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Endo Repro Midterm > Thyroid Gland > Flashcards

Thyroid Gland Flashcards

1
Q

What does thyroid gland produce?

LO 1

A

iodothyronines

  1. Tetraiodothyronine T4
    - 90% secreted
  2. Triiodothyronine T3
    - active hormone

peripheral conversion by deiodinases is key

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2
Q

What is functional unit of the thyroid gland?

  • cell type
  • describe

LO1

A

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
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3
Q

What cells do thyroid glands contain?

LO 1

A

C cells

  • parafollicular cells
  • secrete calcitonin

Rich in blood supply

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4
Q

Synthesis of Thyroid Hormones

LO4

A
  • 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

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5
Q

Thyroid hormones are synthesized by what cells?

A

follicular epithelial cells

- epithelium sits on basal lamina (outermost part of follicle)

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6
Q

Conversion of T4 to T3

  • occurs where
  • clinical conditions

LO3

A

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

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7
Q

Steps/pathway of conversion of T4 to T3

A

Tyrosine-> Monoiodotyrosine (MIT) or Diiodotyrosine (DIT)

DIT+ DIT -> T4
DIT + MIT -> T3

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8
Q

Synthesis of Thyroid Hormone
- transporter on basolateral membrane

LO4

A

Blood/basolateral hormone

  • Na/K ATPase
  • Na/I symporter (NIS, 2/1 ratio)
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9
Q

Organification

A

process of binding iodine with TG

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10
Q

Synthesis of Thyroid Hormone
- colloid

LO4

A

Colloid

- thyroglobulin binds to T4, T3, and intermediates (MIT and DIT)

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11
Q

Synthesis of Thyroid Hormone
- transporter on apical membrane

LO4

A

v=Follicular lumen/apical membrane

  • Pendrin- Cl/I counter-transporter
  • Peroxidase- oxidizes iodide for combination with thyroglobulin
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12
Q

Synthesis of Thyroid Hormone - final steps
- intracellular

LO4

A

intrathyroidal deiodinase
- deficiency of deiodinase mimics dietary I deficiency

Protease- cleave T3 and T4 from thyroglobulin for release into circulation

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13
Q

Synthesis of Thyroid Hormones
- inhibitors of different steps

LO4b

A
  1. Perchlorate, thiocynate- inhibit Na/I cotransporter
  2. PTU inhibits peroxidase
    - multiple layers inhibitions
    - inhibit production of final thyroid products
  3. Wolff-Chaikoff effect
    - inhibits organification
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14
Q

Levels of Iodine/ Iodide in thyroid

  • iodine trap
  • iodine leak
  • in tyrosine

LO4

A

ECF-> iodide trap (120ug) -> thyroid gland

ECF

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15
Q

Transport of Thyroid Hormones

  • types
  • equilibrium
  • circulation

LO5

A

circulate in blood steam either bound to plasma proteins (99%) or free (1%)

equilibrium btw bound and free circulating T3 and T4

  1. thyroxin-binding protein- 70%
    - synthesized by liver T4>T3 affinity
  2. Transthyretin (TTR)- 10-15%
  3. Albumin- 15-20%
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16
Q

Onset and Duration of Action of Thyroid Hormones

  • period
  • time

LO5

A

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
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17
Q

Half life of T4? T3?

A

T4-> 6 days

T3-> 1 day

most circulating thyroid hormone is T4

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18
Q

How can circulating TBG be assessed?
- steps

LO5

A

Indirectly with T3 Resin Uptake Test

  1. TBG w bound T4 or non specific resin which absorvs T3
  2. Unbound and labeled T3 is added
  3. Unbound TBG sites bind labeled T3
  4. 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
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19
Q

T3 Resin Uptake Test Results

- define hyperthyroid and hypothyroid results

A

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
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20
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Hyperthyroidism

LO5

A

increase T3 resin uptake

increase T4

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21
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Hypothyroidism

LO5

A

decreased T3 resin uptake

decreased T4

22
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- High TBG

LO5

A

decreased T3 resin uptake

increased T4

23
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- Low TBG

LO5

A

Increased T3 resin uptake

decreased T4

24
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- hepatic failure (describe more)

LO5

A

increased T3 resin uptake

decreased TGB

increased T4

-followed by inhibition of synthesis of T3, T4 (negative feedback)

25
Q

Changes in T4, T3, or TBG in blood levels or free thyroid hormones
- pregnancy (describe more)

LO5

A

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)
26
Q

HPT axis

  • role of TSH
  • TSH regulate by….
  • rate of TSH secretion
A

Role of TSH

  1. growth of thyroid gland itself (trophic effect)
  2. 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

27
Q

Stimulatory factors affecting Thyroid hormone secretion

A
  1. TSH
  2. Thyroid stimulating immunoglobulins
  3. increased TBG levels ( pregnancy)
28
Q

Inhibitory factors affecting thyroid hormone secretion

A
  1. Iodine deficiency
  2. deiodinase deficiency
  3. excessive iodine intake (Wollf-Chaikoff effect)
  4. Perchlorate, thiocynate (inhibit Na/A cotransport)
  5. Propylthiouracil (PTU, inhibit peroxidase enzyme)
  6. decreased TBG levels (liver disease
29
Q

New proteins synthesis under thyroid hormones

  • general
  • specific to cardiac muscle cells
  • in liver and adipose tissue

LO8

A
  • 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!

