Thyroid Flashcards
vertebral level that thyroid sits at
C5-T1
thyroid sits infront of tracheal rings __+__
2nd-4th
thyoid increases in size physiologically in __/__
pregnancy
menstruation
innervation of the thyroid
parasympathetic from CNX
sympathetic from superior, middle and inferior ganglia of sympathetic trunk
blood supply of thyroid from
superior and inferior thyroid arteries (ECA)
+/- thyroidea ima
veins that drain from thyroid and where they drain to first
sup and middle thyroid - IJV
inferior - brachiocephalics
posteromedial aspect of thyroid is attached by ___ which the ___ travels near to/through
the Berry ligament
recurrent laryngeal n
tyrosine containing thyroglobulin filled spheres in thyroid
colloid
cells that line colloid in the thyroid
follicular cells
cells in thyroid that secret calcitonin
parafollicular C cells
synth and release of thyroid hormones:
___ from blood > ___ cells > ___ thyroglobulin>pinocytosis into ___ cell > lysosome > released into blood
I-
follicular cells
colloid
follicular cell
iodine attaches to ___ on thyroglobulin
1 = __
2 = __
tyrosine residues
MIT (monoiodotyrosine)
DIT
T3 is composed of __+__
MIT and DIT
T4 is composed of __
2x DIT
T3 and T4 are stored in
colloid thyroglobulin
__+___ prevent iodine from binding to form MIT and DIT
carbimazole and propylthiouracil
90% of thyroid hormon secreted is
T4
4x more potent thyroid hormone that is the major biologically active one
T3
T4 is converted to T3 by the __+__
liver kidney
TSH binds to a receptor on ___
follicular cell
T4 and T3 are ___ and so travel bound 70% to __, 20% ___, 5% to ___
inactive when bound
lipophilic
70 - TBG (thyroxine binding globulin)
20 - TBPA (thyroxine binding prealbumin)
5 - albumin
T3 bind __ less avidly to TBG and not significantly to TTR so
10-20x
more rapid onset/offset of action
conditions that can increase TBG levels (doesnt affect free T4 levels)
pregnancy neonate OCP/oestrogens tamoxifen Hep A, biliary cirrhosis porphyria heroin clofibrate
decreases level of TBG
androgens Cushing's - steroids acromegaly liver disease nephrotic syndrome phenytoin carbamezepine
The effects T4 and T3 that cause an increased BMR
increase no. and size of mitochondria
increase O2 use and rate of ATP synth
increase synth of resp chain enzymes
T4 and T3 __ thermogenesis, __ bg, ___ insulin dependent glucose uptake into cells, mobilise fat from ___, ___ FA oxidation, ___ protein synthesis
increase
adipose tissue
GHRH production and secretion requires ___
slucocorticoid-induced GHRH release depends on __ and GH need __ presence for activity
Thyroid hormones
__+___ in foetal and neonatal brain requires thyroid hormones
myelinogenesis and axonal growth
thyroid hormones increase responsiveness to ___+___+__ by increasing __
adrenaline, noradrenaline, sympathetic NS neurotransmitters
increasing number of receptors
hypothalamus = __ > anterior pituitary = __ > thyroid =
TRH
TSH
T4+T3
in babies and young kids __ envnt stimulates TRH release
cold
circadian rhythm of thyroid hormones = increased at __ and decreased at __
up at night and down morning
___ enzymes activate and deactivate thyroid hormones by adding/removing I- from outer ring
delodinase
delodinase 2 function
activates T4 > T3 in tissues
Delodinase 1 is found in __+__
liver and kidney
delodinase 2 is found in (6)
heart skeletal muscle CNS fat thyroid pituitary
delodinase 3 is found in ++_
foetal tissue
placenta
brain (except pituitary)
2ndry hypothyroidism is/not associated with a goitre
isnt
s+s of hypothyroidism
slow relaxing reflexes lethargy weight gain cold intolerance decreased appetite slow pulse mentally sluggish
puffy face in hypothyroidism =
myxoedema
if hypothyroid in baby may cause ___
cretinism - dwarfism and mental retardation
auto anti body in Graves -
causes __thyroidism
TSI
hyperthyroidism
exophthalmos is caused by
water retaining carbohydrates building up behind the eye in Graves disease
s+s of hyperthyroidism
heat intolerance tremor palpitations nervous/v emotional lose weight increased appetite insomnia sweaty
in primary hyperthyroidism T4/3 = and TSH =
T4/3 = high TSH = low
in primary hypothyroidism T4/3 = and TSH =
T3/4 = low TSH = high
2ndry hyperthyroidism T4/3 = TSH =
both high
2ndry hypothyroidism T4/3 = TSH =
both low
subclinical hypothyroidism T4/3 = TSH =
TSH = high T4/3 = normal
myxoedema coma =
severe hypothyroidism
what is myxoedema?
