thyroid martin Flashcards
1
Q
the thyroid gland consists of tow lateral lobes connected by the _
it is located blow and anterior to the _
A
isthmus
larynx
2
Q
what are some abberant locations of thyroid tissue
A
lingual, thyroglossal, substernal
3
Q
describe the HPA axis for thyroid
A
- stimulus like low body temperature will cause the hypothalmus to secrete TRH
- TRH stimulates the AP to secretes TSH
- TSH acts on the thyroid gland to release TH from the follicular cells
- TH through negative feedback stops the production of TSH and TRH when there are adquate levels
4
Q
TH (thyroid hormones) essential action in a _ in basal metabolic rate
A
increase
5
Q
example of TH stimulation
A
increased fatty acid mobilization, increased heart rate, hypertrophy, increases cholesterol synthesis, increased gluconeogensis, increased protein catablism, increased growth, ,increased resportion of bone
decreased TSH and increased GH
6
Q
Th _ growth hormone
A
increases
7
Q
thyroglobulin is synthesized and stored in _. Iodide is transported into the cell and incorporated into TG (thyroglobulin) to form _ _ , TG is _ and cleaved to release _ and _
A
colloid
idodinated tyrosines
endocytosed
T4 and T3
8
Q
the thyroid is divided by thin _ into lobules there are about 20-40 lobules, they are lined by _ to _ _ epitheliun abd are filled with _ positive thyroglobulin
A
septae
low cuboidal (not active)
to low columnar epithelium (active)
PAS+ thyroglobulin
9
Q
the thyroid follicle is formed by simple _ to low _ epithelium = follicular epithelium
A
cuboidal
columnar
10
Q
follicular cells aka _ cells produce
A
principle
T4 and T3
11
Q
_ induces follicular cells to transform from cuboidal to columnar
A
TSH
12
Q
_ and _ regulate cell and tissue basal metabolism, _ production, and influence _ growth
A
T3 and T4
heat production
body growth/development
13
Q
follicles contain colloid what is a prinicple component of colloid?
A
thyroglobulin which is an idoniated glycoprotein (gel like substance)
14
Q
thyrogloblin is not a hormone is stores?
A
inactive form of thyroid hormones
15
Q
thryoid follicles convert thyroglobulin to _ and to a lesser amount of _
A
T4
T3 (lesser)
16
Q
_ and _ trasnport T4 and T3 to the periphery
A
thyroxine-binding globulin and transthyretin
17
Q
_ proteins keep T3 and T4 unbound or free in narrow limits
A
binding
18
Q
majority of T4 deionitaed to _ in the periphery which binds to thryoig hormone nuclear receptors with way greater affinity
A
T3
19
Q
multiprotein hormone receptor complex binds to _ in target genes regulating their transcription
A
thyroid hormone response element
20
Q
upregulation of _ and _ catabolism plus stumulation of _ synthesis results in a new increase in basal metabolic rate
A
carbohydrate and lipid catabolism
protein
21
Q
thyroid hormone has a critical role in _ development of fetus and neonate
A
brain
22
Q
when the TSH reaches its TSH receptor in the thyroid what happens
A
Gs protein activation increased inctracellular CAMP which stimulated thyroid growth
T3 and T4 go to the thyroid hormone receptor and alter gene expression
23
Q
what is a goitrogen?
A
this is an inhbitor of T3 and T4 synthesis with an increase in TSH leading to a hyperplastic goiter
24
Q
what is propylthiouracil (PTU)
A
an antithyroid agent that inhibits oxidation of iodide
thus blocking thyroid hormone production
also blocks peripheral deiodination of T3 to T4 (getting rid of symptoms)
25
what does iodine adminsitration do?
it is adminsitered to people with hyperthyroidism and blocks the release of thyroid hormones
high doses of iodine inhibit proteolysis of thyroglobulin
Th is synthesized by not released
26
what are parafollicular cells?
C cells that are in the periphery of follicular epithelium and lie on the basal lamina of the follicle(they are not expoased to the follicle lumen)
27
what do c cells look like (parafollicular cells)
pale staining, they are solitary cells or small clusters of cells
28
what do c cells secrete?
they secrete calctonin which lowers blood calcium
29
how does calcitonin work
it lowers blood calcium levels. by suppressing osteoclastic activity and promoting calcium deposition in bones
30
secretion of calcitonin is directly regulated by?
