endocrine disease-thyroid Flashcards
histological features of multinodular goitre 5
cystically dilated follicles cholesterol clefts variably sized follicles fibrous septae foamy macrophages
histological features of grave’s disease
papillary architecture
cells have a more columnar appearance
histological features of hashimotos thyroiditis
lymphoid aggregates with germinal centre formation
small lymphocytes
oncocytic epithelial cells
histological features of follicular adenoma
-encapsualted lesion
-made up of thyroid follicles
-clonal population but benign
if capsular or vascular invasion then becomes follicular carcinoma
histological features of follicular carcinoma
tumour invades through fibrous capsule
invasion either vessels or capsular
histological features of papillary carcinoma
intranuclear inclusions
nuclear clearing
nuclear grooves
psammomma bodies (big pink circles)
m:f ratio for hyperthyroidism
6:1
prevalence of thyrotoxicosis
1 in 100
reference ranges for tsh, t4 and t3
- TSH: 0.4-4.5 milliunits/litre
- fT4: 9.0-25.0 picomoles/litre
- fT3: 3.5-7.8 picomoles/litre
what are the most common causes of thyrotoxicosis and in who
- grave’s disease in younger women
- Toxic multinodular goitre in older women
symptoms of hyperthyroidism
- weight loss
- heat intolerance
- tremor
- tachycardia and palpitations: stimulate adrenergic system
- diarrhoea
- light or absent menses
- muscle weakness: catabolism of muscle protein
- irratbility/ anxiety
- dyspnoea: increased co2
- gynaecomastia in males
- osteoporosis
how does gynaecomastia develop in males in hyperthyroidism
liver produces SBHG which binds and inactivates testosterone
-reduced T allows an increased effect of oestrogen on breast tissue
clinical signs on a thyroid exam for hyperthyroid
goitre
- single in grave’s
- multiple in TMNG
Bruit
what eye signs of hyperthyroidism are specific to Grave’s and not specific to grave’s ie thyroid associated orbitopathy TAO
Grave’s
- gritty
- redness
- exopthalmos
non specific -TAO
- lid retraction
- lig lag
hand examination for hyperthyroid
- racing pulse
- palmar erythema
- thyroid achropacy (digital clubbing, swelling, periosteal reaction)
- oncholysis
- tremor
- sweaty skin
what do you need to ask about in past history for hyperthyroid 2
- asthma in case of beta blocker prescription
- heart disease due to tachycardia complication
what other inx should be done on a patient with hyperthyroid
-ecg as can get arrthymias
6 main causes of hyperthyroid
grave's tmng thyroiditis toxic adenoma exogenous thyroxine-factitious thyroiditis toxicosis
values for primary hyperthyroid
high t3 and t4
low TSH
values for subclinical hyperthyroid
normal t3,t4
low tsh
% of hyperthyroid cases caused by grave’s
75%
what is grave’s disease path
- autoimmune
- antibodies attack the thyroid making it overactive
- organ specific autoimmune disorder
- IgG autoantibodies attach and stimulate the THS receptors located on the basolateral side
what are the antibodies in grave’s called
TRABS tsh receptor antubodies
m:f ratio for graves
1:7
triad of grave’s disease
- autoimmune thyrotoxicosis
- eye disease
- pretibial myxoedema
other main signs of grave’s
- smooth symmetrical goitre
- bruit
meaning of these words chemosis exopthalmos lagothalmos diplopia
eye disease
- pain
- chemosis=conjunctival oedema
- conjuctivitis
- exopthalmos: bulging
- lagothalmos: cant close eyelids
- diplopia : double vision
how is exopthalmos caused in grave’s disease
- swelling of retrobullar tissue mediated by t-cell cytokines and TRAB
- Trab activate tsh receptors on fibroblast and adipocytes->
- set off inflammatory process and hydrophilic glycosaminoglyans deposited into extra-ocular muscles in inflammation that cause water retention
dx of grave’s disease
- positive TRAB
- anti TPO but less specific as also raised in Hashimoto’s
- scintigraphy scans using 99m technetium pertechnetate or I-131
management of grave’s disease
- antithyroid drugs
- iodine 131
- surgery thyroidectomy especially if elderly with heart problems
2 regimens of ATH
- block and replace ie give a high dose ATH and then once under control give I thyroxine
- titration: achive euthyroidism
what is the chance of remission for graves
30-40%
grave’s eye disease management
- steroids
- cyclosporin in active disease
- stop smoking
- antioxidant selenium and topical lubricants
- wear dark glasses and elevate bed head
- surgery
what is CI to using radioactive Iodine 131
active grave’s eye disease
other autoimmune conditions assoc. to grave’s
- diabetes 1
- multiple sclerosis
- vitiligo
