Thyroid Gland physiology Flashcards
What hormones does the thyroid gland produce?
Active T3 (triiodothyronine) and inactive T4 (tetraiodothyronine)
Describe the structure of the thyroid gland:
Thyroid follicle are surrounded by epithelial cells. Lumen in the center where thyroid hormones are stored in the colloid.
Also has parafollicular C cells that secrete calcitonin
What is the back bone of the thyroid hormone?
Thyroglobulin
What molecule is important for thyroid hormone synthesis?
Iodine (I2) from diet converted into I- and brought into thyroid gland via the iodide trap. Attached to the thyroid hormone
Draw out the synthesis equation of T3 and T4. What is the major product of this pathway?
Inactive T4. Later converted to T3 when needed via peripheral conversion
Draw the conversion pathway of T4 to T3
Ok
Peripheral conversion of T4 to active T3 can be hindered by …
Fasting
Physical stress
Catabolic disease
Draw the synthesis pathway of T3 and T4 inside the thyroid follicle
Ok
What enzyme recycles Thyroglobulin and Iodine? What happens if this is deficient?
Intrathyroidal deiodinase. Deficiency mimics Iodine dietary deficiency.
If there is low Iodine available, what is the favored product of thyroid synthesis?
T3 (requires less iodine)
What transports Iodine into the lumen of the thyroid follicle?
What happens if there is a mutation in this transporter?
Pendrin (a chloride iodide pump). Mutation = hypothyroidism = goiter and hearing loss since cochlear pendrin is also mutated.
How does hypothyroidism cause goiter?
TSH keeps stimulating the thyroid trying to make it make thyroid hormones = hyperplasia
What is perchlorate and thiocyanate?
Anions that compete with iodine binding to transporter. Decreases synthesis of thyroid hormones
How does PTU disrupt thyroid hormone synthesis?
What effect does this cause?
Disrupts peroxidase (which combines Iodine with TG) Causes buildup of Iodine which inhibits further synthesis of hormoness (Wolff-Chalkoff effect)
How does radioactive iodine uptake relate to thyroid gland activity?
Hyperthyroidism = more iodine uptake Hypothyroidism = less iodine uptake
What are the main binding proteins for thyroid hormones in the bloodstream?
Thyroxine binding globulin (TBG, higher affinity for T4)
Transthyretin (in brain tissue)
Albumin (everything else)
All of these are formed in the liver
Predict the T4 and resin uptake in these conditions (remember the pattern) Hyperthyroidism Hypothyroidism High TBG Low TBG Hepatic failure Pregnancy
Ok
Draw the HPT axis
OK
What is the pathway of TSH action on the thyroid gland?
TSH > GPCR > Adenlyl Cyclase > cAMP > mediate lots of things that help with T3/T4 production as well as thyroid gland growth
What is the mechanism of action of thyroid hormones?
-Act like steroid hormones (nuclear receptor)
Functions of thyroid hormones:
Growth
Synapse plasticity
BMR increase
Increase in cardiac output and B-adrenergic receptors
How exactly do thyroid hormones increase basal metabolic rate?
Thyroid hormone increases activity of Na/K ATPase leading to increase of O2 consumption and heat production]
Effect of T4 (thyroxine) is usually long lasting
Effects of thyroid hormone on lipid metabolism:
- Increase fat mobilization and FA oxidation
- Blood cholesterol level inversely correlated with thyroid hormone levels
- needed for carotene conversion to Vitamin A (eye problems and jaundice in hypothyroid patients)
Describe the effect of thyroid hormones on cardiovascular system:
Thyroid > T4 > T3 > Na/K ATPase > increase tissue thermogenesis > decrease systemic vascular resistance > increase speed and force of cardiac contraction > increase cardiac output > increase blood volume
Describe how thyroid hormones directly stimulate cardiac muscle:
Bind to B1 adrenergic receptors during sympathetic stimulation > increase in cardiac rate
What are the other effects of thyroid hormones?
Growth (working with growth hormone) CNS maturation (synaptic plasticity
What happens to neurons when there is thyroid deficiency?
Abnormal development of synapse, decreased dendrites or myelination
If in prenatal period = congenital hypothyroidism
What happens to TSH levels in primary hyperthyroidism?
How about ins secondary hyperthyroidism?
Lots of Thyroid hormones feedback and stop production of TSH
TSH levels are elevated since the defect is in the AP
What causes grave’s disease?
Thyroid stimulating immunoglobulins act as agonist for TSH which causes release of thyroid hormones that feedback to TSH
Symptoms of Grave’s disease:
Exophthalmos (eyeball protrusion) and periorbital edema
Elevated thyroid hormones, goiter. Presence of TSI in the blood (defining feature of Grave’s)
What are the primary causes of hypothyroid?
Destruction of gland (as in Hashimoto’s thyroiditis)
Thyroid hormone synthesis inhibition
Agenesis of thyroid
Short term reasons (after surgery/postpartum etc.)
How do you treat hypothyroidism?
Replacement doses of T4 (half life increases with age so younger patients need more doses)
Overprescribing T4 can lead to osteoporosis in menopausal women
Hashimoto’s thyroiditis:
Cause
Clinical
-Thyroid gland defective even if I2 is sufficient
Caused by thyroglobulin or TPO antibodies which affects synthesis and secretion
-TSH levels are high because TSH keeps poking the thyroid gland to make hormones (trophic effect = goiter)
Congenital hypothyroidism:
Cause
Clinical
- Iodide deficiency or taking anti-thyroid meds during pregnancy leading to impaired development of thyroid gland
- protruding tongue, curse facial features, growth and mental retardation, hypotonia and jaundice
Iodide deficiency
- No iodine = can’t make proper hormones
- TSH will be elevated since it keeps poking the thyroid gland to make hormones, can lead to goiter
Sheehan syndrome:
Cause
Clinical
- Necrosis of pituitary gland usually postpartum
- difficulties with lactation, no menses ( amenorrhea), hypothyroidism, other endocrine dysfunction also present
Generally what are the symptoms of hyper and hypothyroidism?
Hyper: weight loss, sweating, rapid HR and high BP because there’s too much thyroid in the body and increases body functions
Hypo: weight gain, cold intolerance, fatigue because there’s too little thyroid in the body and decreases body functions
Goiter development in hyperthyroidism:
TSH or something else stimulates/attacks the thyroid gland too much that it swells
Goiter development in hypothyroidism:
I2 deficiency or thyroiditis (TSH pokes the thyroid gland too much in causes it to hypertrophy)
