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Endo/Repro Midterm > Thyroid Gland > Flashcards

Thyroid Gland Flashcards

1
Q

The thyroid gland produces iodothyronines ____ and _____

A

Tetraiodothyronine (T4) aka thyroxine

Triiodothyronine (T3)

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2
Q

Peripheral conversion of iodothyronines by ____ is key

A

Deiodinases

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3
Q

The functional unit of the thyroid gland

A

Thyroid follicle

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4
Q

The thyroid follicle is lined by _____ epithelial cells and the lumen is filled with _____. Follicles also contain parafollicular C cells which secrete _____

A

Cuboidal; colloid; calcitonin

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5
Q

What is the main secretory product of the thyroid?

A

T4 (10x more than T3)

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6
Q

Colloid is composed of newly synthesized thyroid hormones attached to ____

A

Thyroglobulin

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7
Q

Conversion of T4 to T3 occurs in the thyroid and peripherally through the action of ______

A

Deiodinase

[90% is peripherally converted vs. 10% that is directly secreted]

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8
Q

What are some clinical states that are associated with reduced conversion of T4 to T3?

A

Fasting
Medical and surgical stress
Catabolic disease

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9
Q

_______ is often associated with elevated levels of type 1 deiodinase, contributing to elevated T3 in the blood

A

Hyperthyroidism

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10
Q

T4 may be converted to T3 by ____ ring deiodination (activation) by deiodinases type ___ and ___

A

Outer; 1; 2

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11
Q

What is the primary source of dietary iodine?

A

Iodized table salt

[also from dairy products and fish]

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12
Q

Synthesis of thyroid hormone involves basal to apical movement of 2 precursors ____ and _____

A

Thyroglobulin
Iodide

[iodide is taken up from blood; thyroglobulin is assembled from translated amino acids]

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13
Q

______ is the process of binding iodine with thyroglobulin

A

Organification

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14
Q

What are the important transporters in the basolateral membrane of cells synthesizing thyroid hormone?

A

Na/K-ATPase

Na/I symporter (NIS, 2:1 ratio)

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15
Q

What are the important transporters in the apical membrane of cells synthesizing thyroid hormone?

A

Pendrin — Cl/I countertransporter

Peroxidase — oxidizes iodide for combination with thyroglobulin (aka TPO)

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16
Q

After iodination by thyroid peroxidase, thyroglobulin is stored in the lumen of the follicle as colloid.

Within the colloid, thyroglobulin binds to ____, ____, and intermediates ___ and ____

A

T4; T3; MIT; DIT

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17
Q

When iodide availability is restricted, formation of _____ is favored

A

T3

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18
Q

Intracellular steps of thyroid hormone synthesis involve _______ of colloid droplet, at which time ______ cleave T4 and T3 from thyroglobulin for release into circulation

A

Pinocytosis; proteases

[purpose is to rapidly deiodinate MIT and DIT molecules that have been released during proteolysis of thyroglobulin. This iodide is then recycled into T4 and T3 synthesis]

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19
Q

T/F: a deficiency in intrathyroidal deiodinase mimics a dietary iodide deficiency

A

True

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20
Q

What are some inhibitors of NIS transporter in basolateral membrane?

A

Perchlorate; thiocynate

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21
Q

What is the primary inhibitor of TPO?

A

Propylthiouracil (PTU) - inhibits production of final thyroid products

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22
Q

The wolff-chaikoff effect results in inhibition of what step in thyroid hormone synthesis?

A

Organification (process of binding iodine with TG)

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23
Q

Iodine is stored as iodinated _____ of thyroglobulin

Enough hormone is stored as iodinated TG in the follicular colliod to last 2-3 mos. Each TG molecule contains 30 ____ molecules and a few ___ molecules

A

Tyrosine

T3; T4

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24
Q

Activity of the thyroid gland can be assessed by radioactive iodine uptake. Compare levels at 24 hrs in normal thyroid, hyperthyroid, and hypothyroid

A

Normal = 25% at 24 hrs

Hyperthyroid = >60% at 24 hrs

Hypothyroid = <5% at 24 hrs

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25
Q

The majority of thyroid hormone circulates bound to plasma proteins (only 1% is free). What are the main plasma proteins that bind thyroid hormones?

