Thyroid function and dysfunction Flashcards
Which two hormones are released by the thyroid?
T3 and T4
How does hypothalamus communicate with anterior pituitary?
TRH
How does anterior pituitary communicate with thyroid?
TSH
Which two compounds form basis of T3 and T4?
Tyrosine and iodine
What does colloid do?
Production of T3/T4
How are T3/T4 made?
Thyroglobulin made from follicular cells I- and Na+ move into cell (co-transport) I- trapped TPO converts to iodine by H2O2 Binds to tyrosine Forms MIT and DIT 2x DIT makes T4 DIT and MIT makes T3
What does pendrin do?
Pushes iodine into colloid
What does thyroid hormone do?
Increases metabolic activity
Activates via DNA transcription
Half life of T3
1 day
Half life of T4
7 days
Why is more T4 made than T3?
T4 converted to T3
What does TSH do to make T3 and T4?
Stimulates symporter, thyroglobulin synthesis and exocytosis
Thyroid impact on gene expression in nucleus
Stimulates nuclear receptors to activate DNA transcription, receptors are normally occupied by inhibitory repressors which are displaced by T3 to start activation
Thyroid impact on gene expression in mitochondria
Direct action to increase oxidative phosphorylation, stimulates mitochondrial DNA transcription
Thyroid impact on cell membrane in mitochondria
GPCR (Gq) = stimulates nuclear DNA transcription
Action of thyroid hormones
Enhances basal metabolic rate Increases cardiac muscle activity Increases Sympathetic NS activity Protein synthesis Activates GH
Symptoms of hypothyroidism
- Weight gain
- Under-active thyroid:
- Slowed metabolic rate, reduced oxygen consumption, reduced protein synthesis
- Symptoms:
- Lethargy
- Weight gain
- Cold intolerance
- Bradycardia/hypotension
- Slow reflexes and speech
- Dry skin/thinning hair
- Mucopolysaccharide deposits (myxoedema)
- Adult screening not done routinely
- Outer third of eyebrow lost
TSH, T3 and T4 for hypothyroidism
TSH increased, T3 and T4 decreased
Causes of underachieve thyroid
Surgery
Anterior pituitary damage - tumour/surgery
Autoimmune - Hashimoto
Iodine deficiency
What is Hashimoto’s disease?
Normal immune tolerance falls
CD4+ lymphocytes recruit B cells and CD8+ cells to thyroid
Anti-TPO ABs and anti-thyroid cytotoxic T cells result in follicular destruction
Causes of congenital hypothyroidism
Iodine deficiency
Developmental failure
Genetic defects
Symptoms of congenital hypothyroidism
Coarse appearance, floppy, mental retardation, short stature
Symptoms of hyperthyroidism
Weight loss, heat intolerance, tremor, tachycardia, muscle weakness
What is exophthalmos?
Inflammation behind eyes
Causes of hyperthyroidism
TSH secreting tumour on ant. pituitary
Autoimmune (Grave’s or early Hashimoto)
Adenomas
What is Grave’s disease?
Normal immune balance disrupted, anti-TSH receptor ABs generated that mimic TSH and stimulate receptor by binding to it
Summary of Hashimoto
Anti TPO antibodies
Impaired thyroid hormone synthesis
Hypothyroidism
Low T3/4 and high TSH
Summary of Grave’s disease
Anti TSH receptor
Binds to receptor and mimics TSH
Hyperthyroidism
High T3/4, low TSH
Papillary thyroid cancer
Affects papillary cells
Slow growing
Spread to lymph nodes
Good outcome
Follicular thyroid cancer
Affects follicle cells
Spreads to lungs/bones
Good outcome with surgery and iodine
Medullary thyroid cancer
Affects c cells (calcitonin) Aggressive Distant spread Radical surgery needed Fair outcome
Anaplastic thyroid cancer
Affects undifferentiated cells Very aggressive Invades airway Treatments are minimally effective Poor outcome