serum calcium levels
if serum calcium levels are high they calcitonin is secreted to lower them
31
thyrotoxicosis
this is a hypermetabolic state where there is hyperfunctionof the thyroid glands (increased T3 and T4)
32
hyperthyroidism
overactive thyroid that releases preformed T3 and T4
## Footnote
can be used interchangeable with thyrotoxicosis
33
primary hyperthyroidism
secondary hyperthyroidism
primary: thyroid abnormality producing too much T3 and T4
secondary: extrinsic problem (too much TSH)
34
what are the pathologies that have thyrotoxicosis (metablic state) and hyperthyroidism
primary: graves, toxic multinodular goiter, toxic adenoma, iodine induce hyperthyroidism, neonatal thyrotoxicosis associated with maternal graves disease
secondary: TSH secreting pituitary adenoma
35
what are pathologies that are thyrotoxicosis only
granulomatous thyroiditis
subacute lymphocytic thyroiditis
struma ovarii
factitious thyrotoxicosis
36
hyperthyroid clinically is a hypermetabolic state and has overactivity of?
increased _ tone
sympathetic nervous system
increased B adrenergic tone
37
skin in hyperthyroid
soft, warm, flushed
## Footnote
this is due to increased blood flow and peripheral dilation to facilitate heat loss
38
what are symptoms of hyperthyroid
heat intolerance, weight loss, cardiac manifestations, neuromusclar changes, ocular changes, GI system and skeletal muscle changes
39
what are the cardiac manifestations of hyperthyroid
increased cardiac output, tachycardia, palpitation, arrythmias, CHF, thyrotoxic/hyperthyroid cardiomyopathy
## Footnote
earliest symtoms of hyperthyroid
40
what is thyrotoxic/hyperthryoif cardiomyopathy
reversible left ventricular dysfunction and low output heart failure
41
what neuromusclar changes are seen in hyperthyroid
termor, hyperactivity, emotional lability, anxiety
overactive sympathetic nervous system
**thyroid myopathy
42
what is thyroid myopathy
a neuromusclar change that leads to proximal muscle weakness and decreased muscle mass
43
what GI tract changes are seen in hyperthyroid
hypermobility,malabsorption, hyperdefection
## Footnote
not diarrhea
44
what ocular changes are seen in hyperthyroid
wide staring gaze, lid lag
45
true thyroid opthalmopathy is proptosis and is only in _ disease
graves
46
what skeletal muscle changes are in hyperthroid
increased bone resorption and increase porosity so osteoporsis and fractures
47
what other findings are consitent with hyperthyroid
fatty liver, lympoid hyperplasia, atrophy of skeletal mscule
48
how do you diagnose hyperthyroidism
serum TSH
low TSH with high free T4 (primary hyperthyroidism)
49
if TSH is normal or high and T4 is also high then this means?
pituitary associated (secondary )
## Footnote
if the TRH stimulation test normalizes high TSH then this excludes secondary hyperthryoidism
50
radioactive iodine test
graves:
toxic adenoma:
thyroiditis:
graves: diffuse uptake
toxic adenoma: uptake in solitary nodule
thyroiditis: decreased uptake
51
b blocker in hyperthyroid controls
symptoms
52
thionamide blocks
new hormone synthesis
53
iodine blocks
release of hormone
54
radioiodine can be incorptiated into thyroid tissue and will ablate thyroid function over
6-18 weeks
55
graves is?
diffuse hyperplasia
56
what is apethetic hyperthyroidism ?
older adults with hyperthyroisism that has masked symptoms
unexplained weight loss
57
what is a thyroid storm
extreme and abrupt episode of life threatned thyrotoxicosis ( leakage of hormone)
58
thyroid storm is abrupt and severe hypethryoidism that usually has underlying _ disease
graves
59
in thyroid storm there is diffuse _ and enlargement of the thyroid which increases blood flow to the thyroid creating an audible _
hyperplasia
bruit
60
what triggers thyroid storm
infection, surgery, stress!!!
stopping antithyroid medication
pregnancy/postpartum
61
symptoms of a thyroid storm
wide, staring gaze, lid lag
exopthalmos (proptosis), corenal injury
pretibial myedema
weight loss
diarrhea
fever, tachcardia (disprportiant to fever)
62
thyroid storm is a medical emergency and most people die of
arrythmias
63
how do you diagnose thyroid storm
-scoring system
burch wartofsky score
64
in apethetic hyperthyroidism there is thyrotoxicosis in the elderly and unexplained wight loss and worsening of _ issues
cardiovascular
65
hypothyroidism prevelance increases with _ and is more common in _
age
females
66
what is a goiter
thyroid enlargement
67
what is the mutation in thyroid hormone resistance syndrome
THRB mutation
68
what developmental cause would cause hypothyroidism
mutations
thyroid dysgenesis
PAX8
FOXE1
TSH
69
what is autoimmune hypothyroidism
hasimitos thyroiditis
70
what drug can cause hypothyroidism
lithium (for depression)
71
what accounts for the majority of cases of hypothyroidism in high income countries
hasmimotos (autoimmune) and postablative hypothyroidism
72
what is myxedema?
