WEEK 6 Flashcards
Where are T3 and T4 produced?
Thyroid follicular cells (surround follicles in the thyroid)
What is colloid?
The fluid contained in follicles
Where is calcitonin produced and secreted from?
Parafollicular (C) cells (exist outside follicles)
What are the three hormones produced and secreted from the Thyroid gland?
T3 (triiodithyronine)
T4 (tetraiodothyronine/thyroxine)
Calcitonin
What is the action of the thyroid hormones (T3 and T4)?
Control of metabolism (energy generation and use)
Regulation of growth
Multiple roles in development
Describe the process of thyroid hormone synthesis
Synthesised by the thyroglobulin precursor
Iodine is absorbed from the bloodstream and concentrated in follicles which thyroperoxidase binds to tyrosine residues in thyroglobulin molecules to form MIT and DIT (monoiodotyrosine and diiodotyrosine)
What is T3 composed of?
MIT+DIT (3 iodine atoms)
What is T4 composed of?
DIT+DIT (4 iodine atoms)
What negative feedback is received in the hypothalamic–pituitary–thyroid axis?
Secretion of TRH is inhibited by T3
Secretion of TSH is inhibited by T3 and T4
Describe the hypothalamic-pituitary-thyroid axis
TRH secreted from hypothalamus, TSH secreted from anterior pituitary gland, T3 and T4 secreted from thyroid gland to target tissues
What are the steps of the process of thyroid hormone synthesis?
1) TSH binds to TSHR on basolateral membrane of follicular cells
2) Uptake of I- by Na/I symporter (NIS)
3) Iodination of Tg tyrosine residues by TPO (thyroperoxidase)
4) Coupling of iodotyrosine residues by TPO on apical membrane
5) Export of mature Tg to colloid where it’s stored
Which of T3 and T4 is biologically active?
T3
How is T3 produced from T4?
Mono-deiodination of T4 which is most abundant via deiodinase (DI, DII and DIII) enzymes present in peripheral tissue
How are T3 and T4 molecules transported?
Via thyroid hormone binding proteins (albumin/transthyretin/TBG (thyroxine binding globulin))
Why is there such a minor proportion of free T3 and T4?
Most is bound to proteins
What are the tests for thyroid function?
Serum TSH
Serum free T3
Serum free T4
What is Hyperthyroidism?
Overactivity of the thyroid gland
What is Hypothyroidism?
Underactivity of the thyroid gland
What is Goitre?
Enlargement of the thyroid gland
What do tests for thyroid function show for hyperthyroidism?
Decreased serum TSH
Increased serum fT3 and fT4
What do tests for thyroid function show for hypothyroidism?
Increased serum TSH
Decreased serum fT3 and fT4
What is aetiology?
The manner of causation of a disease or condition
Common aetiology for hyperthyroidism
Graves’ hyperthyroidism-most common
Toxic nodular goitre (single or multinodular)
Thyroiditis (silent, subacute): inflammation
Less common aetiology for hyperthyroidism
Exogenous iodine
TSH-secreting pituitary adenoma
Neonatal hypothyroidism
Factitious (taking excess thyroid hormone)
What are the cardiovascular symptoms and signs of hyperthyroidism?
Tachycardia (rapid HR)
AF (atrial fibrillation)
Shortness of breath
Ankle swelling
What are the gastrointestinal symptoms and signs of hyperthyroidism?
Weight loss
Diarrhoea
Increased appetite
What are the neurological symptoms and signs of hyperthyroidism?
Tremor
Myopathy (muscle weakness)
Anxiety
What are the symptoms and signs of hyperthyroidism in eyes/skin?
Sore, gritty eyes
Double vision
Staring eyes
Pruritus (itching)
What is Graves’ disease?
Enlargement of the thyroid gland in connection with enlargement or palpation of the heart
What is the pathogenesis of Graves’ disease?
Pathogenic auto-antibodies bind to TSH receptors on thyroid follicular cells causing unregulated overproduction of thyroid hormones (long-acting thyroid stimulators)
What factors contribute to Graves’ disease risk?
