Thyroid Gland Physiology Flashcards
1
Q
What are the hormones produced by the thyroid gland?
A
Pro-hormone Tetraiodothyronin (T4)
Tri-iodine-thyronine (T3)
2
Q
What is the functional unit of the thyroid gland?
What odes it do?
A
Thyroid follicle
Synthesized thyroid hormones
3
Q
How is the thyroid follicle organized?
A
Surrounded by single layer of epithelial cells that sit on a basal lamina
Follicular lumen - filled w/ colloid
Parafollicular cells
4
Q
What will change the size and amount of colloid?
A
Activity
5
Q
What do parafollicular cells secrete ?
When?
A
Calcitonin
When ca is high
6
Q
What is contained in Colloid?
A
Newly synthesized thyroid hormones attached to TGB
Iodinated tyrosine of TBG
7
Q
Where is iodine stored in thyroid gland?
How much? Allows for?
A
Stored in colloid as iodinated TGB
8000 ug total (600 ug in T4 and T3)
Allows to reservoir that could last body 2-3 mos. if iodine becomes deficient
8
Q
How much hromone will the thyroid follicle cell secrete / day?
A
60 ug
9
Q
What is T3 and T4 collectively called?
A
Iodothyronines
10
Q
What is thyroxine?
What is Tri-iodothyronine?
A
T4 = 2 molecules of DIT
T3 = 1 DIT; 1 MIT
11
Q
What is the major secretory product of the Thyroid follicle?
A
T4
T4 produced 10x more than T3
12
Q
How is T4 converted to T3?
A
De-iodinated type 1 and type 2
13
Q
How is T4 converted to Reverse T3 ?
What is different about reverse T3 from t3?
A
De-iodinase type 3
Reverse T3 = inactive
14
Q
What is the function of peripherally converting T4 to T3?
A
Provides circulating T3 for uptake by other tissue where T3 supply is low
15
Q
When would we want to reduce conversion of T4 —> T3?
A
Fasting
Medical & surgical stress
Catabolic disease
16
Q
What can a deficiency in de-iodinated mimic?
Causing?
A
Mimics dietary iodine deficiency because MIT/DIT is not being recycled
Goiter
17
Q
What is the driving force for the iodide trap?
A
Na-K+ pumps
18
Q
What is the pathway for the synthesis of thyroid hormone?
A
Tyrosine —> Thyroglobulin (TG)
Thru rough Er, golgi out apical side into colloid
Iodide take up by trap — thru pendrin pump to apical membrane
Iodide —thyroid peroxidase (TPO)—> Iodine
iodine + TG —TPO—> iodinated TGB
(has MIT and DIT attached)
Iodinated TGB —TPO—> TGB w/ T3/T4
(Stored as colloid)
TSH stimulation —> TG w/ T3/T4 pinocytosed thru apical membrane
TG w/ T3/T4 —protease—> T3/T4 out basilar membrane
TG w/ MIT/DIT —intrathyroidal Deiodinase —> free TG and free iodide
19
Q
What will be favored when iodide availability is restricted?
A
formation of T3
20
Q
What is pendrin?
A
Chloride - iodide pump located on apical membrane of thyroid follicular cells
21
Q
What is pendred syndrome?
Presents w/?
A
Mutation in pendrin gene (SLC26A4)
Causes defects in transport across apical membrane
Sensorineural hearing loss (affects cochlea)
HYPO-thyroidism w/ goiter
22
Q
What can inhibit the uptake of iodide?
A
Perchlorate, thiocynate
Competes w/ NIS iodide trap to bind iodide
23
Q
What steps in the synthesis of thyroid hormones will PTU affect?
A
PTU will inhibit Thyroid Peroxidase (TPO)
Blocking organification
24
Q
What is organification in the synthesis of thyroid hormone pathway?
A
Thyroglobulin iodination
25
What is the Wolff-chaikoff effect?
Increased iodide will cause decreased T3/T4 production
| Bc organification is inhibited
26
How can you assess the activity of the thyroid gland?
Asses by radioactive iodine uptake
If activity is high, then low amount of T3 resin uptake is seen
27
How are thyroid hormones transported in blood?
Mostly bound to plasma proteins (99%)
Some free (1%)
28
What is the equilibrium of thyroid hormones found in blood?
There is an equilibrium bw/
Free t3/t4 and bound T4/T3
29
What proteins are T3and T4 bound to in blood?
