Thyroid Gland ✅ Flashcards
When does thyroid development start?
About 4 weeks gestation
What does the thyroid develop from?
An outpouching of the floor of the pharynx and bilateral protrusions of the fourth pharyngeal pouches
What is the outpouching of the floor of the pharynx the precursor of?
T4-producing follicular cells
What are the bilateral protrusions of the fourth pharyngeal pouches the precursor of?
The calcitonin secreting cells
What happens to the thyroid during development?
It descends along the thyroglossal tract, which then regresses
What can happen if there are remnants of the thyroglossal tract?
They may form thyroglossal cysts
What does failure of descent of the thyroid result in?
Ectopic thyroid gland (which is a common form of congenital hypothyroidism)
What is the process of thyroid development regulated by?
A number of transcription factors, including PAX-8, FOXE-1, and NKX2
Describe the gross anatomy of the thyroid gland?
It is butterfly shaped with two lobes connected by an isthmus
Where is the thyroid gland located?
Below the larynx, anterior to the second and fourth tracheal rings
What does the thyroid gland consist of?
Spherical iodine-absorbing follicles
What does the lumen of the thyroid follicles contain?
Colloid
What is present of the colloid of the thyroid follicles?
Substrates necessary for thyroid synthesis, particularly thyroglobulin
What are the thyroid follicles surrounded by?
A single layer of epithelial cells
What do the epithelial cells of the thyroid secrete?
T3 and T4
What are found between the follicles of the thyroid?
Parafollicular cells
What do the parafollicular cells secrete?
Calcitonin
What is TSH release regulated by?
Thyrotropin-releasing hormone (TRH)
Where is TRH released from?
Hypothalamus
What is thyroid hormone synthesis stimulated by?
Binding of pituitary-derived TSH to TSH receptor
What kind of receptor is the TSH receptor?
GPCR
What does binding of TSH to the TSH receptor lead to?
Iodine uptake by a sodium-iodine transporter
What happens once iodine has been taken up by the thyroid?
It is transported to the colloid
How is iodine transported to the colloid?
By a protein (pendrin) within the thyrocyte
What happens to iodine in the colloid?
It is oxidised to iodide by hydrogen peroxide
What is responsible for regulating hydrogen peroxide in the colloid?
Thyroid peroxidase (TPO)
What happens once iodine has been oxidised to iodide?
Tyrosyl residues on thyroglobulin are iodinated
What is formed when tyrosyl residues on thyroglobulin are iodinated?
Monoiodotyrosine (MIT) and diiodotyrosine (DIT)
What happens to MIT and DIT after formation?
They are coupled under TPO control to form iodothyronines
What happens following cleavage of thyroglobulin?
Molecules of MIT, DIT, T3, and T4 are released
What is T3 formed by?
Deiodination of T4
Where is T4 produced?
Solely in thyroid
Where is T3 produced?
Majority is produced by deiodination of T4 in peripheral tissues
Compare the potency of T3 to T4?
T3 is 3-4x more potent in it’s physiological actions than T4
What is the inactive form of T4?
rT3
What converts T4 into rT3?
Type III deiodinase
On what systems does thyroxine have an effect?
- Neurological
- Metabolic
- Cardiovascular
What receptors does thyroxine bind to in the heart?
Alpha
What receptors does thyroxine bind to in the brain?
Alpha and beta1
What receptors does thyroxine bind to in the liver?
Beta1 and beta2
What receptors does thyroxine bind to in the pituitary?
Beta2
What receptors does thyroxine bind to in the hypothalamus?
Beta2
What is the fetus largely dependent on during fetal life regarding thyroxine?
Transplacental passage of T3 and T4
What changes are there to the source of thyroxine during fetal life?
There is an increasing contribution from the second trimester onwards of fetally derived thyroxine
Is it maternal or fetally derived thyroxine that protects the fetus from congenital hypothyroidism?
Largely fetally-derived
Describe the thyroxine levels in a premature infant?
Low T3 and 4, but high rT3 levels (as in the fetus)
Is there benefit to thyroxine replacement in premature infants?
Unknown, currently undergoing clinical trials
What happens to thyroid hormone levels postnatally?
There is an acute surge in TSH, T3 and T4 concentrations in the first day or two of life, and then falling to childhood levels by 2 weeks of age
What should the history include in suspected cases of thyroid disease?
- Growth and pubertal development
- Weight
- Bowel habit
- Neurodevelopment
- Sleep patterns
- Behavioural functioning
- Environmental temperature tolerance
What happens to growth in thyroid disorders?
