Thyroid Flashcards
Around ?% of the UK population has hypothyroidism (an under active thyroid gland) whilst around ?% have thyrotoxicosis (an over active gland).
Around 2% of the UK population has hypothyroidism (an under active thyroid gland) whilst around 1% have thyrotoxicosis (an over active gland).
Both hypothyroidism and hyperthyrodism (also known as thyrotoxicosis) are around 10 times more common in women than men.
true
The thyroid gland is one of the largest endocrine organs in the body.
true
Describe the hypothalamus-pituitary-end organ system in thyroid
hypothalamus secretes thyrotropin-releasing hormone (TRH) which stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). This then acts on the thyroid gland increasing the production of thyroxine (T4) and triiodothyronine (T3), the two main thyroid hormones. These then act on a wide variety of tissues, helping to regulate the use of energy sources, protein synthesis, and controls the body’s sensitivity to other hormones.
How are hypothyroid problems classified?
primary hypothyroidism: there is a problem with the thyroid gland itself, for example an autoimmune disorder affecting thyroid tissue (see below)
secondary hypothyroidism: usually due to a disorder with the pituitary gland (e.g.pituitary apoplexy) or a lesion compressing the pituitary gland
congenital hypothyroidism: due to a problem with thyroid dysgenesis or thyroid dyshormonogenesis
there are a number of causes thyrotoxicosis the vast majority are primary in nature
true
secondary hyperthyroidism is rare
true
1% of cases
Congenital thyrotoxicosis is common
false
Congenital thyrotoxicosis is not seen
The majority of thyroid problems seen in the developed world are a consequence of
autoimmunity.
Most common cause thyrotoxicosis
Graves’ disease
Most common cause of hypothyroidism?
Hashimoto’s thyroiditis
most common cause in the developed world
What is hashimotos associated with?
autoimmune disease, associated with type 1 diabetes mellitus, Addison’s or pernicious anaemia
What does hashimotos cause in the acute phase?
transient thyrotoxicosis
List causes of hypothyroid
Hashimotos Subacute thyroiditis (de Quervain's) Riedel Thyroiditis Postpartum thyroiditis Drugs Iodine deficiency
Which drugs cause hypothyroid
lithium
amiodarone
the most common cause of hypothyroidism in the developing world
Iodine deficiency
Which drugs cause thyrotoxicosis
amiodarone
Can also cause hypothyroidism?
Toxic multinodular goitre causes which thyroid picture? What causes it
Thyrotoxicosis
autonomously functioning thyroid nodules that secrete excess thyroid hormones
How does Subacute thyroiditis (de Quervain’s) present
associated with a painful goitre and raised ESR
How does Riedel’s thyroiditis present
fibrous tissue replacing the normal thyroid parenchyma
causes a painless goitre
Symptoms of hypothyroidism?
Weight gain, Lethargy, Cold intolerance, Constipation
Menorrhagia
Decreased deep tendon reflexes
Carpal tunnel syndrome
Dry (anhydrosis), cold, yellowish skin
Non-pitting oedema (e.g. hands, face)
Dry, coarse scalp hair, loss of lateral aspect of eyebrows
Symptoms of thyrotoxicosis
Weight loss
‘Manic’, restlessness
Heat intolerance
Palpitations, may even provoke arrhythmias e.g. atrial fibrillation
Increased sweating
Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
Thyroid acropachy: clubbing
Diarrhoea
Oligomenorrhea
Anxiety, Tremor
TFTs - what does this look at ? How useful is this
these primarily look at serum TSH and T4 levels
T3 can be measured but is only useful clinically in a small number of cases
remember that TSH and T4 levels will often be ‘opposite’ in cases of primary hypo- or hyperthyroidism. For example in hypothyroidism the T4 level is low (i.e. not enough thyroxine) but the TSH level is high, because the hypothalamus/pituitary has detected low levels of T4 and is trying to get the thyroid gland to produce more
TSH levels are more sensitive than T4 levels for monitoring patients with existing thyroid problems and are often used to guide treatment
Describe TFTs in Thyrotoxicosis (e.g. Graves’ disease)
TSH Low
Free T4 High
Describe TFTs in Primary hypothyroidism (e.g. Hashimoto’s thyroiditis)
TSH High
Free T4 Low
Describe TFTs in Secondary hypothyroidism? What is required in addition to main tx
TSH Low
Free T4 Low
Replacement steroid therapy is required prior to thyroxine
Describe TFTs in Sick euthyroid syndrome
TSH Low
Free T4 Low
Common in hospital inpatients. Changes are reversible upon recovery from the systemic illness and no treatment is usually needed
T3 is particularly low in these patients
Describe TFTs in Subclinical hypothyroidism
TSH High
Free T4 Normal
This is a common finding and represents patients who are ‘on the way’ to developing hypothyroidism but still have normal thyroxine levels. Note how the TSH levels, as mentioned above, are a more sensitive and early marker of thyroid problems
Describe TFTs in Poor compliance with thyroxine
TSH High
Free T4 Normal
Patients who are poorly compliant may only take their thyroxine in the days before a routine blood test. The thyroxine levels are hence normal but the TSH ‘lags’ and reflects longer term low thyroxine levels
A number of thyroid autoantibodies can be tested for (remember the majority of thyroid disorders are autoimmune). The 3 main types are:
Anti-thyroid peroxidase (anti-TPO) antibodies
TSH receptor antibodies
Thyroglobulin antibodies
There is significant overlap between the type of antibodies present and particular diseases
true
but generally speaking TSH receptor antibodies are present in around 90-100% of patients with Graves’ disease and anti-TPO antibodies are seen in around 90% of patients with Hashimoto’s thyroiditis.
