Thyroid Gland Flashcards
What does thyroid gland produce?
LO 1
iodothyronines
- Tetraiodothyronine T4
- 90% secreted - Triiodothyronine T3
- active hormone
peripheral conversion by deiodinases is key
What is functional unit of the thyroid gland?
- cell type
- describe
LO1
thyroid follicle
- single layer of epithelial cell
- follicular lumen itself is filled with colloid
- size and amount of epithelial cell and colloid can change with activity
What cells do thyroid glands contain?
LO 1
C cells
- parafollicular cells
- secrete calcitonin
Rich in blood supply
Synthesis of Thyroid Hormones
LO4
- contain a lot of iodine
- occurs part intracellularly and part extracellularly
T4 is major secretory produce
Colloid is composed of new synthesized thyroid hormones- attached to thyroglobulin
Thyroid hormones are synthesized by what cells?
follicular epithelial cells
- epithelium sits on basal lamina (outermost part of follicle)
Conversion of T4 to T3
- occurs where
- clinical conditions
LO3
occurrs through the action of deiodinase
- 80-90% peripherally converted
- 10-20% is directly secreted as T3
Clinical states associated with reduced conversion of T4 to T3
- fasting
- medical & surgical stress
- catabolic disease
Provides circulating T3 for uptake by other tissues in which T3 supply is too low
Fast rxn!
10 times more T4 is produced than T3
Steps/pathway of conversion of T4 to T3
Tyrosine-> Monoiodotyrosine (MIT) or Diiodotyrosine (DIT)
DIT+ DIT -> T4
DIT + MIT -> T3
Synthesis of Thyroid Hormone
- transporter on basolateral membrane
LO4
Blood/basolateral hormone
- Na/K ATPase
- Na/I symporter (NIS, 2/1 ratio)
Organification
process of binding iodine with TG
Synthesis of Thyroid Hormone
- colloid
LO4
Colloid
- thyroglobulin binds to T4, T3, and intermediates (MIT and DIT)
Synthesis of Thyroid Hormone
- transporter on apical membrane
LO4
v=Follicular lumen/apical membrane
- Pendrin- Cl/I counter-transporter
- Peroxidase- oxidizes iodide for combination with thyroglobulin
Synthesis of Thyroid Hormone - final steps
- intracellular
LO4
intrathyroidal deiodinase
- deficiency of deiodinase mimics dietary I deficiency
Protease- cleave T3 and T4 from thyroglobulin for release into circulation
Synthesis of Thyroid Hormones
- inhibitors of different steps
LO4b
- Perchlorate, thiocynate- inhibit Na/I cotransporter
- PTU inhibits peroxidase
- multiple layers inhibitions
- inhibit production of final thyroid products - Wolff-Chaikoff effect
- inhibits organification
Levels of Iodine/ Iodide in thyroid
- iodine trap
- iodine leak
- in tyrosine
LO4
ECF-> iodide trap (120ug) -> thyroid gland
ECF
Transport of Thyroid Hormones
- types
- equilibrium
- circulation
LO5
circulate in blood steam either bound to plasma proteins (99%) or free (1%)
equilibrium btw bound and free circulating T3 and T4
- thyroxin-binding protein- 70%
- synthesized by liver T4>T3 affinity - Transthyretin (TTR)- 10-15%
- Albumin- 15-20%
Onset and Duration of Action of Thyroid Hormones
- period
- time
LO5
Slow Onset
Long Duration
Latent Period before T4 activity begins
- 2-3 d before activity begins
- 10-12 d reach max
- activity persists 6-8 week
Actions of T3 are more rapid
- 6-12 hr before activity begins
- 2-3 d reach max
Half life of T4? T3?
T4-> 6 days
T3-> 1 day
most circulating thyroid hormone is T4
How can circulating TBG be assessed?