A

Thyroxin-binding protein (TBG) = 70%

Transthyretin (TTR) = 10-15%

Albumin = 15-20%

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26
Q

The main plasma protein that binds thyroid hormone is TBG. It is synthesized by the ____ and has greater affinity for ____

A

Liver; T4

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27
Q

Circulating TBG can be indirectly assessed with what test?

A

T3 resin uptake test

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28
Q

Describe T3 resin uptake test

A

Add labeled T3 then add resin as secondary binder

If TBG levels are already occupied, less radioactive T3 will bind and more spots will be available to secondary resin

The amount of T3 bound to resin is then measured

29
Q

What would T3 resin uptake test results be in the case of hyperthyroid vs. hypothyroid?

A

Hyperthyroidism = high T3 resin uptake

hypothyroidism = low T3 resin uptake

30
Q

What would T3 resin uptake test results be in the case of high TBG levels?

A

Increased T4 but decreased T3 resin uptake

31
Q

What would the T3 resin uptake test results be in the case of low TBG?

A

Decreased T4, but increased T3 resin

32
Q

What would T3 resin uptake test results be in the case of hepatic failure?

A

Decreased TBG, but increased T3 resin uptake

33
Q

What would the T3 resin uptake test results be in pregnancy

A

Increased TBG, but decreased T3 resin uptake

34
Q

Changes in blood TBG and free thyroid hormones in the case of hepatic failure

A

Decreased blood TBG

Transient increase in level of free T3 and T4 followed by inhibition of synthesis of T3 and T4 via negative feedback

35
Q

Changes in blood TBG and free thyroid hormones in pregnancy

A

Increased blood levels of TBG

Increased bound forms of T3 and T4 (decreased free)

Transient decrease in free T3; T4 increases synthesis and secretion of T3 and 4

Increase in total levels of T3 and 4 but levels of free, physiologically active thyroid hormones are normal (clinically EUTHYROID)

36
Q

TSH is released from thyrotrophs of anterior pituitary, leading to _____ effect on thryoid gland itself and secretion of thyroid hormone

TSH is regulated by _____ and _____

A

TRH; free T3 (feedback)

37
Q

What transporter is responsible for the entry of T3 and T4 from blood across cell membrane into cytosol?

A

MCT8/10 transporters

[can also occur by diffusion]

38
Q

What are some nuclear receptors/TFs important for conversion of T4 to T3?

A

TRalpha1 (cardiac/muscle)
TRalpha2
TRbeta1 (brain, liver, kidney)
TRbeta2 (pituitary)

39
Q

Physiologic effects of T3 on growth

A

Growth

Bone maturation

40
Q

Physiologic effects of T3 on nervous system

A

CNS maturation

41
Q

Physiologic effects of T3 on BMR

A

Increased Na/K ATPase

Increased O2 consumption

Increased heat production

Increased BMR

42
Q

Physiologic effects of T3 on metabolism

A

Increased glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, and protein synthesis/degradation

43
Q

Physiologic effects of T3 on cardiovascular system

A

Increased cardiac output Upregulation of beta 1 adrenergic receptors

44
Q

T3 generally activates nuclear receptors and _____ second messenger system leading to increased metabolic activity, growth, cardiovascular effects, GI motility, CNS development, and others

A

cAMP

45
Q

Thyroid hormones typically have ____ onset and ____ duration

A

Slow; long

46
Q

There is a 2-3 day latent period before ____ activity begins, and activity persists 6-8 weeks once started

Actions of ____ are more rapid, with a 6-12 hour latent period and 2-3 day maximum

A

T4; T3

47
Q

Thyroid hormone has direct and indirect effects on the CV system including:

______ TPR/systemic resistance

_____ inotropic effects

______ blood volume/preload

A

Decreased

Increased

Increased

48
Q

Thyroid hormone works synergistically with ___ and ___ to promote bone formation

A

GH; somatomedins

49
Q

What are the general effects of thyroid deficiency during perinatal period?

