Thyroid function and dysfunction Flashcards
Where is the thyroid located?
The thyroid is a butterfly-shaped gland located at the base of the neck, just below the Adam’s apple
What is a goitre and a nodule?
A goiter is an enlargement of the thyroid, the H-shaped gland that wraps around the front of your windpipe, just below your Adam’s apple. A goiter can be smooth and uniformly enlarged, called diffuse goiter, or it can be caused by one or more nodules within the gland, called nodular goiter.
What is the cellular level arrangement of the thyroid?
- Thyroid is split into follicles filled with colloid- colloid is where the hormones are produced
- Lined with cuboidal thyroid epithelial cells
- In between cells are c cells which produce calcitonin
What two main hormones are produced by the thyroid?
Triiodothyronine (T3) and Tetraiodothyronine (T4)
How are thyroid hormones produced?
Iodine ions are trapped and moved into the colloid as iodine through the plasma membrane
Thyroid peroxidase and hydrogen peroxide catalyse the addition of iodine into a thyroglobulin protein skeleton
Tri= 3 iodine molecules, tetra= 4
-Enzymes breakdown the colloid and the hormone is then secreted out into the capillaries
What is Tetraiodothyronine also known as?
Thyroxine
Out of T3 and T4, which is the active hormone?
T3
T4 is the inactive form which can be converted to T3 quickly.
What is T3 and T4 bound to in the circulation?
Proteins, most common is thyroxine binding globulin, but also transthyretin and albumin
What percentage of T3 is produced directly from the thyroid gland?
20%
80% produced from peripheral conversion of T4 in liver, kidneys and muscle
How is the thyroid stimulated?
Pituitary produces a hormone called thyroid stimulating hormones which docks to the TSH receptor in the thyroid
What functions is the thyroid hormone involved in?
Growth development
Basal metabolic rate
Activating mental processes
Themogenesis in brown adipose tissuer
What are the symptoms of an overactive thyroid?
Hot, rapid heart rate, sweaty, fast bowel movements, nervous, irritable
What are the symptoms of an underactive thyroid?
Slow heart rate, cold, constipated, low moods and depression
What are the main causes of hyperthyroidism?
Graves disease (75%)
Toxic multinodular goitre
Toxic nodule
Thyroiditis
What is Graves disease?
An autoimmune disease where antibodies attack the thyroid to make it overactive
Can see a smoothly enlarged thyroid (goitre)
Can be associated with eye disease
What is toxic multi nodular goitre?
Toxic nodular goiter involves an enlarged thyroid gland. The gland contains areas that have increased in size and formed nodules. One or more of these nodules produce too much thyroid hormone.
Can you get signs of thyroid eye disease in toxic multi nodular goitre?
Can get eyelid lag or retention but no other features if thyroid eye disease
Does the TSH decrease as there is more toxic nodules on the thyroid?
Decreases- thyroid is producing too much hormone so feedback loops stop production of TSH
What is thyroiditis?
- Temporary overactivity of thyroid
- Can be triggered by pregnancy, infection or some drugs
- Sometimes followed by underactivity period
What are the symptoms of hyperthyroidism?
- Weight loss despite good appetite (often very hungry)
- Tiredness
- Tremor
- Hot, sweaty
- Palpitations
- Diarrhoea
- Light/absent menses (stool)
- Mood: irritable, anxiety
- Eyes (change in appearance, red, gritty, painful, double vision)
- Muscle weakness
On examination, what will you notice about patients with hyperthyroidism?
May have goitre or nodules, fast HR, agitated and talking fast, warm and sweaty, tremor and thyroid eye disease symptoms
What are the eye symptoms related to graves disease?
- redness
- gritty sensation
- dry/watery eyes
- pain on eye movement
- swelling around etes
- propotsis (pushed forward appearance of eyes)
- double vision
- loss of colour vision
What is the pathogenesis of thyroid eye disease?
- Problem initiates with beta cells producing TSH receptor antibodies, which bind to receptors in the thyroid and stimulate the production of T3 and T4
- T3 and T4 feedback and suppress TSH
- Antibodies will also dock with receptors in the recto-orbital tissue
- That causes adipocytes to produce fats and fibroblasts produce glycosaminoglycans which causes water retention and swelling
How do you diagnose Graves disease?
Blood tests- check levels of T3/T4
Check TRAbs (TSH receptor antibodies)
What is scintigraphy and how is it used to diagnose graves disease?
A procedure that produces pictures (scans) of structures inside the body, including areas where there are cancer cells
Can produce imagine of thyroid if TRAbs are negative to diagnose.
What happens if the thyroid gland does not show up on a scintigraphy scan?
May be thyroiditis- the gland has completely disappeared
What happens if the thyroid gland does not show up on a scintigraphy scan?
May be thyroiditis- the gland has completely disappeared
How can T3/T4 levels rise after thyroiditis?
Because gland has been damaged in infection (thyroiditis) and the pre-formed hormone has spilled out
After acute period, T3/4 levels will drop
What is the drug treatment for hyperthyroidism?
Antithyroid drugs such as carbimazole and propylthiouracil. It blocks the enzyme that catalyses the addiction of iodine to the protein sketeton
What medication may be used to help with symptoms of tremor and increased HR?
