Exam 1 --Pt 3 Thyroid Gland-- Endocrinology Flashcards
What do thyroid follicles in the thyroid hold that may be used to make active thyroid hormones for release? How it is “made”?
iodized thyroglobulin
import iodine; create thyroglobulin –> made iodize thyroglobulin (create and release thyroid hormones)
Where is the thyroid gland located?
below larynx on each side of trachea
T/F. The thyroid is one of the largest endocrine glands.
True
What hormones does the thyroid secrete?
- Thyroxine (T4)
- Triiodothyronine (T3)
- Calcitonin
What two hormones does the thyroid secrete that increases the metabolic rate of the body? In what percentage?
- Thyroxine (T4)–93%
- Triiodothyronine (T3)–7%
What happens to T4 when it gets to the tissues?
almost all is converted into T3
Which is more potent, T3 or T4? What is its half life?
T3 is about 4x more potent than T4, BUT it has a 6x shorter half life
What may interfere with T3 that is not biologically active?
Reverse triiodothryonie (rT3)
What does calcitonin do? What does it oppose?
secreted by thyroid; decrease blood Ca++
opposes action of PTH and activated vit. D (aka calcitriol–synthetic)
What is the form of activated Vit. D?
1,25 dihydroxycholicalciferol
The thyroid gland is composed of large number of ____ ____ with ____ and lined with ____ epithelial cells.
closed follicles; colloid; cuboidal
What is colloid?
secretory substance containing thyroglobulin (and thyroglobulin is the precursor for T3 and T4)
T/F. The Thyroid has very poor blood supply.
False— thyroid has rich blood flow (like all glands do)
What role does iodine have for the thyroid?
iodine is required for formation of T3 and T4
- need 1 mg of ingested iodine/wk to form normal qualities of thyroid hormones
Of the iodine absorbed how much is take up by the thyroid? What happens to the other part?
1/5 take up by thyroid
4/5 rapidly excreted by kidneys
Describe Iodine vs Iodide.
Iodine = I (the element 53) Iodide = I- (ion and cannot remain in free state; must combine with other elements to form compound)
How is iodide transported from blood into follicle of thyroid?
Sodium iodide symporter
- co-transport 1 idodide along with 2 Na+ ions
What pump is the sodium iodide symporter coupled with?
Na+/K+ pump
What stimulates the sodium iodide symporter? What diminishes it?
stimulated by TSH
diminished by hypophysectomy (removemal of Ant. Pit.)–therefore no TSH made)
What are 4 things the follicular cells of the thyroid do?
- import iodide
- create thyroglobulin
- make thyroid hormones
- release thyroid hormones
What is the precursor for all thyroid hormones?
thyroglobulin
- large glycoprotein
- 70-130 tyrosine residues (~20% iodinated)–> only 5% become part of ACTIVE thyroid hormones
What are the stages/steps of the thyroglobulin molecule being made in the follicular cells?
Rough ER –> Golgi –> Vesicle –> lumen
What does organification of thyroglobulin mean?
tyrosine (which is the precursor for thyroid hormones) on thyroglobulin will combine with iodide
(this takes place after essential first step)
What is the first essential step in the formation of thyroid hormones?
oxidation of iodide; which requires preoxidase and H2O2 (hydrogen peroxide)
Is the thyroid gland capable of storing thyroid hormones?
yes, it can store large amounts (which is unusual among endocrine glands)
- usually 2-3 month supply at a time
Each thyroglobulin molecule contains up to ___ T4 and a few ___ molecules.
30 T4 and a few T3 molecules
What is the order of synthesis to T4? Which are not biologically active?
Tyrosine–> MIT (monoiodotyrosine) –> DIT (diiodotyrosine ) –> T3 –> T4
MIT and DIT are NOT biologically active
How many iodines does T4 have? How many does T3 have?
T4 has 4 on 3,5,3’,5’
T3 has 3 on 3,5,3’
What stimulates the uptake of Thyroglobulin into follicular cells from follicular lumen? What does this also then stimulate
TSH—> to go through MIT –> DIT –> T3 –> T4 and secrete into extracellular fluids
Describe how thyroid hormones are doubly secreted?
