Week 9 Endocrinology Thyroid Disorders Flashcards
Which is more active T4 or T3
T3
What does the thyroid produce more of T3 or T4?
T4:T3 14:1
What is the chemical difference between T4 and T3?
An Iodine molecule
What is Tri-iodothyronine?
T3
Hint - tri - 3
What is the chemical name for T4?
Thyroxine
Which of these blood plasma proteins binds the most thyroxine?
Transthyretin
Albumin
Thyroxine Binding Globulin (TBG)
Thyroxine Binding Globulin (TBG) 70%
Transthyretin 20%
Albumin 10%
How much of blood plasma thyroxine is free?
How much T3 is made in the thyroid and how much is synthesised in the peripheries?
20% T3 produced from thyroid gland
80% T3 produced from peripheral conversion of T4 in liver, kidney and muscle
What is the enzyme that converts T4 into T3?
T4 converted to T3 by deiodinase enzymes
What parts of the body convert T4 to T3?
liver, kidney
and muscle
Which two things mean the body can access active T3 when it needs?
The fact that most T4 is bound to protiens in the plasma where it is inactive mean there is this huge reserviour which can be freed and accessed and easily converted into T3
What is Grave’s disease?
Most common cause of hyperthroidism at 75%
Auto immune
Anti-bodies attack thyroid making it overactive
In the context of thyroid disorders what does eye disease imply?
Grave’s disease
Eye disease associated with 1/4 cases of Grave’s
What is Toxic Multinodular Goitre (MNG)
- Multiple lumps (nodules) on enlarged thyroid (goitre)
- Often one or more lumps will be overactive
How does MNG change with progression?
As T4 begins to get elevated more nodules appear and you begint o get a tracheal compression/ elevation
What is an overactive thyroid lump celled if there is just one?
Single toxic nodule
What is Thyroiditis?
Temporary overactivity of thyroid
Can be followed by period of underactivity
Triggered by pregnancy, infection or some drugs (eg amiodarone)
4 causes of hyperthyroidism
Gaves ~ 75%
Multinodular goites ~ 15%
Single toxic nodule
Thyroiditis (temp from pregnancy, drugs or infection)
What are these symptoms a history of?
- Weight loss despite good appetite (often very hungry)
- Tiredness
- Tremor
- Hot, sweaty
- Palpitations
- Diarrhoea
- Light/absent menses
- Mood: irritable, anxiety
- Eyes (change in appearance, red, gritty, painful, double vision)
- Muscle weakness
Family history: Autoimmune diseases
Primary hyperthyroidism
What is a goitre?
A swelling int he neck caused by an elarged thyroid
Eyes
When it comes to hyperthyroidism what is the difference between these two sets of eye symptoms?
Set 1:
* Lid retraction
* Lid lag
Set 2:
* Redness
* Gritty sensation
* Dry or watery eyes
* Pain on eye movement
* Swelling around the eyes
* Proptosis (pushed forward appearance of eyes)
* Double vision
* Loss of colour vision
First is Associated with any cause of thyrotoxicosis
Caused by activation of sympathetic nervous system
Second group is eye conditions only assciated with Graves
Why do most of the eye related symptoms such as swelling and proptosis occur in Grave but not other forms of primary hyperthyridism?
Main takeway: It isn’t high T4/T3 that causing the swelling in the eyes but it is the antibodies responsible for Graves themselves
Don’t need to remeber these details but basically the same antibodies that bind to TSH receptors and cause hyperthyroidism bind to receptors in the orbital connective tissue causing imflammtory swelling, build up of adipose tissue and fibrosis.
What is TPO?
Thyroid Peroxidase
The enzyme responsible for thyroxine synthesis
What is TRAbs and what does it have ot do with Graves?
TRAbs (TSH Receptor Antibodies) significantly positive
indicates Graves
What can you give to help with the symptoms of hyperthyroidism?
Beta blockers to help with the heart palpitations
What is going on here?
34 y/o female
Hx of neck discomfort
Prodromal flu symptoms; No FHx of thyroid dysfunction
On examination: HR 98 bpm, no goitre, eyes- normal
TSH <0.05mU/L, f T4 54 pmol/l, TT3-2.7 nmol/l, TRAB<0.9 iU/L
It is hyperthyroidism due to symptoms such as flu like and high BPM plus high TSH and T4/T3.
However without family history, eye symptoms and low TRAb we can rule out Graves. And without any goitre we cna rule out nodules.
This leaves tempory thyroiditis.
What is initial treatment for thyroiditis 0-2 months?
What is the later treatment for thyroiditis 3-5 months?
We don’t want to give anti thyroid drugs as the thyroid is not overactive it is just releasing hormones due to damage.
Initially give beta blockers to help with the cardiac symptoms.
Later as the thyroid has released all it’s hormones you get a bounce back into hypothyroidism requiring levothyroxine.
What is initial treatment for hyperthyroidism due to graves or nodules?
Antithyroid drugs (ATDs) :
Carbimazole and propylthiouracil (PTU)
Both decrease production of thyroid hormone (block TPO enzyme)
Propranolol good for tremor and elevated HR
What are the two antithyroid hormone drugs?
Carbimazole (symptom of hyperthyroidism is high metabolism therefore eating lots but losing weight, “carb ma”)
Propylthiouracil (PTU) (remember because it has thyroid sounding like name)
What is indicated first carbmazole or propythiouracil?
