Physio: Endocrine - Thyroid Gland

Front 1

What type of cell synthesizes thyroid hormones?

Back 1

follicular epithelial cells

Front 2

What is contained in the follicular lumen?

Back 2

colloid (thyroid hormones bound to thyroglobulin)

Front 3

Where is thyroglobulin synthesized, and where is it transported to?

Back 3

synthesized on RER and Golgi of follicular epithelial cells; extruded to follicular lumen via secretory vessels

Front 4

What is the "I- trap"?

Back 4

I- is actively transported across basal membrane from blood into follicular epithelial cells, against chemical and electrical gradients

Front 5

What factors inhibit the I- pump?

Back 5

thiocyanate and perchlorate ions, and high levels of I-, thus inhibiting thyroid hormone synthesis (Wolff-Chaikoff effect); also, very low levels of I-

Front 6

What factors stimulate the I- pump?

Back 6

mild to moderate I- deficiency (compensatory effect)

Front 7

What happens to the I- in the follicular cell?

Back 7

I- gets oxidized to I2 by peroxidase as it is transported across apical membrane

Front 8

What substance inhibits peroxidase, and what effect does this have?

Back 8

propylthiouracil (PTU), used therapeutically to reduce thyroid hormone synthesis in hyperthyroidism

Front 9

What happens to I2 in the follicular lumen?

Back 9

I2 organification. just inside the lumen, I2 reacts with thyroglobulin to form MIT and DIT (which remain attached to thyroglobulin)

Front 10

How are T3 and T4 produced from MIT and DIT?

Back 10

Coupling reactions on TG:
DIT + DIT = T4
MIT + DIT = T3

Front 11

What happens when the thyroid gland is stimulated?

Back 11

TG is endocytosed, lysosomal enzymes digest TG, releasing T4/T3 into circulation, while MIT and DIT are recycled

Front 12

What does thyroid deiodinase do? What happens if there is a deficiency of this enzyme?

Back 12

It deiodinates MIT and DIT so the I2 can be reutilized; deficiency mimics I2 deficiency

Front 13

What is the most common circulating form of T3 and T4?

Back 13

bound to thyroxine binding globulin (acts as a reservoir)

Front 14

What happens to TBG and free hormone levels during hepatic failure?

Back 14

TBG levels decrease, thus decreased total thyroid hormone level, but normal levels of free hormone (maintained by negative feedback)

Front 15

What happens to TBG and free hormone levels during pregnancy?

Back 15

TBG levels increase (estrogen inhibits hepatic TBG breakdown), thus increased total thyroid hormone, but normal levels of free hormone (maintained by negative feedback)

Front 16

What are the differences between T3 and T4? What enzyme catalyzes their conversion?

Back 16

more T4 is produced by the thyroid gland, but T3 is more active. T4 is converted to T3 by 5'-iodinase in peripheral tissues

Front 17

What are the actions of TRH?

Back 17

released from hypothalamus to stimulate release of TSH from a/p

Front 18

What are the actions of TSH?

Back 18

released from a/p to stimulate each step of synthetic pathway and s/c of thyroid hormones ; causes hypertrophy of thyroid w/chronic elevation

Front 19

What negative feedback mechanism regulates thyroid hormone secretion?

Back 19

free T3 feeds back to down regulate TRH receptors in a/p

Front 20

Pt w/high circulating levels of thyroid hormone but low TSH levels. What could be the cause, what is the disease?

Back 20

thyroid stimulating-immunoglobulins (antibodies to TSH receptor) stimulate thyroid gland to produce T3/T4; aka Grave's disease

Front 21

What is the molecular mechanism of action of thyroid hormones?

Back 21

(T4 (via 5' iodinase)-> T3) T3 binds nuclear receptor -> transcription -> translation -> new proteins many physiologic effects

Front 22

What are the major actions of thyroid hormones?

Back 22

promote bone formation, increase BMR, heat production, and O2 consumption, alter cardio/resp fns to increase blood flow/02 delivery to tissues, maturation of CNS in perinatal period

Front 23

What is the main mechanism through which thyroid hormones increase BMR and O2 consumption?

Back 23

increased synthesis and activity of Na-K ATPase

*results in increase in heat production*

Front 24

If thyroid hormones increase O2 consumption, what must happen to metabolism?

Back 24

body needs increased substrates for oxidative metabolism: increased glucose GI absorption, gluconeogenesis, lipolysis, proteolysis

Front 25

Is the overall action of thyroid hormones catabolic or anabolic? Does this cause increased or decreased lean muscle mass?

Back 25

catabolic (even thought they inc both protein synthesis and degradation); decreased muscle mass

Front 26

Thyroid hormones increase O2 consumption. How do thyroid hormones ensure that there is a subsequent increase in O2 delivery to tissues?

Back 26

increased synthesis of beta-1 adrenergic receptors, to increase heart rate and contractility (e.g. cardiac output) (myocardium is thus more sensitive to sympathetic stimulation); also increases ventilation rate

Front 27

Why would propranolol be an effective adjunct therapy for hyperthyroidism?

Back 27

beta-adrenergic blocker -> blocks autonomic effects of thyroid hormones (which upregulate beta-1 adrenergic receptors in heart)

Front 28

What are the effects of thyroid hormones on the CNS during the perinatal period?

Back 28

CNS maturation depends on thyroid hormones; deficiency causes irreversible MR (this is why screening for neonatal hypothyroidism is mandatory)

Front 29

What are the effects of hyperthyroidism on the CNS in adulthood?

Back 29

hyperexcitability and irritability

Front 30

What are the effects of hypothyroidism on the CNS in adulthood?

Back 30

listlessness, slowed speech, somnolence, impaired memory, decreased mental capacity

Front 31

What are some possible causes of hyperthyroidism?

Back 31

Graves disease (antibodies to TSH receptor), excessive exogenous thyroid hormones, thyroid neoplasm, excessive s/c of TSH or TRH

Front 32

Under what conditions would you see elevated T3/T4 levels, but low TSH levels?

Back 32

Graves disease, thyroid neoplasm, exogenous administraion

Front 33

What are the common symptoms of hyperthyroidism?

Back 33

weight loss w/inc food intake, inc metabolic rate, sweating, inc HR, breathlessness on exertion, tremor, nervousness, weakness, goiter

Front 34

What are some common treatments for hyperthyroidism?

Back 34

propylthiouracil (PTU) - inhibits thyroid hormone synthesis by blocking peroxidase

thyroidectomy, or radioactive ablation w/(131)

beta-blockers (adjunct therapy)

Front 35

What are some possible causes of hypothyroidism?

Back 35

autoimmune destruction (thyroiditis), surgical removal, hypothal/pit failure (dec TRH/TSH), I- deficiency, cretinism (aka congenital myxedema)

Front 36

Where would the primary defect be if pt had low T3/T4 levels but increased TSH levels?

Back 36

defect in thyroid/thyroid hormones themselves

Front 37

Where would the primary defect be if pt had low T3/T4 levels and low TSH levels?

Back 37

defect in hypothalamus or a/p

Front 38

What are the common sx of hypothyroidism?

Back 38

dec metabolic rate, weight gain, cold sensitivity, dec HR, slowed mental activity, lethargy, somnolence, periorbital puffiness (drooped eyelids), constipation, hair loss, menstrual dysfn, hypoventilation, sometimes myxedema, goiter (from unrelenting stimulation of thyroid by TSH)

Front 39

What is the common treatment for hypothyroidism?

Back 39

thyroid hormone replacement (usu T4)