Thyroid conditions (Hypo and Hyperthyroidism) Flashcards
What is the most likely cause of hyperthyroidism?
Graves disease
What is some background information of Graves disease? (age at diagnosis, prevalence, m : f ratio)
Normally patients are diagnosed between the ages of 30-60 years
Females are 10x more likely to have Graves disease than men and the prevalence is
20 in 1000 females and 2 in 1000 men
What type of condition is Graves disease?
It is an autoimmune condition where thyroid stimulating antibodies are produced which closely mimics thyroid stimulating hormone which acts on the thyroid stimulating receptor in the thyroid gland, over stimulating it.
What are some of the clinical presentations of Graves disease?
It increases the metabolic rate and therefore Leads to weight loss
Increased appetite
Palpitations
Sweating
Tremor
Anxiety
Diarrhea
Can’t tolerate heat
Tachycardia
Fatigue
Sexual dysfunction
What are the most distinguishable features of Graves Disease?
Exopthalamus (bulging of the eye) which causes further eye complications such as swelling of the eyelids and double vision.
Diffuse goitre with no nodules
Pretibal myxoedema
Which diagnostic tests are used to confirm Graves disease?
Blood tests
Radioactive iodine uptake
Thyroid scan
Doppler blood flow measurement
How are blood tests used to confirm Graves disease?
Can detect thyroid stimulating antibodies or immunoglobulin, and you would expect low TSH and high free T4 and T3 (above the reference range).
What is the normal reference range for T3, T4 and TSH?
T3: (4 - 7.8 pmol/L)
T4: (10 - 24 pmol/L)
TSH: (0.4 - 4.5 microunits/mL)
Describe some of the other possible causes of hyperthyroidism?
Toxic nodular goitre
Thyroid adenomas
What is toxic nodular goitre?
It is the enlargement of the thyroid gland in which contains small round masses or nodules throughout. The enlarged thyroid gland over-secretes the thyroid hormone (T4 and T3) and these nodules act independently from the normal feedback cycle.
What are thyroid adenomas?
Overgrowth of the thyroid tissue (benign tissue) that also over secretes the thyroid hormone.
What is toxic nodular goitre also known as?
Plummer’s disease
What results would you expect of TSH levels, T4 and T3 levels following a routine blood test if there was suspicion of hyperthyroidism?
You would expect:
High T4 and T3 levels (above 10-24 pmol/L and 4-7.8 pmol/L)
Low TSH levels (below 0.4-4.5 uIU/mL)/
Explain the clinical results of TSH, T4 and T3 levels in hyperthyroidism?
In all three clinical examples there has been hyper-secretion of the thyroid hormones (either due to thyroid stimulating antibodies or benign tumours or nodules on the thyroid gland) contributing to high levels of T4 and T3 which then induces a negative feedback cycle resulting in low levels of TSH.
Explain the difference in pathology between primary and secondary hyperthyroidism.
Primary hyperthyroidism is when there is a defect in the thyroid gland itself which causes the over-production of the thyroid hormones (T4 and T3).
Secondary hyperthyroidism is when there is a defect in the hypothylamus or anterior pituitary gland which over secretes thyroid stimulating hormone which then contributes to the high thyroid output.
What is pretibal myxoedmea and when does it occur?
It is a dermological condition caused by deposition of mucin under the skin contributing to a waxy appearance.
The condition is specific to Graves disease and is caused by a reaction of the tissue under the skin with TSH receptor antibodies.
Which demographic would you more likely expect to see with toxic multinodular goitre?
Over 50s
What is the first line treatment of benign thyroid adenomas?
Depending how many adenomas are present but most likely surgery
What are some of the clinical presentations of De Quervain’s thyroiditis?
Painful swelling of the thyroid gland
High temperature
Pain in the neck, jaw or ear
How would you expect the TSH, T4, T3 levels to change with a patient with De Quervain’s thyroiditis?
The first phase is known as the hyperthyroid phase therefore you would expect high levels of T4 and T3 but low levels of TSH.
The second phase is the hypothyroid phase caused by the negative feedback following the hyperthyroid phase so you would expect low levels of T4 and T3 but high levels most likely of TSH.
How long does each phase of De Quervain’s thyroiditis last?
Hyperthyroidism phase (and the symptoms associated with it) lasts a couple of days whereas hypothyroidism (and symptoms) phase can last weeks to months.
