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Therapeutics > Lecture 37: Thyroid Hormones > Flashcards

Lecture 37: Thyroid Hormones Flashcards

1
Q

Thyoid gland

A

-in the neck

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2
Q

Thyroid hormones

A

-Thyroxine (T4) x10
-Triiodothyronine (T3) mor potent

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3
Q

Effect of thyroid hormones on growth and development

A

-essential for brain development
-promote protein synthesis (skeletal/muscle)
-anabolic at normal levels but catabolic at high levels

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4
Q

Cretinism caused by

A

-absent T3

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5
Q

Effects of thyroid hormones on metabolism

A

-increase BMR
-inc oxygen consumption
-starvation lowers T3 and thyroid receptor

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6
Q

Starvation lowers levels of

A

-T3 hormone
-thyroid receptors

-to dec BMR to save energy

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7
Q

Effect of thyroid hormones on Thermogenesis

A

-inc resting heat production
-inability to adjust to environmental temp is characteristic symptom of hyper/hypo thyroidism

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8
Q

Effect of thyroid hormones on cardiovascular system

A

-inc catcholamine sensitivity

  • makes heart beat more
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9
Q

Biosynthesis of Thyroid hormones

A
  1. Dietary Iodine
  2. NIS transport
  3. Pendrin transport and oxidation by thyroid peroxidase
  4. thyroglobulin transport
  5. Iodide Organification
  6. Coupling
  7. Retrievement
  8. Cleavage
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10
Q
  1. Dietary Iodine (I2)
A

-turned to iodide (I-) in tummy

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11
Q
  1. Na+-I- symporter (NIS)
A

-transports iodide into follicular cell

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12
Q
  1. Pendrin transport and Oxidation
A

-iodide passes down electrochemical gradient into follicular COLLOID w help from PENDRIN transporter
-oxidized to I0 at apical membrane by throid peroxidase

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13
Q

Pendrin

A

-apical transport protein
-helps iodide into follicular colloid for oxidation

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14
Q
  1. iodide-free throglobulin transported to
A

apical membrane

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15
Q
  1. Iodide organification
A

-thyroglobulin iodinated at 1 or 2 positions by thyroid peroxidase
-Monoiodotyrosine and di-iodotyrosine (MIT and DIT)

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16
Q
  1. Coupling
A

-MIT + DIT = T3
-DIT + DIT = T4

-dependent on thyroid peroxidase

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17
Q
  1. Thyroglobulin Retrieval
A

-thyroid hormone-containing thyroglobulin is retrieved back into cytosol of follicular cell as colloid droplets by pinocytosis

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18
Q
  1. Cleavage
A

-Lysosomal exopeptidases cleave T4 or T3 from thyroglobulin
=release hormone into circulation where T4 can be converted to more potent T3 by 5’deiodinase

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19
Q

thyroid peroxidase

A

-oxidizes iodide
-iodinates thyroglobulin to MIT or DIT
-couples MIT and DIT

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20
Q

5’ deiodinase

A

-converts T4 to T3
-happens in circulation

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21
Q

Hypothalamus-pituitary-thyroid axis

A

-hypothalamus releases TRH
-stimulates anterior pituitary to relase TSH
-stimulates thyroid to release T3 and T4

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22
Q

negative feedback loop

A

-T3 and T4 inhibit hypothalamus and anterior pituitary directly
-which indirectly inhibits thyroid gland

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23
Q

TRH

A

thyrotropin releasing hormone

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24
Q

TSH

A

thyrotropin

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25
Q

Iodine

A

-used for synthesis of thyroid hormones
-routinely added to table salt

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26
Q

best natural food source for iodine

A

-fish
-seaweed

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27
Q

Iodine deficiency

A

-endemic in inland populations
-goiter and crentinism

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28
Q

goiter

A

enlargement of thyroid gland due to persistent rise in TSH but no iodine to make hormone

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29
Q

crentinism

A

-severely stunted physical and mental growth

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30
Q

Thyroid hormone transport

A

-Thyroxine-binding globulin (TBR) (primary)
-Transthyretin (TTR)
-Albumin

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31
Q

Primary transport protein of thyroid hormones

A

TBG

32
Q

transport proteins have a greater affinity to

A

-T4

33
Q

T4 in the body

A

-only 0.04% is free
-longer half life than T3 but slower onset
-serves as a storage pool (2-3 months)

34
Q

Thyroid hormone mech of action

A

-belong to nuclear receptor family
-similar to steroid
-bind nuclear and inc transcription

35
Q

Metabolism of Thyoid hormones

A

-deiodination
-conjugation to form glucuronide or sulfate w phenolic group
-excreted via bile
-some hydrolyzed by bacteria
-marginal enterhepatic circulation

36
Q

structures

A

slide 14

37
Q

HYPOthyroidism

A

-deficiency of thyroid hormones

38
Q

Symptoms of HYPOthyroidism

A

-dec metabolism = fatigue, mental dullness, lethargy, inattention
-defective thermoreg
-may occur w goiter
-dwarfism/cretinism in infants and children
-Myxoedema coma

