Thyroid Gland Flashcards
What does the thyroid gland produce?
T4, T3
Functional unit of the thyroid gland
Lined by cuboidal cells
Lumen is filled with ____.
Contains C cells (parafollicular cells that secrete ____.)
Thyroid follicle
Colloid
Calcitonin
Thyroid hormone contains ______.
What is the major secretory product of TH synthesis?
Colloid is composed of the newly synthesized thyroid hormones attached to ____.
Iodine
T4
Thyroglobulin
Where is T4 converted to T3?
How?
What states cause this conversion?
In the thyroid and peripherally
Through the action of deiodinase
Fasting, medical and surgical stress, catabolic diseases
Explain the conversion of T4 to T3
Dfdfd
Sources of iodine
Soil, seawater
Cheese, cows milk, eggs, frozen yogurt, ice cream, multivitamins, table salt, saltwater fish, seaweed, shellfish, soy milk, yogurt
TH synthesis:
Two transporters on the basolateral membrane that bring iodine into the cell.
Transporter on apical membrane that takes iodine out of cell.
What oxidizes iodide for combination with thyroglobulin?
What binds iodine to T4 and T3?
What then happens to the colloid droplet?
What cleaves T4 and T3 from thyroglobulin for release into circulation?
Na/K ATPase; Na/I symporter (NIS)
Pendrin (Cl/I counter-transporter)
Peroxidase
Thyroglobulin
Pincoytosis
Proteases
Inhibitors of TH synthesis
What is the Wolff-Chaikoff effect?
Perchlorate and thiocynate: inhibit NIS
Propylthiouracil (PTU): inhibits peroxidase
Inhibits organification
How is iodine stored?
Where?
For how long?
Iodinated as tyrosines of TG (more T3 than T4)
Follicular colloid
2-3 months
How do you assess the activity of the thyroid gland?
Give a dose of radioactive iodine and measure uptake over a period of time
Hyperthyroidism: high uptake
Hypothyroidism: low uptake
How is TH transported in the body?
Circulate in blood by being bound to plasma proteins or free
Binding proteins: thyroxin-binding protein (TBG), transthyreitin (TTR), albumin
How do you assess circulating TBG?
Indirectly with T3 resin uptake test:
Wash TBG with unbound T3 and see how much binds to TBG, and how much T3 is free and absorbed.
What causes changes in blood TBG?
Effects?
Hepatic failure: decreased blood TBG; increase level of free of T3 and T4; followed by inhibition of T3 and T4 synthesis through negative feedback
Pregnancy: increased blood TBG; increased bound (less free) T3 and T4; increases synthesis and secretion of T3 and T4; increase total levels of T3/T4 but free levels are normal
Describe the hormonal control of thyroid hormone and its regulators
Hypothalamus-pituitary-thyroid axis:
TSH released from thyrotrophs of anterior pituitary; causes growth of thyroid gland (tropic effect) and secretion of TH
Regulated by TRH, free T3
Explain thyroid hormone synthesis and secretion
?????
Conversion of T to T3 occurs in ____ though the action of ____.
T3 binds to nuclear receptor/transcription factors of ____.
Thyroid and peripherally; deiodinase
TRalpha1
TRalpha1
TRbeta1
TRbeta2
Actions of TH
Activates nuclear receptors and cAMP
Increased metabolic activity including BMR, CHO, lipid metabolism
Growth of fetus, neonate, adolescence
Increase cardiac output
GI motility
CNS development and excitation
Intracellular actions of TH
Synthesis of new proteins:
Na/K ATPase Transport proteins Beta1-adrenergic receptors Lysosomal enzymes Proteolytic proteins Structural proteins
Cardiac muscle: Myosin, beta1-adrenergic receptors, Ca ATPase
Actions of TH on metabolism
Increased metabolic activity including BMR, CHO, lipid metabolism:
Increase O2 consumption.
Increase activity of Na/K ATPase.
Stimulates lipid mobilization, FA in blood, enhanced fat oxidation.
Cholesterol and TG in blood inversely correlated with thyroid hormone.
Conversion of carotene to vitamin A (hypothyroidism can lead to blindness).
Increase gluconeogenesis, glycogenolysis, insulin-dependent glucos uptake.
Slow onset with lone duration action of TH (latent period)
Actions of T3 more rapid
Before T4 activity begins; 2-3 days before activity begins; 10-12 day to reach maximum; activity persists for 6-8 weeks
6-12 hours before activity begins; 2-3 days to reach maximum
Cardiovascular actions of TH
Increase CO
Direct and indirect effects
Decreased TPR/systemic release
Increase inotropic effects
Increased blood volume/preload
Indirect effects of TH on the cardiovascular system
Direct effects
Increase heat production and CO2 in tissues; decrease systemic vascular resistance; decrease diastolic BP; reflex increase adrenergic stimulation
Increase cardiac m of myosin heavy chain; increase ventricular contractility; decrease systemic vascular resistance
Actions of TH one sympathetic sensitivity
Increased CO
High levels of thyroid hormone increases number of beta1-adrenergic receptors
More sensitive to stimulation by sympathetics
Actions of TH on growth and CNS
Fetus, neonate, adolescence: ???
What are the levels of hyperthyroidism?
Excessive TH production (thyrotoxicosis)
Primary: Graves’ disease
Secondary: TSH secreting pituitary tumor
Changes in TSH levels: decrease because negative feedback of T3 on anterior pituitary
What is Graves Disease?
Hyperthyroidism
Produce antibody (thyroid-stimulating immunoglobulins, TSI) that binds to TSH receptor and constantly turns it on; doesn’t respond to negative feedback mechanisms
Types of hypothyroidism
Gland destruction (Hashimoto’s thyroiditis)
Inhibition of hormone synthesis and release (iodine deficiency)
Hypothalamic disease, pituitary disease, resistance to TH
Treatment of hypothyroidism
Replacement doses of T4
**
Disease caused by thyroid hormone synthesis is impaired by antibodies agains thyroglobulin or TPO, leading to decreased T3 and T4 secretion
TSH levels high, trophic effect leads to goiter
Hashimoto’s thyroiditis
Disease caused by iodide deficiency, maternal intake of anti-thyroid medications leading to impaired development of thyroid gland
Hypothyroidism Cretinism
Hypothyroidism due to iodine deficiency
TSH levels elevated
Goiter
When can a goiter develop?
Imbalances within the HPT axis:
Hyperthyroidism -> Graves’ disease, TSH-producing tumor
Primary hypothyroidism -> lack of iodine in diet, sporadic hypothyroidism, chronic thyroiditis (hashimoto’s disease/thyroiditis, autoimmune-induced deficiency in thyroid fx)
