Thyroid physiology and pathology Flashcards
describe embryology of the thyroid gland
midline thickening on tongue at week 4 migrating downwards
migrates in front of larynx with close proximity to PTH glands
how many people have a pyramidal lobe
15%
what do C cells produce
calcitonin
the point of the tongue at which the thyroid originally existed is a point called
foramen caecum
what hormones does the thyroid secrete
thyroxine
tri-iodothyronine
calcitonin
autonomic innervation to the thyroid
PS - vagus nerve
S - from superior, middle, inferior sympathetic trunk ganglia
what arteries supply the thyroid
superior and inferior thyroid arteries
thyroidea ima
what veins drain the thyroid
superior/middle thyroid veins to IJV
inferior thyroid vein to drain to BCV
what ligaments/muscles support the thyroid
berry ligament
strap muscles
what is a basic follicle of thr thyroid
follicular cells surrounding central colloid mass
parafollicular cells around the outside
describe the thyroid pituitary hypothalamic axis
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
describe synthesis and release of T3/4 in the thyroid follicle
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
what thyroid hormone is secreted most and what one is most biologically active
T4 is secreted most but T3 is biologically active, so T4 is converted to T3 by liver/kidneys
true/false - most thyroid hormones are found ‘free’ in blood
false - most are bound
what transport molecules are thyroid hormones bound to
thyroid binding globulin mainly
also thyroid binding pre albumin, albumin
what causes increase in TBG and how does this affect T4 concns
pregnancy ora contraceptive tamoxifen Hep A chronic active hep biliary cirrhosis increases total T4 but not FT4
what causes decrease in TBG and how does this affect T4 concns
androgens large dose glucocorticoids or cushings syndrome severe systemic illness chronic liver disease nephrotic syndrome decreases total T4 but not FT4
effects of thyroid hormones on metabolism?
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
how does thyroid hormone aid in neural development
myelinogenesis and axon growth need thyroid hormones
what can imbalances in thyroid hormone do to behaviour
hypothyroidism can slow intellectual function and hyperthyroidism can cause nervousness, hyperkinesis and emotional lability
what effect does thyroid hormone have on the lungs, heart and sympathetic nervous system
increased response to NA/adrenaline by increased receptors
increased breathing rate and increased rate and force of heart contraction
where are D1 de-ionase enzymes found and what does it do
breaks T4 to T3
found in liver and kidney
where are D2 de-ionase enzymes found
heart, skeletal muscle, CNS, fat, thyroid, pituitary
where are D3 de-ionase enzymes found and what does it do
break down T3 to inactive T2 and breaks T4 to inactive reverse T3 which is excreted rapidly
found in placenta, foetal tissue and brain
what is the rough weight of the thyroid
15-25g
what vertebral level does the thyroid sit around
C5/6 and can extend to T1
failure of the thyroid to descend results in?
lingual thyroid
excess descent of the thyroid results in?
retrosternal thyroid
histology of follicular cells surrounding colloid mass
flat cuboidal epithelial cells
describe the hormonal release of thyroid hormones
TSH binds to receptor on surface of epithelial cells
GTP to GDP and cAMP to cause exocytosis of thyroid hormones into blood
how does T3 bring about physiological responses within cells
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
autoimmune thyroiditis causes
graves disease
hashimotos thyroiditis
what polymorphisms can cause dysregulated immune system to lead to autoimmune thyroiditis
CTLA-4
PTPN-22
other causes of thyroiditis besides autoimmune
drugs dequervains palpation infection riedels subacute lymphocytic
causes of hyperthyroidism
85% graves thyroiditis ectopic production factitious hyper-functioning nodules TSH secreting pituitary tumour carcinoma/adenoma
who is graves disease more common in
10x young middle aged women
pathophysiology of graves disease
antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
act to stimulate receptor and increase gland function
causes of hypothyroidism
hashimotos thyroiditis iodine deficiency drugs post surgery congenital abnormalities inborn errors of metabolism secondary hypothalamic/pituitary pathology
what is hashimotos thyroiditis associated with genetically and demographically
10-20x women
45-60
other AA disease
