Thyroid Flashcards
What do thyroid follicular cells secrete?
T3 and T4
What are parafollicular C cells responsible for?
Section of calcitonin
What does thyroglobulin contain?
Iodide to supply thyroid hormones for 90 days
What effect does TSH have on thyroid follicular cells?
Stimulates thyroid follicular cells to produce thyronine hormones (T3 and T4)
What role of cAMP have on thyroid cells?
Activates functional aspects of thyroid cells e.g.
Thyroglobulin synthesis
Iodide pumping
Iodination by thyroid peroxidase
Endocytosis, proteolysis and hormone release
Describe the process of iodide transport in follicular cells
Iodide ions are transported from the bloodstream into cells via NIS which transports 2Na+ or each I- anion into the cell
Iodide ions are transported from the cells into the lumen via Pendrin transporter
Once inside the lumen, I- is oxidised into atomic iodine
Describe the action of thyroid peroxidase enzyme
TPO spends the apical membrane and is responsible for the iodination of thyroglobulin
TPO adds iodide onto thyroglobulin backbone - consists of tyrosine residues. Can be added in 2 different places to give mono/di-iodotyrosine
Iodinated thyroglobulin is taken into cells by endocytosis,. Proteolysis occurs by lysosomes which release T2 and T4 from the backbone of thyroglobulin
Give examples of 2 thyroid hormones
Discuss their abundance/characteristics
Thyronine - T3: more active/potent
Thyroxine - T4: major form in the blood and has a longer half life than T3
T4 can be converted to T3 as required to protect the body from excess
Which drugs are used to treat hypothyroidism?
Levothyroxine sodium T4: tablets or oral solution
Liothyronine T3: tablets or slow iv infusion
Which drugs are used to treat hyperthyroidism?
Carbimazole
Propylthiouracil
Describe the characteristics of thyroxine
Insoluble in serum - transported in serum in conjunction with specific binding proteins which are synthesised in the liver
What effect does lover disease have on T4?
Loss of effective T4 transport to peripheral tissues
How doe thyroid hormones enter cells?
Via specific transporters
Describe the location and actions of iodothyronine deiodinases
DIO1 - predominant in the liver, kidney and muscle. Also found in thyroid. Produces most of the circulating T3
DIO2 - predominant in areas of CNS and pituitary thryrotropes. Controls intercellular T3 concentration. Important for feedback regulation. Found in skeletal muscle in some species
DIO3 - produces inactive rT3 and prevents thyroid hormone access to specific tissues
Where are thyroid hormone receptors located?
TR⍺ and TRβ are found in the nucleus
Describe thyroid hormone action
Functions as a transcription factor Bind to thyroid responsive element Higher affinity for T3 and T4 Increases gene transcription Can inhibit gene transcription
Describe the action of thyroid hormones in the anterior pituitary
Thyroid gland predominantly secretes T4
Human serum has a high conc of T4 binding proteins this causes high circulating levels of protein bound T4
Only free T3 and T4 are biologically active
T3 and T4 bind to nuclear hormone receptors to alter gene transcription in target cells
List the biological actions of thyroid hormones
- Control of metabolic rate
- Growth
- Foetal development
- Cardiovascular effects
- Musculoskeletal effects
How are thyroid hormones involved in growth?
What do deficiencies lead to?
Affect most bodily functions
Often synergise with other hormones
Deficiencies lead to abnormal growth, development, reproduction, behaviour and metabolism
How are thyroid hormones involved in foetal development?
What happens when there is a low supply of T4?
Develop neural and skeletal systems
Loss of T4 supply to the foetus leads to irreversible mental impairment and dwarfism - congenital iodine deficiency syndrome.
What are the effects of low T4 on a foetus, neonate and child & adolescent?
Foetus: miscarriage, still births, congenital abnormalities, perinatal morbidity, mortality and congenital iodine deficiency syndrome
Neonate: goitre hypothyroidism and impaired mental function
Child and adolescent: goiter hypothyroidism, impaired mental function, impaired physical development
How are thyroid hormones involved in cardiovascular events?