Other tests (other than TFTs)
nuclear scintigraphy; toxic multinodular goitre reveals patchy uptake
In T3 thyrotoxicosis the free T4 will be
normal
Graves’ disease is the most common cause of thyrotoxicosis. It is typically seen in women aged
30-50 years
Specific signs seen in Grave’s but not in other causes of thyrotoxicosis
eye signs (30% of patients)
pretibial myxoedema
thyroid acropachy, a triad of: digital clubbing, soft tissue swelling of the hands and feet, periosteal new bone formation
Autoantibodies in Grave;s
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)
Graves’ disease accounts for around 50-60% of cases of thyrotoxicosis. Other
Causes
Graves’ disease
toxic nodular goitre
acute phase of subacute (de Quervain’s) thyroiditis
acute phase of post-partum thyroiditis
acute phase of Hashimoto’s thyroiditis (later results in hypothyroidism)
amiodarone therapy
Thyroid eye disease affects between ?% of patients with Graves’ disease.
25-50%
Pathophysiology of thyroid eye disease
it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation
the inflammation results in glycosaminoglycan and collagen deposition in the muscles
Prevention of thyroid eye disease?
smoking is the most important modifiable risk factor for the development of thyroid eye disease
radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves’ disease around 15% developed, or had worsening of, eye disease.
Prednisolone may help reduce the risk
Features of thyroid eye disease?
the patient may be eu-, hypo- or hyperthyroid at the time of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
Management thyroid eye disease?
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
Monitoring patients with established thyroid eye disease the following symptoms/signs should 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 the eyelids are closed
disc swelling
What is thyroid storm?
Thyroid storm is a rare but life-threatening complication of thyrotoxicosis. It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic thyroxine excess does not usually result in thyroid storm.
Precipirtating events thyroid storm?
thyroid or non-thyroidal surgery
trauma
infection
acute iodine load e.g. CT contrast media
Symptoms of thyroid storm?
fever > 38.5ºC tachycardia confusion and agitation nausea and vomiting hypertension heart failure
abnormal liver function test is a feature of thyroid storm
true
jaundice may be seen
Mx 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 - blocks the conversion of T4 to T3
Secondary hypothyroidism occurs due to? Associated conditions?
From pituitary failure
Other associated conditions
Down’s syndrome
Turner’s syndrome
coeliac disease
Hypothyroid mx: initial starting dose of levothyroxine should be lower in whom? What is the dose
elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated
Hypothyroid mx: initial starting dose
patients should be started on a dose of 50-100mcg od
following a change in thyroxine dose thyroid function tests should be checked after
8-12 weeks
What is the therapeautic goal of hypothyroid?
‘normalisation’ of the thyroid stimulating hormone (TSH) level.
As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range
women with established hypothyroidism who become pregnant should be mx how
dose increased ‘by at least 25-50 micrograms levothyroxine’* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value
there is no evidence to support combination therapy with levothyroxine and liothyronine
true
Side-effects of thyroxine therapy
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
Interactions of thyroxine? How to deal with this?
iron, calcium carbonate
as absorption of levothyroxine reduced, give at least 4 hours apart
A hoarse voice is also occasionally noted in hypothyroidism
true
The most common cause of hypothyroidism in children? What other causes?
autoimmune thyroiditis.
Other causes include
post total-body irradiation (e.g. in a child previous treated for acute lymphoblastic leukaemia)
iodine deficiency (the most common cause in the developing world)
What is Sick euthyroid syndrome
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
Is sick euthyroid reversible? How do you mx it
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
What is riedel;s thyroiditis
Riedel’s thyroiditis is a rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma. On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women. It is associated with retroperitoneal fibrosis.
In pregnancy, there is an increase in the levels of
thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.
Pregnancy - Untreated thyrotoxicosis increases the risk of
fetal loss, maternal heart failure and premature labour
most common cause of thyrotoxicosis in pregnancy
Grave’s
How does HCG in pregnancy affect thyroid hormone
It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient gestational hyperthyroidism. HCG levels will fall in the second and third trimester
Describe mx hyperthyroid in pregnancy
‘Propylthiouracil is used in the first trimester of pregnancy in place of carbimazole, as the latter drug may be associated with an increased risk of congenital abnormalities.
