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MB2: Endocrinology > Thyroid physiology and pathology > Flashcards

Thyroid physiology and pathology Flashcards

1
Q

describe embryology of the thyroid gland

A

midline thickening on tongue at week 4 migrating downwards

migrates in front of larynx with close proximity to PTH glands

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2
Q

how many people have a pyramidal lobe

A

15%

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3
Q

what do C cells produce

A

calcitonin

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4
Q

the point of the tongue at which the thyroid originally existed is a point called

A

foramen caecum

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5
Q

what hormones does the thyroid secrete

A

thyroxine
tri-iodothyronine
calcitonin

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6
Q

autonomic innervation to the thyroid

A

PS - vagus nerve

S - from superior, middle, inferior sympathetic trunk ganglia

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7
Q

what arteries supply the thyroid

A

superior and inferior thyroid arteries

thyroidea ima

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8
Q

what veins drain the thyroid

A

superior/middle thyroid veins to IJV

inferior thyroid vein to drain to BCV

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9
Q

what ligaments/muscles support the thyroid

A

berry ligament

strap muscles

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10
Q

what is a basic follicle of thr thyroid

A

follicular cells surrounding central colloid mass

parafollicular cells around the outside

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11
Q

describe the thyroid pituitary hypothalamic axis

A

hypothalamus secretes TRH to ant pituitary that releases TSH and acts on thyroid tissue to secrete T3/4
excess T3/4 in peripheral tissues causes -ve feedback to act on TRH/TSH

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12
Q

describe synthesis and release of T3/4 in the thyroid follicle

A

synthesis of thyroglobulin in follicular cell and storage in colloid
uptake and concn of iodide ions that are oxidised and pass to colloid mass
thyroglobulin is iodised to tyrosine with 1/2 iodines and binds to another with 2
colloid enveloped by microvilli on follicular cell and fuse with lysosomes to cleave T3/4 and release to bloodstream

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13
Q

what thyroid hormone is secreted most and what one is most biologically active

A

T4 is secreted most but T3 is biologically active, so T4 is converted to T3 by liver/kidneys

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14
Q

true/false - most thyroid hormones are found ‘free’ in blood

A

false - most are bound

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15
Q

what transport molecules are thyroid hormones bound to

A

thyroid binding globulin mainly

also thyroid binding pre albumin, albumin

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16
Q

what causes increase in TBG and how does this affect T4 concns

A 
pregnancy 
ora contraceptive 
tamoxifen 
Hep A 
chronic active hep
biliary cirrhosis 
increases total T4 but not FT4
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17
Q

what causes decrease in TBG and how does this affect T4 concns

A 
androgens 
large dose glucocorticoids or cushings syndrome 
severe systemic illness 
chronic liver disease 
nephrotic syndrome 
decreases total T4 but not FT4
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18
Q

effects of thyroid hormones on metabolism?

A

increased BMR with increased number and size mitochondria, increased O2 and increased synthesis resp chain enzymes
increased lipolysis increased glycogenolysis and gluconeogenesis and decreased glycogenolysis - raised BG and insulin dependent glucose uptake
increased thermogenesis

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19
Q

how does thyroid hormone aid in neural development

A

myelinogenesis and axon growth need thyroid hormones

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20
Q

what can imbalances in thyroid hormone do to behaviour

A

hypothyroidism can slow intellectual function and hyperthyroidism can cause nervousness, hyperkinesis and emotional lability

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21
Q

what effect does thyroid hormone have on the lungs, heart and sympathetic nervous system

A

increased response to NA/adrenaline by increased receptors

increased breathing rate and increased rate and force of heart contraction

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22
Q

where are D1 de-ionase enzymes found and what does it do

A

breaks T4 to T3

found in liver and kidney

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23
Q

where are D2 de-ionase enzymes found

A

heart, skeletal muscle, CNS, fat, thyroid, pituitary

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24
Q

where are D3 de-ionase enzymes found and what does it do

A

break down T3 to inactive T2 and breaks T4 to inactive reverse T3 which is excreted rapidly
found in placenta, foetal tissue and brain

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25
Q

what is the rough weight of the thyroid

A

15-25g

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26
Q

what vertebral level does the thyroid sit around

A

C5/6 and can extend to T1

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27
Q

failure of the thyroid to descend results in?

A

lingual thyroid

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28
Q

excess descent of the thyroid results in?