Carbmazole is always given first as has less side effects.
And propythiouracil if not responsing to carbazole particularly before thyroid surgery to bring symptoms under control.
What is the form of thyroxine we give people to raise T4 levels?
Levothyroxine
What is a very dangerous side effect of carbmazole and propythiouracil?
Rare side effect of agranulocytosis ( less than 1/500).
Low WBCs and immune failure. Patients need to be monitered for this.
What is the long term treatment for hyperthyroidism due to graves or MNG?
What is the long term effect of this?
Radioactive Iodine to burn out the thyroid gland.
Surgery.
Both leave patients with perminant hypothyroidism.
Graves might respond to a treatment of ATDs. However MNG will always require radioactive iodine or surgery.
What is the risk of radioactive iodine over surgery?
You can’t have close contact with others during treatment. Therefore it is not suitable for poeple with younge children who won’t inderstand this.
Treatment of graves eye disease
Smoking cessation (smoking makes eye disease 9x more likely)
Topical lubricants
Selenium 200mcg daily (antioxidant)
Steroids
Consider other forms of immunosupression.
For long term damage might need decompression or surgery to repair.
Symptoms of primary hypothyroidism
- Tired
- Weight gain, puffy eyes and skin
- Feeling cold
- Slow heart rate
- Constipation
- Dry hair and skin
- Heavy periods (menorrhagia)
- Hyperlipidaemia
- (Enlarged thyroid = goitre)
Common causes of primary hypothyroidism
- Hashimoto’s thyroiditis:
Antibodies attack thyroid and make it underactive
Permanent
Tendency can run in families
- Iatrogenic (post surgery or radioactive iodine)
- Spontaneous atrophic
Iodine deficiency, however this is not common in the UK
Why do you get an enlarged thyroid in iodine deficiency?
Cannot manufacture enough
thyroid hormone without
iodine
TSH rises in response to fall
in T4
High TSH stimulates
hypertrophy (growth) of the
thyroid gland
What is the common dose of levothyroxine?
100mcg daily before breakfast.
This is normally enough to reach stable and normal levels of T4
Medications that counter levothyroxine absorption?
- Proton Pump Inhibitors eg omeprazole/lansoprazole
- H2 antagonists eg ranitidine
- Iron, calcium, aluminium, bile acid sequestrants
What is a TFT?
Thyroid function test
How does the blood test differ for subclinical hypothyroidism and primary hypothyroidism?
What is a non-thyroidal illness? How does a non thyroidal illness present? How can you tell it apart from a thyroid disorder?
When very sick circulating cytokines can surpress TSH release resulting in low TSH.
Hormone uptake by the liver is also reduced resulting in less T4 getting converted into T3.
The result is low TSH and high circultating free T4 mimiking hyperthyroidism. Except the syptoms will be that of hypothyroidism. Plus the other givaway will be low T3.
Why is hypothyroidism particularly bad during pregnancy?
T4 is essential for foetal neuro development.
T4 requirement in the mother can increase by 50%.
Results in premature births and nurological impairment.
Mothers should be given levothyoxine and TFTs should be done every trimester.
What investigation can confirm the nature of a toxic nodule?
Scintigraphy - usually use technetium
What is a carbimazole side effect?
Can cause agranulocytosis (low white blood cell count)
Symptoms include fever, sweats, chills, weakness, sore throat
You perform a technetium scan to distinguish between what is causing the hyperthyroidism and the result is diffusely increased uptake.
What is this indicative of?
Grave’s
How would the uptake of technecium vary between the different types of hyperthyroidism?
How can the combined contracepetive pill have an effect on total thyroid hormone levels?
What does this mean for thyroid hormone testing?
Oestrogen increases synthesis of TBG
Increased TBG - more bound, total T4/T3 seems normal but available free T3/T4 low therefore leading to hypothyroidism.
Thyroid hormone testing in someone who is on the combined contraceptive pill should always be free T4/T3. And in pregnancy.
What is the difference betweena toxic and cold nodule in the thyroid?
Cold - not productive
Toxic - productive
How do you distinguish between mallignant thyroid nodules?
- Follicular & papillary most common. Generally good prognosis
- Medullary carcinoma (C cells, calcitonin present in fine needle aspiration) less common
- Anaplastic carcinomas and lymphoma present as
rapidly enlarging thyroid mass.
Telltale sign of a thyroid medullary carcinoma?
Cells found ot be expressing calcitonin
Telltale sign of a thyroid nodule which is an anaplastic carcinoma or lymphoma
Anaplastic carcinomas and lymphoma present as rapidly enlarging thyroid mass
What does the term euthyroid mean?
Normal thyroid function.
E.g. Patient present with a lump in the thyroid, they are clincally euthyroid therefore the nodule isn’t toxic.
When would you expect to find high levels anti-TPO antibodies?
In Hashimoto’s
Can also appear in Grave’s however less significantly as the main antibody in grave’s is TRAbs
What is the result of extreme hypothyroidism
Myxedema
This is hypothyroidism with extreme swelling and scalely skin
What is the relationship between hyperthyroidism and hypocortisolism?
High levels of T4/T3 can lead to a faster metabolism which breaks down cortisol faster thus leading to hypocortisolism
