Week 3 Flashcards
What is the functional unit of thyroid gland
Follicle
Describe the structure of a thyroid follicle
Follicular cells arranged into a sphere shape.
Colloid in the centre lumen
Parafollicular cells (C cell) between follicles
Highly vascularised
What is colloid rich of
Thyroglobulin
What type of epithelial cells are follicular cells
Cuboidal cells
Describe the Hypothalamus-pituitary-thyroid axis
- Paraventricular nucleus of hypothalamus stimulated, releases TRH into hypophyseal portal system
- TRH travels to the anterior pituitary gland which stimulates the release of TSH
- TSH travels to thyroid gland through bloodstream and stimulates the synthesis and release of T3 and T4
- T3 and T4 hormones exhibit negative feedback which inhibits the release of TRH and TSH
Which part of the thyroid gland is covering the second tracheal ring
Isthmus
What structures are visible at the posterior aspect of the thyroid gland
Parathyroid glands
What would the TSH/TRH levels be in a hyperactive thyroid gland
Low due to high levels of T3 and T4
What substance is required for the synthesis of thyroid hormones
Iodine
Describe the movement of the thyroid gland from back of the tongue to its current position in an embryo
- Begins at 4th week of embryogenesis. Midline thickening at the back of the tongue
- Moves downwards, eventually reaching in front of the tracheal rings
- becomes in contact with the parathyroid glands which had developed in the area
- The residue of the thyroid gland at the back of the tongue becomes foramen caecum
Describe the development of the thyroid gland
- Endodermal thickening
- migrates downwards to form thyroglossal duct
- the 2 lobes of thyroid gland and the isthmus develop from the thyroglossal duct
- Thyroglossal duct is degraded in most people but not all
- the remnant of thyroglossal duct = pyramidal lobe
When will primitive follicles of the thyroid gland become visible and start trapping iodine
By 12 weeks
Which condition are people at risk of due to thyroglossal duct not disintegrating
Thyroglossal cysts
Where are thyroglossal cysts mostly found
Near the hyoid bone
Where to palpate the thyroid gland
- starting from the chin and moving downwards, palpate the midline
- palpate the first hard structure: thyroid cartilage
- palpate the second hard structure: cricoid cartilage
- move downwards to palpate the first.2 tracheal rings
- the isthmus overlies the second tracheal ring
- go laterally and medially around and upwards
Nerve supply of the thyroid gland
Sympathetic nerve supply: superior, medial, inferior sympathetic trunk
Parasympathetic nerve supply: Vagus nerve
Arterial supply of the thyroid gland
Superior and inferior thyroid arteries
Venous drainage of the thyroid gland
Superior and middle thyroid veins drain into the internal jugular vein
Inferior thyroid vein drains into the brachiocephalic vein
Which ligament is the primary fixation of the thyroid gland to its surrounding structures
Posterior suspensory ligament (Berry ligament)
What nerve is behind the posterior suspensory ligament
Recurrent laryngeal nerve
What structures are innervated by the recurrent laryngeal nerve
All Intrinsic muscles of the larynx except the cricothyroid muscles
Name the intrinsic muscles of the larynx innervated by the RLN
Thyroarytenoid muscle
Posterior cricoarytenoid muscle
Lateral cricoarytenoid muscle
Transverse and oblique cricoarytenoid muscles
Which nerve innervates the cricothyroid muscle
Superior laryngeal nerve - a branch of vagus nerve
Function of the cricothyroid muscle
Stretches and tenses the vocal cords to make forceful voice
Changes tone of voice
Function of the thyroarytenoid muscle
Relax the vocal cords to make softer voice
Function of the posterior cricoarytenoid muscle
Sole muscle that abducts the vocal cords hence opening the rima glottidis
Function of the lateral cricoarytenoid muscle
Major muscle that adducts the vocal cords hence narrowing the rima glottides
Function of the transverse and oblique cricoarytenoid muscles
Adducts the arytenoid cartilage to narrow the laryngeal inlet
Consequence of damage to recurrent laryngeal nerve after thyroidectomy
Hoarseness of voice
Loss of voice
Change in pitch