a symptom of hypothyroidism that presents with weight gain, cold intolerance, low cardiac output, mental sluggishness, dry brittle hair, thick tongue
73
what are causes of congenital hypothyroidism
endemic iodine def. - most common
inborn erroer of thyroid metabolism
thyroid agenesis- no gland
thyroid hypoplasia - small sixe
74
what is an inborn erroer of thyroid metabolism
a dyshormonogentic goiter that has thyroid hormone syntehsis defect
iodide transport
organification (binding to thyroglobulin)
T4 to T3 conversion
issues in any of these steps
75
what are the two causes of inborn thyroid metabolism errors
thyroid peroxidase mutation
pendred syndrome
76
what is pendred syndrome
congenital hyperthyroidism + sensorineural deafness
mutation in SCL26A4
77
pendrin is a?
transporter of throcytes and in the inner ear
78
germeline mutations in thyroid agensis
TTF-2, FOXE1, PAX8
79
what is the TSH receptor germline mutation
thyroid nodules contain activating somating mutations of TSHR
80
what antiboides are in hasimotos thyroidits ( autoimmune)
anti-microsomal, anti-thyroid peroxidase, anti-thyroglobulin
presents with a goiter
81
hasimotos syndrome can sometimes be seen in conjunction with?
APS type 2
82
what is thyroid hormone resistance syndrome mutation
affect
T4, T3, TSH levels
rare, autosomal dominant
mutation in THRB: thyroid hormone receptor mutation
so the hormone cant bind the receptor
increased T4 and T3 and TSH
resistance to hormone
83
iatrogenic hypothyroidism is acquired what treatments can cause this (surgery/drugs)
thyroidectomy
radioiodine
methinmazole, PTU
lithium
84
secondary hypothyroidism is usally central and can be caused by?
pituitary tumor, sheehan syndtome, hypothalamic damage
85
symptoms of hypothyroidism
creatinism and myxedema
86
what is cretinism
hypothyroisim in infancy that causes mental defects
87
what is myxedema
hypothyroidism in older children or adults
"cretinoid state"
88
cretinism is common in areas with?
iodine def endemics
89
what casues creatinism
dyshormonogenetic goiter
iodine def
## Footnote
in infancy
90
creatinism severity of impairement is dependent upon
timing of iodine def in utero
91
maternal t3 and t4 cross the placenta and this is critical for fetal brain development, if maternal hypothyroidism occur before fetal thyroid development there is _ brain def
if it is after fetal thyroid development then the _ fetal brain fxn
severe
normal
92
creatinism features
severe intellectual disability
short stature
coarse facial fatures
protruding tongue
umbilical hernia
93
thyroid hormones regulate transcrption of several _ genes whose products are critical to maintaining efficent cardiac output
sarcolemmal
94
hypothyroidism promotes a _ proflie
atherogenic
increases LDL and cardiovascular mortality
increases accumulation of matrix substanes (mucin) in the skin
95
symptoms of myxedma
can present later
increased LDL
skin accumulation deposits: warts
non pitting edema, coarse facial features, thick tongue
deepening voice
slowing of physcial and mental activity
cold intolerance, cool skin, reduced cardiac output, consipation, decreases sympathetic activity
96
inital symptoms of myxedma minmics?
depression
97
unxplained increase in body weight and hypercholesterolemia should be assessed for
hypothyroidism
98
testing for hypothyroidism
TSH screening
increased TSH in primary hypothyroisim decreased levels of hypothyroidism
99
in hypothyroidism due to hypothalamic or pituitary disease what is TSH levels
normal/low
100
what is thyroiditis
acute illness of the thyroid with severe pain, sudden onset of gland tenderness, fever, chills
101
what are the three most common acute thyroditis
hasimotos
granulomatous thyroiditis
subacute lymphocytic thyroidits
102
hasimotos thyroiditis is gradual thyroid failure due to _ destruction
autoimmune
103
hasimoto thyroiditis is a major cause of _ goiter in pedatric populatoin
nonendemic
104
what polymorphisms are associated with hasimoto
CTLA4
PTPN22
IL2RA
## Footnote
negative regulators of T cell responses
105
dm type 1 and graves disease polymorphisms
CTLA4, PTPN22, IL2RA
## Footnote
associated with hasimotos because there is a break down in immune tolerance
106
in hasimotos there is a breakdown of self tolerance to thyroid _ _
auto antigens
107
what are the circulating antibodies in hasimoto thyroiditis
thyroglobulin and thyroid peroxidase
108
hasimoto thyroditis is an induction of thyroid autoimmunity accompanined by progressive depletion of _ by apoptosis and replacement of thyroid parenchyma by _ and _
thyrocytes
lymphocytic iniltrate and fibrosis
109
what are the three way antibodies kill thyrocytes in hasimoto thyroiditis
CD8+ cytotoxic T cell killing
cytokine mediated death (CD4+)
antibody medicated killing
110
hasimotis histology
cut surface:
infiltrate:
follicles:
cellsK
yellow-tan on cut surface
minonuclear inflammatory infiltrate: lymphs, well developed germinal centers
atrophic follicles
hurthle cells
111
what are hurthle cells
a metaplastic response of low cuboidal epithelium to chronic injury : eosinophilic!