- precursor molecule thyroglobulin is released from apical surface of follicular cell into follicular lumen
- Thyroglobulin is taken back up by follicular cells and degraded to release T4 and T3 which are secreted from basal surfaces into blood
What is the primary thyroid hormone secreted?
Which is the major biologically active form?
T4
T3
(most T4 transformed to T3 at target sites)
Biosynthesis of thyroid hormones depends on the products of three genes expressed primarily in thyroid follicular cells–what do these three genes code for?
- Sodium iodide symporter
- Thyroglobulin
- Thyroid peroxidase
Prior to release of thyroid hormones, what must occur? How much of T4 and T3 are released?
must be cleaved form thyroglobulin
93% T4 (1/2 of T4 converted to T3)
7% T3
How is over 99% of T3 and T4 transported in blood?
bound to plasma proteins (synthesized by liver)–> providing controlled slow release to tissues
What type of onset do thyroid hormones have? What type of duration?
slow onset; but long duration of action
What impact will high serum levels of T4 have on TSH? What about T3?
TSH secretion will be inhibited
T3 has lesser impact
What is TRH? What releases it?
Thyrotropin-releasing hormone; released by hypothalmus
What is TSH controlled by?
TRH (thyrotropin-releaseing hormone) released by hypothalamus – it will bind to TRH receptors on anterior pituitary
What impacts the sensitivity of the pituitary to TRH?
depends on intrapituitary T3 levels:
- when T4 serum levels drop, intrapituitary T3 also drops
- TRH receptors on pituitary increase due to the results of low T3
(need to secrete more TSH in order to make more Thyroid hormones)
What stimulates release of TRH? What does this do to BMR?
exposure to cold; noticed by thermoregulation by hypthalamic centers
increase BMR up to 50%
Where are TSH receptors located? What does it work with?
on surface of thyroid follicular cells
- works with cAMP
What enzyme is used to create AMP from cAMP? Why is this important?
phosphodiesterase
(used along with TSH receptors on thyroid follicular cells)
therefore this enzyme inhibits the effects of thyroid hormones b/c cAMP cannot go phosphorylate things
T/F. TSH increases all known secretory activities of the thyroid glandular cells.
True
What is responsible for mediating TSH effects?
cAMP
What secretory activities of the thyroid glandular cells does TSH increase?
- proteolysis of thyroglobulin
- activity of iodide pump
- iodination of tyrosine
- size and secretory activity of thyroid cells
- number of thyroid cells (cubdoidal to columnar)
What is the major transporter for T4 (thyroxine)?
Thyroxine-binding globulin (TBG)
What transport molecule has the highest affinity for T3 and T4?
Thyroxine-binding globulin (TBG)
- 77% of T4 bound to TBG
What transport molecule has a lesser affinity for T4 and does not effectively bind T3?
Transthyretin (aka TTR or Thyroxine-binding preablumin)
How does T4 get turned into T3 once it gets to the tissues?
5’ monodeidoninase (takes off 5’ iodine)
Can thyroid hormones activate nuclear receptors?
yes, and they increase transcription of a large number of genes
What type of nongenomic cellular effects do thyroid hormones have on cells?
- regulation of ion channels
- regulation of oxidative phosphorylation
- probably involves cAMP-protein kinase activation
How do thyroid hormones affect cellular metabolic activity?
increases it;
- increases number and activity of mitochondria
- increase active transport of ions through cell membranes (Na+/K+ pump
How do thyroid hormones affect grow? What impact does this have?
promote growth
- Hyperthyroid children grow faster (but epiphyseal plates may close sooner and therefore duration of growth is shortened)
What if there is a lack of thyroid function at birth?
intellectual development disorder occurs
thyroid’s affect on growth is very important on the brain, esp. during fetal and neonatal period
What do thyroid hormones decrease the concentration plasma of?