HLA-DR3 and HLA-DR5
describe the pathophysiology of hashimotos thyroiditis
anti-thyroid Ab - anti-thyroglobulin and anti-peroxidase
there is cell mediated cytotoxicity by CD8 t cells when Ab binds
how may hashimotos appear on histology
prominent lymphoid infiltrate
atrophy of follicles and progressive fibrosis
what is hashimotos at risk of and what raises suspicion of it
non-hodgkins B cell lymphoma
sudden enlargement of the gland
what may cause endemic diffuse goitre
goitrogenic substance
iodine deficiency
what may cause sporadic diffuse goitre
females more than males and young adults
ingesting substances limiting T3/4
inborn error metabolism
idiopathic
what mass effects may be seen due to goitre
airway destruction/compression
dysphagia
vessel compression
cosmetic distress
how common is anaplastic thyroid cancer, who gets it, how does it appear
<5%
older pt and hx of differentiated thyroid cancer
undifferentiated, aggressive, rapid growth, involvement of neck structures
death
what genetic and environmental factors may cause papillary carcinoma
MAP kinase pathway
ionising radiation
what genetic, demographic and environmental factors may cause follicular carcinoma
PI3K/AKT pathway
iodine deficiency
women 40-50s
what genetic factors may cause medullary thyroid cancer
MEN2
what genetic factors may cause anaplastic thyroid cancer
p53 and beta-catenin
presentation of papillary cancer
solitary nodule, multifocal, cystic, psammoma bodies lesion in thyroid or cervial node hoarse dysphagia cough SOB
spread of papillary cancer
late spread is usually lymphatic and can be haematogenous to lung but uncommon
overall survival rate for papillary thyroid cancer and what makes prognosis worse
> 95% survival
worse in >40, extra thyroid extension or distal mets
presentation of follicular cell cancer of thyroid
single nodule, slowly enlarging, painless
more solid
more invasive
spread of follicular cell cancer?
haematogenous
mortality of widely invasive follicular cell cancer?
50% at 10y
mortality of locally invasive follicular cell cancer?
10% at 10y
where are medullary cancers of the thyroid derived from, who gets them
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
what are the paraneoplastic syndromes of medullary cancer
diarrhoea due to VIP causing Cl secretion
cushings due to ACTH production
what are good prognostic factors for medullary cancer
young age and females
thyroid confined tumour with no mets
what are adverse prognostic factors in medullar cancer
necrosis, many mitoses, small cell morphology with <50% calcitonin +ve and type of RET mutation
management and recurrence of medullary cancer
total thyroidectomy
recurrence in 30%
who is hypothyroidism more common in
5-10x more women
white populations
older populations
goitrous causes hypothyroidism
hashimotos iodine deficiency drugs maternal transmission hereditary defects
non-goitrous causes hypothyroidism
atrophic thyroiditis
developmental congenital issues
post radiation
post ablation
self limiting causes hypothyroidism
following ATx drugs
postpartum thyroiditis
subacute thyroiditis with transient hypothyroidism
secondary causes hypothyroidism
infection malignancy drugs trauma congenital cranial radiotherapy
what is hashimotos thyroiditis and whos more likely to have it
AA destruction of thyroid gland due to antibodies against thyroid peroxidase
women, FHx of other AA disorders
hair and skin symptoms hypothyroidism
pale, clammy, doughy skin coarse and sparse hair periorbital puffiness vitiligo hypercarotenaemia dull nad expressionless face
cardiac symptoms hypothyroidism
low HR
cardiac dilatation
fluid retention leading to pitting oedema and pericardial effusion
worsening HF
metabolic symptoms hypothyroidism
cold intolerance
weight loss
decreased appetite
hyperlipidaemia
neuro symptoms hypothyroidism
depression/psychosis lowered intellectual/motor ability muscle stiffness peripheral muscle jerks carpal tunnel peripheral neuropathy encephalopathy prolonged tendon jerks decreased visual acuity
respiratory symptoms hypothyroidism
deep and hoarse voice
macroglossia
OSA
gynae symptoms hypothyroidism
menorrhagia
oligo/amenorrhoea
hyperprolactinaemia
GI symptoms hypothyroidism
constipation
megacolon/obstruction
ascites
biochemical features primary hypothyroidism
raised TSH and lowered FT3/4 raised prolactin raised CK raised LDL hyponatraemia macrocytosis \+ve anti-TPO in hashimotos
management of hypothyroidism
50-100micrograms levothyroxine once daily morning before breakfast