At the beginning of the second trimester, the woman should be switched back to carbimazole’
propylthiouracil is associated with an increased risk of what in pregnancy
severe hepatic injury
How should maternal thyroxine levels be controlled in prg? Why
maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism
block-and-replace regimes should be used in pregnancy
FALSE! should NOT
radioiodine therapy is first line in pregnancy
FALSE! should NOT
thyrotrophin receptor stimulating antibodies should be checked at which gestation, why
thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine the risk of neonatal thyroid problems
is thyroxine safe in pregnancy
yes
serum thyroid-stimulating hormone measured when in pregnancy
in each trimester and 6-8 weeks post-partum
women require an increased or decrease dose of thyroxine during pregnancy?
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
is thyroxine safe in breastfeeding
yes
Describe Post-partum thyroiditis
Three stages
- Thyrotoxicosis
- Hypothyroidism
- Normal thyroid function (but high recurrence rate in future pregnancies)
Post-partum thyroiditis antibodies?
Thyroid peroxidase antibodies are found in 90% of patients
Management Post-partum thyroiditis ?
the thyrotoxic phase is not usually treated with anti-thyroid drugs as the thyroid is not overactive. Propranolol is typically used for symptom control
the hypothyroid phase is usually treated with thyroxine
Describe Hashimoto’s thyroiditis
Hashimoto’s thyroiditis (chronic autoimmune thyroiditis) is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women
Features hashimotos
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
neoplasm Assoc hashimotos
MALT lymphoma
Congenital hypothyroidism affects around
1 in 4000 babie
Congenital hypothyroidism should be diagnosed and treated within? Why?
the first four weeks it causes irreversible cognitive impairment
How are children screened for congenital hypothyroidism
Children are screened at 5-7 days using the heel prick test
Features of congenital hypothyroidism?
prolonged neonatal jaundice delayed mental & physical milestones short stature puffy face, macroglossia hypotonia
Subclinical hypothyroidism
Significance?
risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
risk increased by the presence of thyroid autoantibodies
Subclinical hypothyroidism presentation
TSH raised but T3, T4 normal
no obvious symptoms
mx subclinical hypothyroidism can be different depending on which main factor
TSH classify if
TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range
or
TSH is > 10mU/L and the free thyroxine level is within the normal range
also age and symptoms
mx subclinical hypothyroidism if
TSH is > 10mU/L and the free thyroxine level is within the normal range
start treatment (even if asymptomatic) with levothyroxine if <= 70 years
‘in older people (especially those aged over 80 years) follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
mx subclinical hypothyroidism if TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range
if < 65 years with symptoms suggestive of hypothyroidism, give a trial of levothyroxine. If there is no improvement in symptoms, stop levothyroxine
‘in older people (especially those aged over 80 years) follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
if asymptomatic people, observe and repeat thyroid function in 6 months
Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:
normal serum free thyroxine and triiodothyronine levels
with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
causes of subclinical hyperthyroidism
multinodular goitre, particularly in elderly females
excessive thyroxine may give a similar biochemical picture
The importance in recognising subclinical hyperthyroidism lies in the potential effect on
the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and increase the likelihood of dementia
mx subclinical hyperthyroidism
TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention
a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission
what is Toxic multinodular goitre? Ix? Mx?
Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
The treatment of choice is radioiodine therapy.
Features of hyperthyroidism or hypothyroidism arecommonly seen in patients with thyroid malignancies
FALSE
Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones
Describe the percentage of different types of thyroid cancers
Papillary 70% Follicular 20% Medullary 5% Anaplastic 1% Lymphoma Rare
Describe the histology of Papillary carcinoma
Usually contain a mixture of papillary and colloidal filled follicles
Histologically tumour has papillary projections and pale empty nuclei
Seldom encapsulated
Lymph node metastasis predominate
Haematogenous metastasis rare
Who does papillary carcinoma usually present in
Often young females - excellent prognosis
Which two cancers are managed similarily?
What does this include
papillary and follicular cancer
total thyroidectomy
followed by radioiodine (I-131) to kill residual cells
yearly thyroglobulin levels to detect early recurrent disease
Describe presentation of follicular adenoma
Usually present as a solitary thyroid nodule
Malignancy can only be excluded on formal histological assessment
Describe histopathology of Follicular carcinoma
May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
Vascular invasion predominates
Multifocal disease raree
Medullary cancer is associated with which cells
Cancer of parafollicular (C) cells, secrete calcitonin
Medullary cancer is part of which syndrome
MEN2
Familial genetic disease accounts for up to ?% of medullary cancer
20% cases
C cells derived from
neural crest and not thyroid tissue
what type of mets in medullar carcinoma?
Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
Who usually gets anaplastic carcinoma?
elderly females
mx anaplastic carcinoma?
Local invasion is a common feature
Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
Thyroid surgery: complications?
Anatomical such as recurrent laryngeal nerve damage.
Bleeding. Owing to the confined space haematoma’s may rapidly lead to respiratory compromise owing to laryngeal oedema.
Damage to the parathyroid glands resulting in hypocalcaemia.