39
Q

myxoedema coma

A

-end state of untreated HYPOthyroidism
-water intoxication
-shock
-death

40
Q

Causes of HYPOthyroidism

A

-Hashimoto’s thyroiditis
-destruction/removal of gland (no goiter)
-idodine deficiency (goiter)
-congenital cretinism
-secondary: TSH deficiency

41
Q

Hashimoto’s thyroditis

A

-most common cause of HYPOthyroidism
-autoimmune disease that destroys thyroid gland

42
Q

Secondary cause of HYPOthyroidism

A

-TSH deficiency

43
Q

HYPERthyroidism

A

-excessive levels of thyroid hormones (thyrotoxicosis)

44
Q

Symptoms of HYPERthyroidsism

A

-excessive metabolism
-poor thermoreg and weight loss
-inc HR and cardiac output

45
Q

Causes of HYPERthyroidism

A

-Graves’ disease
-Toxic uninodular goiter and toxic multinodular goiter
-Subacute thyroiditis

46
Q

Graves’ Disease

A

-most common cause of HYPERthyroidism
-autoimmune
-thyroid stimulating IgG
-toxic goiter

47
Q

Toxic uni/multi nodular goiter

A

-adenoma producing excess T3
-mostly in older women
-causes HYPERthyroidism

48
Q

Subacute Thyroiditis

A

-viral infection of thyroid gland
-transient release of store thyroid hormones
-HYPERthyroidism

49
Q

HYPOthyroid skin

A

-pale
-cool
-puffy

50
Q

HYPERthyroid skin

A

-warm
-moist
-sweaty

51
Q

HYPOthyroid eyes

A

-droopy eyelids

52
Q

HYPERthyroid eyes

A

-retraction of upper lids
-exophthalmos

53
Q

HYPOthyroidsim CV effects

A

-BRADYcardia
-dec CO
-inc vasc resistance

54
Q

HYPERthyroid CV effects

A

-TACHYcardia
-inc CO
-dec vasc resistance

55
Q

HYPOthyroid CNS

A

-lethargy

56
Q

HYPERthyroidism CNS

A

nervousness

57
Q

HYPOthyroidism metabolism

A

-dec appetite
-dec BMR
-hYPOglycemia
-inc cholesterol and triglycerides
-dec drug metabolism

58
Q

HYPERthyroid metabolism

A

-inc appetit
-inc BMR
-HYPERglycemia
-dec cholesterol and triglycerides
-inc drug metabolism

59
Q

Hypothyroidism treatment

A

-Thyroid Hormone Replacement Therapy

60
Q

Thyroid Hormone Replacement Therapies

A

-Natural Thyroid hormone preparations (not FDA approved)
-Levothyroxine (T4)
-Liothyronine (T3)
-Liotrix (disc)

61
Q

Natural Thyroid hormone preparations

A

-not FDA approved
-HYPOthyroidism treatment
-dessicated thyroid and thyroglobulin (bovine or porcine)
-variable T4/T3 blood levels due to inconsistencies in sources

62
Q

Levothyroxine (T4!)

A

-HYPOthyroidism treatment
-converted to T3 intracellularly
-slow onset
-long half-life (week)
-6-8 weeks to reach steady state levels

63
Q

Liothyronine (T3!)

A

-HYPOthyroidism treatment
-rapid onset
-short duration (24h)
-need multiple daily doses
-greater cardiotoxicity risk
-difficult to monitor via lab tests

64
Q

Liotrix (disc)

A

-4:1 T4 to T3 ratio
-more expensive
-not more effective than T4 admin alone
-discontinued

65
Q

HYPERthyroidism drugs

A

-Thioamides
-131I
-Iodide

66
Q

Thioamides

A

-HYPERthyroidism treatment
-antithyroid
-treat thyrotoxicosis
-inhibit thyroid peroxidase
=block iodine organification and coupling
-slow onset (3-4 weeks)
-require depletion of stored T4

67
Q

Thioamide drugs

A

-Methimazole
-Propylthiouracil

68
Q

131I

A

-HYPERthyroidism
-radioactive iodine
-emit B particles and gamma rays
-8 day half life
-localized destruction of thyroid follicles
-admin orally in solution as Na131I

69
Q

problems w 131I

A

-HYPOthyroidism occurs in 80% of patients
-potential inc in some cancer
-radiation thyroiditis in rare cases (storm?!) = prevent w pretreatment of antithyroid drugs
-radioactive urine

70
Q

131I contraindication

A

-not for pregnant or breastfeeding

71
Q

131I advantage

A

-no surgery
-lower cost

72
Q

Iodide treatment

A

-for HYPERthyroidism
-lots of I- inhibits own uptake , organification, and release of thyroid hormones
-dec vascularity of thyroid gland
-not for long term use

73
Q

Lugol’s solution

A

-aq solution of I and KI
-iodide treatment for HYPERthyroidism

74
Q

Iodide clinical uses

A

-prep for thyroidectomy
-severe thyrotoxicosis
-protection from radioactive iodine fallout (nuclear/military exposure)

75
Q

Iodide side effects

A

-HYPOthyroidism
-sensitivity to idodine in some patitents (angioedema)

Therapeutics (78 decks)

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