- steps
LO5
Indirectly with T3 Resin Uptake Test
- TBG w bound T4 or non specific resin which absorvs T3
- Unbound and labeled T3 is added
- Unbound TBG sites bind labeled T3
- Anti T3 antibody or non specifc resin which absorvs T3
5a. Precipitated- absorbed T3 (T3 uptake)
5b. In solution- TBG with bound T4 and labeled T3 is removed
T3 Resin Uptake Test Results
- define hyperthyroid and hypothyroid results
Hyperthyroid
- more T4 available
- Fewer spaces on TBG availiable for T3
- so more T3 will bind to resin as more T3 is “free”
Hypothyroid
- less total T4 availiable
- more spaces on TBG available for T3
- so less T3 will bind to resin as more T3 is abound by TBG
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Hyperthyroidism
LO5
increase T3 resin uptake
increase T4
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Hypothyroidism
LO5
decreased T3 resin uptake
decreased T4
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- High TBG
LO5
decreased T3 resin uptake
increased T4
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Low TBG
LO5
Increased T3 resin uptake
decreased T4
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- hepatic failure (describe more)
LO5
increased T3 resin uptake
decreased TGB
increased T4
-followed by inhibition of synthesis of T3, T4 (negative feedback)
Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- pregnancy (describe more)
LO5
decreased T3 resin uptake
increased TBG
decreased T4
- followed by increase synthesis and secretion of T3, T4
- increase total levels of T3 and T4, but levels of free, physiologically active, thyroid hormones are normal (clinically euthyroid)
HPT axis
- role of TSH
- TSH regulate by….
- rate of TSH secretion
Role of TSH
- growth of thyroid gland itself (trophic effect)
- secretion of thyroid hormone
* cAMP is secondary messenger of TSH
- regulated by
a. thyrotropin-releasing hormone (TRH) - free T3 ( feedback)
TSH secretion occurs at steady rate
Stimulatory factors affecting Thyroid hormone secretion
- TSH
- Thyroid stimulating immunoglobulins
- increased TBG levels ( pregnancy)
Inhibitory factors affecting thyroid hormone secretion
- Iodine deficiency
- deiodinase deficiency
- excessive iodine intake (Wollf-Chaikoff effect)
- Perchlorate, thiocynate (inhibit Na/A cotransport)
- Propylthiouracil (PTU, inhibit peroxidase enzyme)
- decreased TBG levels (liver disease
New proteins synthesis under thyroid hormones
- general
- specific to cardiac muscle cells
- in liver and adipose tissue
LO8
- Na/K atpase
- transport proteins
- b1 adrenergic receptors
- lysosomal enzymes
- proteolytic proteins
- structural proteins
specific to cardiac muscle cells
- b1 adrenergic receptors-
- myosin
- ca2+ atpase
in liver and adipose tissue
- induce synthesis of key metabolic enzymes!
Thyroid hormone effect on BMR
- how (3)
- lipid metabolism
- carbohydrate metabolism (2)
- diseases
LO8
increase basal metabolic rate
- increased activity of Na/K ATPase
- lead to increase O2 consumption and heat production
- single dose of T4 after several hours (long lasting)
increased CHO (carb metabolism
- increased gluconeogenesis and glycogenlysis => make free glucose
- increase insulin-dependent entry of glucose into cells
increase lipid metabolism
1. stimulate fat mobilization-> increase conc of FA in plasma
2. increase FA oxidation
3. Cholesterol and TG INVERSELY correlated w thyroid hormones
exm high cholesterol in HYPOthyroidism
4. required for conversion of carotene to Vitamin A
- hypothyroid: suffer from blindness or yellow skin
- Hyperthyroidism= high BMR
hypothyroidism= low BMR
Thyroid hormone effect on Cardiovascular
- indirect effect (4)
- direct effect (3)
- blood volume
- TPR
LO8
increased Cardiac Output
indirect effects
- increase heat and CO2 in tissue
- decrease peripheral vascular resistance
- decrease diastolic blood pressure
- increase adrenergic stimulation
direct effects
- increased cardiac muscle
- Na/K atpase
- myosin
- increase # of B1 receptors
- more sensitive to SNS - increases ventricular contractility and fxn
- decreased peripheral vascular resistance
increase blood volume/ preload
Thyroid Hormone effect on Development
- Growth
acts synergistically with GH and somatomedins to promote bone formation
important for Fetal development
Thyroid hormone effect on
CNS
- what happens if deficient
important for CNS maturation