Genetic and environmental
What are the extra-thyroidal manifestations of Graves’ disease?
Eyes: lid lag/retraction, conjunctival oedema (swelling), periorbital puffiness (around eye), proptosis (bulging), ophthalmoplegia (weakness of eye muscle)
Skin: pretibial myxoedema, acropachy
How would you diagnose Graves’ disease?
Decreased serum TSH, Increased serum fT3/T4
Potential clinical features: eye disease/diffuse goitre
TPO Abs (antibodies) +ve
TSHR Abs +ve
Isotope uptake scans (Tc, radioactive iodine)
What are the treatment options for Graves’ disease?
Antithyroid drugs to block hormone synthesis
Surgical removal of thyroid
Radioactive (131I) therapy
What are two types of antithyroid drugs (thionamides)?
Carbimazole or Propylthiouracil (block iodine incorporation and organification through thyroperoxidase inhibition)
When are antithyroid drugs used?
Short-term preparation of patients for definitive treatment-induce Graves’ disease remission
What are considerations to be made over antithyroid drugs?
Side effects: rash, joint pains, sickness, agranulocytosis (no WBCs increasing infection risk), liver disease (w/propylthiouracil)
Low cure rate (30-40%)
What is the surgical procedure done to treat Graves’ disease?
Total thyroidectomy (removal of the whole thyroid)
What are the complications that may arise as a result of a total thyroidectomy?
Hypothyroidism Hypoparathyroidism Recurrent laryngeal nerve damage Bleeding Thyroid storm (release of high conc. of TH into circulation)
What is Iodine-131 and how is it used to treat Graves’ disease?
A capsule ingested usually used after drug pre-treatment and is highly effective
What are the risks of radioactive (131I) therapy?
Hypothyroidism
Cancer
Infertility
Teratogenesis (contra-indicated in pregnancy and breast feeding)
Common aetiology for hypothyroidism
Autoimmune-Hashimoto's Thyroiditis (TPO and Tg antibodies-genetic predisposition) After hyperthyroidism treatment Subacute/silent thyroiditis Iodine deficiency Congenital
What is the process involved in Hashimoto’s Thyroiditis?
Inflammation and goitre/swelling, lymphocytic reaction, fibrosis and shrinkage-inability to produce sufficient thyroid hormones
What is the result of iodine deficiency?
Goitre/Hypothyroidism
How do you treat iodine deficiency in a population?
Supplementation programmes
What are the cardiovascular symptoms and signs of hypothyroidism?
Bradycardia (slow HR)
Heart Failure
Pericardial effusion
What are the symptoms and signs of hypothyroidism in the skin?
Myxoedema
Erythema ab igne
Vitiligo
What are the gastrointestinal symptoms and signs of hypothyroidism?
Weight gain
Constipation
What are the neurological symptoms and signs of hypothyroidism?
Depression
Psychosis
Carpal tunnel syndrome
What is the treatment for hypothyroidism?
Levothyroxine
What is a euthyroid state?
Normal thyroid function
What are thyroid nodules/goitre?
Non-specific enlargement of the thyroid gland
Which is more prevalent, Palpable/Visible goitre?
Palpable goitre
What is the management of Thyroid cancer?
Total or partial thyroidectomy
Radioiodine ablation
Thyroxine suppression
Measurement of serum thyroglobulin
What cells cause most Thyroid cancers?
Follicular cells
What is the aetiology of thyroid cancer?
External irradiation
Iodine deficiency
Oncogene expression
Genetic factors
What is the investigative process of thyroid nodules/goitre?
1) Assessment of thyroid function-serum TSH/fT3/fT4
2) Assessment of thyroid size (X-ray of thoracic inlet/CT or MRI of neck)
3) Assessment of thyroid pathology (differentiation of solid from cystic/single from multiple nodules)
What is the effect of radioactive (131I) therapy?
It is taken up by the thyroid and causes destruction of thyroid cells, decreasing amount of thyroid hormone produced
What is the most common cause of thyroid hormone deficiency world-wide?
Iodine deficiency