What treatment is usually prescribed for De Quervain’s thyroiditis?
NSAIDS for symptomatic relief and possibly beta blockers to help with symptoms associated with hyperthyroidism (palpitations, anxiety, tremor)
What are some of the clinical presentations of thyrotoxic crisis?
Pyrexia
Tachycardia
Delerium
Which demographic would be most likely to experience De Quervain’s thyroiditis?
Women aged 20-50 years
What causes a thyrotoxic crisis to occur?
Normally due to underlying Graves’ disease or toxic multinodular goitre where there is a sudden onset of hyperthyroidism.
What are some of the clinical presentations of a thyrotoxic crisis?
Hyperpyrexia (over 41 degrees)
Heart rate over 140bpm (with or without other arrhythmias or atrial fibrillation)
Nausea
Vomitting
Diarrhoea
Abdominal pain
Confusion
Delirium
Seizures
Coma
When does thyroid storm most likely occur?
In a patient with underlying thyroid conditions in addition to intercurrent illness, trauma or emergency surgery
What does the management of thyroid storm involve?
Fluid resuscitation
Anti-arrhythmias
B-blockers (5mg IV propanolol)
What is the first line treatment for hyperthyroidism in Graves disease?
Anti-thyroid drugs: more specifically Carbimazole
When is normal thyroid levels achieved with Carbimazole?
After 4-12 weeks and then a maintenance dose is introduced.
What are the two options regarding when deciding a maintenance dose of Carbimazole?
Either titrated to maintain normal levels (Titration block) or
Titrated in which all the thyroid hormone is blocked and then replaced with Levothyroxine and is adjusted according to symptoms (block and replace).
How often would you monitor a patient on anti-thyroid medication?
Every 6 weeks until their thyroid hormone levels are within the normal range and then every 3 months.
When does a patient with hyperthyroidism reach remission?
Normally 12 to 18 months of Carbimazole treatment
What is a serious side effect of the second line treatment of hyperthyroidism?
Propyluracil can cause severe hepatic impairment and potentially death
Explain the principle of radioactive iodine therapy?
It is taken orally by the patient and the localised radioactive iodine releases radiation which destroys a portion of the thyroid gland and thyroid secreting cells resulting in a reduced secretion of thyroid hormones.
What is a disadvantage of radioactive iodine therapy?
Remission takes six months
Can overshoot and result in hypothyroidism requiring the needs of levothyroxine
Can’t be pregnant or get pregnant for six months
Can’t be around young children or pregnant women for 3 weeks
Limit contact with anybody for up to 3 days afterwards
Explain the purpose of Beta blocker therapy in those with hyperthyroidism?
Blocks the adrenaline produced side effects such as tachycardia, tremor, anxiety and sweating.
Which beta blocker is usually prescribed in the treatment of hyperthyroidism and why?
Propanolol as it is a non-selective beta blocker and will act on the beta-1, beta-2 and low affinity for beta-3 and therefore reduce symptoms such as tremor, tachycardia etc.
However an additional benefit of propanolol is that it inhibit the peripheral conversion of T4 to the more biologically active hormone, T3.
In which other clinical conditions would propanolol be contra-indicated?
Use with caution in patients who also have diabetes especially those who experience hypoglycaemia (propranolol blocks the adrenegically mediated symptoms of a hypo).
Also those with asthma who are taking Beta-2 agonists.
What would be a suitable alternative when propranolol is contra-indicated in hyperthyroidism?
Diltiazem
What is a disadvantage of surgery for treating hyperthyroidism?
Patient will require levothyroxine for life
Hyperthyroidism can reoccur or hypoparathyroidism.
What is the mechanism of Carbimazole and Propylthiouracil?
They inhibit thyroperoxidase which hence prevents the iodination of thyrosines and hence preventing synthesis of the thyroid hormone.
What is an additional mechanism of Propylthiouracil?
Inhibits T4 to T3 conversion
What are some of the side effects of thioureylenes?
Rashes (in 5% of patients)
Agranulocytosis (in 3% of patients)
What is a crucial counselling point if a patient is on Carbimazole or Propylthiouracil (thioureylenes)?
