Thyroid disease Flashcards
What proportion of the UK population has hypothyroidism?
2%
What is another name of hyperthyroidism?
thyrotoxicosis
What is the gender ratio of thyroid disease?
10:1 F:M
What is the hormone loop that the thyroid is involved in?
- hypothalamus secreted thyrotropin-releasing hormone (TRH) which stimulates the anterior pituitary
- Anterior pituitary gland secretes thyroid-stimulating hormone (TSH)
- TSH acts on the thyroid gland increasing production of thyroxine (T4) and tri-iodothyronine (T3)
What is the role of T4 and T3?
act on variety of tissues helping to regulate use of energy sources, protein systhesis, and controls the body’s sensitivity to other hormones
What are the 3 groups that hypothyroidism can be classified into?
- Primary hypothyroidism
- Secondary hypothyroidism
- Congenital hypothyroidism
What is primary hypothyroidism?
problem with the thyroid gland itself, e.g. autoimmune
What is secondary hypothyroidism?
disorder with the pituitary gland (e.g. pituitary apoplexy) or lesion compressing pituitary gland
What is congenital hypothyroidism?
problem with thyroid dysgenesis or thyroid dyshormonogenesis
What is the most common cause of hypothyroidism?
Hashimoto’s thyroiditis
What are 3 diseases that Hashimoto’s is associated with?
- Type 1 diabetes mellitus
- Addison’s
- Pernicious anaemia
What can Hashimoto’s thyroiditis cause transiently in the acute phase?
thyrotoxicosis (hyPERthyroidism)
What is the commonest cause of thyrotoxicosis (hyperthyroidism)?
Graves’ disease
What is a feature of thyrotoxicosis specific to Graves’ disease?
thyroid eye disease
What are 6 other causes of hypothyroidism, in addition to Hashimoto’s thyroiditis?
- Subacute thyroiditis (de Quervain’s)
- Riedel thyroiditis
- Postpartum thyroiditis
- Drugs - lithium, amiodarone
- Iodine deficiency
- After thyroidectomy or radioiodine treatment
What are 2 features of subacute (de Quervain’s) thyroiditis?
- painful goitre
- raised ESR
What is Riedel thyroiditis?
fibrous tissue replacing the normal thyroid parenchyma
causes a painless goitre
What are 3 drugs which can cause hypothyroidism?
- Lithium
- Amiodarone
- Anti-thyroid drugs e.g. carbimazole
What is the most common cause of hypothyroidism in the developing world?
iodine
In addition to Graves’ disease what are 5 other causes of thyrotoxicosis?
- Toxic multinodular goitre
- Drugs - amiodarone
- Acute phase of subacute (de Quervain’s) thyroiditis
- Acute phase of post-partum thyroiditis
- Acute phase of Hashimoto’s thyroiditis
What is toxic multinodular goitre?
autonomously functioning thyroid nodules that secrete excess thyroid hormones
What are 10 symptoms of hypothyroidism?
- Weight gain
- Lethargy
- Cold intolerance
- Dry, cold, eyllowish skin
- Non-pitting oedema (face, hands)
- Dry, coarse scalp hair, loss of lateral aspect of eyebrows
- Constipation
- Menorrhagia
- Decreased deep tendon reflexes
- Carpal tunnel syndrome
What are 11 symptoms of thyrotoxicosis?
- Weight loss
- Manis, restlessness
- Heat intolerance
- Palpitations, may even provoke arrhythmias e.g. AF
- Increased sweating
- Pretibial myoxedema (above lateral malleoli)
- Thyroid acropachy: clubbing
- Diarrhoea
- Oligomenorrhoea
- Anxiety
- Tremor
What is the principle investigation in thyroid disease?
thyroid function tests
primarily look at serum TSH and T4
Which type of thyroid hormone is rarely used in cases of thyroid disease?
T3 - only clinically useul in small number of cases
What is an easy way to remember how cases of hyper- and hypothyroidism present in terms of TFTs?
often opposite: T4 low, TSH high in hypothyroidism and vice versa in hyperthyroidism
Which thyroid hormone is most sensitive for monitoring patients with existing thyroid problems and for guiding treatment?
TSH
How will thyroid function tests present in thyrotoxicosis e.g. Graves’ disease?
Low TSH, high free T4
How will thyroid function tests present in primary hypothyroidism e.g. Hashimoto’s thyroiditis?
High TSH, low free T4
What will TFTs show in secondary hypothyroidism?
low TSH, low free T4
What will TFTs show in sick euthyroid syndrome?
Low TSH, low free T4
When does sick euthyroid commonly occur and what is the management?
common in hospital inpatients; changes reversible upon recovery frmo systemic illnes and no treatment is usually needed
What are do TFTs show in subclinical hypothyroidism?
