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FHB Block 4 > L7- Thyroid > Flashcards

L7- Thyroid Flashcards

1
Q

What is the innervation of the thyroid gland?

A

Middle and inferior cervical ganglion (of the sympathetic nervous system)

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2
Q

What is the functional unit of the thyroid?

A

Follicle- consists of epithelial cells surrounding the lumen

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3
Q

What is the lumen of the thyroid follicle filled with?

A

30%= colloid (the extracellular storage site of T3/T4 and thyroglobulin)

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4
Q

What are parafollicular cells? What do they produce?

A

Parafollicular cells (C cells) produce calcitonin and other proteins that maintain the follicle

They are found inside the basement membrane - they do not touch the colloid and contain many small granules.

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5
Q

What occurs at the microvilli of the thyroid gland?

A

Microvilli extend into the colloid to facilitate transport of thyroglobulin.

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6
Q

What are the two precursors of the thyroid hormones?

A

Thyroglobulin and iodide

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7
Q

What happens to the dietary excess of iodide?

A

Excess is secreted into the urine as iodine and into the stool

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8
Q

What is the Wolf-Chaikoff effect?

A

Autoregulation of iodide uptake in the thyroid: an intrathyroidal response that assure constancy of iodide storage in the face of changes in dietary iodide

Increases in dietary iodide decreases gland transport (and vice versa)

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9
Q

What is the HPT axis?

A

Hypothalamus: secretes thyrotropin-releasing hormone from the paraventricular nucleus (PVN)

Pituitary: stimulated by TRH, pituitary releases thyroid-stimulating hormone (TSH)

Thyroid: Stimulated by TSH, releases T3/T4

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10
Q

Describe the inhibition of thyrotropes in the pituitary

A

Thyrotropes are tonically inhibited by somatostatin and dopamine .

There is also negative feedback by T3 release - T3 is the “thyroid sensor”

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11
Q

What does it mean that the thyroid follicle is functionally polarized?

A

Apical surface: exposed to lumen (colloid) - responsible for the thyroid hormone synthesis and iodination of thyroglobulin

Basolateral surface: exposed to blood – site of iodine uptake “trap” and thyroid hormone release back into the blood

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12
Q

How is iodide taken up into the thyroid cells?

A

Na+/I- symporter on the basolateral surface of the cells- this is known as iodide trapping

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13
Q

How is iodide converted to iodine?

A

Iodide is oxidized by thyroid peroxidase (TPO) to form iodine

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14
Q

What is/what is the point of “organification”?

A

Organification is the incorporation of iodine into thyroglobulin. This traps iodine in the cell such that it is committed to the production of the thyroid hormones

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15
Q

What is the conjugation step of the synthesis of T3/T4?

A

monoiodothyronine and diiodothyronine are conjugated to form either T3 or T4

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16
Q

What stimulates the production of T3/T4?

A

Thyroid stimulating hormone

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17
Q

How are thyroid hormones the exception to the rules?

A

They are small but have long half-lives (T4= 7 days) and they travel in the blood bound tightly to transport proteins.

They act like steroid hormones, but they are not.

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18
Q

Describe the biologic activity/relative abundance of T3 and T4.

A

Thyroid hormones are primarily released as T4, but T3 is the potent primary effector hormone. T4 is converted to T3 at the target tissue.

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19
Q

What is the action of carbimazole? What is it used for?

A

Carbimazole inhibits thyroid peroxidase. It is used as a treatment for hyperthryoidism

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20
Q

Describe the binding capacity/affinity of T3 for its receptor?

A

T3 binds to the receptor with high affinity but low capacity to the receptor. There are more T3 receptors than available T3 under normal physiologic conditions.

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21
Q

What is the purpose of radioactive iodide uptake scans?

A

They are used to determine function of the thyroid gland.

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22
Q

Differentiate “hot” from “cold” nodules in an radioactive iodine uptake scan. Which are more predictive of malignancy?

A

Hot nodules: area of increased follicular iodide uptake and thyroid hormone synthesis. Usually benign

Cold nodules: inactive/dysfunctional thyroid follicle. Can be benign or malignant.

Cold nodules are more predictive of a malignancy.

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23
Q

Following administration of radioactive iodide, what is the normal uptake after 24 hours? What indicates hyperthyroidism? What indicates hypothyroidism?

A

Normal; 25%
Hyperthyroidism: >60%
Hypothyroidism:

24
Q

How can you test an organification block?