% of cases caused by TNMG
15%
most common in elderly
what is there a high risk of with Grave’s disease assoc. to cold nodules
malignancy
dx of TNMG
- ultrasound and fine needle aspiration
- thyroid isotope
scan of TMNG appearance
get nodules of high activity and then other areas are switched off due to feedback on pituitary from nodules
treatment of TMNG
- ATD to achieve euthyroidism and
- I131 as wont achieve remsission without this
what is thyroiditis
temporarily overactive thyroid followed by underactivity
what causes thyroiditis
- prenancy
- infection eg viral
- drugs eg amiodarone
dx of thyroiditis
- no uptake of technetium on thryoid scan
- raised CRP and ESR
- raised TFT
what is deQuervian thyroditis
- painful thryoid
- subacute thyroiditis
- illness causes release of pre-made thyroid hormones
what is post-partum thyroiditis and prevalence
- 5-10% women
- hyperthyroid phase within4-6 months of delivery then hypot then euthyroid
management of thyroiditis
- self limiting as will progress to hypo
- can give beta blockers in thyrotoxic phase
- dequervian for pain give NSAID
toxic nodule treatment
- I131
- ATD
- thyroidectomy
what is thyrotoxic crisis and symptoms
cardinal signs
- life threatening hyperthyroidism
- reduced conscious level
- hyperthermia
- multisystem organ fail
cardinal signs
- fever
- confusion
- dehydration
what can precipitate thyrotoxic crisis
- thyroid surgery
- radioiodine
- certain contrast agents
- atd withdrawal
- acute illness
treatment of thyrotoxic crisis
- high dose ATD
- potassium iodine
- beta blockers
- steroids
what is apathetic hyperthyroidism
- lack the adrenergic system eg the tremor, heart rate
- usually in elderly
- often misdiagnosed as mimics depression
what is resistance to thyroid hormones
- when tissues are less responsive to TH
- high t3/t4 with normal or elevated TSH
what is T3 toxicosis
excess t3 produced by thyroid without increase in T4
-seen in tmng or early grave’s
management of hyperthyroid
- beta blocker propanolol for tremor
- selenium for eye
- ATD carbimazole and propylthirouracil
- radioactive iodine I131
how do ATD work
interefer with TPO thryoid peroxidase to decrease thyroid hormones
3 main side effects of carbimazole
- rash
- pruritius
- agranulocytosis
prevalence of agranulocytosis and what is it and what to warn patients
<1/100 -life threatening leucopaenia where patient immune system is compromised due to lack of granulocytes especially neutrophils warn patients of -high temperature -sore throat -mouth ulcers
side effect of propylthiouracil
can affect the liver and cause hepatotoxicity
when should propylthiouracil be given instead of carbimazole
in pregnancy to avoid agranulocytosis
effectiveness of RI 131
90% respond after one dose
adverse of I131
long term hypothyroidism is almost inevitable and should be warned about
what is I131 contraindicated in
- children
- pregnancy
- lactating women
- active grave’s eye disease
- vomiting or incontinent urine
precautions that must be taken after I131
- have to sleep in own bed for 4 days
- avoid close contact with children <12 years and pregnant women for 12 days
- then avoid >15 minutes for 25 days
- avoid pregnancy or breast feeding for 6month
- men avoid pregnancy for 4 months
- wear disposable gloves with food prep for 14 days
- use own cutlery
indication for thyroidectomy
- large goitre
- severe
- intolerance to ATD
- RAI is CI
- poorly controlled in pregnancy
- severe eye disease
side effects of thyroidectomy
hypoparathyroidism post surgery recurrent laryngeal nerve palsy-hoarse voice hypocalcaemia haemorrhage thyroid storm
cause of hyperthyroidism in neonates
- usually due to grave’s
- trabs can pass from mother to foetus via the placenta
formation of t3 and t4
- Trap the iodine from plasma
- Oxidation of iodine by a thyroid peroxidase using h2o2
- Incorporation of iodine into tyrosyl residues on thyroglobulin to make mono and di-iodotyrosine
- Coupling of iodotyrosyl residues to make t4, t3 and rt3 on thyroglobulin
- Re-absorption of colloid into cell
- Thyroglobulin proteolysis
- Release of t4 and t3
what is T4 bound to in the blood and %
- 95% bound
- thyroxine binding globulin 70%
- transthyretin 20%
- albumin 10%
where is t3 produced
20% in the thyroid
80% is from t4 conversion at liver, kidney and muscle
ratio of t3/t4
1:14
prevalence of hypothyroidism
15 in 1000 women and 1in 1000men
causes of hypothyroidism
hashimoto
- spontaneous atrophic
- (iodine deficiency)
- temporary thyroiditis
- iatrogenic post surgery or post radiation
- congenital
- dysmorphogenesis