T3 increases cardiac contraction and output heart rate, oxygen supply to tissues and CO2 removal from tissues
What are the direct effects of thyroid hormones on the heart?
Increased myocardial Ca2+ uptake
Increase expression of ⍺-myosin heavy chain and decrease β heavy chain
What are the indirect effects of thyroid hormones on the heart?
Increased metabolism - thermogenesis and vasodilation
Increased sensitivity to catecholamamines
How are thyroid hormones involved in musculoskeletal system?
T3 has potent stimulatory effects on bone turnover, increasing formation and resorption
T3 increases linear bone growth after birth
T3 increase rate of muscle relaxation
Normal skeletal muscle function requires T3
How is calcium involved in bodily functions?
Growth Maintenance of skeletal system Neurotransmitter release Muscle contraction Hormone secretion Blood clotting Intracellular Ca2+ signaling Apoptosis
Give examples of calcium rich foods
Dairy, kale, spinach, organic tofu, broccoli, almonds and flax/sesame seeds
How is calcium homeostasis governed?
Careful balancing of absorption, excretion and storage of ions
Give 2 examples of main hormones involved in the regulation of calcium homeostasis
Calcitonin
Parathyroid hormone
Name the cells involved in bone turnover
Osteoblasts: synthesise bone tissue
Osteoclasts: resorb bone tissue - they are critical in the maintenance and repair of long bones in the mammalian skeleton
Describe primary hyperparathyroidism and treatment
Inappropriate excess production and secretion of PTH
Caused by a single benign growth or nodule in one parathyroid gland
Signs and symptoms: increases calcium in blood and urine and calcium deposits in the kidney
Mild disease doesn’t usually need treatment but should be monitors, can offer vitamin D supplements
Describe secondary hyperparathyroidism and treatment
Long term high PTH levels to attempt to raise blood calcium due to chronic hypocalcaemia
Commonly de to vitamin D deficiency and CKD
Symptoms: muscle aches and weakness
Treat with vitamin D and calcium supplements
Give examples of disease states caused by ineffective Ca2+ homeostasis
Primary hyperparathyroidsim Secondary hyperparathyroidism Osteoporosis Rickets Calcium stones Receptor mutation
What is the function of calcitonin?
Reduce blood concentration Ca2+
It opposes the effect of PTH: reduces osteoclast activity to reduce bone resorption, allows rapid bone deposition by osteoblasts and to reduce blood Ca2+
Describe the parathyroid gland
Most people have 4 parathyroid glands located on the posterior surface of the thyroid
Has 2 cell types: chief cells and oxyphil cells
Chief cells are responsible for the production of PTH
Describe parathyroid hormone
Small helical protein
T half life <20 mins
Function is to increase blood concentration of Ca2+ when it gets too low
Opposes effect of calcitonin
Describe the action of parathyroid hormone
Low calcium is detected by GPC Ca2+ sensing receptors
Indirectly stimulate oesteoclasts to release more Ca2+ from bone resorption
Increases renal Ca2+ reabsorption, reducing excretion through infiltration
Increases production of vitamin D - increases absorption of Ca2+ from the intestine
How is parathyroid hormone regulated?
Regulation occurs through negative feedback
- increase in blood decreases PTH secretion
- increases bone formation
What are the different levels of thyroid disease?
Primary thyroid disease: affects production of T3 and T4
Secondary thyroid disease: affects pituitary glands, there are problems with T3 and T4 but also with TSH
Tertiary thyroid disease: knocks out THR
What are the causes of primary hypothyroidism?
Autoimmune - most common
Result of previous treatment for hyperthyroidism
Iodine imblanace
Congenital hyperthyroidism
What are the symptoms of hypothyroidism?
