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FHB Endocrinology > L74: Thyroid > Flashcards

L74: Thyroid Flashcards

1
Q

Where is the thyroid gland located?

A

Anterior to cricoid cartilage

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2
Q

What supplies the thyroid gland with blood?

A

Superior (ext carotid) and Inferior (thyrocervical trunk) thyroid arteries

Venous plexus on surface -> superior, middle, inferior thyroid veins -> drain into internal jugular vein

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3
Q

What innervates the thyroid gland?

A

Sympathetic NS by the middle and inferior cervical ganglion

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4
Q

What are the cellular components of the thyroid gland?

A 
Follicle: has lumen filled with colloid with thyroglobulin (TG)
Parafollicular Cells (C Cells): produce calcitonin and maintain follicle

Epithelial cells
Fibroblasts
Lymphocytes
Adipocytes

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5
Q

What is the colloid?

A

extracellular storage site of T3/T4 and thyroglobulin found in follicle

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6
Q

Where are hte parafollicular cells located?

A

Inside the basement membrane -> do not touch the colloid

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7
Q

What are 2 requirements for thyroid hormones?

A

Thyroglobulin and Iodide

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8
Q

What happens to excess iodide?

A

Excreted in urine as iodine

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9
Q

How much iodide intake is needed to avoid thyroid hormone deficiency?

A

20ug/day

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10
Q

What is the Wolf-Chaikoff Effect?

A

Intrathyroidal response that ensures constant iodide storage with changing dietary iodiede intake

Increased intake -> decreased gland transport and hormone synthesis
Decreased intake -> increased gland transport and hormone synthesis

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11
Q

How can the Wolf-Chaikoff effect be used clinically?

A

Use very high doses of iodide to rapidly shut down thyroid hormone production in hyperthyroid patients

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12
Q

What is the HPT Axis?

A

Hypothalamus (PVN) -> TRH -> Pituitary (Thyrotropes) -> TSH -> Thyroid gland

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13
Q

What regulates thyroid hormone release?

A

Neg Feedback by T4/T3 at hypothalamus
Neg Feedback by T4 at pituitary
Tonic inhibition by somatostatin and dopamine

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14
Q

What is the sequence of events of hte HPT Axis?

A

TRH from PVN neurons bind to GPCRs on thyrotrope cells in ant. pituitary -> activate DAG/IP3 -> release TSH -> bind to receptors in basolateral side of follicular epithelial cells -> stimulate T4/T3 synthesis and release from follicle -> deiodinase peripherally -> Intracellular T3 ->neg feedback to inhibit TRH and TSH

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15
Q

Where are T4 molecules deiodinated to T3?

A

In the thyrotopes and braine by Type II deiodinase

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16
Q

What is the thyroid sensor?

A

Type II Deiodinase

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17
Q

How is the thyroid follicle polarized?

A

Apical: exposed to lumen (colloid); thyroid hormone syntehsis and iodination of TG

Basolateral: Exposed to blood; Iodine uptake/trap; Thyroid hormone release

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18
Q

What are the steps in thyroid hormone syntehsis?

A

Iodide Trapping: TSH stimulates NIS co transporter in basla membrane of follicular epithelial cell to trap iodide

Transport: I- transported to follicular lumen and oxidized by TPO to form iodine; TG transported to lumen

Iodination: Iodinate tyrosyl residues on TG

Conjugation: Conjugate iodinated tyrosines to make T4 andT3 linked TG

Endocytosis: Conjugated TG with T4/T3 enters follicular epithelial cells and packaged in endosomes

Proteolysis: TG, MIT, DIT, T4, T3 released from vesicle

Secretion: T4/T3 secreted into circulation at basal membrane

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19
Q

Which form of thyroid hormone has the longer half life?

A

T4 > T3

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20
Q

Which is the primary active form of thyroid hormone?

A

T3

Converted intracellularly from T4 and binds with high affinity to receptor

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21
Q

What is rT3?

A

Reverse triiodothyronine -> biologically inactive

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22
Q

How is T3 formed?

A

Coupleing 1 MIT and DIT residues

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23
Q

How is rT3 formed?

A

Inactive

Presence of two iodinated residues on outer ring

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24
Q

How is T4 formed?

A

Couple 2 DIT residues

25
Q

What is radioactive iodide uptake scan?

A

Diagnostic tool to measure iodide uptake in thyroid epithelial cell using radioactive iodide and anions -> determines funciton of thyroid gland

26
Q

What mediates the transport of iodide in the thyroid epithelial cell?

A

NIS (Sodium iodide symporter)

27
Q

What is normal uptake of iodide after 24 hours?

A

25%

28
Q

What is considered hyperthyroid/hypothyroid?

A

Hyperthyroid: >60% iodide uptake after 24 hours
Hypothyroid:

29
Q

What is an organification defect?