- Delayed in hypothyroidism
- Advanced in hyperthyroidism
What happens to weight in thyroid disorders?
Loss in hyperthyroidism
What happens to bowel habit in thyroid disorders?
- Constipation in hypothyroidism
- Diarrhoea in hyperthyroidism
What happens to neurodevelopment in thyroid disorders?
Delayed in hypothyroidism
What happens to sleep pattern in thyroid disorders?
- Excess fatigue in hypothyroidism
- Reduced sleep requirements in hyperthyroidism
What happens to behavioural functioning in thyroid disorders?
- Deteriorating school progress in hypothyroidism
- Poor attention span in hyperthyroidism
What happens to environmental temperature tolerance in thyroid disorders?
- Cold intolerance in hypothyroidism
- Heat intolerance in hyperthyroidism
What general clinical observations might suggest hypothyroidism?
- Short stature
- Overweight
- Delayed puberty
- Dry skin
- Increased hair
- Vitiligo
Why does precocious puberty sometimes (but rarely) happen in hypothyroidism?
Due to cross-stimulation of FSH receptors by TSH
What general clinical observations might suggest hyperthyroidism?
- Tall statue
- Underweight
- Facial flushing
- Tremor
- Sweatiness
Why are hyperthyroid children underweight?
Because of increased metabolic rate
What should be looked for in the neck in thyroid disease?
Goitre
Describe the goitre in Hashimoto’s disease?
Nodular
Describe the goitre in Grave’s disease?
Smooth, homogenous, occasionally associated with a bruit
What happens to the pulse in thyroid disease?
- Slow in hypothyroidism
- Fast, and associated with flow murmurs, in hyperthyroidism
What might be found on MSK examination in thyroid disease?
- Proximal muscle weakness in hypothyroidism
- Tremor and choreiform movements in hyperthyroidism
What might be found on neuro examination in thyroid disease?
Relaxation of the ankle jerk is prolonged in hypothyroidism, but reduced in hyperthyroidism
What might be found on ophthalmological examination in thyroid disease?
Exophthalmos and occasionally ophthalmoplegia
What is the importance of exophthalmos and ophthalmoplegia in thyroid disease?
These findings are pathognomonic for Grave’s disease
What might the presence of deafness suggest in congenital hypothyroidism?
Pendred syndrome
What might the presence of a lump at the back of the throat suggest in congenital hypothyroidism?
Ectopic thyroid
What % of circulating T3 and T4 are bound to TBG?
50% of T3
70% of T4
What is most of the remainder of T3 and T4 circulating bound to?
Other proteins, such as albumin
What % of T3 and T4 circulates unbound?
- 3% of T3
0. 03% of T4
What is the result of the majority of T3 and T4 circulating bound?
The measurement of free hormones (T3, T4, and TSH) provides a more relevant assessment of thyroid function than total thyroxine
What is total thyroxine a better measurement of?
TBG levels
What antibodies are usually positive in Graves’ and Hashimoto’s?
TPO (thyroid peroxidase)
What investigation finding indicates Graves’ disease?
Excess titres of TSH receptor antibodies (TRAb)
How is congenital hypothyroidism usually detected?
Screening with capillary blood spot TSH
What investigations are performed in congenital hypothyroidism (in addition to formal thyroid function testing)?
Ultrasound or isotope scanning
What is the purpose of ultrasound or isotope scanning in congenital hypothyroidism?
To clarify if gland is absent, hypoplastic, or ectopic
What suggests dyshormonogenesis in isotope scanning for congenital hypothyroidism?
Abnormalities of iodine uptake and trapping
What is essential when a thyroid nodule or cancer is suspected?
Imaging
What investigation should be done in suspected thyroid cancer?
Calcitonin
What does a raised plasma calcitonin indicate in suspected thyroid cancer?
Medullary thyroid cancer
How common is congenital hypothyroidism?
Common, affects 1:3,500 births
What is the importance of congenital hypothyroidism?
It is the most common treatable cause of learning disability worldwide
What is congenital hypothyroidism most commonly caused by?
Maternal iodine deficiency
What are the most common form of congenital hypothyroidism in developed countries?
Ectopic gland most common, followed by aplasia and hypoplasia
How important are transcription factor mutations as a cause of congenital hypothyroidism?
They are responsible for less than 2% of dysgenesis cases
What causes dyshormonogenesis?
