Thyroid Flashcards
How does iodine get from the gut into thyroid cells?
Iodine enters the GI tract and is converted
into iodide
TSH controls uptake of iodide to the thyroid
(blocked by perchlorate)
Iodide goes through the basement membrane
via Na+/K+ ATPase
How is thyroxine made?
The iodine is then taken up
by thyroglobulin and then converted into
thyroxine through a number of processes
The iodination of tyrosine residues
in thyroglobulin leads to the
formation of monoiodotyrosine and diiodotyrosine
How is thyroxine used?
Once the thyroxine (T4) is produced, it is stored within the thyroid gland
When it needs to be released, it travels through the basement membrane and is secreted into
the capillary lumen
In the periphery, T4 will be converted to T3
Which thyroid hormones can be measured?
T3 and T4 can be measured in the blood circulation
o You can also measure TSH, thyroglobulin and thyroid peroxidase
o Note: TRH is rarely measured
How is thyroid hormone transported?
A very small proportion is active (free)
thyroxine (fT4)
o Only 0.03% of thyroxine in the
circulation is active
Most of it is bound to thyroxine binding
globulin (TBG)
o NOTE: if you are lacking
albumin, your TBG levels will
go down
Thyroxine can also bind to thyroxinebinding pre-albumin (TBPA) and albumin
Draw out the HPT axis
What is primary and secondary hypothyroidism?
Most hypothyroidism is PRIMARY hypothyroidism (i.e. pathology with the thyroid gland itself)
Secondary hypothyroidism – pathology in pituitary gland (5%)
What is hashimotos thyroiditis?
Autoimmune disease
Goitre due to lymphocytic and plasma cell infiltration
Anti-thyroid antibodies including anti-thyroid peroxidase, anti-thyroglobulin and TSH-receptor blocking antibodies
What is atrophic thyroiditis?
Autoimmune disease
Tends to affect women aged 40-60 years
Pathology: atrophic thyroid gland with lymphocytic infiltration and fibrous tissue replacing normal thyroid parenchyma
No goitre
Anti-TSH receptor antibodies blocking action of tsh
What is Post-Graves’ disease (radioactive iodine, surgery, natural history or thionamines)?
Post-thyroiditis o Drugs (amiodarone, lithium)
Thyroid agenesis or dysgenesis o Iodine deficiency (severe iodine deficiency is commonest cause worldwide) and dyshormonogenesis
Secondary hypothyroidism, pituitary disease (TSH no utility)
Peripheral thyroid hormone resistance – receptors in tissues do not respond to thyroxine
Iodine excess (Wolff-Chaikoff effect)
What are the clinical features of hypothyroidisn?
o Metabolic rate
o Cardiovascular (e.g. bradycardia)
o GI (e.g. constipation)
o Respiratory (e.g. laboured breathing)
o Reproductive (e.g. oligomenorrhoea)
o Others (e.g. pituitary symptoms such as visual symptoms due to optic chiasm being
affected)
o Weight gain with decreased resting energy expenditure and poor appetite
o Cold and dry hands, feels cold
o Hyponatraemia – thyroxine is involved with sodium transport in kidneys
o Normocytic anaemia due to bone marrow depression, unless pernicious
anaemia (another autoimmune condition which will cause macrocytic anaemia)
o Myxoedema: swelling of face and legs, and dry waxiness of skin
o Goitre
o Subtle in elderly
o Proximal myopathy
What investigations would be positive in hypothyroidism?
o High TSH + low T4 in primary hypothyroidism
o Thyroid peroxidase autoantibodies (if present, suggests autoimmune
hypothyroidism)
o Think of other autoimmune conditions that the patient may also have (e.g. pernicious
anaemia, coeliac disease, Addison’s disease)
What is the management of hypothyroidism?
ECG
Levothyroxine 50-125-200 µg/day titrated to a normal TSH
Note: rule out underlying adrenal insufficiency before starting thyroid hormone replacement as it can precipitate and Addisonian crisis
Why should you do an ECG in someone with hypothyroidism?
If someone with hypothyroidism has underlying cardiovascular disease and
you give them thyroxine, their myocardial contractility will increase and they
may be at risk of ischaemia
So, you would want to start on a very low dose of thyroxine and build up if
the patient has cardiovascular disease
What is myxoedema coma?
o Severe hypothyroidism leading to decreased mental status, hypothermia and reduced
function of multiple organs
o Medical emergency
What is the treatment of myxoedema coma?