Patients need to report to their GP if they experience any of the following side effects due to risk of agranulocytosis:
Sore throat
Mouth ulcers
Fever
Malaise
Bruising or bleeding
Patient also needs to be aware of how to recognize signs of liver disorder such as:
Persistent nausea, vomitting
Malaise
Jaundice
They should discontinue medication immediately and report to their GP.
What happens in agranulocytosis?
Depletes neutrophils leading to increased susceptibility of bacterial infections
Depletes red blood cells leading to increased risk of bleeding
When does the maximum effect of radiotherapy iodine occur?
After 4 months of treatment
When is high doses of iodine given?
When preparing for surgery or during a thyroid storm
When is the effect of Lugol’s iodine felt the most?
Symptoms subside after 1-2 days and then the maximum effect is felt 10-15 days and then effect decreases
Which drug can induce thyroid dysfunction?
Amiodarone (used for cardiac arrthymias) can induce either hypo or hyperthyroidism
Which monitoring parameters would you assess before prescribing amiodarone?
Baseline TFTs before prescribing and then at every six months of taking the medication.
When are people most likely to be diagnosed with hypothyroidism?
Between the age of 30-60 years and women are 10x more likely to have hypothyroidism than men.
What is the most common causes of hypothyroidism in the developed world?
Hashimoto’s thyroiditis
What is Hashimoto’s thyroiditis?
It is an auto-immune disease in which the body produces anti thyroid perioxidase antibodies or anti thyroglobulin antibodies against thyroglobulin (essential for the synthesis of T4 and T3.
Aside from Hashimoto’s thyroiditis what are the other causes of primary hypothyroidism?
Due to lack of dietary iodine, quite common in the developing world
or drug induced (amiodarone)
What are some of the clinical presentations of Hashimoto’s thyroiditis and hypothyrodism in general?
Mainly goitre and then when hypothyroidism sets in, there are many clinical presentations such as:
Tiredness
Muscle weakness
Slow speech
Dry skin
Constipation
Bradycardia
Cold intolerance
Depression
Weight gain
Sparse thin hair
Fluid retention
Amenerrhoea
What is the main symptom of hypothyroidism in children?
Growth failure
Describe the difference between primary, secondary and tertiary hypothyroidism?
Primary hypothyroidism occurs when there is a defect with the thyroid gland and hence insufficient thyroid hormone is secreted (e.g Hashimoto’s syndrome in children)
Secondary hypothyroidism is caused due to a defect with the anterior pituitary which means it can no longer produce sufficient levels of TSH (due to a pituitary tumour).
Tertiary hypothyroidism is caused by a defect with the hypothylamus and secretes low levels of TRH/
Geographically, in the world where is hypothyroidism due to iodine deficiency most likely to occur?
Hypothyroidism due to iodine deficiency is most likely to occur in developing countries inland with no access to the sea. In these countries there would be little incorporation of fish into their diet, which is one of the richest sources of iodine (specifically shellfish). Closer to the sea there is also richer iodine in soil.
Apart from shellfish which other foods have high levels of iodine?
Dairy
Eggs
Some fruits such as strawberries, cranberries and pineapple
Fish in general (seaweed)
When does congenital myxoedema occur?
During pre-natal development
What is congenital myxoedema and what are some of the clinical presentations in infancy?
A severe thyroid condition which occurs in infancy and some of the clinical presentations include difficulties feeding, sleeping, constipation and jaundice.
Are babies tested for hypothyroidism?
Yes in the UK all babies are tested soon after birth by taking blood from a heel prick test. If there is a suspicion of hypothyroidism, then additional tests will be conducted such as a scan of the neck to confirm the presence of the thyroid gland.
What are some of the clinical presentations of severe congenital hypothyroidism in childhood?
Growth failure
Intellectual disability
Dystrophy of the bones
Low basal metabolism
What is myxoedema coma and when does it occur?
It is a rare, life-threatening condition due to severe, untreated hypothyroidism. It is when the mechanisms the body has adapted to using to compensate for low T4 and T3 levels fail to maintain homeostasis and become overwhelmed by hypothermia, infection or other precipitating factors.
What are some of the clinical presentations of myxoedema coma?
Usually begin to present with some of the usual symptoms of hypothyroidism (dry skin, weight gain, thin sparse hair etc).
May have cognitive decline (memory loss, confusion, low mood).
