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RDS Test 4 > B8.058 Prework 1: Thyroid Gland > Flashcards

B8.058 Prework 1: Thyroid Gland Flashcards

1
Q

describe the H-P-T axis

A 
hypothalamus > TRH
anterior pituitary (thyrotropes) > TSH
thyroid gland (thyrocytes) > thyroid hormones
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2
Q

importance of iodide

A

necessary for synthesis of thyroid hormones
minimum - 75 ug/day
recommended - 150 ug/day

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3
Q

where is iodide stored in the body

A

thyroid (8000 ug)

hormone pool, in circulation within T3 and T4 (600 ug)

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4
Q

primary steps in thyroid hormone synthesis and secretion

A
  1. stimulated by TSH
  2. uptake of iodide
  3. thyroglobulin: iodination, organification, and coupling
  4. secretion
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5
Q

composition of thyroid tissue

A

numerous follicles

  • lined by thyrocytes (functional cells that make hormone)
  • filled with colloid containing thyroglobulin
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6
Q

description and regulation of iodide uptake

A 
active process:
-achieved via Na/I symporter
-requires energy
regulation:
-internal autoregulatory mechanisms
-TSH drives iodide from blood into lumen of thyroid follicle
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7
Q

where is TPO found

A

membrane bound in lumen of follicle

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8
Q

TPO requirements for function

A

Tg (substrate)
iodide
H2O2 (NADPH oxidase)

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9
Q

what is thyroglobulin (Tg)

A

660 kD homodimer
regulated by TSH
contains 120-140 tyrosine residues
iodinated by TPO

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10
Q

function of TPO

A

responsible for iodination/organification and coupling of Tyr in Tg molecules

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11
Q

result of TPO

A

20-30 Tyr become iodinated
20-25% (6-8) of the MIT/DIT become coupled
stored in this form

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12
Q

secretion of thyroid hormone

A

stimulated by TSH

  1. pinocytosis
  2. lysosome fusion
  3. hydrolysis
  4. secretion
  5. deiodination
    * *hormone is cleaved out of the Tg before moving into circulation
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13
Q

thyroid hormone in circulation

A

exist both in free and bound form
70-75% is bound to thyroid binding globulin (TBG)
<1% is free, but this amt is biologically important

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14
Q

describe TBG

A

made in the liver
high affinity for T4/T3
70-75% of T4/T3 is bound to TBG

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15
Q

increased expression of TBG

A

pregnancy
newborns
oral contraceptives (due to E)

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16
Q

decreased expression of TBG

A 
androgens (anabolic steroids)
large doses of glucocorticoids
chronic liver disease
severe systemic illness
active acromegaly
kidney disease with proteinuria
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17
Q

other thyroid binding proteins in circulation (not TBG)

A 
transthyretin/thyroxine binding pre-albumin (TBPA)
-10% of T4
albumin
-low affinity
-15% of T4/T3
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18
Q

T4 half life

A

8 d

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19
Q

T3 half life

A

1-3 d

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20
Q

conversion of T4

A

40% of secreted T4 is converted to T3 in the periphery (majority of what is secreted is T4)
30% of secreted T4 is converted to rT3 in the periphery

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21
Q

5’ Deiodinase

A

converts T4 to T3
type 1: thyroid, kidney, liver
type 2: pituitary, brain, brown adipos

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22
Q

5 Deiodinase

A

converts T3 to T2
converts T4 to rT3
inactivates hormone at target tissues
found in kidney, liver, skin, and placents

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23
Q

mechanism of propylthiouracil

A

inhibits type 1 5’ Deiodinase and TPO

used in hyperthyroidism to maintain T4 state (less potent)

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24
Q

potency of thyroid hormones

A

T3 > T4 (10x)