A

retrosternal thyroid

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29
Q

histology of follicular cells surrounding colloid mass

A

flat cuboidal epithelial cells

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30
Q

describe the hormonal release of thyroid hormones

A

TSH binds to receptor on surface of epithelial cells

GTP to GDP and cAMP to cause exocytosis of thyroid hormones into blood

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31
Q

how does T3 bring about physiological responses within cells

A

binds to receptor in target cells to form complex
translocates to nucleus and binds to thyroid response elements on target genes to increase BMR and stimulates these genes

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32
Q

autoimmune thyroiditis causes

A

graves disease

hashimotos thyroiditis

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33
Q

what polymorphisms can cause dysregulated immune system to lead to autoimmune thyroiditis

A

CTLA-4

PTPN-22

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34
Q

other causes of thyroiditis besides autoimmune

A 
drugs 
dequervains
palpation 
infection 
riedels 
subacute lymphocytic
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35
Q

causes of hyperthyroidism

A 
85% graves 
thyroiditis 
ectopic production 
factitious 
hyper-functioning nodules 
TSH secreting pituitary tumour 
carcinoma/adenoma
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36
Q

who is graves disease more common in

A

10x young middle aged women

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37
Q

pathophysiology of graves disease

A

antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
act to stimulate receptor and increase gland function

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38
Q

causes of hypothyroidism

A 
hashimotos thyroiditis 
iodine deficiency 
drugs 
post surgery 
congenital abnormalities 
inborn errors of metabolism 
secondary hypothalamic/pituitary pathology
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39
Q

what is hashimotos thyroiditis associated with genetically and demographically

A

10-20x women
45-60
other AA disease
HLA-DR3 and HLA-DR5

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40
Q

describe the pathophysiology of hashimotos thyroiditis

A

anti-thyroid Ab - anti-thyroglobulin and anti-peroxidase

there is cell mediated cytotoxicity by CD8 t cells when Ab binds

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41
Q

how may hashimotos appear on histology

A

prominent lymphoid infiltrate

atrophy of follicles and progressive fibrosis

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42
Q

what is hashimotos at risk of and what raises suspicion of it

A

non-hodgkins B cell lymphoma

sudden enlargement of the gland

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43
Q

what may cause endemic diffuse goitre

A

goitrogenic substance

iodine deficiency

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44
Q

what may cause sporadic diffuse goitre

A

females more than males and young adults
ingesting substances limiting T3/4
inborn error metabolism
idiopathic

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45
Q

what mass effects may be seen due to goitre

A

airway destruction/compression
dysphagia
vessel compression
cosmetic distress

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46
Q

how common is anaplastic thyroid cancer, who gets it, how does it appear

A

<5%
older pt and hx of differentiated thyroid cancer
undifferentiated, aggressive, rapid growth, involvement of neck structures
death

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47
Q

what genetic and environmental factors may cause papillary carcinoma

A

MAP kinase pathway

ionising radiation

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48
Q

what genetic, demographic and environmental factors may cause follicular carcinoma

A

PI3K/AKT pathway
iodine deficiency
women 40-50s

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49
Q

what genetic factors may cause medullary thyroid cancer

A

MEN2

50
Q

what genetic factors may cause anaplastic thyroid cancer

A

p53 and beta-catenin

51
Q

presentation of papillary cancer

A 
solitary nodule, multifocal, cystic, psammoma bodies
lesion in thyroid or cervial node
hoarse 
dysphagia 
cough 
SOB
52
Q

spread of papillary cancer

A

late spread is usually lymphatic and can be haematogenous to lung but uncommon

53
Q

overall survival rate for papillary thyroid cancer and what makes prognosis worse

A

> 95% survival

worse in >40, extra thyroid extension or distal mets

54
Q

presentation of follicular cell cancer of thyroid

A

single nodule, slowly enlarging, painless
more solid
more invasive

55
Q

spread of follicular cell cancer?

A

haematogenous

56
Q

mortality of widely invasive follicular cell cancer?

A

50% at 10y

57
Q

mortality of locally invasive follicular cell cancer?