- cholesterol
- phospholipids
- triglycerides
What will an increase in thyroid hormones (T3/T4) have on cholesterol?
increases rate of cholesterol secretion into bile and increase fecal loss
increases LDL receptors on liver cells and promotes rapid removal of LDL from plasma by the liver
What are thyroid hormones affect on: vitamins? BMR? Body weight? Digestive system?
- increase requirement for vitamins
- increase BMR
- decrease body weight
- increase appetite, food intake, GI tract motility, secretion of digestive juices
What are the effects of thyroid hormones on the cardiovascular system?
- increase blood flow
- increase cardiac output (direct and indirect)
- increase HR and strength of contraction
- increase systolic and decrease diastolic due to decrease Total Peripheral Resistance–> causing mean arterial pressure to be unchanged
What effects do thyroid hormones have on the CNS?
increase rapidity of cerebration (thought)
What effect does hyperthyroidism have on the CNS?
- extreme nervousness/hyperexcitability
- incrase startle response
- psychoneurotic tendencies (anxiety, worry, paranoia, irritability)
- hyperreflexia
What effect does T3/T4 have on skeletal muscle at normal levels?
enhances muscle contraction
What effect does T3/T4 have on skeletal muscle when in excess?
weakens muscle contraction due to excessive protein catabolism
What effect does T3/T4 have on skeletal muscle in hypothyroidism?
cause molecules to be sluggish and they contract slowly after a contraction
What is a characteristic sign of hyperthyroidism dealing with skeletal muscle?
is fine muscle tremor (10-15Hz)*
What effect does hypothyroidism have on sexual function?
in both men and women leads to loss of libido (sex drive)
- in excess for men may cause impotence
What do hypothyroid women usually have that relates to sexual function?
menorrhagia (excessive uterine bleeding) or polymenorrhea (diminished menstrual flow)
What do hyperthyroid women have that relates to sexual function?
oligomenorrhea (diminished menstrual flow) and occasionally amenorrhea (no menses)
How do thyroid hormones have on effect the gonads?
both direct and indirect acting through feedback effects on the anterior pituitary
Describe the effects/actions on metabolism that thyroid hormones have.
- control BMR
- stimulate anabolic and catabolic pathways
- increase O2 consumption and heat production
- mitoch. increase in size and number (hyperth.)
- membrane more permeable = Na+/K+ ATPase pumps run harder
What part of the ANS do thyroid hormones interact with?
Sympathetic nervous system
Increase secretion of thyroid hormones will exaggerate mediated responses of what (when related to ANS)?
of NTs NE and Epi from both SNS and adrenal medulla
What do many symptoms of hyperthyroidism resemble?
sympathicotonia (excessive sympathetic activity)–> increase HR, tremor, sweating
increase SNS mimics hyperthyroidism too (NE and Epi ass. with T3/T4)
How do T3/T4 affect Beta-receptors? What about G proteins?
increases beta-receptors for NE/Epi in myocardium and other tissues
increase Gs proteins and decrease Gi proteins
What effect does SNS have on local convertion of T4–> T3?
it accelerates the local conversion
If someone was on pharmacologic blockage of beta-receptors, what are you thinking they may have?
they are useful to lessen effects of hyperthyroidism
When someone has excitement and anxiety that is stimulating the SNS, how does this affect thyroid function?
cause an acute decrease in TSH secretion due in part to increase in metabolic rate and body heat production —> which suppresses TSH release via inhibition of TRH
What happens if the hypophysial stalk (infundibulum stalk) is cut?
effects are abolished of thyroid hormones; demonstrating hypthalamic control
What affect do thyroid hormones have on skeletal muscle?
- increased Na+/K+ ATPase membrane pumps
- increase Ca++ into sarcoplasmic reticulum
- increased muscle mass
- increase glycogen synthesis
- diminishes glycogen breakdown (therefore glycogen accumulates)
What affect do thyroid hormones have on cardiac muscle?
increased HR, contractability and cardiac output
- increased Na+/K+ ATPase membrane pumps
The action of hypothyroid is to _____ physiological action, while the action of hyperthyroid is to ______ physiological action. What is the one exception that hyperthyroid with decrease?
decrease; increase; hyperthyroid will decrease serum levels of cholesterol*