High TSH, normal T4
What does subclinical hypothyroidism represent?
common finding, represents patients on the way to developing hypothyroidism but still have normal thyroxine levels
What do TFTs show in poor compliance with thyroxine?
TSH high, T4 normal
What causes the abnormal TFTs in poor thyroxine compliance?
if poorly compliant may only take thyroxine in days before routine blood test, so thyroxine levels normal but TSH lags and reflects longer term low thyroxine levels
What are the 3 main thyroid autoantibodies that can be tested for in thyroid disease?
- Anti-thyroid peroxidase (TPO) antibodies - Hashimoto’s thyroiditis
- TSH receptor antibodies - Graves’ disease
- Thyroglobulin antibodies
What thyroid condition are TSH receptor antibodies associaed with?
Graves’ disease (90-100% of cases)
What thyroid condition are anti-TPO antibodies associated with?
Hashimoto’s thyroiditis
In addition to TFTs what is another test sometimes performed in thyroid disease and what can it show?
nuclear scintigraphy: toxic multinodular goitre reveals patchy uptake
What is the treatment of hypothyroidism?
thyroxine given in form of levothyroxine
What are 3 things that patients with thyrotoxicosis may be treated with?
- Propranolol - thyrotoxic symptoms e.g. tremor
- Carbimazole
- Radioiodine treatment
How does carbimazole work to treat thyrotoxicosis?
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin - reduces thyroid hormone production
What is an important adverse effet of carbimazole to be aware of?
agranulocytosis
What may be seen in TFTs when steroid therapy is being used?
low TSH, normal T4
What can cause secondary hypothyroidism?
pituitary failure
What are 3 conditions that can be associated with hypothyroidism (in addition to the autoimmune conditions)?
- Down’s syndrome
- Turner’s syndrome
- Coeliac disease
What is the commonest cause of hypothyroidism in children (juvenile hypothyroidism)?
autoimmune thyroiditis
What are 3 causes of hypothyroidism in children?
- Autoimmune thyroiditis
- Post total-body irradiation eg. treatment for acute lymphoblastic leukaemia
- Iodide deficiency
What is the danger of not treating congenital hypothyroidism in babies?
irreversible cognitive impairment
What are 5 features of congenital hypothyroidism?
- Prolonged neonatal jaundice
- Delayed mental and physical milestones
- Short stature
- Puffy face, macroglossia
- Hypotonia
What is the significant of subclinical hypothyroidism?
risk of progressing to overt hypothyroidism 2-5% (higher in men)
Whatt are 2 factors that increase the risk of subclinical hypothyroidism becoming overt hypothyroidism?
- Male
- Presence of thyroid autoantibodies
What is the managemet of subclinical hypothyroidism if TSH is between 4-10 U/L (normal 0.5-5) and the patient is younger than 65?
- if <65 years with symptoms suggestive of hypothyroidism, give trial of levothyroxine
- if asymptomatic, observe and repeat thyroid function in 6 months
What is the managemet of subclinical hypothyroidism if TSH is between 4-10 U/L (normal 0.5-5) and the patient is older than 65?
follow watch and wait strategy, genearlly avoiding hormonal treatment
What is the management of subclinical hypothyroidism if TSH is >10 mU/L?
start treatment even if asymptomatic with levothyroxine if 70 years old or younger
in older people, especially over 80, follow watch and wait strategy, avoiding hormonal treatment
What are 3 key features of Hashimoto’s thyroiditis?
- Features of hypothyroidism
- Goitre: firm, non-tender
- Ant-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
What are 2 types of antibodies which may be present in Hashimoto’s thyroiditis?
- Anti-thyroid peroxidase (TPO)
- Anti-thyroglobulin (Tg)
What are 4 associations of Hashimoto’s thyroiditis?
- Coeliac disease
- Type 1 diabetes mellitus
- Vitiligo
- MALT lymphoma
What is thought to cause subacute (de Quervain’s) thyroiditis?
thought to occur following viral infection, typically presents with hyperthyroidism
How does subacute (de Quervain’s) thyroiditis typically present?
hyperthyroidism
What are the 4 phases of subacute (de Quervain’s) thyroiditis?
- Phase 1: (lasts 3-6 weeks) hyperthyroidism, painful goitre, raised ESR
- Phase 2: (1-3 weeks): euthyroid
- Phase 3: (weeks - months): hypothyroidism
- Phase 4: thyroid structure and function goes back to normal
How long does each phase of subacute (de Quervain’s) thyroiditis last?
- Phase 1: 3-6 weeks
- Phase 2: 1-3 weeks
- Phase 3: weeks- months
- Phase 4: back to normal
What is a useful investigation in subacute (de Quervain’s) thyroiditis and what does it show?
Thyroid scintigraphy: globally reduced uptake of iodine-131
What are 3 aspects of management of subacute/de Quervain’s thyroiditis?