Dyspnea
Dysphagia
Why can dyspnea occur due to RLN damage
Because it can cause the paralysis of posterior cricoarytenoid muscle which is the only muscle that can abduct the vocal cords to open the rima glottidis
What is thyroglobulin rich of
tyrosine amino acids
Steps of thyroid hormone synthesis
- Thyroglobulin synthesised by follicular cells
- uptake and concentration of iodide into the colloid
- Iodide moves into follicular cells
- Oxidation of 2 iodide ions into iodine in the follicular cells
- Iodine passed into the colloid
- iodination of thyroglobulin
Describe the iodination of thyroglobulin to form T3 and T4
- Peroxidase enzyme in colloid links iodine to tyrosine amino acids in thyroglobulin
- Forms 2 intermediaries: tyrosine + 1 iodine and tyrosine + 2 iodine
T3 is formed by those 2 intermediaries joining together
T4 is formed by linkage of 2 tyrosine + 2 iodine
Where is thyroglobulin stored in till it is needed
Colloid
Which thyroid hormone is more potent
T3
Which drugs are used to treat hyperthyroidism
Carbimazole
Propylthiouracil
Mechanism of action of carbimazole
Inhibits thyroid peroxidase enzymes which are required for iodination of thyroglobulin
Which thyroid hormone makes up 90% of the thyroid hormones secreted
T4
Which thyroid hormone is biologically active
T3
Why does T4 need to be converted to T3
To become metabolically active
Which organs are responsible for the conversion of T4 into T3
Liver and kidney
How are thyroid hormones transported to target cells
Bound to serum proteins
What are the serum proteins that thyroid hormones can bind to
Thyroxine binding globulin
TTR (transthyretine)
Thyroxine binding pre-albumin
Albumin
Are most thyroid hormones unbound or bound to serum proteins
Bound to serum proteins
Only 0.015% of total T4 are free T4
Only 0.33% of total T3 are free T3
Bound / unbound thyroid hormones can enter the cells
Unbound
Why does T3 have a more rapid onset and offset of actions
Because it is bound less strongly by TBG (thyroxine binding globulin) than T4 and it is not bound significantly by TTR (transthyretin; transports thyroxine and vitamin A aka retinol)
Which, unbound or bound thyroid hormone concentration, correlates more closely to the metabolic state
Unbound
Effects of thyroid hormones
Increase metabolic rate
Increase in gluconeogenesis and glycogenolysis
Increase in lipolysis
Increase in respiratory rate and heart rate
Growth and development
Why does thyroid hormones cause an increase in gluconeogenesis and glycogenolysis
To increase the amount of glucose available for respiration; since increase in metabolic rate = increase in respiration = increase in glucose substrate needed
Why does thyroid hormone cause an increase in respiratory and heart rate
To meet the increase in demand of O2 due to the increase in metabolic rate
Thyroid hormones metabolic effects
Increases metabolic rate and thermogenesis
Increase blood glucose
Increase lipolysis
Increase FFA oxidation
Increase in protein synthesis
Why do thyroid hormones have effects on growth and development
Because the GHRH (growth hormone releasing hormone) and GH requires presence of thyroid hormone for activity
What can occur if a child has hypothyroidism
Growth retardation
What happens to the development of CNS in the child if the mother has hypothyroidism
The baby can have slower congnitive and intellectual functions
What enzymes are responsible in degrading t3 and T4
D1, D2, D3
Where is D3 found
Fetal tissue
placenta
Brain except pituitary
Which thyroid degrading enzyme is found in the pituitary
D2
Majority of T3 and T4 are degraded by which enzyme
D3
Causes of hypothyroidism
Primary thyroid gland failure
Secondary to TRH or TSH deficiency
Lack of iodine in diet
What is goitre
Enlargement of the thyroid
Symptoms and signs of hypothyroidism
Weight gain (due to decrease in BMR)
Slow heart rate
Fatigue
Cold intolerance
Goitre
Constipation
Dry hair
Brittle nails
Vitiligo
Mneumonic for symptoms of hypothyroidism (MOM’S SO TIRED)
Memory loss
Obesity (weight gain)
Menorrhagia
Slowness mentally and physically
Skin and hair dryness
Onset is gradual
Tiredness
Intolerance to cold
Raised BP
Enlarged thyroid gland
Depression