if deficient during perinatal period
- abnormal synapses development
- decreased dendritic branching and myelination
- effects irreversible => lead to cretinism
Hyperthyroidism
- general effects
too much thyroid hormone
increase bodily fxn speed
- weight loss
- sweating
- increase HR
- increase BP
Hypothyroidism
- general effects
not enough thyroid hormon
- slow down bodily fxn
- fatigue
- weight gain
- cold intolerance
Hyperthyroidism
- describe different levels
LO(
Excessive thyroid hormone production (thyrotoxicosis)
Primary Hyperthyroidism
-GRAVES most common cuase
Secondary hyperthyroidism
- exm TSH- secreting pituitary
Changes in TSH level
- decreases due to negative feedback of T3 on anterior lobe of pituitary gland
- if defect on anterior pituartary itself-> TSH levels will elevate
Hyperthyroidism: Graves Disease
- describe
- clinical signs
- diagnosed
LO12
thyroid stimulating immunoglobins stimulate TSH receptor without TSH present
- loss of feedback, TSH levels are lower
Clinical signs
- exophthalmos (abnormal protrusion of eyeball)
- periorbital edema
Diagnoses
- elevated serum free ad total T4 and T3 levels
- goiter and ophthalmophaty
- presence of circulating TSI
- helps distinguish GRAVES from adenoma of pituitary thryotrophs
Hypothyroidism
-causes (7)
LO12
- agenesis
- gland destruction- surgical removal , irradiation, autoimmune disease
- hashimotos - inhibition of thyroid hormone synthesis and release
- iodine deficiency, inhereited enzyme defect s - Transient
- hypothalamic disease
- pituitary disease
- resistance to thyroid hormones
Treatment for hypothyroidism
LO9,12
replacement doses of T4
-T4 metabolism decrease and plasma half life increases with age
Hypothyroidism: Hashimoto’s Thyroiditis
LO11,12
thyroid hormone synthesis impaired by thyroglobulin or TPO antibodies, leading to decreased T3 & T4 secretion
TSH levels are high- trophic effect leading to GOITER
Hypothyroidism: Cretinism
- Causes
- symptoms
LO10
Causes
- Iodide defiency
- maternal intake of anti-thyroid medications
- **impaired developement of thyroid gland
- inherent deficit in synthesis of thyroid hormones
Symptoms
- feeding problem
- respiratory difficulty
- protruding tongue
- curse facial features
- growth retardation
- mental retardation
- jaundice
- dry skin
- hypotonia
Elaborate on hypothyroidism due to iodine deficiency
lo12
transient decrease in synthesis of thyroid hormones
**TSH levels are elevated
Goiter
- can not maintain normal blood levels of thyroid hormone
Euthyroid and Asymptotic
- gland
gland maintains normal blood levels of thyroid hormones
Goiter
LO12
multiple imbalances and diseases within HPT axis
- hyperthyroidism
- graves
- TSH producing tumor (secondary hyperthyroidism) - Primary hyperthyroidism
- lack of inadequate iodine in diet
- sporadic hypothyroidism of unknown etiology
- chronic thyroiditis (hashimotos, thyroiditis, autoimmune)
Graves Disease Level
- TSH
- T3/T4 ratio
- TSI
- radioactive iodine uptake test
- TSH decrease
- T3/T4 ratio increase
- TSI: +
- radioactive iodine uptake test: increase
Hashimoto’s DIsease
- TSH
- T3/T4 ratio
- antithyroid antibody
- TSH increase
- T3/T4 ratio : decrease or normal
- antithyroid antibody: +
Thyroid Pathophysiology: Metabolism
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
Excess
- heat intolerance
- weight loss
- increase BMR
Deficiency:
- cold tolerance
- weight gain
- decrease BMR
Thyroid Pathophysiology: Bone
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
Excess
- osteoporosis
Deficiency:
-stunted growth
Thyroid Pathophysiology: CNS
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
Excess
- agitation
- anxiety
- difficulty concentrating
- hyperflexia
Deficiency
- cretinism (congenital)
- listlessness
- slowed movement
- somnolence
- impaired memory
- decrease mental capactiy
Thyroid Pathophysiology: Skin
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
Excess
-sweating
defiency
- dry
- myxedema
Thyroid Pathophysiology: CV system
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
excess
- tachycardia
- atrial fibrillation
- palpitations
- high output heart failure
deficiency
- brachycardia
- decrease contractility
- decrease cardiac output
- heart failure
Thyroid Pathophysiology: Intestine
- excess thyroid hormone
- deficiency in thyroid hormone
LO8
excess
- diarrhea
defiency
- constipation
