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FHB Endocrinology > L74: Thyroid > Flashcards

L74: Thyroid Flashcards

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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?

Study These Flashcards
A

Couple 2 DIT residues

25
What is radioactive iodide uptake scan?
Diagnostic tool to measure iodide uptake in thyroid epithelial cell using radioactive iodide and anions -> determines funciton of thyroid gland
26
What mediates the transport of iodide in the thyroid epithelial cell?
NIS (Sodium iodide symporter)
27
What is normal uptake of iodide after 24 hours?
25%
28
What is considered hyperthyroid/hypothyroid?
Hyperthyroid: >60% iodide uptake after 24 hours Hypothyroid:
29
What is an organification defect?
When iodide cannot be incorporated into tyrosine -> Test by blockiing NIS with perchlorate and measure radioactive iodide uptake
30
What is Type I Deiodinase?
Outer and inner ring deiodinase -> forms T3 Found in: Liver, Kidney, Thyroid, Skeletal muscle Primary source of T3 in circulation
31
What is Type II Deiodinase?
Outer ring deiodinase -> forms T3 | Found in: Brain, Pituitary, Placenta, Cardiac Muscle
32
What is Type III Deiodinase?
Inner ring deiodinase -> forms rT3 | Found in: brain, placenta, skin
33
Which is produced more and stored in the thyroid?
T4
34
Which deiodinase is the thyroid hormone sensor in the pituitary?
Type II deiodinase
35
What % of thyroid hormones are bound in circulation?
>99% TBG(70%) Transthyretin (TTR): 10% Albumin: 15-25%
36
What is TBG?
Thyroxine binding globulin-> made in liver | T4 has highest affinity for TBG
37
What increases TBG levels?
Estrogen, hepatitis
38
What decreases TBG levels?
Nephrotic syndrome | Steroids
39
How does a decrease in TBG change free T4/T3 levels?
No net change; Changes in TBG dont usually affect bioavailable T3-> DOES affect TOTAL T4/T3 levels
40
How does the thyroid hormone receptor work?
Nuclear receptor that forms heterodimers with retinoic acid receptor (RXR) -> complex binds to DNA -> recruit coregulatory proteins-> transcriptional activation
41
Where are thyroid hormone receptors found?
Every cell type
42
How does BMR change with hypo/hyperthyroid
Hypo: deceased Hyper: increased
43
How does thyroid hormone affect carbohydrate metabolism?
Increase gluconeogenesis and glycogenolysis | normal glucose serum
44
How does thyroid hormone affect protein metabolism?
Increase protein synthesis + Inc proteolysis => muscle wasting
45
How does thyroid hormone affect lipid metabolism?
Inc Iipogenesis, inc lipolysis, dec serum cholesterol
46
How does thyroid hormone affect thermogenesis?
Hypo: Decreased -> cold intolerant Hyper: Increased-> heat intolerant
47
What does T3 do in terms of cellular metabolism?
Increases cellular oxygen consumption and heat production by increasing mitochondrial activity
48
What are the effects on the CNS by thyroid hormone?
T3 is critical for normal brain development Neuronal cell migration/differentiation Myelination Synaptic transmission
49
What is Cretinism?
Caused by iodine deficiency during development leading to short stature/impaired bone formation mental retardation delayed motor development
50
What are the effects of thyroid hormone on the heart?
T3 increases cardiac output -> inc SV and HR Hyperthyroidism can cause arrhythmias
51
What is a goiter and what causes it?
Enlarged thyroid | Caused by thyroid cancer and both hypothyroidism and hyperthyroidism
52
What is Graves Disease?
Hyperthyroid condition due to autoimmunity -> Antibodies stimulate TSH receptors -> inc T4/T3 levels Causes goiter with hyperthyroid sx
53
What is noted on the histology of thyroid gland from a Graves Disease patient?
Scant colloid Tall Columnar ACtivated Follicular cells Infiltration of lymphocytes
54
What is Hashimoto's Thyroiditis?
Hypothyroid condition due to autoimmune destruction of thyroid follicles Antibodies target TPO and TG Forms a diffuse goiter with hypothyroid sx
55
Why does hypothyroidism cause a goiter?
lack of neg feedback by T4/T3 causes increased, continuous secreiton of TSH from pituitary
56
What are hyperthyroid sx?
``` tachycardia opthalmopathy irritability/hyperactivity Heat intolerance Weight loss Muscle Wasting ```
57
What are hypothyroid sx?
``` lethargy/fatigue Hair loss Cold Intolerance Brittle nailes Decreased appetite Weight gain ```
58
What is a thyroid storm
``` 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
What are the treatmetns for a thyroid storm?
PTU: acute treatment Carbimazole Beta Blockers to normalize heart function

FHB Endocrinology (10 decks)

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