case 9 - thyroid gland and thyroid hormone Flashcards
where is TRH released from
the hypothalamus and acts on the anterior pituitary
what does the anterior pituitary then release
TSH from the anterior pituitary
what does this TSH do
it activates the thyroid - T3 and T4 secretion
what is thyroid hormone formed from
sequential iodination of tyrosine
what is thyroid hormone stored as in the thyroid gland
colloid
what is T4 produced by
entirely by the thyroid
what is T3 produced by
partially by the thyroid, however peripheral T4 mono-deiodination in the liver and kidney make it metabolically active??
what is the half life of T3 and T4
half life of T3 is 1-3 days and half life of T4 is 5-7 days
T3 has to be given three times daily, T4 once daily
what does TR do
acts in the nucleus on gene expression, therefore thyroid hormone effects are slow
what does TR do
acts in the nucleus on gene expression, therefore thyroid hormone effects are slow
what is the HPT axis regulated according to
the principles of negative feedback; for primary thyroid disorders, TSH indicates thyroid status - a biomarker
what is a goitre
an enlarged thyroid gland
what is the active form of thyroid hormone
T3
where does T4 get converted
in the peripheral tossues
what does T3 do
regulates gene expression - for it to have effect it has to get into the cell and turn genes on - it is a slow process
what is the aetiology of primary hypothyroidism
autoimmune thyroiditis (Hashimoto disease)
4.1/1000 females; o.6/1000 males per year over 20 years, increasing
5% of over 60s
Classic Hashimoto (goitrous)
Atrophic (non-goitrous)
In reality, a mix of antibody mediated/ T cell mediated
TPO, TSHR, Tg auto-antibodies - most important one is TSH
what drugs can cause hypothyroidism
drugs (amiodarone, iodides, lithium) - these can cause hypothyroidism
what is the aiteology of secondary hypothyroidsm
pituitary adenoma, congenital deficiency, irradiation
Sarcoid, infection
what are the symptoms and signs of hypothyroidism
insidious
Weight gain
Cold intolerance, particularly at extremities
Fatigue, leathery
Depression
Mentally slowed, dull, expressionless
Coarse skin, puffy, (possible carpal tunnel syndrome) - aminoglycans
Dry, brittle, thinning hair
Hoarse voice
Constipation, faecal loading
Menstrual disturbance
Muscle stiffness, cramps, slow-relaxing reflexes
Generalised weakness and paraethesias
Cerebellar ataxia
Bradycardia
Macroglossia
family history
History of other autoimmune disorders
what are some examples of organ-specific autoimmune diseases that increase the risk
graves disease
Autoimmune hypothyroidism
Pernicious anaemia
Addison disease
Autoimmune atrophic gastritis
Type 1 diabetes mellitus
what does pernicious anaemia arise from
arises from autoimmune destruction of the parietal cells, loss of intrinsic factor secretion and consequently vitamin B12 deficiency
what are the investigations done
blood tests
(TFTs)
Normochromic normocytic anaemia
Macrocytosis (also to do with B12 deficiency), mixed dyslipidaemia
Consider other autoimmune endocrinopathies
Adrenal, ovary, T1DM, pernicious anaemia, vitiligo
no need for an ultrasound scan
what is the treatment for hypothyroidism
once daily thyroxine, lifelong, usually 100 mcg; young, rapid start; elderly, gentle increment
Goal; normalise TSH, repeat blood tests after 4-6 weeks
what is *fT4↓; fT3↓; TSH↑ treated with
thyroxine
what is *fT4 →; fT3 →; TSH treated with
nothing - this is normal - never treat with thyroxine
what does *fT4 →; fT3 →; TSH↑ mean
compensated response -
if there are symptoms - treat with thyroxine
if there are no symptoms - wait and repeat test
what does *fT4↓; fT3↓; TSH ↓ or → mean
consider potential pituitary disease / sick euthyroid syndrome
what is a major cause of goitre and hypothyroidism
iodine deficiency
what is thyrotoxicosis
excess circulation thyroid hormone - this is not hyperthyroidism
what is hyperthyroidism
an over active thyroid gland
what are symptoms of hyperthyroidism
(From most common to less usual)
*Irritability, nervousness
*Hyperactivity
*Heat intolerance, sweating
*Palpitations
*Weight loss
*Dyspnoea
*Fatigue, weakness
*Increased appetite
*Increased bowel frequency
*Altered mood
*Insomnia
*Oligo/amenorrhoea
*Hair loss
*
*Sore throat
*Family history
*History of other autoimmune disorders (Graves disease)
what would inspection show if got hyperthyroidism
Inspection: (clothing, weight, hair loss, eye disease, obvious goitre, ask patient to swallow)
what would hands show if got hyperthyroidism
Hands: (warm moist palms, fine tremor, palmar erythema, onycholysis, pulse rate and rhythm)
what does percussion have
retrosternal goitre
what are the extra findings
Extra findings: (hyperreflexia, muscle weakness, congestive cardiac failure)
what are the Graves specific findings
Graves-specific: (thyroid orbitopathy, pretibial myxoedema, vitiligo)
what is the integrate clinical thyroid statuses
Hyperthyroid
Euthyroid
Hypothyroidism
what is the differential diagnosis for primary hyperthyroidism
(transient thyroiditis)
Graves disease
Toxic nodule (part of multinodular goitre)
Pituitary adenoma
Thyroid hormone resistance symtoms
what would thyroid function test show
fT4 increases, fT3 increases, TSH decreased
fT4 —>; fT3—> TSH decreased: subclinical hyperthyroidism
thyroid auto-antibodies (stimulatory, mimic TSH) - helps distinguish
what would an ultrasound of primary hyperthyroidism show
Increased echogenicity: homogenous (Graves) or heterogenous (MNG)
what is the treatment for hyperthyroidism
block thyroid hormonogenesis
- Thionamide: Carbimazole or propylthiouracil (use PTU if trying for pregnancy)
- Goal: restore normal thyroid hormone levels; in time TSH should normalise
Definitive treatment options (radioiodine or surgery; radioiodine is very useful for toxic nodule)
what is Graves diseae
autoimmune characteristics
Associated with T1DM, Addison’s disease, vitiligo, pernicious anaemia, alopecia areata, myasthenia gravis, coeliac disease
what is the major autoantigen involved in graves disease
TSHR
what are the symptoms of graves disease
Thyroid eye disease / Graves orbitopathy
pretibial myxoedema
what is the treatment for Graves disease
–Carbimazole (immunosuppressive; N.B. agranulocytosis)
–Carbimazole + thyroxine
–Beta blockers for symptomatic relief
–Monitor thyroid function test
–Trial off treatment
–1/3 ‘cure’; 1/3 relapse sometime; 1/3 relapse soon
what is graves orbitopathy
inflammation of the extra ocular eye muscles, causing increases retro-orbital pressure - proptosis or optic nerve damage
what are the aggravates in graves orbitopathy
radioiodine aggravates
what is it treated with
Treated with artificial tears, immunosuppression, debatable effects of radiotherapy
