Matthew (Thyroid disorders) Flashcards
Thyroid anatomy
Located at base of neck below Adams apple and above clavicle.
The thyroid gland is made up of the pyramidal lobe, right lobe, isthmus, left lobe. It has 2 parathyroid glands; superior and inferior.
Functions of the thyroid
Synthesis of thyroid hormones (T3 and T4) which have direct effects on body systems:
1) Cardiovascular- thyroid hormone increases heart rate and cardiac contractibility and therefore increases cardiac output
2) Metabolic- thyroid hormone increases mitochondrial activity in the cells and increases energy uptake. Uses energy from fats to patients may lose weight
3) Developmental- can influence growth rate which is why they are so important in foetal development and pregnancy
4) Other- affects levels of sleep, libido, mood, increased speed of though but less focused
Functions of parathyroid
Maintenance of serum calcium and phosphate levels through secretion of parathyroid hormone (PTH).
PTH increases blood calcium levels by directly stimulating bone cells to break down and release the calcium stored in them.
Also increases gastrointestinal calcium absorption by activating the vitamin D and promoted calcium conservation by
promoting calcium reabsorption in the kidneys.
Regulates serum phosphate in the kidneys by inhibiting proximal tubular reabsorption of phosphorus through activation of vitamin D.
Thyroid hormone synthesis
T3 and T4 are synthesised when diatary iodide ions are transported from the bloodstream into the follicle cell plasma and become oxidised in the cell.
Iodide turned to iodine which can cross into the colloid which is a space in the thyroid follicle cell that is the chief site of throyoid production. 1 or 2 iodine molecules
bind to thyroglobulin (monoiodithyronine (MIT) or diiodothyronine (DIT)).
These complexes dissociate back and covaneltly bond to each other to produce T3
or T4 e.g. a MIT and a DIT bond together to form a T3.
T3 and T4 are stored in the colloid until stimulated for release.
Thyroid hormones
- TSH comes from anterior pituitary gland and stimulates the release of T3 and T4.
- TSH is stimulated by release of TRH (thyrotropin releasing hormone) which is released from the hypothalamus.
- These hormones are released in response to a demand for increased metabolic rate e.g. going for a run. Does this through a positive/negative feedback loop. If thyroid hormone is used up there will be
lower circulating levels in the blood stream which is detected by the anterior pituitary and also in the hypothalamus which will produce TRH to produce TSH which causes more thyroid hormone to be released. - Ratio of T4 to T3 is 10:1. (90% is inactive T4, 9% is active T3, and 1% is rT3).
- Both T3 and T4 are highly protein bound. T3 is 99.8% protein bound and T4 is 99.9% bound. Binds to either thyroid binding globulin or transthyretin or albumin within the plasma.
rT3 is reverse T3.
Thyroid disorders introduction
Hypothyroidism (not enough)
- Primary hypothyroidism
- Overt
- Subclinical
- Secondary hypothyroidism
- Pituitary-hypothalamic dysfunction
- Peripheral hypothyroidism
Hyperthyroidism (too much)
- Thyroidal origin
- Pituitary disease
- Extrathyroidal origin
Hypothyroidism
- Most prevalent in countries where iodine deficiency is common- due to poor diet. e.g. lower socioeconomic economic countries.
- Only affects 1-2% of the UK population as we fortify our foods (add minerals/vitamins).
- 10x more common in women than men and more so in older women. Most common age is between 30-60 (mainly in latter end).
Primary hypothyroidism
- Accounts for 95% of cases.
- Can be subcategorised into overt or sub-clinical.
- Most commonly a result of autoimmune diseases, e.g. celiac, and the body attacks the thyroid destroying the thyroid follicle cells reducing its ability to make the thyroid hormone.
- Can also be due to iron deficiency or as a side effect of treatment (amiodarone or lithium) or surgery
Secondary hypothyroidism
- Arises from reduced thyroid stimulation due to dysfunction outside of the thyroid most commonly from the anterior pituitary or hypothalamus. May be problems with receptors on those glands.
- Can be caused by a variety of diseases- cancer is a common cause (pituitary adenomas causing dysfunction within that gland), infiltrative disorders e.g. amyloidosis,
can be medication induced.
Peripheral hypothyroidism
- Very rare. Where circulating levels of T3 and T4 and TSH are all fine but there is resistance in peripheral tissues. The tissue that the active T3 wants to act on doesn’t get the same response when it binds to the receptor. Sometimes patients aren’t able to convert T3 to T4 as well. Some neonates are born with their thyroid gland completely absent (called thyroid agenesis). Known as congenital hyperthyroidism.