accumulation of hydrophilic mucopolysaccharides in ground substance of dermis and other tissues > doughy induration of the skin (usually shins) seen in Graves
primary causes of goitrous primary hypothyroidism
Hashimoto’s thyroiditis - AI
iodine deficiency
amiodarone
lithium
non goitrous primary causes of hypothyroidism
congenital developmental defect, atrophic thyroiditis, post-ablative, postradiation
selflimiting causes of primary hypothyroidism =
after withdrawal of suppressive thyroid therapy, subacute thyroiditis, postpartum thyroiditis
2ndry causes of hypothyroidism
hypothalamic - encephalitis, sarcoid, malig
panhypopituitarism or isolated TSH deficiency
most common cause of hypothyroidism in Western world and in developing countries
western = hashimotos dev = iodine deficiency
Ig present in Hashimotos
TPO (thyroid peroxidase)
on microscopy of hashimotos =
T cell infiltrate and inflammation
fT4 is a better indication of hypothyroidism as __
there is preferential conversion to T3
s+s of hypothyroid: hair = face = periorbital \_\_\_ skin = hyper\_\_\_
coarse and sparse hair dull expressionless face periorbital puffiness pale cool doughy skin - maybe vitiligo and hypercarotenaemia hyperlipidaemia
gynae symptoms of hypothyroidism
menorrhagia > later = oligo/amennorhoea
hyperprolactinaemia as increased TRH causes increased PRL
other blood results for hypothyroidism other than hormones
macrocytosis
increased CK and LDL
hyponatraemia
hyperprolactinaemia
starting dose of thyroxine in young and in elderly with HD
young = 50-100microg/day elderly = 25-50microg/day
TSH receptor Ig inGraves : Hashimotos % and its effect in both
Graves = 70-100% - stimulating Hashimotos = 10-20% - blocking
3 Igs in Graves and Hashimotos
anti TPO
anti thyroglobulin
TSH receptor
check TSH every __ after thyroxine dose change and ___ once stabilised
2mnths
12-18mnths
in pregnancy dose of thyroxine =
can increase by 25-50% as TBG increased
if secondary hypothyroidism treated with levothyroxine then monitor __ not __
fT4 not TSH (as it stays low)
ECG and resp signs of myxoedema coma
bradycardia, low voltage complexes, heart block, T wave inversion, QT interval prolonged
Type 2 resp failure - hypoxia, hypercarbia, resp acidosis
myxoedema coma is typically in
elderly F with longstanding but freq unrecognised and untreated hypothyroidism
Rx for myxoedema coma
ICU passively rewarm cardiac monitor fluids and electrolytes Abx broad spectrum thyroxine cautiously posssibly with hydrocortisone
hyperthyroidism s+s arrhythmia GI visual hair nail gynae muscles
AF
diarrhoea
chemosis, lid lag, lid retraction, diplopia, exophthalmus
brittle thinning hair
fast growing nails
lighter periods and less frequent
muscle weakness esp thighs and upper arms
causes of hyperthyroidism =
Graves multinodular goitre toxic nodule (adenoma) subacute/postpartum thyroiditis kelp amiodarone/lithium
Graves tends to fluctuate/stay constant
50% __ at 18m and 50% __
fluctuate
burn out
relapse
graves goitre is ___
smooth and symmetrical
scintigraphy result in graves
diffuse increased uptake
Rx for grave eye disease
lubricants steroids short term inflam decrease radiotherapy Sx stop smoking
age range typical of graves and gender split
F2:1M
20-50yo
demographic of nodular thyroid disease
older patient
nodular thyroid disease goitre -
asymmetrical
scintigraphy result for nodule thyroid disease goitre
patchy increased uptake
Signs of Thyroid storm
sever hyperthyroidism respiratory and CV collapse hyperthermia exaggerated reflexes need ventilation
Rx for thyroid storm
lugols iodine (stuns thyroid) steroids PTU beta blockers fluids and monitor
can cause agranulocytosis this drug can
carbimazole
hyperthyroid drug preferred in pregnancy
PTU
in Graves start carbimazole __ and __ over 12-18 months
high dose
taper
symptomatic control in hyperthyroidism =
beta blockers
if have had radioiodine what precautions must you take?