They have a core body temperature of below 35.5 degrees
Normally hypotensive and bradycardic
Hypoxia and Hypercapnia
What would you expect the lab results to be in a patient with hypothyroidism?
You would expect:
Low T4 and T3 levels (below 10-24 pmol/L and 4-7.8 pmol/L)
High TSH levels (above 0.4-4.5 uIU/mL)/
Explain the TSH, T4 and T3 levels in a patient with hypothyroidism?
As insufficient T4 and T3 levels are produced from the thyroid gland so there is no negative feedback loop acting on the anterior pituitary so it continues to produce high concentrations of TSH to try and stimulate the thyroid gland.
Which treatments for hyperthyroidism can induce hypothyroidism?
Carbimazole
Prophylthiouracil
Radioactive iodine
Thyroid surgery
What is hypopituitism?
When the pituitary gland fails to secrete TSH and therefore insufficient levels fail to stimulate sufficient T4 and T3 from the thyroid gland.
What are some of the causes of hypopituitism?
Pituitary adenomas
Infections
Vascular (Sheehan’s syndrome, significant blood loss following childbirth)
Radiation
How do levels of TSH, T4 and T3 differ for secondary hypothyroidism and why?
You would expect:
Low T4 and T3 levels (below 10-24 pmol/L and 4-7.8 pmol/L)
Low TSH levels (below 0.4-4.5 uIU/mL)
As the anterior pituitary is failing to produce sufficient TSH, there is lack of stimulation on the thyroid gland and hence low levels of T4 and T3 are produced.
What is the first line treatment and starting dose for hypothyroidism?
Oral Levothyroxine
Starting dose: 50-100mcg to be taken in the morning on an empty stomach
25mcg for elderly
How does levothyroxine work?
It is synthetic T4 which is metabolised to T3 (more biologically active) in the liver and kidney.
T3 stimulates protein synthesis and energy metabolism
How regularly do you monitor TSH levels for a patient taking oral levothyroxine?
It can take up to 6 months for TSH levels to remain in the reference range and therefore you would usually measure TSH levels every 2-3 months after beginning.
How would you titrate the dose of levothyroxine according to TSH levels?
If the TSH levels are too high, the dose of levothyroxine is too low and therefore increase the dose by 25-50 mcg.
If the TSH levels are too low, the dose is too high and therefore reduce the dose by 25-50mcg.
What is the usual maintenance dose of levothyroxine?
100-150 mcg
When is Liothyronine used and why?
It is used during a hypothyroid crisis as it is synthetic T3 and is therefore more rapidly acting than levothyroxine as it does not have to be metabolised first.
What additional testing is required for Liothyronine?
Blood levels of TFTS to ensure hyperthyroidism does not occur.
Aside from Levothyroxine and Liothyronine what additional drug can be used in the treatment of hypothyroidism?
Iodine, specifically used in iodine deficiency.
Describe the anatomy of the thyroid gland.
It is a small butterfly shaped gland in the neck in front of the larynx (voice box) and is highly vascular, transporting synthesised hormones to their target organs and glands.
What are the two hormones produced by the thyroid gland?
Thyroid hormone- thyroxine (T4) and tri-iodothyronine (T3)
Calcitonin- regulates calcium metabolism
What are some of the functions of T4 and T3?
T4 is metabolised into the more biologically potent T3, which has many functions including when it is produced:
It increases the basal metabolic rate
Increases heat production
Influences synthesis and degradation of major fuels in the body
Increases response to catecholamines
Stimulates growth hormone and IGF-1 secretion
Activity of the CNS
What is the structural and functional unit of the thyroid gland?
Thyroid follicles which are comprised of follicular (epithelial cells).
Describe the thyroid hormone release cycle starting from the hypothalamus.
In the hypothalamus the paraventricular nucleus (neurons) secretes thryrotropin releasing hormone (TRH). The TRH then stimulates tyrotropes in the anterior pituitary, which then pump out thyroid stimulating hormone (TSH). TSH then circulates in the blood and acts on the receptor on the outside of thyroid cell. The G stimulatory protein becomes bound to GDP and then binds to adenylyl cyclase, triggering the cAMP signalling pathway. Protein kinase A phosphorylates a transcription factor which then promotes genes for hormone synthesis.
How is T4 converted to T3?
Both T4 and T3 are synthesised by iodination of tyrosine.