Hypothyroidism signs and symptoms
- Brain fog- can affect memory and ability to think clearly
- Thinning hair-can cause you to lose hair on scalp, face and body
- Mental health issues- contribute to depression and sadness
- Peripheral neuropathy- can interfere with how the nerves send signals to and from your brain, spinal cord, and body
- Jaundice
- High blood pressure
- Goiter- abnormally enlarged thyroid gland
- Heart attack risk- may increase cholesterol levels and narrow arteries
- Slow metabolism- can lead to weight gain as glucose isn’t being used as readily so will be stored as fat
- Gallstones- hard pieces made up of cholesterol or bile that form in gallbladder
- Constipation- slowed movement of food through intestines
- Stomach bloating- slows movement of food through digestive tract
- Heartburn- slowed digestion can lead to heartburn
- Menstrual changes- irregular periods and heavier flow, can affect fertility making it harder to become pregnant
- Dry skin- can also cause thickening and scaling
- Weakness- can leave muscles weak, achy or stiff
Patients with secondary will have mainly the same symptoms as primary but may present with additional symptoms e.g. severe recurrent headaches, visual disturbances, or specific to anterior pituitary- erectile dysfunction and amenorrhoea and Cushings syndrome.
Congenital hypothyroidism is hard to diagnose as babies cannot communicate how they feel. Also symptoms such as not feeding or sleeping well are common anyway in newborns so can’t be taken as a symptom of hypothyroidism. They are screened by taking bloods for a variety of diseases including hypothyroidism (test for thyroid hormone).
Causes of hypothyroidism
- Autoimmune thyroiditis- main cause, autoimmune attack on thyroid
- Iodine deficiency- not common in UK but depends on diet
- Post thyroidectomy or radioactive iodine treatment- aim of this treatment is to damage thyroid and sometimes too much is damaged leading to hypothyroidism
- Drug induces
- Peripheral resistance to thyroid hormone
- congenital diseases e.g. thyroid agenesis
Diagnosis of hypothyroidism
1) Symptoms- diagnosis based on clinical presentation
2) Biochemical testing- Thyroid function tests (TSH and free T4 tested (‘free’ is tested as it is usually highly protein bound)). NICE guidelines say to test TSH first. If TSH is found to be in range then you can rule out hypothyroidism. If it is out of range then you need to do the additional free T4 test. In practise you just do both tests together. Ideally all the tests should be taken from the same sample.
Interpreting thyroid function tests
If the TSH level is raised and the FT4 result is low this suggests overt primary hypothyroidism. (High stimulation but still not producing enough hormone).
If the TSH level is slightly raised but the FT4 level is still within the normal reference range this is subclinical primary hypothyroidism.
If the TSH level is low and the FT4 result is low this is suggestive of secondary hypothyroidism arising from hypothalamic or pituitary dysfunction. (Problem with stimulation).
If the TSH, FT4, and FT3 levels are all within reference range then rarely we will test rT3 levels to ascertain peripheral T4 to T3 conversion. If rT3 result is low this is suggestive of peripheral hypothyroidism. (when rT3 is low the patient is not getting adequate conversion of T4 to T3)
Additional investigations
Thyroid antibodies testing (can be used to give a definitive answer to the cause but not needed):
- Thyroid Peroxidase Antibodies (TPOAb)
- Thyroglobulin Antibodies (TgAb)
- Thyroid stimulating hormone receptor antibodies (TSHRAb aka TRAb)
Glucorticoid deficiency (always have to test for this when doing additional investigational tests):
- Short synacthen test
Treatment of hypothyroidism
1st line= levothyroxine (T4) replacement
- Usual starting dose 1.6 micrograms per kg rounded to nearest 25 microgram dose
- Reduced starting dose of 25-50 microgram OD in patients >65 years or pre-existing CVD due to risks of over treatment.
- Congenital hypothyroidism- start at 10-15 microgram per kg for first 3 months of life (they need more as they are growing so much).
- Those with glucorticoid deficiency should be given replacement before starting thyroxine
Monitoring
Initially TFTs every 3 months until stable then annually.
Can take up to 6 months for TSH to normalise. Most adult patients will be stabilised on doses between 100 and 200 micrograms daily. (If patient go above this it is usually due to poor compliance)
Dose is titrated in steps of 25 micrograms until therapeutic effect achieved.
If TSH within normal limits and symptoms still present test FT4 to investigate for secondary hypothyroidism.
When monitoring secondary hypothyroidism only adjust dose dependant on FT4.
Poor adherence regimens or for those who can’t safely self medicate (i.e. those with learning difficulties) can have once weekly administrations e.g. 700 micrograms once a week.