no close prolonged contact with kids/preg F
dont share bed with partner for 2-3days
avoid preg for 6 months
ensure not preg
subacute thyroiditis aka F:M age range triggered by a phases
De Quervain's thyroiditis F>M 20-50yo virally hyper>hypo>eu
scintigraphy results for De Quervains thyroiditis
reduced uptake
2% of patients on amiodarone get __
13% get ___
each more common if __ iodine intake
2 = thyrotoxicosis - low iodine intake 13 = hypo - high iodine intake
thyroid embryology:
develops from evagination of ___ -descends through ___ along the ___
pharyngeal epithelium
foramen caecum
thyroglossal duct
embryology: if thyroid fails to descend =
lingual thyroid
if thyroid descends excessively =
retrosternal in mediastinum
can occur anywhere along the path of descent of the thyroid
thyroglossal duct cyst
the histology of cells that make up the thyroid
flat to cuboidal follicular epithelial cells
struma ovarii =
monodermal teratoma that is composed of thyroid tissue = ectopic production
on microscopy of graves =
scalloping and paling of colloid
HLA gene associated with Hashimoto’s
HLA DR3+5
polymorphisms in these 2 immune regulation associated genes are a component of Hashimotos
CTLA 4 (-ve regulator of T cell responses) PTPN-22 (inhibits T cell function)
Hashimotos increases risk of __ and of developing ___ in affected gland
other AI conditions
B cell NHL
diffuse goitre - usual cause =
F:M
age
eu/hyper/hypo?
idiopathic
F>M
young adults
euthyroid usually - T3/4 normal but TSH increased/ULN
follicular adenoma description of its appearance =
discrete solitary mass - encapsulated by a collagen cuff
follicular adenoma are usually ___ but can lead to TSH independent ___
non-functional
thyrotoxicosis
__+___ mutations in a follicular adenoma can lead to it being functional
TSHR
G protein
Thyroid carcinomas: age, gender
4 types
F>M, early adulthood papillary (75-85%) follicular (10-20%) medullary (5%) anaplastic (<5%)
5 causes of papillary thyroid carcinoma
ionising radiation active MAP kinase pathway rearrangements of RET/NTKR1 activating point mutation in BRAF ras mutation
the appearance of papillary thyroid carcinoma
usually solitary nodule, can be multifocal, often cystic
may be calcified = psammoma bodies
10 yr survival rate for papillary thyroid carcinoma
95%+
cause of follicular thyroid carcinoma (3)
iodine deficiency
P13K/AKT pathway mutations
ras (usually N-ras) mutations
age and gender of follicular thyroid carcinoma
F>M
40-50yo
Describe follicular thyroid carcinoma
usually single nodule (slowly enlarging painless non-functional , may be part capsule, vascular/capsular invasion distinguishes it from adenoma)
spread of follicular thyroid carcinoma
not usually lymphatic - usually haematogenous
spread of papillary thyroid carcinoma
usually lymph nodes
mortality of follicular thyroid carcinoma at 10yrs
high stage = 50%
minimally invasive = >90%
medullary thyroid carcinoma marker =
calcitonin
MTC is associated with this genetic condition
MEN2 - germline RET mutations - can be very young patient
If familial then MTC =__/__
bilateral/multicentric
70% of MTC are sporadic and these usually develop at age ___ and are a ___
40-50yo
solitary nodule
MTC derived from ___
C cells
describe appearance of MTC -
spindle/polygonal cells in nests, trabeculae or follicles
associated with amyloid deposition (of calcitonin)
MTC are usually ___ and need a total ___
aggressive
thyroidectomy
paraneoplastic syndromes (2) associated with MTC
diarrhoea (VIP)
Cushing’s (ACTH)
2 mutations associated with anaplastic thyroid carcinoma
p53 and beta catenin mutations
Anaplastic thyroid carcinoma: __+___
age, in patients with a Hx of ____,
undifferentiated and aggressive
older patient
differentiated thyroid carcinoma
anaplastic thyroid carcinoma grows ___ and can involve ___
rapidly
other neck structures
Thy1 on FNA means
insufficient/uninterpretable
Thy2 on FNA means
benign
Thy3 on FNA means
atypia probably benign
Thy4 on FNA means
suspicion of malignancy
Thy 5 on FNA =
malignant
most differentiated thyroid cancers take up ___ and secrete ___
they are ___ driven
I-
thyroglobulin
TSH
factors associated with increased risk of differentiated thyroid cancers
Female (2/3:1M) not afro-caribbean radiation (strong link) increased TSH or parity thyroid adenomata
majority of differentiated thyroid cancers present with __
some =
palpable nodules
chance finding on histology
differentiated thyroid cancers = __+__
follicular and papillary variants