What can occur in babies due to hypothyroidism
Dwarfism
Intellectual defects
Slow growth and development (reach milestones later or not at all)
What is Grave’s disease
Autoimmune disease that causes hyperthyroidism
Symptoms and signs of hyperthyroidism
Sweating
Bulging eyes (proptosis)
Goitre
Weight loss
Insomnia
increased nervousness and excessively emotional
Fast heart rate
Heat intolerance
What would the thyroid hormones level be in primary hypothyroidism
Low T3/T4
High TSH
What would the thyroid hormones level be in secondary hypothyroidism
Low T3/T4
Low/normal TSH
Why is TSH level called “inappropriately normal” in secondary hypothyroidism
In secondary hypothyroidism, the low T3/T4 level should cause a high TSH level but because the secondary hypothyroidism is caused by a defect in the pituitary gland, TSH level is low/normal
What will the thyroid hormone level in secondary hyperthyroidism be
High T3/T4
High or normal TSH
Hypothyroidism is more common in which type of people
Females
White populations
People in areas with high iodine intake
What is secondary hypothyroidism
Hypothyroidism not due to thyroid dysfunction
Goitrous causes of primary hypothyroidism
Hashimoto’s thyroiditis
iodine deficiency
Amiodarone induced hypothyroidism
Non-goitrous causes of primary hypothyroidism
Atrophic thyroiditis
Congenital hypothyroidism
Post partum thyroiditis
What is Hashimoto’s thyroiditis
it is an autoimmune destruction of thyroid gland causing reduction in thyroid hormone production
Which group of people are more at risk of Hashimoto’s thyroiditis
Family history of autoimmune conditions (e.g. T1 diabetics)
Family history of autoimmune thyroiditis (grave’s / Hashimoto’s)
Turner’s and Down syndrome
Males
What are the secondary causes of hypothyroidism
Malignancies
Infections
Trauma
Surgery
Congenital
Radiotherapy
What is the most common antibody present in Hashimoto’s thyroiditis
Anti- thyroid peroxidase antibodies (anti-TPO)
Can you diagnose Hashimoto’s thyroiditis just based on elevated anti-TPO
No, because anti-TPO is not specific to Hashimoto’s. It can be present in Grave’s disease (hyperthyroidism) and in healthy people too
What test should be done to diagnose hypothyroidism/hyperthyroidism and how do you differentiate whether it is primary or secondary
TSH and T3/T4 level
Autoantibodies not required because these are not specific
Primary hypothyroidism: T3/T4 low TSH high
Secondary hypothyroidism: T3/T4 low TSH low/normal
Primary hyperthyroidism: T3/T4 high TSH low
Secondary hyperthyroidism: T3/T4 high TSH high/normal
Amiodarone most commonly causes hypothyroidism or hyperthyroidism
Hypothyroidism
How does amiodarone cause hypothyroidism
Wolff Chaikoff effect; Amiodarone contains iodide
Excess iodine blocks the iodination of thyroglobulin causing a reduction in levels of thyroid hormone
What is atrophic thyroiditis
Non-goitrous cause of primary hypothyroiditis; antibody attack causing the thyroid gland to be severely shrunken
What causes congenital hypothyroidism
Dyshormonogenesis (defect in synthesis of thyroid hormone)
Abnormal gland development
What is postpartum thyroiditis
Self limiting inflammation in women after giving birth. Typically progresses from hyperthyroidism into hypothyroidism
Who is most at risk of postpartum thyroiditis
Pregnant women with T1 diabetes
What respiratory symptoms can be seen in hypothyroidism
Deep hoarse voice
Macroglossia (abnormally large tongue)
Obstructive sleep apnoea (goitre blocking airway)
What gynaecological symptoms can be seen in hypothyroidism
Menorrhagia - heavy menstrual bleeding
amenorrhea - absence of periods
oligomenorrhea - infrequent periods
Hashimoto’s thyroiditis is Th1/Th2 predominant
Th1
What cardiac symptoms may occur in hypothyroidism
Bradycardia
Cardiac dilatation
Pericardial effusion
Heart failure
Management of hypothyroidism
Gradual restoration of thyroid hormones using Levothyroxine
What is levothyroxine
Synthetic version of T4
Why is it important to restore the thyroid hormone level gradually instead of rapidly
Gradual restoration prevent cardiac arrhythmias
Is levothyroxine safe during pregnancy
Yes
Should you change the dosage of levothyroxine during pregnancy