A

When iodide cannot be incorporated into tyrosine -> Test by blockiing NIS with perchlorate and measure radioactive iodide uptake

30
Q

What is Type I Deiodinase?

A

Outer and inner ring deiodinase -> forms T3
Found in: Liver, Kidney, Thyroid, Skeletal muscle

Primary source of T3 in circulation

31
Q

What is Type II Deiodinase?

A

Outer ring deiodinase -> forms T3

Found in: Brain, Pituitary, Placenta, Cardiac Muscle

32
Q

What is Type III Deiodinase?

A

Inner ring deiodinase -> forms rT3

Found in: brain, placenta, skin

33
Q

Which is produced more and stored in the thyroid?

A

T4

34
Q

Which deiodinase is the thyroid hormone sensor in the pituitary?

A

Type II deiodinase

35
Q

What % of thyroid hormones are bound in circulation?

A

> 99%

TBG(70%)
Transthyretin (TTR): 10%
Albumin: 15-25%

36
Q

What is TBG?

A

Thyroxine binding globulin-> made in liver

T4 has highest affinity for TBG

37
Q

What increases TBG levels?

A

Estrogen, hepatitis

38
Q

What decreases TBG levels?

A

Nephrotic syndrome

Steroids

39
Q

How does a decrease in TBG change free T4/T3 levels?

A

No net change; Changes in TBG dont usually affect bioavailable T3-> DOES affect TOTAL T4/T3 levels

40
Q

How does the thyroid hormone receptor work?

A

Nuclear receptor that forms heterodimers with retinoic acid receptor (RXR) -> complex binds to DNA -> recruit coregulatory proteins-> transcriptional activation

41
Q

Where are thyroid hormone receptors found?

A

Every cell type

42
Q

How does BMR change with hypo/hyperthyroid

A

Hypo: deceased
Hyper: increased

43
Q

How does thyroid hormone affect carbohydrate metabolism?

A

Increase gluconeogenesis and glycogenolysis

normal glucose serum

44
Q

How does thyroid hormone affect protein metabolism?

A

Increase protein synthesis + Inc proteolysis => muscle wasting

45
Q

How does thyroid hormone affect lipid metabolism?

A

Inc Iipogenesis, inc lipolysis, dec serum cholesterol

46
Q

How does thyroid hormone affect thermogenesis?

A

Hypo: Decreased -> cold intolerant
Hyper: Increased-> heat intolerant

47
Q

What does T3 do in terms of cellular metabolism?

A

Increases cellular oxygen consumption and heat production by increasing mitochondrial activity

48
Q

What are the effects on the CNS by thyroid hormone?

A

T3 is critical for normal brain development
Neuronal cell migration/differentiation
Myelination
Synaptic transmission

49
Q

What is Cretinism?

A

Caused by iodine deficiency during development leading to
short stature/impaired bone formation
mental retardation
delayed motor development

50
Q

What are the effects of thyroid hormone on the heart?

A

T3 increases cardiac output -> inc SV and HR

Hyperthyroidism can cause arrhythmias

51
Q

What is a goiter and what causes it?

A

Enlarged thyroid

Caused by thyroid cancer and both hypothyroidism and hyperthyroidism

52
Q

What is Graves Disease?

A

Hyperthyroid condition due to autoimmunity -> Antibodies stimulate TSH receptors -> inc T4/T3 levels
Causes goiter with hyperthyroid sx

53
Q

What is noted on the histology of thyroid gland from a Graves Disease patient?

A

Scant colloid
Tall Columnar ACtivated Follicular cells
Infiltration of lymphocytes

54
Q

What is Hashimoto’s Thyroiditis?

A

Hypothyroid condition due to autoimmune destruction of thyroid follicles
Antibodies target TPO and TG
Forms a diffuse goiter with hypothyroid sx

55
Q

Why does hypothyroidism cause a goiter?

A

lack of neg feedback by T4/T3 causes increased, continuous secreiton of TSH from pituitary

56
Q

What are hyperthyroid sx?

A 
tachycardia
opthalmopathy
irritability/hyperactivity
Heat intolerance
Weight loss
Muscle Wasting
57
Q

What are hypothyroid sx?

A 
lethargy/fatigue
Hair loss
Cold Intolerance
Brittle nailes
Decreased appetite
Weight gain
58
Q

What is a thyroid storm

A 
Emergency life threatening sitation in which hyperthyroid is coupled with severe acute illness leading to:
High fever
Tachycardia
AMS
NVD
Circulatory collapse
Possibly death
59
Q

What are the treatmetns for a thyroid storm?

A

PTU: acute treatment
Carbimazole
Beta Blockers to normalize heart function

FHB Endocrinology (10 decks)

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