A

Abnormal synaptic development

Decreased dendritic branching and myelination

Cretinism

50
Q

Effects of hyperthyroidism vs. hypothyroidism on metabolism

A

Hyper:
Heat intolerance
Weight loss
Increased BMR

Hypo:
Cold intolerance
Weight gain
Decreased BMR

51
Q

Effects of hyperthyroidism vs. hypothyroidism on bone

A

Hyper: Osteoporosis (or stunted growth in adolescents)

Hypo: stunted growth

52
Q

Effects of hyperthyroidism vs. hypothyroidism on CNS

A 
Hyper: 
Agitation
Anxiety
Difficulty concentrating
Hyperreflexia
Hypo:
Cretinism
Listlessness
Slowed movement
Somnolence
Impaired memory
Decreased mental capacity
53
Q

Effects of hyperthyroidism vs. hypothyroidism on skin

A

Hyper:
Sweating

Hypo:
Dry
Myxedema

54
Q

Effect of hyperthyroidism vs. hypothyroidism on CV system

A 
Hyper: 
Tachycardia
Afib
Palpitations
High output heart failure
Hypo:
Bradycardia
Decreased contractility
Decreased CO
Heart failure
55
Q

Effect of hyperthyroidism vs. hypothyroidism on GI system

A

Hyper: Diarrhea

Hypo: constipation

56
Q

Most common cause of primary hyperthyroidism

A

Graves disease

57
Q

Example of secondary hyperthyroidism

A

TSH-secreting pituitary tumor

58
Q

Major clinical signs of graves disease

A

Exophthalmos

Periorbital edema

59
Q

Diagnosis of graves disease

A

Elevated serum free and total T4 and T3 levels

Goiter and ophthalmopathy

Presence of circulating thyroid stimulating immunoglobulins (helps distinguish graves from adenoma of pituitary thyrotrophs)

60
Q

Why are TSH levels low in graves disease?

A

Thyroid stimulating immunoglobulins stimulate the TSH receptor without TSH present - so there is loss of feedback and TSH levels are lower

61
Q

In what condition would you see rapid uptake of radioactive iodine within 6 hrs followed by high turnover rate?

A

Graves disease

62
Q

Primary causes of hypothyroidism

A 
Agenesis
Gland destruction (surgical, hashimotos, irradiation)
Inhibition of thyroid hormone synthesis and release (iodine def)

[may also be transient d/t postpartum, thyroiditis, etc.; hypothalamic disease, pituitary disease, resistance to thyroid hormones]

63
Q

Treatment for hypothyroidism involves replacement doses of ___

A

T4

[note that metabolism of T4 decreases with age, higher doses needed in younger patients; also overprescription in postmenopausal women contributes to osteoporosis]

64
Q

Hashimoto’s thyroiditis

A

Thyroid hormone synthesis impaired by antibodies against thyroglobulin or TPO, leading to decreased T3 and T4 secretion

TSH levels are high - trophic effect leading to goiter

65
Q

What causes cretinism?

A

Iodide deficiency

Maternal intake of antithyroid meds

Impaired development of thyroid gland

Inherent deficit in synthesis of thyroid hormones

66
Q

Symptoms of cretinism

A 
Feeding problems
Respiratory difficulty
Protruding tongue
Growth retardation
Mental retardation
Jaundice
Dry skin
Hypotonia
67
Q

Hypothyroidism due to iodine deficiency leads to transient decrease in synthesis of thyroid hormones, _____ levels of TSH, and goiter

A

elevated

68
Q

Goiters can develop in response to multiple imbalances and diseases within the HPT axis

What are examples of these imbalances?

A

Hyperthyroidism - Grave’s disease or secondary cause

Primary hypothyroidism - lack of adequate iodine, sporadic hypothyroid of unknown etiology, chronic thyroiditis

Endo/Repro Midterm (14 decks)

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