Oxygen
Rewarming
Rehydration
IV T4/T3: liothyronine (IV T3) has faster onset of action
IV hydrocortisone
Treat underlying cause e.g. infection
Why does subclinical hypothyroidism exist?
The T4 level is NORMAL but TSH is HIGH
However, the pituitary gland senses that level of T4 and thinks that the thyroid hormone
is NOT producing enough thyroxine so it produces more TSH
Sometimes referred to as compensated hypothyroidism
These patients may not have clinical signs as T4 is normal
If TPO antibodies are positive, it suggests that the patient may go on to develop thyroid
disease
Subclinical hypothyroidism is UNLIKELY to be the cause of their presenting symptoms
Hypothyroidism is associated with hypercholesterolaemia, so this may be the only benefit of
treating subclinical hypothyroidism
What is hypothyroidism after radio iodine treatment?
RAI is treatment for hyperthyroidism
Most patients with this condition will become hypothyroid within 1 year of receiving
radioiodine treatment
However, it may take many years in some patients (up to 15) – so ask about PMH of
hyperthyroidism
Why does thyroid change happen in pregnancy?
Thyroid hormone levels
change during pregnancy
hCG has a similar structure
to TSH - so if you have too
much hCG, it can make the
thyroid gland produce too
much thyroxine (as it will
bind to same receptors as
TSH)
o Note: a malignancy
producing hCG will
cause rise in
thyroxine
How does thyroid change during pregnancy?
The rise in hCG in the first trimester of pregnancy makes your free T4 levels increase slightly
This is a normal physiological process, so the ‘normal ranges’ of TSH and T4 in pregnancy are slightly different
TBG levels increase dramatically in pregnancy because it is under the control of oestrogen
o But TBG cannot be measured in serum
Later on in pregnancy, hCG levels will drop and, consequently, T4 levels will also go down
and the TSH levels will rise slightly (back to normal population levels)
How is neonatal hypothyroidism found?
Incidence: 1:3500
This is diagnosed in the Guthrie test
It is important to capture hypothyroidism at the correct time - if you measure it too early, their
TSH level may be erroneously high because of the presence of maternal TSH in the blood. If
done too late, it can cause problems in baby
The Guthrie test is usually done at 48-72 hours and the TSH detected is coming from the baby
not the mother
What is sick euthyroid?
Alteration in pituitary thyroid axis in non-thyroidal systemic illness
Biochemistry
o Low T4 and T3
o Normal/high TSH
(May have normal T4 and high rT3)
This can happen in any severe illness e.g. sepsis
If you are very sick, your thyroid will shut down to try and reduce the basal metabolic rate
These patients do NOT have hypothyroid symptoms and giving thyroxine will NOT improve their symptoms
Hence always do TFTs in context of patient symptoms and signs
What are the causes of hyperthyroidism?
Graves’ disease
Toxic multinodular goitre
Single toxic adenoma
Other causes: subacute thyroiditis, post partum thyroiditis, silent thyroiditis, factitious thyroiditis, TSH induced, thyroid cancer, trophoblastic tumour and struma ovarii
What differentiates Graves’ disease, toxic multinodular goitre and single toxic adenoma?
o Graves’ disease (40-60%)
TSH-receptor stimulating auto-antibodies
Cause smooth thyroid enlargement
o Toxic multinodular goitre (30-50%)
Aka Plummer’s disease
Multiple autonomously functioning nodules (function independently of TSH)
o Single toxic adenoma (5%)
An autonomously functioning thyroid nodule
NOTE: a technetium scan can be used to see which parts of the thyroid are
producing excessive thyroid hormone. All three of the above conditions will
show increased uptake of technetium
Why does thyroid have anything to do with pregnancy?
