Thyroid Flashcards
Where is thyroid gland located?
Located in neck
Wraps around trachea
Description of thyroid gland
25-30g
Brownish red
Thin fibrous capsule of connective tissue
Left and right lobes united by a narrow isthmus
Cell types in thyroid gland
Parafollicular cells
Follicle cells
Description of follicle cells
Produce hormones
Simple cuboidal epithelial lining
Colloid - contains mature thyroid hormones
What is the role of thyroid hormones?
- Control of metabolism
Energy generation and use - Regulation of growth
- Multiple roles in development
Where are thyroid hormone receptors in the body
Every organ of the body
Control of thyroid hormone secretion:
Hypothalamus - secreted TRH
Anterior PG - secretes TSH
Thyroid gland - secretes T3 and T4
T3 Targets tissue
T3 negatively feeds back and decreases TRH and TSH secretion
Main target tissues of T3
Cardiovascular
Digestive
Neurological
What produces thyroid hormones?
Follicular thyroid cells
What precursor are thyroid hormones synthesised from?
Thyroglobulin
What is absorbed from the bloodstream and concentrated in follicles
Iodine
The function of thyroperoxidase (TPO)?
Enzyme
That binds iodine to tyrosine residues in thyroglobulin molecules to form MIT and DIT
MIT + DIT forms
T3
DIT + DIT forms
T4
What are MIT and DIT?
Thyroid hormone precursors
The mechanism of production of T3/ T4 in follicular cells?
- TSH binds to TSHR (receptors on follicles)
- Iodine uptake by NIS (Na/I symporter)
- Iodisation of thyroglobulin tyrosyl residues by TPO
- Coupling of iodotyrosyl residues by TPO
- Export of mature thyroglobulin into colloid
Which thyroid hormone is biologically active
T3
HOW IS T3 PRODUCED FROM T4
By mono deionisation of T4
3 types of deiodinase enzymes (D1, D2, D3) present in peripheral tissues
What hormone does thyroid gland majorly produce?
80% T4 which then gets deiodinised
20% originally T3
What protein carriers to T4 and T3 bind to?
TBG
Albumin
Transthyretin
What is the percentage of free t4
0.03%
What is the percentage of free T3
0.3%
3 main test for thyroid function
- Serum TSH (best)
- Serum T4
- Serum T3
What would be the test results for hyperthyroidism?
Low serum TSH
High serum free T4
High serum free T3
Due to negative feedback
The test results for primary hypothyroidism?
High serum TSH
Low serum free T3 and T4
Prevalence and incidence of hyperthyroidism
What thyroid disease has the largest prevalence?
Goitre
24.4%
Is prevalence of hyperthyroidism bigger in females or males
Females
Main Aetiology (causes) of hyperthyroidism:
- Graves hyperthyroidism
- Toxic nodular goitre (single or multinodular)
- Thyroiditis - inflammation following a viral infection
What are the other causes of hyperthyroidism?
- Exogenous iodine
- Factitious (taking excessive thyroid hormone)
- TSH secreting pituitary adenoma (benign)
- Neonatal (newborn) hyperthyroidism
Percentage of cases of hyperthyroidism that are Graves’ disease?
60-80%
Most prevalent autoimmune disorder in UK and US
What are the environmental factors causing Graves’ disease?
Interplay between genetic (80%) and environmental factors (20%)
Gender - more common in females
Stress
Infection
Pregnancy
Drugs
How does Graves’ disease cause hyperthyroidism?
Autoimmune disease that cause IMS to target thyroid gland and make it overactive - unregulated overproduction of thyroid hormones
Pathogenic antibodies bind to TSH receptor on thyroid follicular cells
Antibodies are “long acting thyroid stimulators”
Cardiovascular symptoms and signs of hyperthyroidism:
- Tachycardia (rapid heart rate)
- Atrial fibrillation
- Shortness of breath
Atrial fibrillation?
Irregular and abnormally fast heart beat
That can lead to blood clotts in the heart
Neurological signs and symptoms of hyperthyroidism?
- Tremor
- Myopathy (muscle weakness)
- Anxiety
Gastrointestinal symptoms and signs of hyperthyroidism?
