11 Thyroid Pathophysiology and Diagnostic Evaluation Flashcards by Jim Paulo Sarsagat

When is the thyroid anlage is first recognizable

Embryonic day 16 or 17

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

Embryonic day 50

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

2nd month

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The thyroid primordium comes into contact with which pharyngeal pouch?

4th pharyngeal pouch

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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?

3rd month

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

13-14 weeks

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

29th day

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

11th week

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

14th week

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

Between 18 and 28 weeks

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TBG is detectable in the fetal serum by ____ gestational week

10th gestational week

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Normal thyroid gland weight

15-20 g

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Normal isthmus dimensions (3)

0.5 cm thick
2 cm wide
1-2 cm high

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Pyramidal lobe arises near the midline, usually on which side

Left

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Thyroid lobe that is normally more vascular and is often larger

Right lobe

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Normal blood flow range in the thyroid

4-6 mL/min/g

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Superior thyroid artery arises from which artery

External carotid artery

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Inferior thyroid artery arises from which artery

Subclavian artery

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Average diameter of thyroid follicle

200 nm

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Parafollicular or C cells are derived from: (2)

Neural crest
Endoderm

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T4 is composed of how many percent iodine by weight?

65%

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

MCT8

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Enzyme that deiodinates MIT and DIT

Iodine dehalogenase or DEHAL1

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Quantity of daily iodine intake to allow thyroidal uptake

60-75 mcg

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Usual fecal losses of iodine

10-20 mcg

Normal absorption of iodine in healthy adults

90%

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

100 mcg

Iodine deficiency is common in these regions of the earth

Mountainous and formerly glaciated regions

Most prevalent preventable cause of mental impairment

Iodine deficiency

Most common thyroid-related human illnesses

Iodine deficiency disorders

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

60-70%

Where is iodide largely confined in the body?

Extracellular fluid

Normal concentration of iodide in ECF

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

Content of peripheral pool of iodide (mcg)

250 mcg

Largest pool of body iodine

Thyroid

Normal pool of iodine in the thyroid

8 mg

Normal fractional turnover of iodine

1% per day

Recommended daily intake of iodine: Adults

150 mcg

Recommended daily intake of iodine: During pregnancy

220 mcg

Recommended daily intake of iodine: Children

90-120 mcg

Gene that encodes sodium-iodide symporter NIS

SLC5A

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

Pertechnetate Perchlorate Thiocyanate

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

Pendrin

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

Kidney Inner ear

Gene that encodes pendrin

SLC26A4

Major phenotypic manifestation of Pendred syndrome

Deafness or hearing impairment

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

Anoctamin 1

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

Organification

Iodinations that lead to formation of iodotyrosines occur within this protein

Thyroglobulin

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

DUOX1 and DUOX2

The major thyroid microsomal antigen

TPO

Proposed evanescent products (3) of the peroxidation of iodide

Hypoiodite Hypoiodous acid Iodonium

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

DUOXA2

TPO-catalyzed fusion of two DIT molecules

Coupling reaction

Catalyzes coupling reaction in the thyroid

TPO

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

3-4

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

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

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

0.4

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

250 mcg

Amount of T4 in normal human thyroid

5000 mcg

Normal Tg concentration

50 ng/mL

First step in thyroid hormone release

Endocytosis of colloid

Predominant process in the endocytosis of colloid in humans

Micropinocytosis

Most important inhibitor of T4 release

Iodide

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

Phospholipase C pathway Intracellular Ca2+ pathway

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

Protein kinase A pathway

Type of human iodothyroinine selenodeiodinase that has high susceptibility to PTU

Type 1

Type of human iodothyroinine selenodeiodinase decreases in response to increased T4

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

Type 1

Subcellular location of type 1 deiodinase

Plasma membrane

Subcellular location of type 2 deiodinase

Endoplasmic reticulum

Subcellular location of type 3 deiodinase

Plasma membrane

Deiodinase type that is found in the heart

Type 2

Deiodinase type that is found in brown adipose tissue

Type 2

Gene that encodes TBG

SERPINA7 gene

Gene that encodes TBG is found in this chromosome

X chromosome

Normal human serum concentration of TBG

270 nmol/L (21 mcg/dal)

Prevalence of congenital deficiency of TBG

1 in 5000 newborns

Population groups with increased fractions of acidic TBG (3)

Pregnant patients OCP use Acute hepatitis

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

Septic patients Following cardiopulmonary bypass surgery

Protein with the highest T4 binding capacity

Albumin (50,000 mcg T4/dL)

Thyroid hormone-binding protein with the highest T4 turnover rate

Transthyretin

Major thyroid hormone-binding protein in the CSF

Transthyretin

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

Phenytoin Salicylate Salsalate Furosemide Fenclofenac Mitotane

Albumin binds how many percent of the plasma thyroid hormones?

10%

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

3-6%

Percent of T3 derived from peripheral tissues

80%

Percent of total T4 normally bound to TBG

68%

Free T4 is approximately __% of the total

0.02%

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

Allan-Herndon-Dudley syndrome

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

OATP1C1

MCT8 mutation is associated with this psychiatric disorder

ADHD

Enzyme that primarily catalyzes inner ring deiodination of T4

Most important pathway for T4 metabolism

Outer ring 5’ monodeiodination

Iodine acceptor during deiodination reactions

Selenium

TFTs in biallelic mutation of SECIS-binding protein 2

⬆️ TSH, T4, fT4, rT3 ⬇️ T3, fT3

General mechanism of TSH stimulation: ⬆️ iodide in follicular lumen

PLC

General mechanism of TSH stimulation: Delayed ⬆️ in NIS expression

cAMP

General mechanism of TSH stimulation: ⬆️ thyroid blood flow

⬆️ nitric oxide synthesis

General mechanism of TSH stimulation: Hydrogen peroxide stimulation

PLC

General mechanism of TSH stimulation: Thyroglobulin and TPO synthesis

cAMP

General mechanism of TSH stimulation: Pinocytosis of thyroglobulin

cAMP

General mechanism of TSH stimulation: Release of Tg into plasma

cAMP

Subcellular location of 90% of intracellular T3

Cytosol

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

Piuitary (50% are in the nucleus)

Preferred substrates of D1 (2)

rT3 T3SO4

Deiodinase that has access to extracellular thiols

Most important thyroid hormone deactivating enzyme

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

TR beta 2

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

Increased

Half-life of T4

6.7 days

Volume of distribution of T4

10 L

Volume of distribution of T3

40 L

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

T3 or T4? Higher metabolic potency

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

T3 or T4? Higher volume of distribution

Half-life of T3

0.75 days

Half-life of D2

20-30 mins

Half-life of D1 and D3

>12 hours

Half-life of TBG

5 days

Fraction of T3 bound by TBG

75-80%

Escape from Wolff-Chaikoff effect does not occur in:

Third trimester fetus

Normal TSH concentration

0.4-4.2 mU/L

Plasma TSH half life

30 mins

TSH pulsatility is characterized by fluctuations at intervals of:

1-2 hours

Magnitude of TSH pulsations is decreased by (3)

Fasting Stress Surgery

Circadian variation of TSH is characterized by

Nocturnal surge that precedes the onset of sleep

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

Bexarotene

Increased / decreased / unchanged: T3 levels during iodine deficiency

Unchanged

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

75 mcg/day

Organic iodine content of one 200-mg tab of amiodarone

75 mg

Iodine content of povidone-iodine

10 mg/mL

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

>30 mg/day

Drug that blocks synthesis of TBG

L-asparaginase