A

10% at 10y

58
Q

where are medullary cancers of the thyroid derived from, who gets them

A

c cells
sporadic, MEN in young pt or FHx in 40-50s
sporadic MEN is a solitary nodule usually and FHx is often bilateral/multicentric c cell hyperplasia

59
Q

what are the paraneoplastic syndromes of medullary cancer

A

diarrhoea due to VIP causing Cl secretion

cushings due to ACTH production

60
Q

what are good prognostic factors for medullary cancer

A

young age and females

thyroid confined tumour with no mets

61
Q

what are adverse prognostic factors in medullar cancer

A

necrosis, many mitoses, small cell morphology with <50% calcitonin +ve and type of RET mutation

62
Q

management and recurrence of medullary cancer

A

total thyroidectomy

recurrence in 30%

63
Q

who is hypothyroidism more common in

A

5-10x more women
white populations
older populations

64
Q

goitrous causes hypothyroidism

A 
hashimotos 
iodine deficiency 
drugs 
maternal transmission 
hereditary defects
65
Q

non-goitrous causes hypothyroidism

A

atrophic thyroiditis
developmental congenital issues
post radiation
post ablation

66
Q

self limiting causes hypothyroidism

A

following ATx drugs
postpartum thyroiditis
subacute thyroiditis with transient hypothyroidism

67
Q

secondary causes hypothyroidism

A 
infection 
malignancy 
drugs 
trauma 
congenital 
cranial radiotherapy
68
Q

what is hashimotos thyroiditis and whos more likely to have it

A

AA destruction of thyroid gland due to antibodies against thyroid peroxidase
women, FHx of other AA disorders

69
Q

hair and skin symptoms hypothyroidism

A 
pale, clammy, doughy skin 
coarse and sparse hair 
periorbital puffiness 
vitiligo 
hypercarotenaemia 
dull nad expressionless face
70
Q

cardiac symptoms hypothyroidism

A

low HR
cardiac dilatation
fluid retention leading to pitting oedema and pericardial effusion
worsening HF

71
Q

metabolic symptoms hypothyroidism

A

cold intolerance
weight loss
decreased appetite
hyperlipidaemia

72
Q

neuro symptoms hypothyroidism

A 
depression/psychosis 
lowered intellectual/motor ability 
muscle stiffness
peripheral muscle jerks 
carpal tunnel 
peripheral neuropathy 
encephalopathy 
prolonged tendon jerks 
decreased visual acuity
73
Q

respiratory symptoms hypothyroidism

A

deep and hoarse voice
macroglossia
OSA

74
Q

gynae symptoms hypothyroidism

A

menorrhagia
oligo/amenorrhoea
hyperprolactinaemia

75
Q

GI symptoms hypothyroidism

A

constipation
megacolon/obstruction
ascites

76
Q

biochemical features primary hypothyroidism

A 
raised TSH and lowered FT3/4 
raised prolactin 
raised CK 
raised LDL
hyponatraemia 
macrocytosis 
\+ve anti-TPO in hashimotos
77
Q

management of hypothyroidism

A

50-100micrograms levothyroxine once daily morning before breakfast
titrate with weekly bloods for 4 weeks then TSH 2m post dose change and 12m annual

78
Q

what can impair levothyroxine uptake

A

food
iron
calcium
PPI

79
Q

true/false - in secondary hypithyroidism titrate levothyroxine to TSH

A

false - TSH is unreliable so do FT4

80
Q

typical dose of levothyroxine to elderly pt with IHD

A

25-50 micrograms

81
Q

who is more likely to have myxoedema coma

A

undiagnosed hypothyroidism or poor treatment complicance

elderly women with hypothyroidism long standing

82
Q

features of myxoedema coma

A

bradycardia, prolonged QT, low voltage ECG complexes
T2 resp failure with hypoxia/hypercarbia
hypothermia
respiratory acidosis
adrenal failure 10%

83
Q

management of myxoedema coma

A 
ICU 
rewarm passively 
gradual increase dose levothyroxine 
hydrocortisone in adrenal failure 
broad spec ABx if needed 
cardiac monitor, monitor urine output, fluid balance, CVP, blood sugars and pulse ox
84
Q

excess thyroid stimulation causes of hyperthyroidism

A 
graves disease 
hashitoxicosis 
thyroid cancer 
choriacarcinoma 
thyrotropinoma
85
Q