Yes, double the dose during pregnancy
What is subclinical hypothyroidism
When the patient has elevated TSH but normal T3/T4
Do you need to treat subclinical hypothyroidism
No unless the patient becomes symptomatic and develop goitre / T3 and T4 level dropped
Otherwise, keep routinely check their TSH and T3/T4 level
What is myxoedema
Clinical emergency due to severe hypothyroidism
Which group of people are at risk of myxoedema
Elderly
Long standing, untreated hypothyroidism
Signs of myxoedema
Bradycardia
Abnormal ECG
Type 2 resp failure
Hypothermia
Adrenal failure
What abnormalities on ECG can be seen in myxoedema
Heart block
Prolonged QT
T wave inversion
Management of myxoedema
ABCDE
Passively rewarm the patient
IV levothyroxine
IV hydrocortisone (if there is adrenal failure)
What is thyrotoxicosis
Clinical state arising when the tissues are exposed to excess thyroid hormones
What is hyperthyroidism
Overactivity of thyroid gland leading to excess thyroid hormones
Is hyperthyroidism the only cause of thyrotoxicosis
No, thyrotoxicosis can also be due to e.g. ingestion of excess thyroid hormones
Causes of primary hyperthyroidism
Grave’s disease
Hashitoxicosis
Toxic multi nodular goitre
Toxic solitary nodule
De Quervain’s thyroiditis
What is Grave’s disease
Autoimmune condition with TSH receptor antibodies acting like TSH causing excessive stimulation of the thyroid gland
What can happen to the thyroid hormone levels of patients with Grave’s disease over time
Can switch from hyperthyroidism to hypothyroidism
Risk factors of Grave’s disease
Young
Family history of autoimmune disease
PMH of autoimmune disease
Smoking
What is toxic multi nodular goitre
Multiple autonomous nodules develop that are capable of producing and secreting thyroid hormones
What is toxic solitary goitre
Single autonomous adenoma develop and can produce + release thyroid hormones
What is Hashitoxicosis
Early stage of Hashimoto’s thyroiditis
In early stage of Hashimoto’s thyroiditis, there can be a period of hyperthyroidism then progresses into hypothyroidism
Causes of secondary hyperthyroidism
Postpartum thyroiditis
Amiodarone induced thyroiditis
Overtreatment with levothyroxine
Struma ovarii
Pituitary adenoma
Lithium
What is De Quervain’s thyroiditis
A self limiting condition that causes the thyroid gland to swell rapidly and causes hyperthyroidism
What may eventually occur to the thyroid hormone levels in patients with De Quervain’s thyroiditis over time
Hyperthyroidism -> hypothyroidism
Due to depletion of colloid and reduction in TSH production
What is amiodarone induced thyrotoxicosis type 1
Jod Basedow phenomenon which states that excess iodine intake causes excess thyroid hormone synthesis
What is amiodarone induced thyrotoxicosis type 2
Destructive thyroiditis due to direct toxic effect on follicular cells with resultant release of thyroid hormone
Which conditions can lead to both hyperthyroidism and hypothyroidism
Hashimoto’s (hashitoxicosis)
Grave’s (progresses into hypothyroridism)
Postpartum thyroiditis
Amiodarone induced
De Quervain’s thyroiditis (progresses into hypothyroiditis)
What is struma ovarii
Thyroid hormone released from ectopic thyroid tissue related to ovarian teratoma and dermoid tumours
Except from thyroid hormone levels, what other labratory test findings can present in Grave’s disease
Hypercalcaemia
Increase in alkaline phosphatase
Leucopenia (decrease in WCC)
TSH receptor antibody
Why is an elevated level of TSH receptor antibody a good indication for Grave’s disease
Because it is present in 90% of patients with Grave’s. Although it is can also be present in Hashimoto’s disease, it is only present in 10-20% of patients
Which cardiac arrhythmia can be caused by thyrotoxicosis
Atrial fibrillation
What are the neurological signs of thyrotoxicosis
Anxiety
Nervousness
Sleep disturbance
Tremor
Sweating
What symptoms are specific to Grave’s disease
Pretibial myxoedema
Thyroid acropachy
Thyroid bruit
Grave’s opthalmopathy
What is thyroid bruit
Continuous sound heard over thyroid mass, only heard in Grave’s
What causes thyroid bruit
Enlarged thyroid gland causes proliferation of blood supply and the hypervascularity of thyroid causes the bruit
