Endocrine - thyroid and anti-thyroid Flashcards
(35 cards)
thyroid hormones function
liver - lipid turnover, gluconeogenesis
muscle - insulin sensitivity, glucose utilisation, oxidative metabolism
adipose - lipolysis
heart - diastolic (relaxation), increase contractility of heart
vessels - vasodilation, decrease resistance, increase venous tone
synthesis of T3/T4 requirements
Na/I symporter
- > TPO oxidation (thyroid peroxidase)**
- > iodination**
- > conjugation
- > endocytosis
- > proteolysis
- > D1/D2 (deiodinases) converts T4 -> T3
wolff-chaikoff effect
when there is iodine exposure, excess iodine gets transported into the gland via Na-I symporters-> inhibition of TPO -> decrease synthesis of thyroid hormones
so administer KI during emergency hyperthyroidism
causes of hypothyroidism
primary:
- autoimmune: Hashimoto’s thyroiditis - antibodies attack TPO in thyroid gland
- iodine def
- drugs with high iodine (amidarone) - wolff chaikoff effect
secondary:
- pituitary failure: decrease in TSH secretion
- hypothalamic failure: decrease TRH
congenital hypothyroidism
hypothyroidism symptoms
- fatigue, lethargy
- mental slowness
- dry skin
- weight gain
- irregular menses
- hair loss/ puffy eyes
drugs for hypothyroidism
isomers of the thyroid hormones
- levothyroxine (T4)
- liothyronine (T3)
levothyroxine
- method
- onset
- half-life
- clinical use
- monitoring
- method: oral/ IV
- onset: oral (3-5); IV (6-8)
- half-life: 1wk
- clinical use: (IV) myxedema coma (decreased mental status w/ hypothermia) + congenital hypothyroidism
preferred over liothyronine
need to monitor thyroid fn 6-8wks after therapy
liothyronine
- method
- onset
- half-life
- clinical use
- method: oral/ IV
- onset: 3hrs
- half-life: 1 day
- clinical use: (IV) myxedema coma
for rapid onset - not to be used for chronic replacement of thyroid hormones
thyroid replacement therapy ADR
CVS: tachycardia, palpitations, hypertension, cardiac arrest
heat intolerance
hyperactivity, insomnia, irritability
bone: bone resorption, reduced bone mineral density
levothyroxine DDIs and food interaction
30-45 minutes on empty stomach
DDI w/ estrogen hormone replacement: increase thyroxine-binding globulin levels -> bind to thyroxine -> reduce free thyroxine to cure the hypotension
levothyroxine in subclinical hypothyroidism (normal T4, raised TSH)
only to be used if TSH > 10
does not reduce CVS/mortality in these pts
levothyroxine in elderly
elderly: decrease lean body mass w/ age -> decrease thyroid degradation
causes reduced bone mineral density, increasing risk of fractures
need to start with small dose then slowly titrate
levothyroxine in pregnancy
hypothyroidism can impair fetus neuropsychological development, miscarriage, premature death, low birth weight
so need to increase levothyroxine dosage (30-50%) during pregnancy + 4-6wks during pregnancy
levothyroxine in IHD pts
full dose of levothyroxine can ppt acute coronary syndrome, cause of +ve inotropic & chronotropic effects of T4 on heart
start w/ small dose then titrate up
hyperthyroidism signs and symptoms
increased metabolism -> increased appetite + weight loss
heat production - flushed, warm moist skin
tachycardia, anxiety
causes of hyperthyroidism
- autoimmune: Grave’s disease
thyroid stimulating ab pretends to be TSH and binds TSH receptors -> stimulates thyroid hormone synthesis + gland growth - hyperactive thyroid nodules
- iodine consumption
- thyroid hormone consumption - drugs
- inflammation -> release of stored hormones
Grave’s signs and symptoms
- bilateral proptosis
- periorbital edema
- lid retraction
- skin lesions
- clubbing
drugs for hyperthyroidism**
- thioamides (anti-thyroid)
- high conc of iodine
- radioactive iodine
thioamides drugs (2)
carbimazole* - more common in SG
propylthioracil (PTU) - black box warning
thioamides MOA
inhibit TPO
inhibits iodination: interferes w/ incorporation of iodine into thyroglobulin
specific to each drug:
PTU - inhibits T4->T3 deionisation
Carbimazole - converted to thiamazole - anti-thyroid
PTU - half life - absorption method - metabolism - excretion - dosing freq - does it cross placenta - affects breast milk? difference from carbimazole
- half life: ~ 1hr
- absorption method: oral
- metabolism: hepatic
- excretion: urine - 35% gets excreted within a day
- dosing freq: 1-4 times/day
- does it cross placenta: yes
- affects breast milk? no
used during thyroid storm: extra effect of blocking peripheral conversion of T4 -> T3
carbimazole
- half life
- absorption method
- metabolism
- excretion
- dosing freq
- does it cross placenta
- affects breast milk?
- half life: ~ 4-6hrs
- absorption method: oral
- metabolism: hepatic
- excretion: urine
- dosing freq: 1/2 times/day
- does it cross placenta: yes
- affects breast milk? no
thioamides clinical use
+ onset time
- graves
- thyroid storm: PTU
- overactive thyroid gland
- radioiodine therapy/ thyroidectomy prep
- slow onset (3-12 wks)**
thioamides ADR
quite low incidence rate
- possible agranulocytosis**(leukopenia - decreased WBC) (first 3 mths) - watch out signs of sore throat, fever, infection -> do complete blood count
- purpuric papular rash
- cholestatic jaundice
- liver failure if severe - esp if PTU: black box warning
