tyrosines
Iodine |
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Where do the thyroid hormones form and get stored?
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WITHIN the thyroglobulin molecules
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What must happen to iodide in order to form thyroid hormone?
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It must be oxidized to Iodine so that it can combine with tyrosine
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What is responsible for this important oxidation of iodine?
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Peroxidase and hydrogen peroxide.
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Where is peroxidase located?
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Within the apical membrane or attached to it.
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So where is iodine oxidized?
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At the point where thyroglobulin enters the colloid.
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What will happen if peroxidase is absent or blocked?
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No thyroid hormone gets made.
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What is the binding of iodine to thyroglobulin called?
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Organification of thyroglobulin
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What enzyme makes organification in thyroid cells fast?
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Iodinase
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When thyroglobulin is released from the Golgi and into the colloid, how much gets iodinated immediately? What are the products called?
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1/6 of the Tyrosine residues get organified immediately --> forms MIT + DIT
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So what makes T4?
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DIT + DIT
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What makes T3?
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MIT + DIT
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How many T4 can one thyroglobulin molecule store?
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Up to 30
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How much T4 does the thyroid store at one time?
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Enough to maintain sufficient blood levels for 2-3 months in the absence of hormone production.
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What is the effect of the vast amount of thyroid hormone stored?
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Physiologic effects of deficiency won't be seen for a few months.
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What must occur for thyroglobulin to release T3/T4?
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-Pinocytosis from colloid
-Lysosome fusion w/ vesicle -Protease cleaveage of the hormones from thyroglobulin |
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How do free T3/T4 get from the epithelial cell to the blood?
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By diffusion
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Does all iodinated Tyrosin on thyroglobulin become thyroid hormone?
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No; actually 75% doesn't
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What happens to the iodinated tyrosines on thyroglobulin that don't make it to the hormone level?
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They get deiodinated after digestion in lysosomes, and iodine is once again put into the colloid.
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What results from congenital absence of Deiodinase enzyme?
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Iodine deficiency due to lack of recycling.
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How much iodized iodine do we normally take in form the diet?
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500 ug
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How much of that iodine goes to the thyroid?
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~120 ug
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Where does the other 380 ug go?
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To the urine
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Of the 120 ug iodide that goes to the thyroid how much gets put into thyroid hormones?
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70 ug
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Where does the other 50 ug form the thyroid go?
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To the urine
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What happens to the iodine after thyroid hormone exerts its effects on target tissues?
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It gets metabolized and excreted
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How much metabolized iodine from thyroid hormones gets excreted in the urine? feces?
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Urine = 55 ug
Feces = 15 ug |
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So of the 500 ug iodide that we taken in daily how much do we excrete?
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500 ug - MASS BALANCE
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What is the half life of
-T4 -T3 |
T4 = 6.2 days
T3 = 1 day |
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Why do the thyroid hormones have such a long half life?
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Because they circulate bound to plasma proteins and are protected from degradation.
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What are the 3 plasma proteins that bind Thyroid hormones?
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-Thyroxine binding globulin TBG
-TBPA (transthyretin) -Albumin |
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Of the total free T4 pool how much is bound to protein? What about for T3?
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99.97% - T4
99.7 - T3 |
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So does that mean that there is more free T3 than T4?
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No; there is much less T3 than T4 circulating, just a higher percentage is free.
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Why is there more T3 free than T4?
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Because it is bound less tightly by proteins
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Does TBPA bind T3?
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No - it is thyroxine binding pre-albumin
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How does the fact that thyroid hormones are protein-bound affect their action?
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They have a SLOW ONSET and LONG DURATION of action
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How long does it take to see a metabolic rate increase after injecting a large amt of T4?
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About 2-3 days
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How many days does it take for the injection to reach its max effect?
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10-12 days
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How many days does it take for metabolic rate to return to normal?
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15
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If you were to give the same large dose but of T3 instead of T4, how would the response time differ?
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Metabolism rate would increase in 6-12 hours and max at 2-3 days!! much faster
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In a nutshell what is the general effect of Thyroid hormone?
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Increased transcription of large numbers of genes.
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In what body cells does this increase in transcription occur?
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Virtually all of them
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What happens to thyroxine before it exerts its effect on gene transcription?
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One iodine is removed to form T3
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Why is T4 converted to T3 before exerting its effect?
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Because intracellular thyroid hormone receptors have a much higher affinity for T3
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Where is most thyroid hormone receptor found?
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On DNA Thyroid Hormone Response Elements where it is complexed with Retinoid X Receptor (RXR)
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What happens when T3 binds its receptor on the thyroid hormone response element?
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It increases transcription, translation, and new protein synthesis.
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What is the intracellular enzyme that converts T4 to T3 before binding its receptor?