- Weight loss
- Diarrhoea
- Increased appetite
Signs and symptoms of eyes/skin with hyperthyroidism?
- Sore gritty eyes
- Staring eyes
- Pruritus (itching)
If a patient has family history of Graves’ disease what is likely to happen
Patient will present at a younger age
Inverse relationship between age an diagnosis
How are Extrathyroidal manifestations caused in Graves’ disease
Long acting antibodies that attach to TSH receptors on follicular cells can also attach to skin and soft tissues in the eyes
Extrathyroidal manifestations in the eyes in Graves’ disease:
- Lid lag/ retraction
- Conjunctival oedema (swelling)
- Proptosis/ unilateral proptosis (bulging)
- Ophthalmoplegia (weakness of eye muscles)
Extrathyroidal manifestations on the skin in Graves’ disease:
Pretibial myxoedema - waxy, discolored induration of the skin
Acropachy - soft-tissue swelling of the hands and clubbing of the fingers
How does neonatal hyperthyroidism occur?
If mother has Graves’ disease, TSH-R antibodies cross the placenta
Treatment: control hyperthyroidism in mother during pregnancy
May cause fatal death
How is hyperthyroidism diagnosed?
- Clinical features of graves
- Consider iodine uptake scan
- Consider isotope imaging
- TPO absence in 75% of graves
- measure TSH receptor antibodies
Treatment of hyperthyroidism
- Anti thyroid drugs to block hormone synthesis
- Surgical removal of thyroid
- radioiodine therapy
Examples of anti thyroid drugs
- Carbimazole
- Propylthiouracil
How do anti thyroid drugs (thionamides) work?
Block iodine incorporation and organification through inhibition of thyroperoxidase TPO
What is the role of TPO?
Assists the chemical reaction that adds iodine to thyroglobulin
Thionamide therapy side effects
Rash
Joint pain
Sickness
Agranulocytosis: no WBC infection risk
Liver disease with propylthiouracil
Pancreatitis with carbimazole
What is the cure rate of thionamide drugs?
30-40%
Is surgery for hyperthyroidism used frequently?
No
What is the pre treatment of surgery for hyperthyroidism?
Antithyroid drugs
Indications that surgery are needed for hyperthyroidism:
- Large goitre (co-existing thyroid cancer)
- Pregnancy (thionamide drugs have serious side effects)
- Pronounced opthalmopathy
- patient preference
What is radioiodine treatment? Adv and Dis
Iodine-131
Capsule (fixed dose)
Usually pre treatment with drugs
Adv:
Highly effective (85% cure)
Dis:
May worsen eye disease (steroidS)
Risks of using radioiodine therapy to treat hyperthyroidism?
- Hypothyroidism (60%)
- Cancer due to radioactive
- Infertility
- Teratogenesis (congenital malformations produced in an embryo/ fetus)
What are the treatment aim of treating thyroid diseases?
- To relieve symptoms
- To restore T4 and T3 values within an normal range
- To obtain long-term normal thyroid function
Prognosis of thyroid disease treatments
- 30% of patients with Graves’ disease have normal thyroid function long term following drugs
- 131-I and surgery associated with >50% risk of long term hypothyroidism
Prevalence of hypothyroidism in females:
40/1000
Aetiology of hypothyroidism:
- Autoimmune - Hashimoto thyroiditis (TPO and Tg antibodies - genetic predisposition
- After treatment of hyperthyroidism
- Subacute/ silent thyroiditis
- Iodine deficiency
- Congenital (having it since birth)
What is the indication of high Tg antibodies?
Antithyroglobulin antibodies can be a sign of thyroid gland damage via the immune system
Autoimmune disease like Hashimotos/ Graves’ disease
What is subacute/ silent thyroiditis?
Most common in women in postpartum period
Symptoms starts with hyperthyroidism, then hypothyroidism, then the recovery period to euthyroid period
What is the congenital cause of hypothyroidism?
Born with thyroid deficiency
Thyroid agenesis:
Missing the thyroid
Severely reduced in size
Located ectopically
Ectopically?
Placed abnormally
The effects of Tg antibodies in Hashimotos thyroiditis?