commonest histological type of thyroid cancer (76%) =
papillary thyroid cancer
papillary thyroid cancer tends to spread via
lymphatics
thyroid cancer associated with Hashimotos
Papillary thyroid cancer
2nd commonest histological type of thyroid cancer (17%) =
follicular
follicular carcinoma of thyroid tends to spread via
haematogenous spread
incidence of follicular carcinoma is slightly increased in areas with ___
low iodine intake
Ix for differentiated thyroid cancers =
US FNA
may involve an excision biopsy of lymph node
if suspect vocal cord palsy = pre-op laryngoscopy
6 clinical predictors of malignancy in thyroid cancers
Male new nodule age <20 or >50 increasing size of nodule >4cm diameter Hx of head and neck irradiation vocal cord palsy
risk stratification used in post-op for thyroid cancers = ___ which stands for +++
AMES age (older = worse) metastases extent size of primary tumour
Sx given to low risk AMES patients with differentiated thyroid cancers,<1cm papillary cancers and minimally invasive follicular ca with capsular invasion only
lobectomy with isthmusectomy
in differentiated thyroid cancer this is the Sx given if high risk AMES, extra thyroidal spread, multifocal, distant met.s, nodal involvement
sub/total thyroidectomy
if a patient with differentiated thyroid cancer has macroscopic lymph node disease Rx =
nodal clearance (Sx)
nodal clearance for papillary thyroid cancer with lymph node disease =
central compartment clearance and lateral lymph node sampling
nodal clearance for follicular thyroid cancer with lymph node disease =
central compartment clearance
check calcium within __ of thyroid Sx - replace if ___ and give IV if __/___
24hrs
<2mmol/l
<1.8/symptomatic
whole body iodine scan is done in patients who have had ___
usually ___ post-op
stop T4 __ and T3 ___ before scan
sub/total thyroidectomy
3-6months
T4 - 4wks
T3 - 2 wks
senstitivy of iodine body scan is determined by ___
the elevation of TSH
long term affects of thyroid remnant ablation can be ___
small increase in AML incidence - mainly if cumulative I-131 doses >800mCi and repeated therapy does in 12months
thyroid remnant ablation process
pre treat with rhTSH >
2/3GBq I-131 capsules >
discharge pt when <500cps at 1m count rate >
usually give levothyroxine long term post this
rationale behind thyroid remnant ablation
to suppress TSH to <0.1mU/l and fT4 <25
ablate any microfoci in residual thyroid tissue and remove as source of Tg
permit predictably useful scanning in whole body scane
C lymph node recurrence is more/less common in papillary over follicular thyroid cancer
more
___ is a tumour marker in diferentiated thyroid cancers
thyroglobulin
must measure ___ before thyroid remnant ablation because not everyone secretes it
also measure ___ as can affect titre
thyroglobulin
anti-Tg Igs
if after Rx for differentiated thyroid cancer the Tg levels are rising but pt has a -ve whole body iodine scan what do you do?
possible PET scan to determine if Sx/radio appropriate + target specific tissue
S+S of congenital hypothyroidism
delayed jaundice
poor feeding but “normal” wt gain
skin and hair changes
hypotonia (umbilical hernia, constipation)
screening test for congenital hypothyroidism = __
done at day __
Guthrie test (TSH and fT4) 5
s+s of hyperthyroidism in kids
behaviour problems sleep disturbance eating difficulties goitre fast HR precocious puberty
treatment for hyperthyroidism in kids
beta blocker
carbimazole+/thyroxine for at least first 2 yrs
then Sx/radio-iodine
causes of primary congenital hypothyroidism
gland dysplasia+/- abnormal site
inborn error of TH metabolism
4 factors that cause T4 to be converted to inactive rT3
stress
fasting
illness
cortisol
3 thyroid autoIgs
antiTPO
anti thyroglobulin
TRAb
treatment of thyroid storm =
high dose carbimazole beta blockers hydrocortisone K+ iodide/lugol IV fluids +/- inotropes
one of the most common benign thyroid nodules =
colloid nodule
most penetrant feature of MEN2
MTC
MTC causes excess secretion of __ => present with___
calcitonin
diarrhoea
Rx for TMNG =
radio-iodine unless occupation is a contraindication
If have only taken carbimazole for few days before blood test (poor compliance) it will show =
normal fT4 but raised TSH as it has not had time to reduce yet
carbimazole is a very effective drug and so if it is not working it is usually due to ___
non-compliance
in hypopituitarism if give thyroxine before cortisol it may cause ___
Addison’s crisis as it increases the BMR
