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PSBEDM Review > 11 Thyroid Pathophysiology and Diagnostic Evaluation > Flashcards

11 Thyroid Pathophysiology and Diagnostic Evaluation Flashcards

1
Q

When is the thyroid anlage is first recognizable

A

Embryonic day 16 or 17

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2
Q

When does the thyroid primordium come into fontact and fuse with the fourth pharyngeal pouch?

A

Embryonic day 50

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3
Q

Normally, the thyroglossal duct undergoes dissolution and fragmentation by about how many months after conception?

A

2nd month

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4
Q

The thyroid primordium comes into contact with which pharyngeal pouch?

A

4th pharyngeal pouch

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5
Q

In the thyroid, complex interconnecting cordlike arrangements of cells interspersed with vascular connective tissue replace the solid epithelial mass and become tubule/like structures at about what month of fetal life?

A

3rd month

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6
Q

At how many weeks of fetal life does colloid begin to fill thyroid follicles?

A

13-14 weeks

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7
Q

Future follicular cells acquire the capacity to form thyroglobulin as early as ____ day of gestation?

A

29th day

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8
Q

Follicular cells acquire the capacities to concentrate iodide and synthesize thyroxine at how many weeks’ gestation?

A

11th week

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9
Q

Capacity of pituitary to synthesize and secrete TSH is not apparent until the how many weeks of gestation?

A

14th week

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10
Q

As a consequence of hypothalamic maturation and increasing secretion of TRH, TSH concentration increases between ____ and ____ weeks of gestation.

A

Between 18 and 28 weeks

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11
Q

TBG is detectable in the fetal serum by ____ gestational week

A

10th gestational week

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12
Q

Normal thyroid gland weight

A

15-20 g

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13
Q

Normal isthmus dimensions (3)

A

0.5 cm thick
2 cm wide
1-2 cm high

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14
Q

Pyramidal lobe arises near the midline, usually on which side

A

Left

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15
Q

Thyroid lobe that is normally more vascular and is often larger

A

Right lobe

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16
Q

Normal blood flow range in the thyroid

A

4-6 mL/min/g

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17
Q

Superior thyroid artery arises from which artery

A

External carotid artery

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18
Q

Inferior thyroid artery arises from which artery

A

Subclavian artery

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19
Q

Average diameter of thyroid follicle

A

200 nm

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20
Q

Parafollicular or C cells are derived from: (2)

A

Neural crest
Endoderm

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21
Q

T4 is composed of how many percent iodine by weight?

A

65%

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22
Q

T4 and T3 are transported across the basolateral portion of the follicular cell through this channel

A

MCT8

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23
Q

Enzyme that deiodinates MIT and DIT

A

Iodine dehalogenase or DEHAL1

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24
Q

Quantity of daily iodine intake to allow thyroidal uptake

A

60-75 mcg

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25
Q

Usual fecal losses of iodine

A

10-20 mcg

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26
Q

Normal absorption of iodine in healthy adults

A

90%

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27
Q

Amount of iodine per day that is required to eliminate all signs of iodine deficiency

A

100 mcg

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28
Q

Iodine deficiency is common in these regions of the earth

A

Mountainous and formerly glaciated regions

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29
Q

Most prevalent preventable cause of mental impairment

A

Iodine deficiency

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30
Q

Most common thyroid-related human illnesses

A

Iodine deficiency disorders

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31
Q

How much of the filtered load of plasma iodide is reabsorbed?

A

60-70%

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32
Q

Where is iodide largely confined in the body?

A

Extracellular fluid

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33
Q

Normal concentration of iodide in ECF

A

10-15 mcg/L (~10^-7 mmol/L)

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34
Q

Content of peripheral pool of iodide (mcg)

A

250 mcg

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35
Q

Largest pool of body iodine

A

Thyroid

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36
Q

Normal pool of iodine in the thyroid

A

8 mg

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37
Q

Normal fractional turnover of iodine

A

1% per day

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38
Q

Recommended daily intake of iodine:
Adults

A

150 mcg

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39
Q

Recommended daily intake of iodine:
During pregnancy

A

220 mcg

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40
Q

Recommended daily intake of iodine:
Children

A

90-120 mcg

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41
Q

Gene that encodes sodium-iodide symporter NIS

A

SLC5A

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42
Q

Aside from iodine, NIS also transports these ions: (3)

A

Pertechnetate
Perchlorate
Thiocyanate

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43
Q

Highly hydrophobic membrane glycoprotein and multianion exchanger in the apical membrane of thyrocytes that facilitates transport of iodine into the follicular lumen

