endo: thyroid Flashcards
thyroid hormones are impt for
normal growth, development and for controlling energy metabolism
production of thyroid hormones are dependent on
TSH
- secreted by the pituitary gland, in response to stimulation from hypothalamus in the brain
our thyroid gland secretes 3 main hormones:
T4: thyroxine, or tetra-iodothyronine
T3: tri-iodothyronine
Calcitonin - involved in the control of plasma Ca2+ and is used to treat osteoporosis and other metabolic bone diseases
T4 converted to T3 by the body
where it is transferred by blood to tissues of the body, where it acts
regulation of thyroid hormone secretion
- myrial neural inputs influence hypothalamic secretion of thyrotropin-releasing hormone (TRH)
- TRH stimulates release of thyrotropin (TSH, thyroid-stimulating hormone) from the anterior pituitary
- TSH stimulates the synthesis and release of the thyroid hormones (T3 and T4)
- T3 and T4 feedback to inhibit synthesis and release of TRH and TSH
- Low levels of I- are required for T4 synthesis, but high levels inhibit T4 synthesis and release
wolff-chaikoff effect
autoregulatory phenomenon
- during initial iodine exposure, excess iodine is transported into the thyroid gland by the sodium-iodide symporter > this transport results in transient inhibition of thyroid peroxidase and a decrease in the synthesis of thyroid hormone
s/sx of hypothyroidism
- fatigue and lethargy
- mental slowness
- dry skin
- weight gain
- irregular menses
- hair loss
when is liothyronine preferred over levothyroxine?
when a rapid onset of action is needed:
- less desirable for chronic replacement therapy due to short half life coupled with cost
- iv for treatment of myxedema coma (severe presentation of hypothyroidism, state of emergency)
overdosing of levothyroxine or liothyronine can cause
cardiac arrest, hypertension, palpitations, tachycardia, anxiety, heat intolerance, hyperactivity, insomnia, irritability, weight loss
- in children: insomnia, restlessness, accelerated growth and bone maturation
long term use of high dose levothyroxine has been associated with
incr bone resorption and reduced bone mineral density, esp in post-menopausal women
onset of action - levothyroxine vs liothyronine
3-5 days (oral), within 6-8hrs (iv)
VS 3hrs (oral or iv)
persistently elevated TSH levels despite treatment with levothyroxine may happen due to
inadequate dosing, poor compliance, malabsorption, drug or food interaction
levothyroxine should be taken (time of the day)?
30-45mins before breakfast, on an empty stomach
with estrogen hormone replacement treamtent, incr/decr in levotyroxine dose required?
incr, due to incr thyroxine-binding globulin levels > binds levothyroxine and reduces the amt avail for action
drugs and supplements that reduces absorption of levothyroxine
iron, calcium carbonate, cholestyramine, soya, fiber, caffeine, antacids
drugs and supplements that increases clearance of levothyroxine
phenytoin, carbamazepine, phenobarbital, rifampicin
drugs and supplements that increases binding of levothyroxine
estrogen hormone replacement therapy
levothyroxine enhance effects of (drugs)
warfarin, amitriptyline
levothyroxine decr effects of (drugs)
propranolol
when should we treat subclinical hypothyroidism? and w what?
TSH>10mIU/L, levothyroxine shown to reduce cv events and mortality
levothyroxine dose requirement gradually incr or decr w age? and why?
decr, due to age-related decr in thyroxine degradation and in lean body mass
levothyroxine replacement may precipitate ___ in an elderly person with asymptomatic IHD
severe angina or myocardial infarction
in people >65yo, levothyroxine should be
started at a small dose and dose titration should be carried out slowly
over-replacement of levothyroxine in the elderly population have been associated with
reduced bone mineral density and incr risk of fractures
thyroid hormone insufficiency in pregnancy can result in
impaired neuropsychological development of the offspring (who only starts developing thyroid hormone after 12 weeks)
maternal hypothyroidism is associated with
miscarriage, premature death, and low birth weight - can be prevented with optimum thyroid hormone replacement
most women with known hypothyroidism need a _____ incr/decr dose of levothyroxine during pregnancy
30-50% incr, as early as first 4-6 weeks of gestation
- patients will need a reduction of their levothyroxine dose after pregnancy
general consensus that subclinical hypothyroidism in pregnant women should or should not be treated?