What is thyroid acropachy
Periostitis, nail clubbing, swelling of the fingers / toes
What is pretibial myxoedema
Specific sign of Grave’s disease; thick scaly skin and swelling of the leg due to build up of glycosaminoglycans within the dermis
What are the eye abnormalities seen in Grave’s disease
Proptosis (bulging of eyes)
Intolerance of bright lights
Excessive dryness
Swelling
Sight loss
What are the signs that indicate moderate to severe grave’s ophthamolpathy
Diplopia
Significant lid retraction
Significant soft tissue involvement
Exopthalamos > 3mm
Optic neuropathy
Corneal breakdown
What is diplopia
Double vision
Management of mild Grave’s opthalmopathy
Topical lubricants
Advise to elevate head when sleeping / wear sunglasses
Management of severe Grave’s opthalmopathy
Steroids
Surgery
Radiotherapy
Management of hyperthyroidism
- Carbimazole / propylthiouracil
+ Beta blockers for symptomatic relief
- Radioiodine therapy
- Surgery
Which beta blocker is used in hyperthyroidism
Propanolol
Contraindications for beta blockers
Patients with asthma because beta blockers can cause bronchospasm
Which drug should be used for hyperthyroidism if beta blockers are contraindicated
Calcium channel blocker (dilitiazem)
Why are beta blockers used for symptomatic relief in hyperthyroidism
Because they can reduce the activity of the sympathetic nervous system hence reduce symptoms caused by it until thioamides take effect
Examples of thioamides
Carbimezole
Propylthiouracil
How do thioamides treat hyperthyroidism
By blocking peroxidase to reduce thyroid synthesis
Contraindication for carbimazole
Pregnant / planning to become pregnant
Deranged LFT
Why is carbimazole contraindicated in pregnant women
Because it is associated with congenital malformations
What tests should be done before giving thioamides
FBC and LFT (to check transaminase levels)
Pregnancy test
Severe side effect of thioamides
Agranulocytosis - absence / reduction of granulocytes especially neutrophils, puts patients at risk of severe infection and sepsis
Indications for radioiodine therapy
Toxic multi nodular goitre
Toxic solitary goitre
Difference between nodular thyroid disease and Grave’s disease
Nodular thyroid disease - absent TSH receptor antibodies
Nodular thyroid disease causes asymmetrical goitre whereas Grave’s disease causes smooth goitre
Nodular thyroid disease more common in older patients whereas Grave’s disease more common in younger patients
Contraindications for radio iodine therapy
Pregnant women / breastfeeding
Those with active thyroid eye disease
Side effects of radio iodine therapy
Exacerbate thyroid eye disease
Hypothyroidism
When is surgery used for hyperthyroidism
Other management contraindicated
Recurrent hyperthyroidism
Goitre obstructing other structures
Complications of thyroidectomy / hemithyroidectomy
RLN damage
Hypothyroidism
Hypocalcaemia
How may thyroidectomy lead to hypocalcaemia
Damage to parathyroid glands which produce parathyroid hormones
Types of thyroid cancer
Papillary thyroid cancer
Follicular thyroid cancer
Anaplastic thyroid cancer
Medullary thyroid cancer
What is medullary thyroid cancer
Thyroid cancer derived from parafollicular C cell
Associated with MEN 2
Hormone levels in medullary thyroid cancer
Calcitonin raised
Serum Ca2+ reduced (hypocalcaemia)
Function of calcitonin
Opposes action of PTH, reduces Ca2+ level
Which thyroid cancer is the most common
Papillary
Which thyroid cancer has the worst prognosis
Anaplastic, it is the most aggressive form
Difference between papillary thyroid cancer and follicular thyroid cancer
Papillary cancer is associated with Hashimoto’s thyroiditis whereas follicular cancer is not
Papillary cancer spreads via lymphatics and rarely by blood whereas follicular cancer spreads via blood and rarely lymphatics
Papillary cancer is not related to iodine whereas follicular cancer is related to iodine deficiency
Differentiated thyroid cancer is driven by which hormone
driven by TSH hormone
Risk factors of thyroid cancer
Radiation exposure (esp during childhood)
Female
Family history
What are the symptoms and signs of thyroid cancer
Palpable thyroid nodules
Cervical lymphadenopathy
Stridor
Hoarseness / change in voice