A

Test by blocking the Na/I- symporter with perchlorate.

25
Q

What is the primary enzyme responsible for the peripheral conversion of T4 to T3?

A

Type 1 deiodinase

26
Q

In what tissues do you find Type I deiodinase

A

Liver, kidney, thyroid and skeletal muscle

27
Q

Where is type II deiodinase found?

A

Brain, pituitary, placenta and cardiac muscle

28
Q

Where is type III deiodinase found?

A

brain, placenta and skin

29
Q

What is the biologic activity of reverse T3?

A

Reverse T3 is biologically inactive

30
Q

About what percent of T4 is converted in the periphery to T3/

A

80%

31
Q

What is the affinity of T4 for its receptor?

A

low

32
Q

What enzyme is the thyroid hormone “sensor” in the pituitary?

A

Type II deiodinase

33
Q

How does thyroid hormone travel in the blood?

A

More than 99% of thyroid hormone is bound in circulation

70% bound to Thyroxine-binding globulin
10% bound to transthyretin (TRR)
15-20% bound to albumin

34
Q

Where is thyroxine binding globulin made?

A

The liver

35
Q

What is the affinity of T4 for TBG?

A

T4 has a high affinity for TGB

36
Q

How do changes in TGB affect the total T4/T3 levels?

A

Changes in TBG don’t usually affect bioavaiable T3, but it does affect the total T4/T3 levels.

TBG can reversibly release T4 to target tissues.

37
Q

What is unique about T4 binding to TBG?

A

TBG can reversibly release T4 to target tissues - it can bind more T4 right away

38
Q

How does the thyroid hormone receptor work?

A

The thyroid hormone receptor forms a heterodimer with the retinoic acid receptor

39
Q

Where is the thyroid hormone receptor in the body?

A

Expressed in nearly every cell type

40
Q

What are the binding kinetics of T3 to the thyroid hormone receptor?

A

High affinity, low capacity binding to T3

41
Q

What are futile cycles?

A

T3 stimulates” futile cycles” - stimulation of opposing loops to maintain a normal metabolic rate.

42
Q

How is serum glucose levels affected by thyroid imbalance?

A

Serum glucose is unaffected by thyroid inbalances

43
Q

How is protein metabolism affected by thyroid imbalance?

A

Muscle wasting occurs with hyperthyroidism

44
Q

How is lipid metabolism affected by thyroid imbalance?

A

Hypothyroid: increased serum cholesterol
Hyperthyroid: decreased serum cholesterol

45
Q

How is thermogenesis affected by thyroid imbalance?

A

Hypothyroid: cold intolerant
Hyperthyroid: heat intolerant

46
Q

What role does T3 play in normal brain development?

A

T3 is critical for normal brain development. It plays a role in the regulation of neuronal cell migration/differentiation, myelination, and synaptic transmission

47
Q

What is cretinism?

A

Iodine deficiency during development

Short stature/impaired bone formation, mental retardation and delayed motor development

48
Q

How does T3 affect cardiac output?

A

T3 increases cardiac output by increasing resting heart rate and stroke volume

49
Q

What is the most common cause of hyperthyroidism in the us?

A

Grave’s disease

50
Q

What are two causes of hypothyroidism?

A

Hashimoto’s thyroiditis and iodine deficiency

51
Q

What is Grave’s disease?

A

Autoimmune disease in which antibodies stimulate the TSH RECEPTOR.

This leads to very high levels of T3/T4, but low levels of TSH itself (because T3/T4 is so high)

52
Q

What are symptoms of Grave’s disease?

A

Tachycardia, ophthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, and muscle wasting

53
Q

What is Hashimoto’s thyroiditis?

A

Autoimmune destruction of thyroid follicles- antibodies specifically against TPO (thyroperoxidase) and TG

54
Q

What are the symptoms of Hashimoto’s thyroiditis?

A

Diffuse goiter with hypothyroid symptoms: lethargy, fatigue, hair loss, cold intolerance, brittle nails, decreased appetite, weight gain

55
Q

What is thyroid storm?

A

Acute emergency- hyperthyroid coupled with severe acute illness,
- High fever, tachycardia, altered mental status, severe nausea, vomiting and diarrhea in addition to severe circulatory collapse

56
Q

What is the treatment for thyroid storm?

A

Propylthiouracil, carbimazole (inhibits TPL), and beta blockers to restore normal heart function

FHB Block 4 (15 decks)

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