T4 contains four iodines whereas T3 only has three. Therefore T4 is converted to T3 by de-iodinases in tissues.
What is the thyroid hormone transporter and why is it required?
Thyroxine binding globulin and it is required due to the hydrophobic nature of the hormone.
What two proteins does thyroid hormone bind to?
Albumin and transthyretin
What is the function of thyroglobulin in the synthesis of the thyroid hormone?
Thyroglobulin is produced as a downstream product of the cAMP. Thyroglobulin contains tyrosine amino acids in its peptide chain. Iodine then attaches to the tyrosine residue of the thyroglobulin.
How is iodide converted to iodine?
Oxidised into the iodine by thyroid peroxidase.
How are iodide ions transported into the follicular cells?
There are low concentrations of iodide ions in the blood but high concentrations within the cell. Therefore iodide has to be transported against its concentration gradient by a Na+I- co-transporter. Sodium moves down its concentration gradient into the cell and brings iodide with it. It is an example of secondary active transport.
How is T4 synthesised?
By fusion of two di-iodotyrosine molecules (overall four iodine molecules)
How is T3 synthesised?
By fusion of one mono-iodotyrosine and one di-iodotyrosine (overall three iodine molecules).
How do plasma iodine levels control the synthesis of thyroid hormone?
Increase in iodine uptake, increases T3 and T4 synthesis and decreases thyroid stimulating hormone.
Decrease in iodine uptake, decreases T3 and T4 synthesis and increases thyroid stimulating hormone.
What are the four T3 receptors?
Alpha 1
Alpha 2
Beta 1
Beta 2
When one of the T3 receptors are activated what are some of the downstream signalling effects?
Alters stimulation in genes responsible for the control of metabolic activity.
This results in an increase in:
O2 consumption
Body temperature
Cardiac output
Breakdown of energy stores
Aside from thyroid hormones what other hormones affect metabolism?
Insulin and Catecholamines
What are the average ages of developing thyroid cancer?
More prevalent in women than men and occurs at a younger age in women (35-39) whereas men the average age is 70.
What is the survival rate of thyroid cancer?
85%
What is the most common type of thyroid cancer?
Papillary thyroid cancer (90% of all cases).
Where can papillary and follicular thyroid cancer spread to?
Papillary cancer can spread to the lymph nodes in the neck or surrounding tissue.
Follicular thyroid cancer can spread to the lungs or bones.
How does the demographic diagnosed with thyroid cancer differ between papillary and follicular and Hurthle cell thyroid cancer?
Papillary tends to be younger whereas follicular occurs in middle aged and Hurthle cell tends to be older women.
Are Hürthle cell tumours benign or malignant ?
They can be either
What is the most serious type of thyroid cancer?
Anaplastic thyroid cancer which is a very aggressive form of cancer and is highly likely to metasises. Tends to be diagnosed in older women.
Describe medullary thyroid cancer.
It is a rare type of thyroid cancer originating from C-cells and about 25% of cases are inherited by a faulty gene.
What are some risk factors of thyroid cancer?
Females are more likely than males
Exposure to high levels of radiation
Benign thyroid disease
Being overweight
First generation relative
Inherited faulty genes
What was given to citizens in nearby countries following the Chernobyl disaster?
They given potassium iodide tablets which floods the thyroid with iodine and prevents the radioactive iodine from being absorbed (6-12 hrs before exposure).
What are some of the main symptoms of thyroid cancer?
Lump in the neck
Hoarse voice
Sore throat
Difficulty swallowing
What treatment is usually given for thyroid cancer?
Surgery
Radioactive iodine
Chemotherapy
Targeted chemotherapy (when above options have not worked)
Which chemotherapeutic are usually given for thyroid cancer?
Doxorubicin or Cisplatin
What do targeted chemotherapies for thyroid cancer target?
The vascular endothelial growth factor receptor pathway and other growth factor pathways as the thyroid is vascular rich
Give some examples of targeted chemotherapies and their therapeutic targets?
Vandetanib – inhibits VEGFR2 and EGFR and is used in the treatment of medullary thyroid cancer
Cabozantinib – inhibts c-Met and VEGFR2, also used in the treatment of medullary thyroid cancer
Lenvatinib – inhibits VEGFR and FGFR used to treat papillary and follicular thyroid cancer