Thyroxine-binding globulin (TBG)-70%
Transthryretin
Albumin
30
Where is thyroxine-binding globulin synthesized?
What does it have a higher affinity for?
In liver
Higher affinity for T4
31
What is the half life of T4/T3?
T4 = 6 days
T3 = 1 day
32
How will levels of T4 and T3 resin uptake change in
Hyperthyroidism?
Increase in T4
High T3 resin reuptake bc no open spots on TBG
33
How will levels of T4 and T3 resin uptake change in
HYPOthyroidism?
Low T4
Low T3 resin reuptaken (bc more was able to bind TBG)
34
How will levels of T4 and T3 resin uptake change in
HIGH TBG?
Increase T4
Low levels of T3 resin reuptaken (bc so much TBG it can bind to)
35
How will levels of T4 and T3 resin uptake change in
LOW TBG?
low T4 (not enough TBG for it to bind to)
High T3 resin reuptaken (bc not enough TBG for it to bind to)
36
How will levels of T4 and T3 resin uptake change in
Hepatic failure?
Low TBG (bc synthesized in liver)
High T3 resin reuptaken (bc not enough TBG for it to bind to)
37
How will levels of T4 and T3 resin uptake change in
Pregnancy?
High estrogen —> high TBG
| LOW T3 resin reuptaken
bc so much TBG for it to bind to
38
How does hepatic failure and its resultant change in TBG level alter reaction of free thyroid hormones?
Will cause transient increase in level of FREE t3,t4
Followed by INHIBITION of SYNTHESIS of T3,T4 (negative feedback)
39
How does pregnancy and its resultant change in TBG level (increased) alter reaction of free thyroid hormones?
What is the term for this clinically?
Increase in bound T3, T4
Transient decrease in free T3, T4 (causes increase in synthesis and secretion of T3, T4)
Increase in total levels of T3 and T4 but now free and bound are back in equilibrium
==clinically EUthyroid
40
What hypothalamic hormones will be secreted in the HP-thyroid axis?
Thyrotropin releasing hormone (TRH)
41
What pituitary hormones will be secreted in the HP-Thyroid axis?
Thyroid stimulating hormone (TSH)
42
What regulates the HP-Thyroid axis?
T3 acts back on pituitary and hypothalmus to inhibit
| Long loop negative feedback
43
What is the role of thyroid stimulating hormone?
◦ Regulate growth of Thryoid gland
‣ Trophic effect
◦ secretion of thyroid hormones
44
What is TSH regulated by?
TRH and T3
45
What is the second messenger system used by TSH?
Adenylate cyclase (cAMP)
46
What characterizes the release of TSH?
Constant
| Unlike GH which was pulsatile
47
What are the factors that will stimulate thyroid hormone secretion?
Thyroid stimulating hormone
Thyroid-stimulating immunoglobulins
Increased TBG levels in pregnancy
48
What are the factors that will inhibit thyroid hormone secretion?
```
Iodide deficiency
Deiodinase deficiency
Excessive I- intake (Wolff Chaikoff effect)
Perchlorate, thiocynate
◦ Inhibits Na+/I- cotrnasport
(= no iodide)
Decreased TBG levels
◦ Liver disease
Free T3
```
49
What is the function of Thryoid hormones?
Acts at Thryoid hormone receptor at DNA and influences gene transcription
Thus influences synthesis of proteins
50
How does TSH change during primary HYPOthyroidism?
Increased levels (no t3 to act back)
51
How do TSH levels change during secondary/tertiary Hypothyroidism?
Decreased levels
52
How do TSH levels change during primary HYPERthyroidism?
Decreased (lots of T3 to act back on it)
53
How do TSH levels change during secondary/tertiary hyperthyroidism?
Increased TSH levels
| Will see goiter
54
What are thyroid stimulating immunoglobulins?
Stimulatory factors that will stimulate TSH R. In absence of TSH hormone
55
What effect will thyroid stimulating immunoglobulins have on the HP-Thyroid axis?
Will increase levels of Thyroid hormones = HYPER thyroidism
Decrease TSH levels
Could cause Graves’ disease
56
What charaterizes HYPER thyroidism?
* Increased BMR
* Weight loss
* Negative nitrogen balance
* increased heat production
* Sweating
* Increased cardiac output
* Displeasure
* Tremor, msucle weakness
* Exophthalmos
* Goiter (depends)
57
What proteins will thyroid hormones produce?