What is stridor
Harsh, high pitched noise heard on inspiration due to upper airway obstruction
Often described as “barking” sound
Because most palpable nodules are benign, what other clinical signs are more suggestive of malignancies
Nodule rapidly increasing in size
Vocal cord palsy
Lesion > 4 cm
History of neck or head irradiation
Male (although thyroid cancer is more common in females, males have a worse survival and more aggressive disease)
Thyroid cancer is more common in female / male
Female
Which thyroid cancer is associated with hashimoto’s thyroiditis
Papillary
What investigations should be done if you suspect thyroid cancer
TFT - TSH / T4/ T3
Fine needle aspiration
Fine needle aspiration cytology
Patient specific investigations i.e. if they have certain signs
What patient specific investigations can be done if you suspect thyroid cancer
Present with vocal palsy - laryngoscopy
Present with suspicious lymph nodes - CT/MRI scan
What is AMES
pre-operative risk stratification depending on
Age
Metastases
Extent of primary tumour
Size of primary tumour
Surgical options for thyroid disease
Lobectomy
Hemithyroidectomy
Total thyroidectomy
Indications of hemithyroidectomy / total thyroidecomy
High AMES risk
Lymph involvement
Distant metastases
Extra-thyroidal invasion
Indications of lobectomy
Papillary microcarcinoma <1cm diameter
low AMES risk
minimally invasive follicular carcinoma
Complications of thyroid surgery
RLN damage
hypothyroidism
hypoparathyroidism
What happens as a result of hypoparathyroidism
Hypocalcaemia
because parathyroid glands produce parathyroid hormone to increase blood calcium levels so damage to those glands can lead to hypocalcaemia
What can hypocalcaemia lead to
Muscle spasms
Muscle weakness
Seizures
QT prolongation
Predisposition to ventricular arrhythmias
Why do you need to monitor calcium levels closely after thyroid surgeries
To check for hypocalcaemia due to parathyroid gland damages
What should you do if calcium levels are too low after thyroid surgeries
Start calcium replacement / IV calcium
Prevent overtreating to prevent hypercalcaemia
What ECG changes can happen due to hypercalcaemia
shortened QT interval
Which hormone acts against parathyroid hormones to decrease blood calcium level
calcitonin produced by thyroid gland
Post op care for patients after total thyroidectomy / hemi thyroidectomy
Surpress TSH level (if papillary / follicular)
Levothyroxine therapy
Whole body iodine scan
Radioiodine ablation (if there are remnants
What should be monitored if the patient had surgery due to medullary thyroid cancer
Calcitonin and calcium level
What should be done before taking the whole body iodine scan
Increase TSH level to above 20 by injecting rhTSH
Why does TSH level need to be increased before taking whole body iodine scan
Because differentiated thyroid cancer (papillary, follicular) is TSH driven hence TSH will stimulate the remaining cancer cells to take up iodine. This allows the cancer cells to light up on the scan
What is the use of radio iodine ablation
To destroy the remnant thyroid tissue to prevent recurrence of cancer / increase chance of long term remission
What safety cautions should the patient be aware of after they receive radio iodine ablation
Cannot mother / father a child
Avoid pregnant women / child
Avoid close contact with other people
Till safe
Why should TSH level be suppressed after thyroid cancer surgery
To prevent recurrence of the cancer
How do you suppress TSH level after thyroid cancer surgery
Put the patient on levothyroxine to suppress TSH
What can happen if the patient overdoses on levothyroxine
Heart failure
Atrial fibrillation
Osteoporosis
What can be measured to assess for residual tissue / recurrent disease for those that got total thyroidectomy +/- radioiodine ablation
Thyroglobulin
Mneumonic for symptoms of hypothyroidism (MOM’S SO TIRED)
Memory loss
Obesity (weight gain)
Menorrhagia
Slowness mentally and physically
Skin and hair dryness
Onset is gradual
Tiredness
Intolerance to cold
Raised BP
Enlarged thyroid gland
Depression
What is sick euthyroid syndrome
Hypothyroidism that occurs in any systemic illnesses but tend to not have any symptoms