A

Pendrin

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44
Q

In addition to the thyroid, pendrin is also expressed in: (2)

A

Kidney
Inner ear

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45
Q

Gene that encodes pendrin

A

SLC26A4

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46
Q

Major phenotypic manifestation of Pendred syndrome

A

Deafness or hearing impairment

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47
Q

Calcium-activated anion channel involved in mediating apical efflux of iodine

A

Anoctamin 1

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48
Q

Oxidation of iodide into the incorporation of the resulting intermediate into the hormonally inactive iodotyrosines

A

Organification

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49
Q

Iodinations that lead to formation of iodotyrosines occur within this protein

A

Thyroglobulin

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50
Q

Enzymes (2) that generate H2O2 required during oxidation of thyroidal iodide

A

DUOX1 and DUOX2

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51
Q

The major thyroid microsomal antigen

A

TPO

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52
Q

Proposed evanescent products (3) of the peroxidation of iodide

A

Hypoiodite
Hypoiodous acid
Iodonium

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53
Q

Resident ER protein and maturation factor required for maturation, plasma membrane localization of DUOX2, and H2O2 generation

A

DUOXA2

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54
Q

TPO-catalyzed fusion of two DIT molecules

A

Coupling reaction

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55
Q

Catalyzes coupling reaction in the thyroid

A

TPO

56
Q

Each molecule of human Tg normally contains how many T4 molecules?

A

3-4

57
Q

Each molecule of human Tg normally contains how many T3 molecules in normal individuals

A

0.2 (only 1 in 5 Tg molecule contains a T3 molecule)

58
Q

Each molecule of human Tg normally contains how many T3 molecules in those with Graves disease

A

0.4

59
Q

Amount of T4 in per g of wet weight of normal human thyroid

A

250 mcg

60
Q

Amount of T4 in normal human thyroid

A

5000 mcg

61
Q

Normal Tg concentration

A

50 ng/mL

62
Q

First step in thyroid hormone release

A

Endocytosis of colloid

63
Q

Predominant process in the endocytosis of colloid in humans

A

Micropinocytosis

64
Q

Most important inhibitor of T4 release

A

Iodide

65
Q

Induction of signal by the TSHR via these pathways (2) regulates iodide efflux, H2O2 production, and Tg iodination

A

Phospholipase C pathway
Intracellular Ca2+ pathway

66
Q

Induction of signal by the TSHR via this pathway stimulates growth and regulates iodine uptake and transcription of Tg, TPO, and NIS

A

Protein kinase A pathway

67
Q

Type of human iodothyroinine selenodeiodinase that has high susceptibility to PTU

A

Type 1

68
Q

Type of human iodothyroinine selenodeiodinase decreases in response to increased T4

A

D2

69
Q

Type of human iodothyroinine selenodeiodinase that is not found on the CNS

A

Type 1

70
Q

Subcellular location of type 1 deiodinase

A

Plasma membrane

71
Q

Subcellular location of type 2 deiodinase

A

Endoplasmic reticulum

72
Q

Subcellular location of type 3 deiodinase

A

Plasma membrane

73
Q

Deiodinase type that is found in the heart

A

Type 2

74
Q

Deiodinase type that is found in brown adipose tissue

A

Type 2

75
Q

Gene that encodes TBG

A

SERPINA7 gene

76
Q

Gene that encodes TBG is found in this chromosome

A

X chromosome

77
Q

Normal human serum concentration of TBG

A

270 nmol/L (21 mcg/dal)

78
Q

Prevalence of congenital deficiency of TBG

A

1 in 5000 newborns

79
Q

Population groups with increased fractions of acidic TBG (3)

A

Pregnant patients
OCP use
Acute hepatitis

80
Q

Cleaved TBG that has lower affinity to T4 is found in: (2)

A

Septic patients
Following cardiopulmonary bypass surgery

81
Q

Protein with the highest T4 binding capacity

A

Albumin (50,000 mcg T4/dL)

82
Q

Thyroid hormone-binding protein with the highest T4 turnover rate

A

Transthyretin

83
Q

Major thyroid hormone-binding protein in the CSF

A

Transthyretin

84
Q

Drugs that inhibit binding of T4 and T3 to TBG (6)

A

Phenytoin
Salicylate
Salsalate
Furosemide
Fenclofenac
Mitotane

85
Q

Albumin binds how many percent of the plasma thyroid hormones?