Inflammation
Goitre
Swelling
Fibrosis and shrinkage - unable to produce sufficient thyroid hormones
What is the major cause of hypothyroidism world wide and UK?
WORLD WIDE: iodine deficiency
UK: Hashimoto’s disease
What country doesn’t suffer from iodine deficiency?
Japan
How is iodine deficiency combatted?
Supplementation programs
E.g. salt and flour is iodinated
Where are the main sources of iodine?
Milk
Diary
Cause of congenital hypothyroidism (cretinism) ?
Lack of iodine in mother - Affects fetus
Random mutation
Cardiovascular symptoms and signs of hypothyroidism?
- Bradycardia (slow heart rate)
- Heart failure
- Pericardial effusion
Pericardial effusion?
Excessive fluid build up in the sac like structure that covers the heart, the pericardium
Gastrointestinal symptoms and signs of hypothyroidism?
- Weight gain
- Constipation
Skin symptoms and signs of hypothyroidism?
- Myxoedema
- Rash on legs
- Vitiligo
Neurological symptoms and signs of hypothyroidism?
- Depression
- Psychosis
- Carpal tunnel syndrome
Treatment of hypothyroidism?drug names
Levothyroxine - 3rd most prescribed med in UK
Goal: restore patients to euthyroid state and to normalise serum T4 and TSH conc
Is hypothyroidism the most common endocrine condition?
Yes
What are thyroid nodules and goitres?
Goitre is an enlargement of the thyroid can be uniform and smooth
Nodular goitre is multiple enlargements at thyroid
Epidemiology
Incidence
Detriments
Distribution
Possible control of disease
In a certain population
How may nodules be discovered?
Palpating
Imaging
Incidentally
What gender and age is thyroid nodules more common in?
Most common in women 4:1
Older population
Common cause of thyroid nodules:
Increased in areas of low iodine uptake
What would thyroid nodules cause?
Cause Thyroid dysfunction
Cause Compression
Prevalence of malignancy in goitre:
4-6.5%
What is a pet scan?
3D image produced
Scans for specific diseases
Cancer, heart disease and brain disorder
Percentage risk of PET positive thyroid nodule?
27%
Does risk of cancer depend on nodule size?
No
Prevalence (percentage) of nodules in the population?
50%
How are nodules found incidentally?
Found when patients are undergoing imaging (CT, MRI, carotid Doppler)
Clinical features associated with increased risk of malignancy? LIST
- Age <20 or >60
- Firmness of nodule on palpating
- Rapid growth
- Fixation to adjacent structure
- Vocal cord paralysis
- History of neck irritation
- Family history of thyroid cancer
To investigate thyroid nodules:
- Assessment of thyroid function
- Assessment of thyroid size
- Assessment of thyroid pathology
What are the assessment of thyroid function in investigation of thyroid nodule?
Serum TSH
Serum free T4 and T3
Thyroid antibodies
What are the assessments of thyroid size in the investigation of thyroid nodules?
Symptoms
X ray thoracic inlet
CT or MRI of neck
Respiratory flow loop
Assessment of thyroid pathology in investigation of thyroid nodules? (Is this cancer?)
Radionuclide scanning
Ultrasound scanning
Fine needle aspiration cytology
What is the criteria for malignancy of thyroid nodules?
Irregular margin
Calcifications
Solidity
Increased blood flow
What does ultrasound allow differentiation of when investigating a thyroid nodule?
Differentiation of a solid from a cystic nodule
Differentiation of single from multiple nodules (can be superior to palpation - hidden nodules)
What does ultrasound provide guidance for?
Fine needle aspiration
Main type of thyroid cancer (72-85%)
Epithelial cell malignancy showing differentiation in follicular cells
What is the cause of medullary carcinoma (1.7-3%)
Malignant differentiation of C cells in medulla of thyroid gland
Causes of thyroid cancer:
- External irradiation e.g. Chernobyl accident
- Iodine deficiency
- Oncogene expression
- Genetic factors
Treatments for thyroid cancer:
- Surgery - doesnt always remove all thyroid
- Radioiodine
- Drugs