thyroid nodules with autonomous function causing hyperthyroidism

A

toxic solitary nodule

toxic multinodular goitre

86
Q

thyroid inflammation causing hyperthyroidism

A

de quervains
postpartum
drug induced

87
Q

exogenous thyroid hormones causing hyperthyroidism

A

over-treatment with levothyroxine

thyrotoxicosis factitia

88
Q

ectopic thyroid tissue causing hyperthyroidism

A

metastatic thyroid carconoma

struma ovarii

89
Q

cardiac symptoms thyrotoxicosis

A

AF
palpitations
increased HR
heart failure

90
Q

sympathetic symptoms thyrotoxicosis

A

tremor

sweating

91
Q

CNS symptoms thyrotoxicosis

A

nervousness, irritability, sleep disturbance, anxiety

92
Q

GI symptoms thyrotoxicosis

A

frequent loose bowel movements

93
Q

metabolic symptoms thyrotoxicosis

A

heat intolerance
increased appetite
weight gain

94
Q

hair, skin and msk symptoms thyrotoxicosis

A

proximal muscle weakness
rapid fingernail growth
thin and brittle hair

95
Q

gynae symptoms thyrotoxicosis

A

lighter bleeds and less frequent periods

96
Q

vision symptoms thyrotoxicosis

A

lid retraction
double vision
proptosis

97
Q

signs of hyperthyroidism specific to graves

A

pretibial myxoedema
thyroid acropachy
thyroid bruit

98
Q

investigating graves

A

decreased TSH and raised T3/4
hypercalaemia and raised Alk phos
leucopenia
TSH receptor Ab or anti-TPO but not as sensitive

99
Q

whos more likely to have graves

A

females

20-50

100
Q

how many patients have graves eye disease and what is it associated with

A

20% graves pt

smoking

101
Q

true/false - graves eye disease is always unilateral

A

false- but one eye is usually affected worse

102
Q

mild graves eye disease management?

A

lubricants

103
Q

moderate/severe graves eye disease management

A

steroids, radiotherapy, surgery

104
Q

what may you see on investigation of nodular thyroid disease

A 
asymmetric goitre 
raised T3/4 and low TSH 
Ab -ve 
high uptake on scinitgraphy 
thyroid USS
105
Q

presentation of thyroid storm?

A

severe hyperthyroidism
respiratory and cardiovascular collapse
hyperthermia
exaggerated reflexes

106
Q

management of thyroid storm

A 
ventilation if needed 
HDU/ICU
propranolol except asthma then give rate limiting CCB
fluids 
montitor 
glucocorticoids 
lugols iodine
107
Q

first line management of thyrotoxicosis and how does it work

A

carbimazole
once daily
blocks TPO to block thyroid hormone synthesis

108
Q

risk of carbimazole

A

aplasia cutis in early pregnancy

109
Q

when is propylthiouracil first line and how does it work

A

1st trimester pregnancy

inhibits T4 to T3 by DIO1

110
Q

risk of PTU AT drug

A

liver failure

111
Q

general side effects of AT drugs

A

cholestatic jaundice
increased liver enzymes
FHF
agranulocytosis

112
Q

true/false - after episode of agranulocytosis AT drug can be used again

A

false

113
Q

when is the risk of agranulocytosis highest

A

<6wks

114
Q

when is radioidodine treatment contraindicated and what is the risk in graves

A

graves eye disease unless steroid cover, pregnancy

hypothyroidism in graves

115
Q

risks to surgery for hyperthyroidism

A

recurrent laryngeal nerve
hypothyroidism
hypoparathyroidism

116
Q

causes of thyroiditis

A 
hashimotos 
dequervains 
drug induced 
post-partum
radiation 
acute suppurative thyroiditis
117
Q

who is de quervains thyroiditis more common in, symptoms and trigger

A

females and 20-50
viral infection
neck tenderness, fever, self limiting

118
Q

how does amiodarone cause thyroid issues

A

inhibits DIO1 so there is normal TSH but high FT4 and low FT3
hypothyroidism is more common but hyper can also occur

119
Q

true/false - in a pt with pneumonia check thyroid function

A

false - theyre likely to have sick euthyroid syndrome

120
Q

what is subclinical hypothyroidism, when to treat?

A

normal FT3/4 but high TSH
higher risk in +ve TPO
treat in pregnancy and if TSH >10

121
Q

what is subclinical hyperthyroidism, what is it associated with and when is it treated

A

normal FT3/4 and low TSH multinodular goitre, AF, osteoporosis
treat if TSH <0.1 or pre existing osteoporosis /AF

MB2: Endocrinology (13 decks)

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