```
◦ Proteins:
‣ Na-K ATPase
‣ Transport proteins
‣ B1-adrenergic receptors
‣ Lysosomal enzymes
‣ Proteolytic proteins
‣ Structural proteins
◦ Proteins in Cardiac Msucle cells
‣ Mysosin
‣ B-1 adrenergic receptors
‣ Ca ATPase
◦ Proteins in Liver and Adipose tissue
‣ Key metabolic enzyme
```
58
What are the functions of thyroid hormones?
```
‣ Growth
‣ CNS maturation
‣ Increase Basal Metabolic Rate
‣ Increase Metabolsim
‣ Increase Cardiac output
• Due to upregulation of B1 adrenergic Rs.
```
59
How do thyroid hormones increase Basal Metabolic Rate (BMR)?
◦ Increase in Na-K ATPase —> increases Metabolic rate
| ‣ Leads to increased O2 consumption and heat production
60
What characterizes the increase in BMR produced by a single dose of T4?
Takes several hours to occur
But has long lasting effect (>30 days)
61
How does thyroid hormones increase lipid metabolism?
Effect on plasma concentration of cholesterol and triglycerides?
‣ Stimulates fat mobilization —> increases [FAs] in plasma
‣ Enhanced oxidation of FA
‣ LOW plasma concentration of cholesterol and triglycerides
62
What conversion needs thyroid hormones?
Carotene —> Vitamin A
63
How does thyroid hormones increase carbohydrate metabolism?
‣ Increase in gluconeogenesis and glycogenolysis
• Generates free glucose
‣ enhances insulin dependent entry of glucose into cell
64
How do thyroid hormones act on the cardiovascular system?
How?
Increase cardiac output
Stimulates Cardiac Beta1 adrenergic receptors
Increases number of B1 receptors (=more sensitive to stimulation by sympathetic nervous system) (increased cardiac chronotropy and ionotropy - speed and force)
65
How do thyroid hormones increase growth?
◦ Act w/ Growth hromone and Somatomedins to promote bone formation
66
How does Thyroid hormone cause CNS maturation?
Increases development of synapses, dendritic brnach in ad myelination
67
What happens if thyroid hormones are deificient during perinatal period?
‣ Abnormal development of synapses
‣ Decreased dendritic branching and myelination
Irreversible neural changes that could lead to Congenital hypothyroidism if not treated after birth (cretinism)
68
What are the steps from T3 —> increased cardiac output?
T3–> increased tissue thermogenesis
Heat —> decreases systemic vascular resistance
Decr. SVR —> decr. BP —> decr. After load
Decr. After load —> increase speed and force of cardio —> increased cardiac output
Decr. BP—>Renin-angio-aldo axis —> increases preload—> increased cardiac output
69
How does HYPOthyroidism affect metabolism?
Low BMR
Weight gain
Cold intolerance
High blood cholesterol concentration
‣ Bc fat is not being mobilized by thyroid hormones
blindness & yellowing of skin
‣ Bc carotene is not being converted to vitamin A (need thyroid hormones for this)
70
How does hypothyroidism affect bone?
‣ Stunted growth
| • Bc THs no longer working with GH to promote bone formation
71
How does HYPOthyroidism affect the CNS?
```
‣ Cretinism
‣ Listlessness
‣ Slowed movemnt
‣ Somnolence
‣ Impaired memroy
‣ Decreased mental capacity
```
72
How does HYPOthyroidism affect the skin?
Myxedema
73
How does HYPO-thyroidism affect the CV system?
‣ Bradycardia
‣ Decreased contractility
‣ Decreased cardiac output
‣ Heart failure
74
How does HYPO-thyroidism affect the intestine?
Constipation
75
How does HYPER-thyroidism affect metabolism?
‣ High BMR
• More thyroid hormones ==> increased Na-K ATPase synthesis ==> increased metabolic rate
‣ Heat intolerance
‣ Weight loss
76
How does HYPER-thyroidism affect bones?
Osteoporosis
77
How does HYPER-thyroidism affect the CNS?
‣ Agitation
‣ Anxiety
‣ Difficulty concentrating
‣ Hyper reflexia!!!!!!!!!
78
How does HYPERthyroidism affect skin?
Sweating
79
How does HYPERthyroidsim affect the CV system?
‣ Tachycardia
‣ Atrial fibrillation
‣ Palpitation
‣ High output heart failure
80
How does HYPERthryoidisim affect the GI system?