- Usually self-limiting - most patient’s don’t require treatment
- Thyroid pain may respond to aspirin or other NSAIDs
- In more severe cases steroids are used, particularly if hypothyroidism develops
What is found on examination in Riedel’s thyroiditis?
hard, fixed, painless goitre
What age/gender group is Riedel’s thyroidit typically seen in?
middle-aged women
What is an association of Riedel’s thyroiditis?
Retroperitoneal fibrosis
What are 4 patient groups in whom the starting dose of levothyroxine should be lower when treating hypothyroidism?
- Elderly patients / patiennts >50 years
- Ischaemic heart disease
- Other cardiac disease
- Severe hypothyroidism
What starting dose of levothyroxine is recommended in severe hypothyroidism or in patients over 50?
25mcg od
How is the dose of levothyroxine changed over time in those who start on a lower dose?
titrated slowly
If a lower than normal dose is not indicated, what is the usual dose of levothyroxine that patients are started on?
50-100mcg od
Following a change in thyroxine dose in those being treated for hypothyroidism, when should TFTs be checked?
after 8-12 weeks
What is the therapeutic goal in hypothyroidism?
normalisation of the thyroid stimulating hormone (TSH) level - usually 0.5 - 2.5 mU/L so preferable to aim in this range
When should the dose of levothyroxine be increased and by how much?
women who become pregnant should have it increased by at least 25-50 mcg due to increased demands of pregnancy
What monitoring should be performed when adjusting the levothyroxine dose in pregnancy?
monitor TSH carefully, aiming for low-normal value
What are 4 side-effects of thyroxine therapy?
- Hyperthyroidism: due to over treatment
- Reduced bone mineral density
- Worsening of angina
- Atrial fibrillation
What are 2 drug interactions with levothyroxine?
- Iron
- Calcium carbonate
What must be done due to the risk of interaction of levothyroxine with iron or calcium carbonate?
they reduce absorption of levothyroxine so give at least 4 hours apart
In which age and gender group is Graves’ disease typically seen?
women aged 30-50 years
What are 3 features seen in Graves’ disease but not other causes of thyrotoxicosis?
- Eye signs
- Pretibial myxoedema
- Thyroid acropachy
What are the 2 key eye signs of Graves’ disease?
- Exophthalmos
- Ophthalmoplegia
What are the 3 things in the triad of thyroid acropachy?
- Digital clubbing
- Soft tissue swelling of hands and feet
- Periosteal new bone formation
What are 2 autoantibodies seen in Graves’ disease?
- TSH receptor stimulating antibodies (90%)
- Anti-thyroid perixodiase antibodies (75%)
What are 4 treatment options for the management of Graves’ disease?
- Anti-thyroid drugs e.g. carbimazole
- Block-and-replace regimes
- Radio-iodine treatment
- Surgery
What is often given initially when a diagnosis of Graves’ disease is made and why?
Propranolol - block adrenergic effects
What dose of carbimazole is started and continued in Graves’ disease?
started at 40mg, reduced gradually to maintain euthyroidism
How long is treatment with carbimazole usually contined in Graves’ disease?
12-18 months
What is the benefit of a carbimazole titration regime for Graves’ disease?
patients suffer fewer side-effects than those on a block and replace regime
What does a block-and-replace regime for Graves’ disease involve?
carbimazole started at 40mg, thyroxine then added when patient is euthyroid
How long does block-and-replace treatment for Graves’ disease last?
6-9 months
What are 2 absolute and one relative contraindication for radioiodine treatment for Graves’ disease?
- Absolute: pregnancy
- Absolute: age <16 years
- Relative: thyroid eye disease
Why is thyroid eye disease a relative contraindication for radioiodine treatment of Graves’ disease?
may worsen condition
How long should pregnancy be avoided for following radioiodine treatment for Graves’ disease?
4-6 months
What does hypothyroidism following radioiodine treatment for Graves’ disease depend on? How comon is it?
dose given
majority will require thyroxine supplementation after 5 years
What proportion of patients with Graves’ disease are affected by thyroid eye disease?
25-50% of patients
What is thought to be the pathophysiology behind thyroid eye disease?
- thought to be caused by autoimmune response against autoantigen, possibly the TSH receptor –> retro-orbital inflammation
- inflammation results in glycosaminoglycan and collagen deposition in the msucles
What is the most improtant modifiable risk factor for the development of thyroid eye disease?
smoking
What therapy can increase the inflammatory symptoms seen in thyroid eye disease?
radioiodine treatment
What is a drug that may help reduce the risk of worsening thyroid eye disease with radioiodine treatment?
prednisolone
What thyroid status might a patient have at the time of presentation with thyroid eye disease?
may be eu-, hypo- or hyperthyroid
What are 5 possible features of thyroid eye disease?