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25
negative feedback of T4/T3 on HPT axis
1. hypothalamus - decreased TRH 2. pituitary - predominant mechanism - T4 conversion to T3 by type 2 5'DI - decreases response to TRH by decreasing TRH-R expression - decreases synthesis and secretion of TSH
26
why does a goiter form
iodide deficiency leads to low thyroid hormone synthesis/secretion increased activity in gland to attempt to stimulate production > larger gland
27
thyroid hormone receptors
nuclear; alter gene expression (slow) - at least 6 types - number is regulated (decreased by fasting) - bind T3 with higher affinity than T4 - expressed in most tissues/cells
28
primary roles of thyroid hormone
``` regulate protein metabolism regulate glucose metabolism regulate lipid metabolism regulate basal metabolic rate (BMR) important during CNS fetal development ```
29
TH and protein metabolism
growth permissive effects - stimulates GH expression (and IGF) - stimulates metabolic proteins and enzymes (mitochondria) - promotes calcification within cartilage
30
effect of EXCESS TH on protein metabolism
protein catabolism
31
TH and glucose metabolism
potentiated actions of insulin | -stimulates glycogen synthesis and glucose utilization
32
effect of EXCESS TH on glucose metabolism
reverse of normal effect - increases glycogenolysis - altered glucose utilization - enhances actions of epinephrine via induction of B-AR expression
33
TH and lipid metabolism
stimulates cholesterol synthesis and also its conversion to bile (decreases cholesterol levels)
34
effect of EXCESS TH on lipid metabolism
increases lipolytic actions of other hormones | results in increased fat metabolism
35
effect of LOW TH on lipid metabolism
can lead to hypercholesterolemia | -regulates hepatic LDL-R
36
TH and basal metabolic rate (BMR)
regulates oxidative phosphorylation (Na+/K+ATPase) - transcription and activity - altered oxygen consumption and heat production
37
effect of LOW TH on BMR
can lead to a 50% decrease
38
effect of EXCESS TH on BMR
can increase BMR 80%
39
effect of TH on bone
stimulates linear growth and development and bone maturation (via GH)
40
effect of TH on skin & hair
required for normal follicle development and epidermis renewal
41
effect of TH on GI tract
can increase GI motility
42
effect of TH on the heart
regulates sensitivity of B1 receptors increased CO by increasing HR and SV excess TH will cause vasodilation
43
effect of TH on brain development
promotes dendritic branching promotes proliferation of axons promotes formation of synpases regulates myelinization within the cortex
44
symptoms of hypothyroidism
``` weight gain cold intolerance decreased perspiration constipation bradycardia fatigue muscle stiffness depression dry skin and hair menstrual disturbances ```
45
symptoms of hyperthyroidism
``` weight loss heat intolerance increased sweating frequent BMs tachycardia and palpitations fatigue muscle weakness and hypotrophy increased excitability and nervousness moist skin and hair menstrual disturbances ```
46
assessment of thyroid hormone levels
TSH assay total T4 or T3 assays free T4 rT3 assay
47
other assessments of thyroid function
``` anti-thyroid Abs -TPO -thyroglobulin -TSI TBG assay (carrying capacity) RAIU and thyroid scans fine needle aspiration cytology ```
48
TRH test process
assess the responsiveness of pituitary thyrotropes to exogenous administration of TRH outcomes: 1. excess TH > reduced response due to downregulation of the TSH receptor by TH 2. deficient TH > increased response due to upregulation of the TSH receptor from reduced TH negative feedback
49
characterize thyroid disorders in general
very common | women are affected more often than men (10:1)
50
causes of hypothyroidism
``` iodide deficiency congenital/cretinism non-thyroidal illness thyroiditis endemic goiter sporadic goiter ```
51
congenital hypothyroidism
deficiency in utero | mental and growth retardation (can be treated)
52
non-thyroidal illness (euthyroid sick syndrome)
shift in conversion of T4 from T3 to rT3 (inactive)
53
types of thyroiditis
1. subacute - granulomatous (deQuervain) 2. Reidel 3. Hashimoto
54
subacute, granulomatous (deQuervain) thyroiditis
viral infection, URI | typically resolve over time
55
reidel thyroiditis
rare | fibrosis, calcification of gland
56
hashimoto thyroiditis
autoimmune disease that attacks/ destroys the thyroid gland | autoreactive T cells and Abs to thyroid antigens (TPO or Tg)
57
sporadic goiter
due to mutations in Tg or TPO
58
treatment of hypothyroidism
``` exogenous T4 (levothyroxine) -better than T3 because it has a longer half life and is less potent so there's not as much of a risk of overdose ```
59
etiologies of hyperthyroidism
Graves disease adenomas of the thyroid gland pituitary adenomas thyrotoxicosis
60
what is Graves disease
autoimmune disease thyroid stimulating immunoglobulins (TSI) directed against the TSH-R, inducing function no negative feedback on TSH production
61
epidemiology of Graves
5:1 , F:M 60-80% of hyperthyroidism most prevalent autoimmune disorder in the US
62
predisposing factors for Graves
sex (female) stress smoking
63
symptoms of graves
``` nervousness fatigue rapid heartbeat or palpitations weight loss 50% get ophthalmopathy (exophthalmos) ```
64
treatment of hyperthyroidism
``` radioactive iodine to destroy gland thyroidectomy (avoid parathyroid glands) antithyroid drugs -PTU -carbimazole/ methimazole ```
65
carbimazole/ methimazole mechanisms
TPO inhibition
66
hot thyroid nodules
functional - take up radiotracer secrete thyroid hormone -hyperthyroidism ablate w radiotracer
67
cold thyroid nodules
nonfunctional- do not take up radiotracer non-secretory increased association with malignancy -FNA cytology > surgery
68
primary hypothyroidism findings
T4 low | TSH high
69
secondary hypothyroidism findings
T4 low | TSH normal or low

RDS Test 4 (17 decks)

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