Lethargy Weakness Dry scaly skin Dislike of cold weather Depression Hair loss Memory loss Weight gain Constipation Gruff voice
What would TFTs should in hypothyroidism?
Increase in TSH and decrease in free T4
What is the initial treatment for hypothyroidism?
In adults ≤50 years
- 50-100µg Levothyroxine OD
- adjusted by 25-50µg every 3-4 weeks
Adults >50 years and in heart disease
- 25µg OD
- adjusted by 25µg every 4 weeks
Congenital hypothyroidism
- 10-15µg/kg for neonates
- adjusted by 5µg/kg every 2 weeks
Elderly adults and neonates have similar initial doses
What is the maintenance treatment for hypothyroidism?
Adults: 100-200µg
Children: 50-200µg
Monitor TSH yearly - should be in the lower half of reference range
Can be used as a combination treatment for hypothyroidism?
Liothyronine and levothyroxine
Give the counselling points for a patient with hypothyroidism
Life long treatment
Single daily dose
Don’t take at the same time as calcium/iron preparations
3 strengths of tablet
Need monitoring
Entitled to medical exemption certificate
What are the symptoms of hyperthyroidism?
Anxious Palpitations Tremour Weight loss Tachycardia Goitre Sleeping Diarrhoea
What would TFTs should in hyperthyroidism?
Reduced TSH and increased T4
Which patient groups are thioanamides preferred as treatment for hyperthyroidism?
Children, Pregnancy, Breast feeding, Uncomplicated disease in young adults Acute phase prior to surgery
How do thionamadies work?
Interfere with thyroid hormone synthesis by inhibiting thyroperoxidase activity in the follicular lumen
Which drug is is first line in hyperthyroidism?
How should it used?
Carbimazole
15-40mg OD initially depending on severity
Maintain until TFTs are normal (4-8 weeks)
Maintenance for 12-18 months
What is the blocking replacement regimen in hyperthyroidism?
Carbimazole 40-60mg for 4 weeks then
Carbimazole 40-60mg + thyroxine 50-100mg
Give the counselling points for a patient with hyperthyroidism
Carbimazole OD
Tell them duration of treatment and tapering
Short term use of beta blockers
Report signs of agranulocytosis and hepatic dysfunction
Regular medicines review
Management of relapse
What is the treatment regime for propylthiouracil?
200-400mg daily initial and in divided doses
Reduce to 50-150mg daily maintenance
What are the disadvantages of propylthiouracil and carbimazole?
They cause drug induced agranulocytosis - bone marrow suppression
White cell count is suppressed which increases risk of infection
When would radioactive iodine be used in hyperthyroidism?
When patient has failed to respond to drug treatment, relapse after drugs and toxic nodular goitre
When would surgery be used in hyperthyroidism?
Oesophageal obstruction
Intolerance to drug treatment
Young age
What is adjuvant therapy in hyperthyroidism?
Beta blockade
Provides rapid relief of symptoms within 4 days
Which drugs can induce thyroid disease?
Iodine
Aminodarone
Lithium
How does iodine induce thyroid disease?
Acute overdose: inhibits release of T3/T4
Prolonged overdose: suppressed T3/T4
Iodine deficiency can cause hypothyroidism due to inability to produce T3/T4
How does amiodarone induce thyroid disease?
Contains organic organic iodine
Hypothyroidism: can occur at any time in treatment, causes inhibition of synthesis and release of T3 and T4. Continue amiodarone and start replacement T4 therapy is necessary
Mild hyperthyroidism: blocks conversion of T4 to T3, this increases TSH and T4. Transient when treatment is started but normalised in 3-4 months
Severe hyperthyroidism: increased production of T4 because of iodine content. Direct thyroiditis - excessive release of T4 into circulation. Withdraw treatment or use carbimazole
How does lithium induce thyroid disease?
Causes hypothyroidism
Inhibits iodine uptake and prevents T3 and T4 release
Can be transient and subclinical
Hyperthyroidism: rare paradoxical effect