112
_ cells + heregenous population of _ = hashimotos
hurthle
lymphs
113
clinical course of hasimotos
painless elnargment of thyroid and hypothyroidism develops gradually
decreased T3 and T4 , increased TSH
114
what is hashitoxicosis
transient thyrotoxicosis that is caused by diruption of gollicles with release of thyroid hormones
brief change from normal (increased T3 and T4 and decreased TSH)
115
hasimotos has an increased risk of?
b cell non hodgkins lymphoma and other autoimmune disorders (DM1, SLE, MG)
116
what is subacute lymphocytic/post partum/painless thyroiditis
a painless thyroiditis that is an autoimmune disorder with antithyroif peroxidase antibodies
117
in painless thyroiditis there is transient _ thyroidism but it is mostly _ thyroidism
there is a painless _ enlargement
hyperthyroidism
hypothyroidism
goiter
118
in postpartum thyroiditis can resmeble
antibodies
graves disease
antithyroid peroxidase antibodies
## Footnote
normal thyroid without one year post partum
119
painless and postpartum thyroditis are variants of _ thyroiditis
hasimotos
## Footnote
all have anti-thyroid peroxidase antibodies
1/3 of the cases can progress to hypothyroidism and resemble hasimotos
120
histology of postpartum/painless/subacute lymphocytic thyroiditis
lymphocytic infiltration with hyperplastic germinal centers
## Footnote
no fiboris and no hurtlthle cells
121
what is granulomatous thyroiditis = de quervain
thyroditis that is triggered by a viral infection.URI
it is painful
**peaks in summer
## Footnote
coxsackievirus, mumps, measles
122
theory behind granulomatous thyroiditis
expsoure of viral or thyroid antigen released secondary to virus induced host damage, antigen stimulates CD8+ T cells that damage the thyroid
## Footnote
limited process- initiated by virus
123
granulomatous causes a transient _ thyroid for 2-6 weeks and the will return back to normal function
hyperthyroidism
124
serum for granulomatous thyroiditis
increased T4 and T3
decreased TSH
decreased radioactive iodine uptake
125
histology of granulomatous thyroiditis
chronic inflammatory infiltrate with giant cells
126
what is riedel thyroiditis?
what cells are involved
extensive fibrosis of the thyroid and surrounding neck structures
plasma cells and lymphocytes
127
riedel thyroditis is a hard and fixed thyroid mass that stimulates _
carcinoma
128
what antiboides are seen in riedel thyroiditis
igG4 and anti-thyroid antibody
129
gross apperance of riedel thyroiditis
histology :
pale white color with replacement of thyroid tissue with fibrous tissue
histology: fibrosis
130
what is the triad of graves disease
hyperthyroidism (diffuse)
exopthlamos
pretibial myxedema (scaly thicking over shins)
## Footnote
more common in women
131
describe grave infiltrative opthalmopathy (exopthalmos)
there is in increase volune of the retro-orbital connective tissues and extraocular muscles
- infiltration by T cells
- -inflammation, edema and swelling
- accumulationof ECM (glycosaminoglycans)
- increase adipocytes
displacement of the eyeball and interefernce of extraocular muscles (tendons are spared)
132
polymorphisms in graves
CTLA4, PTPN22, IL2RA
## Footnote
increase risk for other autoimmune disorders
133
antibodies in graves
TSH (most important)
TSI (thyroid stimulating immunoglobulin)- most common
TSH receptor blcoing
134
in graves disdease it is not unsual to see both stimulating and inhibiting igs in serum this explains episodes of _ in graves
hypothyroidism
135
labs for graves
increased T3 and T4
decreased TSH
increased iodine uptake
high TSI ig
136
histology of graves
diffuse hypertrophy and hyperplasia of the follicular cells
tall and crouded cells
small papillae that project into the follicular lumen
scalloped pale colloid
lymphoid infiltrate, generminal centers
137
why are the margins of colloid scalloped and pale in graves
increased thyroglobulin utilization
actively resrob colloid in the centers of the follicles
138
treatment of graves
B blockers
and reduce thyroid hormone synthesis
radioiodine ablation
surgical intervention