titrate with weekly bloods for 4 weeks then TSH 2m post dose change and 12m annual
what can impair levothyroxine uptake
food
iron
calcium
PPI
true/false - in secondary hypithyroidism titrate levothyroxine to TSH
false - TSH is unreliable so do FT4
typical dose of levothyroxine to elderly pt with IHD
25-50 micrograms
who is more likely to have myxoedema coma
undiagnosed hypothyroidism or poor treatment complicance
elderly women with hypothyroidism long standing
features of myxoedema coma
bradycardia, prolonged QT, low voltage ECG complexes
T2 resp failure with hypoxia/hypercarbia
hypothermia
respiratory acidosis
adrenal failure 10%
management of myxoedema coma
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
excess thyroid stimulation causes of hyperthyroidism
graves disease hashitoxicosis thyroid cancer choriacarcinoma thyrotropinoma
thyroid nodules with autonomous function causing hyperthyroidism
toxic solitary nodule
toxic multinodular goitre
thyroid inflammation causing hyperthyroidism
de quervains
postpartum
drug induced
exogenous thyroid hormones causing hyperthyroidism
over-treatment with levothyroxine
thyrotoxicosis factitia
ectopic thyroid tissue causing hyperthyroidism
metastatic thyroid carconoma
struma ovarii
cardiac symptoms thyrotoxicosis
AF
palpitations
increased HR
heart failure
sympathetic symptoms thyrotoxicosis
tremor
sweating
CNS symptoms thyrotoxicosis
nervousness, irritability, sleep disturbance, anxiety
GI symptoms thyrotoxicosis
frequent loose bowel movements
metabolic symptoms thyrotoxicosis
heat intolerance
increased appetite
weight gain
hair, skin and msk symptoms thyrotoxicosis
proximal muscle weakness
rapid fingernail growth
thin and brittle hair
gynae symptoms thyrotoxicosis
lighter bleeds and less frequent periods
vision symptoms thyrotoxicosis
lid retraction
double vision
proptosis
signs of hyperthyroidism specific to graves
pretibial myxoedema
thyroid acropachy
thyroid bruit
investigating graves
decreased TSH and raised T3/4
hypercalaemia and raised Alk phos
leucopenia
TSH receptor Ab or anti-TPO but not as sensitive
whos more likely to have graves
females
20-50
how many patients have graves eye disease and what is it associated with
20% graves pt
smoking
true/false - graves eye disease is always unilateral
false- but one eye is usually affected worse
mild graves eye disease management?
lubricants
moderate/severe graves eye disease management
steroids, radiotherapy, surgery
what may you see on investigation of nodular thyroid disease
asymmetric goitre raised T3/4 and low TSH Ab -ve high uptake on scinitgraphy thyroid USS
presentation of thyroid storm?
severe hyperthyroidism
respiratory and cardiovascular collapse
hyperthermia
exaggerated reflexes
management of thyroid storm
ventilation if needed HDU/ICU propranolol except asthma then give rate limiting CCB fluids montitor glucocorticoids lugols iodine
first line management of thyrotoxicosis and how does it work
carbimazole
once daily
blocks TPO to block thyroid hormone synthesis
risk of carbimazole
aplasia cutis in early pregnancy
when is propylthiouracil first line and how does it work
1st trimester pregnancy
inhibits T4 to T3 by DIO1
risk of PTU AT drug
liver failure
general side effects of AT drugs
cholestatic jaundice
increased liver enzymes
FHF
agranulocytosis
true/false - after episode of agranulocytosis AT drug can be used again
false
when is the risk of agranulocytosis highest
<6wks
when is radioidodine treatment contraindicated and what is the risk in graves
graves eye disease unless steroid cover, pregnancy
hypothyroidism in graves
risks to surgery for hyperthyroidism
recurrent laryngeal nerve
hypothyroidism
hypoparathyroidism
causes of thyroiditis
hashimotos dequervains drug induced post-partum radiation acute suppurative thyroiditis
who is de quervains thyroiditis more common in, symptoms and trigger
females and 20-50
viral infection
neck tenderness, fever, self limiting
how does amiodarone cause thyroid issues
inhibits DIO1 so there is normal TSH but high FT4 and low FT3
hypothyroidism is more common but hyper can also occur
true/false - in a pt with pneumonia check thyroid function
false - theyre likely to have sick euthyroid syndrome
what is subclinical hypothyroidism, when to treat?
normal FT3/4 but high TSH
higher risk in +ve TPO
treat in pregnancy and if TSH >10
what is subclinical hyperthyroidism, what is it associated with and when is it treated
normal FT3/4 and low TSH multinodular goitre, AF, osteoporosis
treat if TSH <0.1 or pre existing osteoporosis /AF