Post-partum thyroiditis
In pregnancy, the body may produce antibodies that stimulate the
thyroid gland to release excess amounts of thyroxine
These two have LOW uptake in a technetium scan
Trophoblastic tumour and Struma ovarii
Due to excessive hCG production
Struma ovarii: rare form of ovarian tumour (usually a teratoma) that
contains mostly thyroid tissue and produces thyroxine
What are the clinical features of hyperthyroidism?
o Increased metabolic rate
o Cardiovascular (tachycardia)
o GI (e.g. diarrhoea)
o Respiratory (e.g. tachypnoea)
o Skeletal – thyroxine has direct effect on osteoclasts (e.g. osteopaenia/osteoporosis)
o Reproductive (e.g. irregular periods)
What would you find on investigation of hyperthyroidism?
o Low TSH
o High T4 and T3
o Technetium scan may show high or low uptake
o Thyroid autoantibodies (thyroid microsomal (aka thyroid peroxidase antibody))
What is the management of hyperthyroidism?
o Beta-blocker if pulse > 100 bpm
o Other autoimmune conditions (e.g. coeliac disease, Addison’s disease)
o ECG
o Bone mineral density
o Radioactive iodine
What warnings should you give for radio iodine?
The radioactive iodine is taken up by the thyroid gland, which then releases
radiation to destroy the thyroid gland
DANGER: it can precipitate a thyroid storm -> can become cardiovascularly
decompensated
It can make the thyroid gland underactive (i.e. hypothyroidism)
Stop thionamine if using radioactive iodine
Side effects: ophthalmopathy/tracheal compression
What may Graves’ disease present with?
o Diffuse goitre
o Thyroid-associated ophthalmopathy (due to TSH receptors on eye muscles)
IMPORTANT: radioiodine treatment can make Graves’ eye disease worse
o Thyroid-associated dermopathy (pretibial myxoedema)
o Thyroid acropachy (soft tissue swelling of the hands and clubbing of fingers)
o Other autoimmune conditions
What is the pharmacology of thionamides?
o Examples: carbimazole, propylthiouracil
o They work by preventing the conversion of iodide to iodine by thyroid peroxidase
o There are several possible side-effects including rash
o IMPORTANT: a rare side-effect of thionamides is agranulocytosis (<1%)
Patients should be advised to STOP the treatment if they develop a sore
throat or fever and they should immediately seek medical attention to do an
FBC
o These medications are either titrated to achieve normal T4 levels or they can be block
and replaced (a high dose of thionamides are used to block the thyroid gland
completely, then they are given thyroxine to maintain normal T4 levels)
What does potassium perchlorate and thionamides do?
o Potassium perchlorate can be given to hyperthyroid patients before surgery to block
the uptake of iodide by the thyroid cells
o Thionamides inhibit thyroid peroxidase, thereby preventing the conversion of iodide
to iodine
What is thyroiditis?
o Inflammation of thyroid gland
o De Quervain’s (viral) thyroiditis involves painful dysphagia and pyrexia
o You may get the condition without being symptomatic
o Most of the patients will have some form of pain in the neck
o With thyroiditis, you initially get inflammation of the thyroid gland resulting in excessive release of thyroid hormone
o Then, eventually, the thyroid hormone will stop working completely
Whereas in Graves you get continuous thyroid production
o The long-term treatment of thyroiditis is thyroid hormone replacement
o Thyroiditis patients are likely to present at the stage where their TSH is high and their T4/T3 is low
o REMEMBER: the treatment for viral or post-partum thyroiditis is different to hyperthyroidism
What is thyroid cancer?
Types (MOST COMMON):
o Papillary thyroid cancer
o Follicular thyroid cancer
This is typically a slow-progressing cancer
What is the treatment of thyroid cancer?
Treatment: usually a total thyroidectomy
o Radioiodine treatment may be given after surgery to remove any remaining thyroid cells
o After this, patients are given high doses (suprafollicular doses) of thyroxine (this
lowers the TSH levels so that TSH does NOT stimulate any remaining thyroid cancer cells)
What is the use of thyroglobulin?
Thyroglobulin in the serum can be measured as a tumour marker to see whether the thyroid cancer has come back
o TG indicates functioning thyroid tissue
o This can be measured when TSH is suppressed or when TSH is stimulated
What is a medullary carcinoma of the thyroid gland?
o This is RARE but can be devastating
o It can be sporadic, familial or part of MEN 2
o It is a cancer of the C cells of the thyroid gland (these produce calcitonin)
o Tumour markers:
Calcitonin
CEA (carcinoembryonic antigen)
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