Thyroid and Gastrointestinal Hormone Physiology

Question 1

draw out the hypothalamic-pituitary-thyroid (HPT) negative feedback loop

Answer 1

Question 2

the human thyroid gland is the ___ gland in the body

Answer 2

largest

Question 3

is the thyroid gland well-vascularized?

Answer 3

yes

Question 4

describe inactive thyroid glands

Answer 4

• colloid (thyroglobulin) is abundant
• follicles are large
• cells lining the follicle are flat

Question 5

describe active thyroid glands

Answer 5

• follicles are small
• cells lining the follicle are cuboid
• edges are scalloped with many small resorption gaps resulting from the uptake of colloid

Question 6

what are the two primary functions of the thyroid?

Answer 6

1. secretion of the two biologically active thyroid hormones by follicular cells:
   
   1. thyroxine (T4)
   2. triiodothyronine (T3)
2. secretion of calcitonin by parafollicular cells (aka C cells)

Question 7

thyroid hormones stimulate enzymes involved with glucose oxidation, thus increasing ___ and ___

Answer 7

• basal metabolic rates
• heat production (calorigenic)

Question 8

describe parafollicular c-cells

Answer 8

• dispersed throughout the thyroid
• parathyroids and thymus release calcitonin in response to high blood calcium levels
  
  • calcitonin lowers blood calcium levels by inhibiting the resorption of bone by osteoclasts

Question 9

which 3 key hormones regulate calcium homeostasis?

Answer 9

• 1,25-dihydroxycholecalciferol
  
  • formed from vit D in the skin via the sun and successive hydroxylations in the liver and kidneys
• parathyroid hormone (PTH)
  
  • secreted by chief cells of the parathyroid glands in response to low blood Ca2+
• calcitonin (CT)
  
  • secreted by parafollicular cells in the thyroid glands in response to high blood Ca2+

Question 10

thyroid hormones (T3 and T4) are synthesized from ___ and ___

Answer 10

iodine and tyrosine

Question 11

describe the production of T3 and T4

Answer 11

• T3 is primarily produced extrathyroidally (mostly in the liver) from its precursor, T4
• T4 is produced exclusively in the thyroid

Question 12

describe the potency of T3 relative to T4

Answer 12

T3 is 4x more potent than T4

Question 13

although the vast majority of the thyroid hormones produced by the thyroid is ___, almost all of the ___ produced gets quickly converted to ___ peripherally once the hormones are released from thyroglobulin stores

Answer 13

• T4
• T4
• T3

Question 14

what is rT3?

Answer 14

• “reverse T3”
• inactive form
• made mostly in the liver
• 20% of T3 formed from T4 is converted to rT3

Question 15

what enzyme is responsible for converting T4 to T3 and rT3?

Answer 15

• 5’ de-iodinase enzyme converts T4 to T3
• 5 de-iodinase enzyme converts T4 to rT3
• important to realize that the # (T4, T3) is referring to the number of iodines bound

Question 16

HPT axis:

hypothalamus stimulates the anterior pituitary to produce ___, (aka thyrotropin), which stimulates the thyroid gland to produce ___, which can then be converted to ___

Answer 16

• thyroid stimulating hormone (TSH)
• T4
• T3

Question 17

what 3 things can increase T4 and T3 production?

Answer 17

• low T4
• low T3
• cold exposure
• increasing T4 and T3 is calorigenic
  
  • increase basal metabolic rate (BMR) and body temperature

Question 18

T3 is mainly produced extrathyroidally. what does this mean in relation to HPT axis regulation?

Answer 18

T3 can act independently of HPT axis regulation in peripheral tissues

Question 19

describe how thyroid hormones target nuclear receptors and modulate gene expression

Answer 19

• stress, dietary iodine, illness, fasting, and cortisol (steroids) can alter activity of deiodinase enzymes
• under stress/fasting, body convertes less T4 to T3, and more T4 to rT3

Question 20

without sufficient ___, thyroid hormones are not released and TSH builds up.

Answer 20

• iodine
• can cause goiter

Question 21

describe how thyroid hormones are calorigenic

Answer 21

cause cells to consume more energy and produce heat as a byproduct

Question 22

the amount of T4 produced and releasd by the thyroid gland is controlled directly by TSH released by the ___

Answer 22

anterior pituitary

Question 23

what is the best known stimuli for increasing the rate of TSH secretion by the anterior pituitary?

Answer 23

exposure to cold

Question 24

what amino acid is thyroid hormone derived from?

Answer 24

tyrosine

Question 25

what receptors do thyroid hormones bind to?