primary hypothyroidism markers
high tsh
low T4
low/n t3
subclinical hypothyroidism markers
high TSH
normal t3 and t4
secondary hypothyroidism
low TSH
low t4
lowt3
non thyroidal illness
low tsh
high t4
low t3
symptoms of hypothyroidism
- tired
- cold intolerance
- weight gain and puffy
- slow HR
- constipation
- heavy periods menorrhagia
- dry skin and coarse hair
- goirtre
- hyperlipidaemia and hypercholestrolaemia
- carpal tunnel syndrome-pain in hands
- myxoedematous: hoarseness and deafness
- slow relaxing reflexes
inx of hypothyroidism
- low free t4, high TSH and anti-tpo antibodies
- hyperlipid and hypercholesterol
what is hashimoto thyroditis and how do patients often present
- antibodies against TPO
- often euthyroid as only 25% hypot on presentation
what is hashitoxicosis
initial release of preformed thyroid hormones=transient hyperthyroidism
most common cause of hypot in the UK
spontaneous atrophic/ myxoedema thyroid
what causes spontaneous atrophic hypothyroid
- thyroid infiltrate with lymphocytes (hallmark of chronic inflammation)
- destroy follicular cells lining the thyroid follicles
- fibrous tissue and atrophy
how does dysmorphogenesis cause hypothyroidism
- bad hormone synthesis ie abnormal
- specific inborn errors of metabolism eg inability to trap iodine, deficiency in iodination of thyroglobulin, defects in thryoglobulin metabolism
what syndrome is deficiency in iodination of thyroglobulin part of
Pendred syndrome
what is used to dx congenital hypothyroidism
heel prick
prevalence of congenital hypothyroid
1 in 3,500-4,000
what causes and what are the risks of congenital hypothyroid
- mother doesnt have enough iodine in pregnancy
- risk of creinism=stunted physical and mental growth
what drugs induce hypothyroidism
lithium
amiodarone
what causes scondary hypothyroidism
panhypo-pituratism ie low pituitary TSH produce
symptoms of pituitary failure
-sexual dysfunciton-hypogonadism
-tiredness-hypoadrenal
dizzy-low bp
-bitemporal hemianopia if tumour in pituitary pressing on optic chiasm
management principle of hypopituratism
replace cortisol first then replace thyroid otherwise get hypoadrenal crisis
what is sheehan’s syndrome
severe blood loss during labour can cause an infarction in pituitary secondary to hypotension causing hypopituratism
what is myxoedema coma
rare severe life threatening hypothyroidism precipitated by infection
-reduced consciouss level, hypothermia, resp depression
treatment myxoedema coma
- t3/t4 administer
- antibiotic cover after culture
- steroid cover as assoc. to adrenal dysfunction
main cause of subclinical hypothyroidism
-autoimmune chronic thyroiditis
but doesnt really cause symptoms other than cardiac adverse lipids..
what drug is used in hypothyroidism
levothyroxine t4 replacement drug which is converted to t3 active
what happens if you take too much levothyroxine and needs to be cautioned in who
can get factitious hyperthyroidism that can lead to arrhythmias
-so in heart disease start on low dose as it increases o2 demand of tissues
effectiveness of levothyroxine
-doesnt work for all so others want to use t3 or dessicated but not available
how to take levothyroxine
empty stomach before breakfast
medications that impair t4 absorption and advice
-proton pump inhibitors
-h2 antagonist eg rantidine
-some antacids
-calcium and iron supplements
so dont take within 4 hrs of these meds
what medication means t4 requirement needs to be increased and why 2
-starting oestrogen (OCP, HRT)
-anti-convulsants eg epilepsy
both induce liver enzymes that break down thyroxine
what is liothyronine
t3 replacement
how does non-thyroidal illness affect t3/t4
low levels of TSH and T3 can also be caused by NTI
-Acute illness – may cause elevated FT4 and suppressed TSH
how does non-thyroidal illness suppress tsh
- range of mechanism: IL1, TNFa, glucocorticoids
- TRH release suppressed by cytokines and glucocorticoids
- some drugs eg dopamine inhibit TSH release
rises on recovery
what converts t3 to t4
deiodinases
what causes hypothyroidism in pregnancy
foetus needs t4 so uses maternal t4 so requirenment increases by 50% so need to increase dose
what can untreated overt hypot in pregnancy lead to
- infertility
- miscarriage
- pre-eclampsia
- premature delivery
- increased foetal mortality
- impaired neurological development
- neurodevelopmental delay
- placental abruption
what hormones should be checked in pregnancy
free t3 and t4 as TBG increases in pregnancy due to oestrogen so give false result
grave’s triad
thyroid eye disease
thyroid acropachy
pretibial myxoedema