Defects in a range of genes encoding proteins involved in thyroid hormone biosynthesis
How does dyshormonogenic thyroid appear on ultrasound?
Normal
What % of cases of congenital hypothyroidism are caused by dyshormonogenesis in the UK?
10-15%
What is the purpose of the newborn screening programme for hypothyroidism?
To identify cases to be started on thyroxine treatment before 2 weeks of age
What is the aim of starting thyroxine early in congenital hypothyroidism?
Aims to normalise thyroid function within 2 weeks, to optimise neurodevelopment outcomes
What are changes in the dose of thyroxine guided by in congenital hypothyroidism?
Recurrent elevations in TSH
What should be done if a dose increase has not been done by the 3rd birthday in congenital hypothyroidism?
Consideration should be given to temporary withdrawal of therapy, to establish if lifelong thyroxine treatment is actually required
What does long-term follow up for congenital hypothyroidism require?
Monitoring of growth and neurodevelopment
What might acquired hypothyroidism be due to?
- Iodine deficiency
- Autoimmunity
- Irradiation
- Antithyroid drugs
- Goitrogens
- Diseases affecting pituitary or hypothalamus
Give an example of an autoimmune cause of hypothyroidism?
Hashimoto’s disease
Give 3 examples of goitrogens?
- Iodide
- Cabbage
- Soya
What does management of acquired hypothyroidism involve?
Thyroxine replacement
What is the prognosis of treated acquired hypothyroidism?
Good
What might cause transient hyperthyroidism in children of affected mothers?
Graves’ disease, due to TRAb (thyroid-stimulating hormone receptor antibody) crossing the placenta and causing transient hyperthyroidism in the offspring of affected mothers
What might the early stages of Hashimoto’s disease be associated with?
Transient hyperthyroidism
What are the rare causes of hyperthyroidism in children?
- Autonomous nodules
- TSH hypersecretion
- Activating mutation of the TSH receptor
What is the initial treatment for Graves’ disease?
Carbimazole or methimazole
What can be used for initial Graves’ treatment if adverse reactions are experienced with carbimazole or methimazole?
Propylthiouracil
How do carbimazole, methimazole, and propylthiouracil act?
By blocking synthesis of thyroxine
How can emergency control of symptoms be achieved in severely thyrotoxic patients?
Propanolol and Lugol’s iodine solution
What should be done if relapse occurs after withdrawal of anti-thyroid medication after 2 or 3 years?
More definitive treatment in the form of radio iodine or surgery may be considered
How serious is neonatal thyrotoxicosis due to maternal Graves’ disease?
Self-limiting
When does neonatal thyrotoxicosis caused by maternal Graves’ disease resolve?
Once maternally derived TRAbs have disappeared, within 3 months of birth
What might be required in neonatal thyrotoxicosis caused by maternal Graves’ disease?
Anti-thyroid treatment may be required in early weeks after birth
What is the thyroid hormone resistance?
An unusual inherited disorder due to a mutation in the beta-thyroid hormone receptor gene
What does the mutation in the beta-thyroid hormone receptor gene in thyroid hormone resistance result in?
Reduced feedback inhibition, leading to elevated T4 and T3 concentrations but inappropriately normal or raised TSH levels
How is thyroid hormone resistance treated?
It doesn’t require therapy in most cases
Does thyroid hormone resistance cause symptoms?
Sometimes
Why are the symptoms of thyroid hormone resistance variable?
Because of variable tissue sensitivity to thyroid hormones, which can lead to some irritating symptoms of hyperthyroidism in certain individuals
What are most thyroid nodules in childhood?
Cysts or benign adenomas
Of what type are most malignant nodules in childhood?
Papillary or follicular carcinomas
How might thyroid cancers in childhood present?
Painless, rapidly enlarging mass, sometimes with lymphadenopathy
How should suspected thyroid cancer in children be investigated?
Ultrasound and fine needle aspiration
What does treatment require in thyroid cancer?
Surgery and aggressive thyroxine replacement
What is the purpose of aggressive thyroxine replacement after surgery for thyroid cancer?
To suppress TSH levels, which may be a risk factor for recurrence
Why are high TSH levels a risk factor for recurrence of thyroid cancer?
Due to trophic effects on thyroid tissue growth
How is metastatic thyroid cancer treated?
Radioiodine therapy is given post-op
How is the recurrence of functioning thyroid tissue monitored in treated thyroid cancer?
Thyroglobulin measurements
What is the prognosis of thyroid cancer in children?
Generally good