Answer 25

nuclear receptors (lipophilic)

Question 26

thyroid hormones form complexes that act as \_\_\_\_

Answer 26

hormone-activated transcription factors

Question 27

thyroid hormones act by modulating gene expression to \_\_\_

Answer 27

direct protein synthesis

Question 28

thyroid gland stores huge reservoirs of both T3 and T4 incorporated in \_\_\_, the protein in which the hormones are assembled and stored

Answer 28

thyroglobulin (TGB)

Question 29

\_\_\_ is essential for normal thyroid function

Answer 29

iodine

Question 30

thyroid cells are the only cells in the body that can absorb \_\_\_

Answer 30

iodine

Question 31

how is iodine deficiency defined by WHO?

Answer 31

* urine iodine excretion of \>70% of dietary iodine intake * for adults, that is urine excretion of \>/=105 mcg/day

Question 32

what is goiter?

Answer 32

* the result of excessive tissue growth when the thyroid cells are exposed chronically to too much TSH or hCG * exogenous hCG shots for weight loss can also cause goiter * may also results from iodine deficiency, but more often results during pregnancy or chronic autoimmune hashimoto's disease or thyroid cancer

Question 33

what can prevent most iodine deficiency in the USA?

Answer 33

iodine supplementation in salt

Question 34

name 5 medications that may promote goiter often by interfering with iodine uptake in the thyroid gland

Answer 34

* anti-thyroid medications * sulfonamide antimicrobials * amiodarone * lithium * salofalk (mesalazine is active ingredient)

Question 35

what environmental compounds may promote goiter?

Answer 35

* mercury, arsenic, and some other heavy metals * nitrates * pesticides

Question 36

describe congenital hypothyroidism (cretinism)

Answer 36

* cretinism is the most extreme manifestation of iodine deficiency disorder * can be hereditary, but more often due to deficiency of iodine in the mother's diet during pregnancy, resulting in fetal and/or neonatal hypothyroidism from birth

Question 37

how can too much or too little thyroid hormone lead to goiter?

Answer 37

* hypothyroidism - hashimotos disease * reduced T4 and T3 causes overproduction of TSH by the anterior pituitary, causing goiter * hyperthyroidism - graves disease * auto-antibodies attach thyroid, thyroid defensively overproduces thyroid hormones, leading to goiter

Question 38

what are 4 functions of the GI?

Answer 38

* secretion * digestion * absorption * gut motility

Question 39

the regulation of GI function involves what 3 forms of hormonal communication?

Answer 39

* endocrine * paracrine * neurocrine

Question 40

describe endocrine regulation of the GI

Answer 40

* hormones released in response to meal consumption travel in the bloodstream and have distant effects on target cells in the GI, pancreas, or both

Question 41

describe paracrine regulation of the GI

Answer 41

* provide local effects on neighboring cells

Question 42

describe neurocrine regulation of the GI

Answer 42

* connections from both the CNS and the enteric nervous system integrate central regulation of the gut in response to changes in the luminal environment

Question 43

what is an example of a hormone that can act in neurocrine, endocrine, and paracrine fashion in the regulation of the GI?

Answer 43

cholecystokinin (CCK)

Question 44

how are normal GI functions regulated?

Answer 44

balance of positive and negative hormonal events

Question 45

what is the source, stimuli for release, and action of gastrin?

Answer 45

* source: G cells in stomach * stimuli: consumption and peptides in gastric lumen * action: stimulates gastric acid secretion and proliferation of gastric mucosa

Question 46

what is the source, stimuli for release, and action of cholecystokinin (CCK)?

Answer 46

* source: I cells in duodenum and jejunum * stimuli: digestive products of fats, fatty acids, and monoglycerides * action: contracts gallbladder, expelling bile into small intestine

Question 47

what is the source, stimuli for release, and action of secretin?

Answer 47

* source: S cells in duodenum * stimuli: acidic pH in lumen of small intestine * action: stimulates pancreas to release bicarbonate to neutralize acids

Question 48

what is the source, stimuli for release, and action of gastric inhibitory protein?

Answer 48

* source: mucosa of upper small intestine * stimuli: fatty acids \> amino acids \> CHOs * action: inhibits gastric secretions and motility, and increases insulin release when duodenum is overloaded and blood glucose is elevated

Question 49

name the pancreatic hormone with the following characteristics: * purpose: counter-regulatory assistance for insulin * action: release of glucose from cells * released due to: low blood sugar * inhibited by: high blood sugar * deficiency: hypoglycemia * excess: hyperglycemia

Answer 49

glucagon

Question 50

name the pancreatic hormone with the following characteristics: * purpose: regulate blood glucose * action: adsorption of glucose from cells * released due to: high blood sugar * inhibited by: low blood sugar * deficiency: diabetes * excess: hypoglycemia

Answer 50

insulin

Question 51

name the pancreatic hormone with the following characteristics: * purpose: regulates GI hormones in pancreas and GI tract * action: slows production of insulin, glucagon, gastrin, and other hormones * released due to: high hormone levels * inhibited by: low hormone levels * excess: diabetes

Answer 51

somatostatin