Propanolol, good for tremor and increased HR (contradicted in asthma though)
What are treatments for hyperthyroidism?
- Drugs
- Radioactive iodine
- Surgery
What are the complications with using radioactive iodine?
I- 131 leads to risk of long term hypothyroidism
Also have to restrict contact with children under 12 and pregnant women.
What are the risks with surgery to treat hyperthyroidism?
Risk of long term hypothyroidism or damage to recurrent laryngeal nerve
When is thyroid eye disease treated with steroids?
When the disease is active (redness, swelling, pain, change in visual function)
When the disease is inactive there may be severe damage left behind but does respond to steroids
What are treatment options for thyroid eye disease?
Steroids
Selenium 200mcg daily
Topical lubricants
Smoking cessation
If there do not work, additional immunosuppressant treatment and orbital radiotherapy
What are the symptoms of hypothyroidism?
- Tired
- Weight gain, puffy eyes and skin
- Feeling cold
- Slow heart rate
- Constipation
- Dry hair and skin
- Heavy periods (menorrhagia)
- Hyperlipidaemia
If a patient has normal thyroid function tests but the symptoms of hypothyroidism, should they be given thyroxin?
There is no evidence for it
What are the common causes of hypothyroidism?
Hashimoto’s thyroititis
Iatrogenic
Spontaneous atrophy of thyroid
Temporary thyroiditis e.g. viral or postpartum
What is Hashimoto’s thyroiditis?
Antibodies attack thyroid and make it underactive
It is permanent and runs in families
Why is iodine deficiency not a issue in the UK for hypothyroidism?
There is a iodine level screening test for babies in the UK
What is the manufactured version of thyroid hormone?
Levothyroxine
What are the tests for diagnosis of hypothyroidism?
If T4 is low and TSH is high, no further tests needed
What is the half life of levothyroxine?
7 days
When is levothyroxine best taken?
In the morning on an empty stomach
What medications can impair levothyroxine absorption?
Omeprazole and lansoprazole (proton pump inhibitors)
H2 antagonists (ranitidine)
Iron, calcium, aluminium (OTC medication)
What medications require an increased levothyroxine requirement?
Oestroegen or anticonvulsants
What is the first sign of hypothyroidism or sub-clinical hypothyroidism?
TSH is more sensitive than T4, so even if T4 levels are still within reference range, TSH will rise up outwit the normal range
What is the main cause of subclinical hypothyroidism?
Autoimmune chronic thyroiditis
What were the risk factors found for women for hypothyroidism in the Wickham study?
Raised TSH
Positive peroxidase antibodies
Both= much greater chance
What are the symptoms of primary, subclinical and secondary hypothyroidism?
What indicates non-thyroidal illness that is having an effect on the thyroid?
Low T3
Why can some non-thyroidal illness cause a rise in free T4 in early stage of illness?
Illness can effect thyroid hormone binding proteins which reduces total hormone but initially raises free hormone
Why does free T3 fall in non thyroidal illness?
There is an impaired T4 hepatic uptake and conversion to T3 during illness
What controls TSH release and how can it be suppressed?
Thyrotropin releasing hormone controls TSH release- it can be suppressed by cytosines and glucocorticoids (e.g. cortisol and stress hormone)
What causes suppression of TSH?
Dopamine
Suppressed TRH
Modified carbohydrate residues
Should thyroid function tests be performed on patients with chronic or acute illness?
No, unless thyroid disease is considered to be the cause of their presenting complaint
What test results will non-thyroidal illness produce?
Elevated free T4 levels, and suppressed TSH (similar to primary hyperthyroidism) but with low T3
When does the foetus require T4?
- The foetus needs thyroxin from about 4th or 5th week- important for CNS and development of foetus
- Foetus uses maternal T4 exclusively up to 10 weeks and partially thereafter.
What is untreated hypothyroidism associated with in pregnant women?
Infertility, miscarriage
Pre-eclampsia, Premature delivery
Increased foetal mortality, impaired neurological development
What is subclinical hypotension (untreated) associated with in pregnant women?
Neurodevelopmental delays, placental abruption
What happens when a hypothyroid women becomes pregnant?
The thyroxine dose needs to increase straight away
Why at the start of pregnancy can TSH levels drop and T3/4 levels rise?
- Early stage of pregnancy, HCG rises (hormone in pregnancy). HCG is structurally similar to TSH and mimics some functions of TSH.
- This is why there is low TSH levels- is suppressed and high FT4 and FT3 levels
- This is temporary and no thyroid drugs are needed.
What is HCG?
Human chorionic gonadotropin
Why do you only check free hormone levels of T3/4 in pregnancy?
In pregnancy, only check free hormone, not bound hormone as oestrogen can increase the number of proteins that the hormones can bind to
Why is it important to measure TRAb’s in pregnancy patients with Graves disease?
TRAbs can cross placenta and act on the fetal thyroid gland by 20 weeks to cause neonatal hyperthyroidism
Why is a thyroid uptake scan not necessary for all patients to make a diagnosis of hyperthyroidism?
If TRABs are positive scan is not needed?
What is the 131I-uptake test and scan used for?
Used to see what areas of the scan are producing iodine- different patterns for different causes of hyperthyroidism
How does carbimazole exert its antithyroid activity?
Inhibits T4/3 synthesis by inhibiting thyroid peroxidase