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Iodinase
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What broad effect does thyroid hormone gene activation have on the body?
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Increased metabolic rate
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What are 4 specific systems that are affected by TH?
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-Growth
-CNS development -CV system -Metabolism |
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If target cells can make T3 from T4, can they make T4 from T3?
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Nope; only the one way of T4 to T3
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How does thyroid hormone affect metabolism?
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It increases food breakdown - both carb and proteins.
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What is Cretinism?
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Neonatal mental retardation due to a lack of Thyroid hormone
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What must be done to prevent Cretinism?
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Thyroid hormone administration of levothyroxine given immediately at birth.
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What results if thyroid hormone is not given at birth?
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Irreversible failure of CNS development.
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What is an adverse effect of overproduction of thyroid hormone and overstimulation of metabolic rate?
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Relative vitamin deficiency
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How is the target of thyroid hormone within the nervous system?
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The sympathetic adrenergic system
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How does thyroid hormone affect the symp adrenergic system?
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It increases B-adrenergic receptors in the heart, liver, muscle, and fat cells.
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What is the effect of increased b-adrenergic receptors?
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Increased b-adrenergic responses
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What is the main regulatory hormone that affects thyroid secretion?
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TSH from the pituitary gland
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What type of hormone is TSH?
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A glycoprotein
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What exactly does TSH do?
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Increases all known secretory activities of the thyroid glandular cells
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What is the most important early affect of TSH?
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Initiation of Thyroglobulin proteolysis and release of T3/T4
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Where are the TSH receptors on the thyroid gland?
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On the basal surface of follicular cells
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What is the direct effect of TSH binding its receptor?
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Increased cGMP
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So the 2 resulting effects of TSH stimulation of the thyroid:
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1. Immediate release of TH
2. Prolonged growth of the thyroid glandular tissue itself (Tropic + Trophic) |
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What is the major controller of thyroid hormone release?
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TSH
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What is the major controller of TSH release?
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T3/T4 - via negative feedback
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What is the role of TRH then?
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To adjust the setpoint of the pituitary. When more T3/T4 is needed than normal, TRH will increase, and vice versa.
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What is primary hypothyroidism?
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Decreased thyroid hormone due to a problem with the thyroid gland itself.
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What is the name for primary hypothyroidism?
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Hashimoto's thyroiditis
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What happens in Hashimotos?
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An autoantibody develops against the thyroid and causes destruction of the gland.
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What is the basis for diagnosing Hashimoto's?
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Low free T4 + High TSH
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What is 2ndary hypothyroidism?
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Decreased thyroid hormone due to decreased TSH - hypopituitarism
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What is the basis for diagnosing 2ndary hypothyroidism?
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Low Free T4 + normal/low TSH
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What is the treatment for low thyroid hormone (whether primary or secondary)?
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Levothyroxine
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What is the most common form of hyperthyroidism?
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Primary - an overproduction due to a problem with the gland itself.
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What is primary hyperthyroidism called?
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Grave's disease
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What is the pathology of Grave's?
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An autoantibody to the TSH receptor develops and results in overstimulation of thyroid hormone release.
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What is the basis for diagnosing Grave's disease?
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-High Free T4
-Low TSH |
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What is an interesting sign of Grave's disease?
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The pemberton sign - guy turn's red when he raises his arms.
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So the best screening test for diagnosing a thyroid disorder is:
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Serum TSH
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Graves disease:
-Total T4 -TBG -Free T4 -TSH |
Total T4 = High
TBG = normal Free T4 = high TSH = low |
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Hashimoto's Thyroiditis:
-Total T4 -TBG -Free T4 -TSH |
Total T4 = Low
TBG = normal Free T4 = Low TSH = High |
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Pregnancy
-Total T4 -TBG -Free T4 -TSH |
Total T4 = High
TBG = High Free T4 = N TSH = N |
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Why do TBG/T4 increase in pregnancy?
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Because estrogen stimulates the liver to make more TBG, which stimulates an increase in T4.
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What are 3 types of treatment for hyperthyroidism?
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1. Radioactive Iodine injection
2. Surgical removal 3. Drugs |
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What does radioactive iodine injection do?
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Destroys the thyroid gland - it melts!
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When is radioactive iodine treatment bad? Why?
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In pregnant women - it crosses the placenta
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So what should you ALWAYS do before prescribing radioactive iodine treatment?
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A pregnancy test (in women of course)
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What is the only certified drug for treating hyperthyroidism in pregnancy/
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PT4
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Why is drug treatment not the preferable method?
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Because as it blocks organification of thyroglobulin, the resulting decrease in T3/T4 results in increased TSH release - always chasing your tail.
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What type of treatment is most commonly used for thyroid cancer?
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Surgical thyroidectomy
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