Levothyroxine counselling
- Importance of compliance and effects of taking ‘treatment holidays’.
- Long life need regardless of ‘feeling well’
- How to take - 30-60 minutes before food or other medication so usually easiest taken in the morning on waking - allows it to go through GI system and start to be absorbed before anything else is there
- Interactions
- Food (e.g. milk/calcium)
- Drugs (e.g. calcium supplements, oral iron, or PPIs, growth hormone can increase thyroid metabolism requiring higher doses of T4)
- Disease (e.g. IBD, coeliac- might not absorb it as well)
- Monitoring requirements- blood tests, free prescriptions
- Pregnancy and breastfeeding advice if applicable- safe to breastfeed but in pregnancy thyroid disorder can be dangerous due to the need for correct hormone levels for foetal growth
- Side effects- flushing, restlessness, palpitations, insomnia, angina, thyroid crisis
Liothyronine
- Synthetic form of T3 .
- Similar pharmacological action to Levothyroxine but is 5x more potent- rapid onset of action because it is freely ready to act rather than levothyroxine which still needs to be converted in the body.
- Not recommended due to lack of clinical evidence
- Specialist services underwent work to actively switch all on liothyronine to levothyroxine- patient don’t like to switch as it made them feel unwell
- Only now rarely used in treatment of myxoedema coma, a severe complication of hypothyroidism, due to more rapid onset of action
Pregnancy
- Uncontrolled hypothyroidism can impair fertility.
- Insufficient thyroid hormone can have teratogenic effects as essential fro growth and even lead to miscarriage.
- Patients with confirmed thyroid disease planning. pregnancy will need to consult with their GP/specialist and have frequent TSH level monitoring.
- Once pregnant they should increase their levothyroxine dose by 25-50 micrograms immediately and have their TSH checked.
- TSH monitored every 4-6 weeks during the pregnancy. Target TSH level of <2.5mU/L in 1st trimester and <3.0mU/L in 3rd trimester.
- 2-4 weeks post birth TSH level should be rechecked and most patients can return to their previously stable dose.
Levothyroxine is safe in breastfeeding and patients should be supported with this should they wish
Myxoedema crisis
Extreme manifestation of hypothyroid.
Rare but potentially fatal.
Requires IV treatment
Symptoms are that of hypothyroidism but more exaggerated:
- Hypothermia
- Macroglossia (swollen tongue)
- Ptosis (upper eyelid droop)
- Periorbital swelling
- Puffy face
Precipitated by
- Stress
- Infection
- Trauma
- Drugs e.g. beta blockers
Hyperthyroidism
When disproportionally high quantities of thyroid hormone are produced.
Lead to infestations of hypermetabolic diseases.
10x more prevalant in women than males. Occurs in ages of 30-50.
0.5-2% of women in UK are affected where as only 0.2% of men are.
Incidence does not increase with advancing age.
Hyperthyroidism signs and symptoms
- Reduced focus- erratic thoughts, can’t stay focused on a single task, too much stimulation so jump from one to ask to another
- Mental health issues- can contribute to mood swings causing anxiety, irritability and a nervous disposition
- Brittle hair and hair loss
- Eyelid retraction- gives a widened eye appearance, occurs due to muscle inflammation from autoimmune inflammation
- Bulging eyes- muscle and fatty tissue around eyes is attacked making them appear swollen
- Insomnia- due to increased metabolic rate and energy consumption patients can struggle to get good quality sleep
- Enlarged thyroid or loiter
- Irregular heart rhythm- over stimulated cardiac rate and output leading to palpitations, tachycardia and arrhythmias
- Weight loss- increased metabolic weight leads to vast energy consumption
- Diarrhoea- food goes through GI tract too quickly
- Nausea and vomiting- parasympathetic nervous system is unregulated so stomach churning when it doesn’t need to be, leads to nausea
- Decreased appetite
- Irregular menstruation- can cause amenorrhoea leading to fertility issues
- Muscle weakness- occurs as a result of muscle breakdown and ketosis for additional energy to feed the increased metabolic rate
- Sweating- increased metabolic rate leads to excessive heat production and hyperhidrosis
Hyperthyroidism diseases
Graves’ disease- most common, accounts for 70-80% of hyperthyroidism cases, an autoimmune condition.
Thyroid nodular disease- second most common, specific physical problem with certain part of the thyroid, tens to get gaiters or enlargement.
Thyroiditis- inflammation of thyroid- can be autoimmune mediated, while it is inflamed thyroid hormone will leak from the follicles which causes a transient rise in thyroid hormones for a short period of time. Can turn into hypothyroidism
Pituitary disease- overstimulation, very rare
