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