A

10%

86
Q

How much of plasma T4 and T3 are bound to lipoproteins?

A

3-6%

87
Q

Percent of T3 derived from peripheral tissues

A

80%

88
Q

Percent of total T4 normally bound to TBG

A

68%

89
Q

Free T4 is approximately __% of the total

A

0.02%

90
Q

X-linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia, spastic paraplegia, and elevated serum T3

A

Allan-Herndon-Dudley syndrome

91
Q

Transfer of T4 into the choroid plexus or into the tanycytes is mediated by this protein

A

OATP1C1

92
Q

MCT8 mutation is associated with this psychiatric disorder

A

ADHD

93
Q

Enzyme that primarily catalyzes inner ring deiodination of T4

A

D3

94
Q

Most important pathway for T4 metabolism

A

Outer ring 5’ monodeiodination

95
Q

Iodine acceptor during deiodination reactions

A

Selenium

96
Q

TFTs in biallelic mutation of SECIS-binding protein 2

A

⬆️ TSH, T4, fT4, rT3
⬇️ T3, fT3

97
Q

General mechanism of TSH stimulation:
⬆️ iodide in follicular lumen

A

PLC

98
Q

General mechanism of TSH stimulation:
Delayed ⬆️ in NIS expression

A

cAMP

99
Q

General mechanism of TSH stimulation:
⬆️ thyroid blood flow

A

⬆️ nitric oxide synthesis

100
Q

General mechanism of TSH stimulation:
Hydrogen peroxide stimulation

A

PLC

101
Q

General mechanism of TSH stimulation:
Thyroglobulin and TPO synthesis

A

cAMP

102
Q

General mechanism of TSH stimulation:
Pinocytosis of thyroglobulin

A

cAMP

103
Q

General mechanism of TSH stimulation:
Release of Tg into plasma

A

cAMP

104
Q

Subcellular location of 90% of intracellular T3

A

Cytosol

105
Q

90% of intracellular T3 is located in the cytosol, except in this organ

A

Piuitary
(50% are in the nucleus)

106
Q

Preferred substrates of D1 (2)

A

rT3
T3SO4

107
Q

Deiodinase that has access to extracellular thiols

A

D3

108
Q

Most important thyroid hormone deactivating enzyme

A

D3

109
Q

Thyroid receptor expressed in hypothalamus, pituitary, cochlea, and retine

A

TR beta 2

110
Q

Increased / decreased / unchanged:
Effect of recombinant growth hormone on T3:T4 ratio

A

Increased

111
Q

Half-life of T4

A

6.7 days

112
Q

Volume of distribution of T4

A

10 L

113
Q

Volume of distribution of T3

A

40 L

114
Q

T3 or T4?
Higher production rate (nmol/L)

A

T4

115
Q

T3 or T4?
Higher metabolic potency

A

T3

116
Q

T3 or T4?
Higher fraction of total hormone in free form

A

T3

117
Q

T3 or T4?
Higher volume of distribution

A

T3

118
Q

Half-life of T3

A

0.75 days

119
Q

Half-life of D2

A

20-30 mins

120
Q

Half-life of D1 and D3

A

> 12 hours

121
Q

Half-life of TBG

A

5 days

122
Q

Fraction of T3 bound by TBG

A

75-80%

123
Q

Escape from Wolff-Chaikoff effect does not occur in:

A

Third trimester fetus

124
Q

Normal TSH concentration

A

0.4-4.2 mU/L

125
Q

Plasma TSH half life

A

30 mins

126
Q

TSH pulsatility is characterized by fluctuations at intervals of:

A

1-2 hours

127
Q

Magnitude of TSH pulsations is decreased by (3)

A

Fasting
Stress
Surgery

128
Q

Circadian variation of TSH is characterized by

A

Nocturnal surge that precedes the onset of sleep

129
Q

Pharmacologic agent used in the treatment of T-cell lymphoma that suppresses TSH sufficiently to cause central hypothyroidism

A

Bexarotene

130
Q

Increased / decreased / unchanged:
T3 levels during iodine deficiency

A

Unchanged

131
Q

Compensatory alterations in thyroid function come into operation when total iodine intake falls below:

A

75 mcg/day

132
Q

Organic iodine content of one 200-mg tab of amiodarone

A

75 mg

133
Q

Iodine content of povidone-iodine

A

10 mg/mL

134
Q

Quantity of iodine required to suppress radioactive iodine uptake to <2%

A

> 30 mg/day

135
Q

Drug that blocks synthesis of TBG

A

L-asparaginase

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