- Exophthalmos
- Conjunctival oedema
- Optic disc swelling
- Ophthalmoplegia
- Inability to close eyelides - may lead to sore, dry eyes, risk of exposure keratopathy
What are 4 aspects of the management of thyroid eye disease?
- Topical lubircants may be needed to help prevent corneal inflammation caused by exposure
- Steroids
- Radiotherapy
- Surgery
What are 6 signs in established thyroid eye disease that indicate the need for urgent review by an ophthalmologist?
- Unexplained deterioration in vision
- Awareness of change in intensity or quality of colour vision in one or both eyes
- History of eye suddenly ‘popping out’ (globe subluxation)
- Obvious corneal opacity
- Cornea still visible when eyelide are closed
- Disc swelling
What proportion of patients taking amiodarone develop thyroid dysfunction?
1 in 6 patients
What is thought to be the pathophysiology of amiodarone-induced hypothyroidism?
high iodine content of amiodarone causing Wolff-Chaikoff effect - autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide
What are 2 overall effects that amiodarone can have on the thyroid?
- Amiodarone-induced hypothyroidism
- Amiodarone-induced thyrotoxicosis
What are the 2 types of amiodarone-induced thyrotoxicosis?
- AIT type 1
- AIT type 2
What is the pathophysiology of AIT type 1?
excess iodine-induced thyroid hormone synthesis
What is the pathophysiology of AIT type 2?
amiodarone-related destructive thyroiditis
In which type of amiodarone-induced thyrotoxicosis is goitre present?
AIT type 1
What is the management of AIT type 1? 2 options
carbimazole or potassium perchlorate
What is the management of AIT type 2?
corticosteroids
In amiodarone-induced thyrotoxicosis vs amiodarone-induced hypothyroidism, when should you stop amiodarone?
can continue if desirable in hypothyroidism but must stop in AIT
What is thyroid storm?
rare but life-threatening complication of thyrotoxicosis; usually established thyrotoxicosis rather than presenting feature
What cause of thyrotoxicosis does not usually cause thyroid storm?
iatrogenic thyroxine excess
What are 4 types of precipitating events of thyrotoxicosis?
- Thyroid or non-thyroidal surgery
- Trauma
- Infection
- Acute iodine load e.g. CT contrast media
What are 7 clinical features of thyroid storm?
- Fever > 38.5oC
- Tachycardia
- Confusion and agitation
- Nausea and vomiting
- Hypertension
- Heart failure
- Abnormal liver function test - jaundice may be seen
What are 6 aspects of the management of thyroid storm?
- Symptomatic treatment e.g. paracetamol
- Treatment of underlying precipitating event
- Beta blockers: typically IV propranolol
- Anti-thyroid drugs e.g. methimazole or propylthiouracil
- Lugol’s iodine
- Dexamethasone e.g. 4mg IV qds
Why is dexamethasone useful to treat thyroid storm?
blocks conversion of T4 to T3
What physiological changes to thyroid hormones occur in pregnancy?
increase in levels of thyroxine-binding globulin (TBG) this causes an increase in the levels of total thyroxine but does not affect the free thyroxine level
What are 3 risks of thyrotoxicosis in pregnancy?
- Fetal loss
- Maternal heart failure
- Premature labour
What is the most common cause of thyrotoxicosis in pregnancy?
Graves’ disease
What can cause transient gestation hyperthyroidism? How does this change throughout pregnancy?
activation of the TSH receptor by hCG
hCG levels will fall in second and third trimester
What is drugs are used to manage thyrotoxicosis in pregnancy (depending on the point in pregnancy)?
- first trimester: propylthiouracil
- at start of second trimester: switch to carbimazole
What is the risk of using carbimazole in the first trimester of pregnancy?
may be associated with increased risk of congenital abnormalities
What should be the aim for maternal free thyroxine levels when treating thyrotoxicosis in pregnancy and why?
should keep in the upper third of the normal reference range
to avoid fetal hypothyroidism
What investigation should be performed during pregnancy with thyrotoxicosis and when?
thyrotrophin receptor stimulating antibodies, at 30-36 weeks gestation
Why is it recommended to check thyrotrophin receptor stimulating antibodies at 30-36 weeks gestation in the case of thyrotoxicosis?
helps determine risk of neonatal thyroid problems
What are 2 types of treatment for thyrotoxicosis that should not be used in pregnancy?
- Block and replace regimes
- Radioiodine therapy
What is safe for the management of hypothyroidism in pregnancy?
thyroxine
What monitoring should be performed in a woman being treated for hypothyroidism in pregnancy and when?
Serum thyroid-stimulating hormone (TSH) in each trimester and 6-8 weeks post-partum
How does the treatment of hypothyroidism change in pregnancy?
require increased dose of thyroxine, by up to 50% as early as 4-6 weeks of pregnancy
Is breastfeeding safe while the mother is on thyroxine?
yes