30
Q

Thyroid hormone effect on BMR

  • how (3)
  • lipid metabolism
  • carbohydrate metabolism (2)
  • diseases

LO8

A

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

  1. increased gluconeogenesis and glycogenlysis => make free glucose
  2. 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
31
Q

Thyroid hormone effect on Cardiovascular

  • indirect effect (4)
  • direct effect (3)
  • blood volume
  • TPR

LO8

A

increased Cardiac Output

indirect effects

  1. increase heat and CO2 in tissue
  2. decrease peripheral vascular resistance
  3. decrease diastolic blood pressure
  4. increase adrenergic stimulation

direct effects

  1. increased cardiac muscle
    - Na/K atpase
    - myosin
    - increase # of B1 receptors
    - more sensitive to SNS
  2. increases ventricular contractility and fxn
  3. decreased peripheral vascular resistance

increase blood volume/ preload

32
Q

Thyroid Hormone effect on Development

- Growth

A

acts synergistically with GH and somatomedins to promote bone formation

important for Fetal development

33
Q

Thyroid hormone effect on
CNS
- what happens if deficient

A

important for CNS maturation

if deficient during perinatal period

  • abnormal synapses development
  • decreased dendritic branching and myelination
  • effects irreversible => lead to cretinism
34
Q

Hyperthyroidism

- general effects

A

too much thyroid hormone

increase bodily fxn speed

  • weight loss
  • sweating
  • increase HR
  • increase BP
35
Q

Hypothyroidism

- general effects

A

not enough thyroid hormon

  • slow down bodily fxn
  • fatigue
  • weight gain
  • cold intolerance
36
Q

Hyperthyroidism
- describe different levels

LO(

A

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
37
Q

Hyperthyroidism: Graves Disease

  • describe
  • clinical signs
  • diagnosed

LO12

A

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
38
Q

Hypothyroidism
-causes (7)

LO12

A
  1. agenesis
  2. gland destruction- surgical removal , irradiation, autoimmune disease
    - hashimotos
  3. inhibition of thyroid hormone synthesis and release
    - iodine deficiency, inhereited enzyme defect s
  4. Transient
  5. hypothalamic disease
  6. pituitary disease
  7. resistance to thyroid hormones
39
Q

Treatment for hypothyroidism

LO9,12

A

replacement doses of T4

-T4 metabolism decrease and plasma half life increases with age

40
Q

Hypothyroidism: Hashimoto’s Thyroiditis

LO11,12

A

thyroid hormone synthesis impaired by thyroglobulin or TPO antibodies, leading to decreased T3 & T4 secretion

TSH levels are high- trophic effect leading to GOITER

41
Q

Hypothyroidism: Cretinism

  • Causes
  • symptoms

LO10

A

Causes

  1. Iodide defiency
  2. maternal intake of anti-thyroid medications
  3. **impaired developement of thyroid gland
  4. 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
42
Q

Elaborate on hypothyroidism due to iodine deficiency

lo12

A

transient decrease in synthesis of thyroid hormones

**TSH levels are elevated

Goiter

  • can not maintain normal blood levels of thyroid hormone
43
Q

Euthyroid and Asymptotic

- gland

A

gland maintains normal blood levels of thyroid hormones

44
Q

Goiter

LO12

A

multiple imbalances and diseases within HPT axis

  1. hyperthyroidism
    - graves
    - TSH producing tumor (secondary hyperthyroidism)
  2. Primary hyperthyroidism
    - lack of inadequate iodine in diet
    - sporadic hypothyroidism of unknown etiology
    - chronic thyroiditis (hashimotos, thyroiditis, autoimmune)
45
Q

Graves Disease Level

  • TSH
  • T3/T4 ratio
  • TSI
  • radioactive iodine uptake test
A
  • TSH decrease
  • T3/T4 ratio increase
  • TSI: +
  • radioactive iodine uptake test: increase
46
Q

Hashimoto’s DIsease

  • TSH
  • T3/T4 ratio
  • antithyroid antibody
A
  • TSH increase
  • T3/T4 ratio : decrease or normal
  • antithyroid antibody: +
47
Q

Thyroid Pathophysiology: Metabolism

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

Excess

  • heat intolerance
  • weight loss
  • increase BMR

Deficiency:

  • cold tolerance
  • weight gain
  • decrease BMR
48
Q

Thyroid Pathophysiology: Bone

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

Excess
- osteoporosis

Deficiency:
-stunted growth

49
Q

Thyroid Pathophysiology: CNS

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

Excess

  • agitation
  • anxiety
  • difficulty concentrating
  • hyperflexia

Deficiency

  • cretinism (congenital)
  • listlessness
  • slowed movement
  • somnolence
  • impaired memory
  • decrease mental capactiy
50
Q

Thyroid Pathophysiology: Skin

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

Excess
-sweating

defiency

  • dry
  • myxedema
51
Q

Thyroid Pathophysiology: CV system

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

excess

  • tachycardia
  • atrial fibrillation
  • palpitations
  • high output heart failure

deficiency

  • brachycardia
  • decrease contractility
  • decrease cardiac output
  • heart failure
52
Q

Thyroid Pathophysiology: Intestine

  • excess thyroid hormone
  • deficiency in thyroid hormone

LO8

A

excess
- diarrhea

defiency
- constipation

Endo Repro Midterm (12 decks)

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