Diarrhea
81
What is congenital hypothyroidism (Cretinism)?
deficient Thyroid hormones during perinatal period
◦ Have major effect on CNS
◦ Mental and physical deficits
82
What could cause congenital hypothyroidism (Cretinism)
‣ Iodide deficiency
‣ Maternal intake of anti-thyroid medication
‣ Impaired development of thyroid gland
‣ Inherent deficit in the synthesis of thyroid hormones
83
What are the SXs associated with Congenital HYPOthyroidism (Cretinism) ?
```
‣ Feeding problems
‣ Respiratory difficulty
‣ Protruding tongue
‣ Curse facial features
‣ Growth retardation
‣ Mental retardation
‣ Jaundice
‣ Dry skin
‣ Hypotonia
```
84
What is primary HYPERthyroidism also called?
Graves’ disease
85
What can cause SEcondary hyperthyroidism?
TSH-secreting PITUITARY tumor
86
What is the treatment for hyperthyroidism?
Thyroidectomy
Propylthiouacil (PTU) - inhbits TPO
87
What is Graves’ disease?
Caused by ?
Primary HYPERthyroidism
Stimulation of TSH R. By thyroid stimulating IMMUNOGLOBULINS
88
How will TSH levels appear in primary hyperthyroidism?
Low bc high T3 feedbacks and inhibits it
89
What is a characteristic sign of Grave’s disease?
Caused by?
‣ Exophthalmos
• Abnormal protrusion of eyeball and periorbital edema
◦ Due to recognition by anti-TSH abs within orbital cells
90
How will levels of TSH, TSI and T3,T4 present in Graves’ disease?
T3,T4 = high
Thyroid stimulating immunoglobulins = high
TSH = low
91
Will a Goiter be present in Graves’ disease?
Yes
Bc TSI is still over stimulating the thyroid gland
(But TSH is low)
92
What is primary HYPOthyroidism?
Low T3,T4 secreted by thyroid gland
93
What is Hashimoto thyroiditis?
What will this present with?
Common cause of HYPOthyroidism in iodine sufficient parts of world
THs synthetics impaired by TG or TPO ABs
Will have low T3,t4 but HIGH TSH
=goiter
94
What could cause PRIMARY HYPOthyroidism?
Gland destruction via surgery, irradiation, autoimmune diseases, idiopathic atrophy
Hashimoto’s thyroiditis
Iodine deficiency, enzyme defects
Transient low t3,t4 bc of postpartum, thyroiditis, therapeutic radiation
Agenesis of gland
95
What can cause secondary/tertiary HYPOthyroidism?
Hypothalamic disease
Pituitary disease (Sheehan syndrome)
Resistance to Thyroid hormones
96
How can you treat HYPOthyroidism?
Replacement doses of T4
| Younger patients need more bc they have faster metabolism of it and it has shorter half life
97
What are the risks of administering T4 to women beyond menopause?
Can cause osteoporosis
98
What are the sympoms of HYPOthyroidsim?
Fatigue
Weight gain
Cold intolerance
99
Will grave’s disease have goiter?
Due to what?
Yes
Due to overstimulation of thyroid gland by Thyroid Stimulating Immunoglobulins
100
Will TSH secreting tumors present with a goiter?
Why?
Yes
Bc TSH is constantly stimulating the thyroid gland
101
Will ingestion of T4 cause a goiter?
Why?
No
Does not cause growth of thyroid gland
102
What is another name for Hashimoto’s thyroiditis?
Autoimmune thyroiditis
103
Will Hashimoto’s thyroiditis cause a goiter?
Why?
Yes
Bc thyroid hormones are not being synthesized due to TG or TPO abs
But low levels of T3,T4 cause HIGH TSH
—> Goiter
104
Will TSH deficiency cause a goiter?
No
| Idiots
105
Will iodide deficiency present with a goiter?
Why?
Yes
Bc no iodide = no T3, T4
Elevates TSH —> overstimulates gland —>
GOITER
106
When could a patient with iodide deficiency present as asymptomatic and euthyroid?
If gland can maintain normal blood levels of thyroid hormones
(Pregnancy)
107
When could Iodide deficiency cause a patient to be hypothyroidic?
If gland cannot maintain normal levels of thyroid hormones
108
What is Sheehan syndrome?
Sxs?
Goiter?
HYPO-pituitarism due to necrosis of pituitary gland
```
Seen after pregnancy
• Agalactorrhea
• Difficulties in lactation
• Amenorrhea common
• Hypothyroidism sometimes present
```
NO goiter bc pituitary is damaged = no TSH to stimulate thyroid gland