should be treated, with levothyroxine
prolonged untreated hypothyroidism can lead to
persistent bradycardia, an adverse atherogenic lipid profile, and deterioration in myocardial function
newly diagnosed hypothyroid patients with IHD should be started on
small dose of levothyroxine, slowly titrated up every 4-6 weeks until euthyroidism is achieved
- positive inotropic and chronotropic effects of thyroid hormone on the heart: starting full dose of levothyroxine could precipitate ACS in hypothyroid patients with silent IHD
s/sx of hyperthyroidism
- increased motor activity, metabolism
- incr heat production (flushed, warm moist skin)
- incr appetite, and weight loss w insufficient intake
- incr hr, anxiety
causes of hyperthyroidism
- grave’s disease: caused by thyroid stimulating antibody (binds to TSH receptors on the thyroid glands), stimulates both thyroid hormone synthesis and thyroid gland growth resulting in hyperthyroidism and thyromegaly
- hyperactive thyroid nodules
- incr iodine consumption
- incr thyroid hormone consumption
- inflammation and release of stored thyroid hormones
what is grave’s disease precipitated by?
environmental factors like stress, smoking, infection, iodine exposure, pregnancy
moa of thioamides
thought to inhibit thyroid peroxidase enzyme (TPO) and interfere with incorporation of iodine into tyrosyl residues of thyroglobulin (iodination)
inhibit coupling of iodotyrosyl residues to form iodothyronines
PTU additional MOA
inhibits deiodination of T4 to T3
carbimazole is converted to active metabolite
thiamazole, after absorption
- anti-thyroid effects are due to thiamazole
PTU vs carbimazole: dosing frequency
1-4 times daily, once or twice daily
PTU vs carbimazole: plasma half life
75mins vs 4-6hrs (thiamazole: 5-13hrs)
PTU vs carbimazole: which is preferred for treatment of thyroid storm?
PTU, has a small but additional effect of blocking the peripheral conversion of T4 to T3
when can we expect improvement of grave’s disease following thioamide treatment?
3-6 weeks
therapeutic uses of thioamides
- grave’s disease
- thyroid storm
- overactive thyroid gland
- to attain a euthyroid state rapidly in preparation for radioiodine therapy or thyroidectomy
most serious reaction seen to develop from PTU or thiamazole
agranulocytosis: sore throat, fever, or other signs of infection
- more common within the first 3 months of use
- reversible upon discontinuation of the offending drug
-> STOP and have a complete blood count
most common reaction from thioamides
mild, occasionally purpuric, urticarial papular rash
- often subsides spontaneously without interrupting treatment
black box warning for PTU
liver failure
hyperthyroidism in pregnancy
thyroid dysfunction diminishes as pregnancy proceeds
- hence, reduction of dosage of thioamides may be possible
PTU use during pregnancy
readily crosses placental membranes, can induce goiter and even cretinism in the developing fetus - important that a sufficient but not excessive dose be given
- warn pt of the rare potential hazard to the mother and fetus of liver damage
*PREFERRED agent during organogenesis (first trimester of pregnancy)
BUT given potential maternal adverse effects of PTU eg. hepatotoxicity, may be preferable to switch from PTU to thiamazole for the 2nd and 3rd trimesters
thiamazole use in pergnancy
may be associated with rare development of fetal abnormalities such as aplasia cutis and choanal atresia, only used in 2nd and 3rd trimester
effect of iodide once discontinued
effect may not be maintained
- may produce severe exacerbations of thyrotoxicosis when the gland ‘escapes’ from iodide block, following withdrawal of the iodides
iodide moa
high conc of iodide can
- suppress iodination of tyrosine and also coupling of the monoiodotyrosyl and diiodotyrosyl residue, thus inhibiting thyroid hormone synthesis
- decrease thyroid gland size and vascularity when given over 1-2 weeks
- can be used to temporarily inhibit T4 and T3 synthesis and release into the circulation (useful in thyroid storm)
can iodide be used in pregnancy and lactation?
no, crosses the placenta and may cause fetal goiter
therapeutic uses of iodide
- In the preoperative period, in preparation for thyroidectomy, as it reduces
thyroid hormone synthesis and release, and reduces thyroid size and
vascularity. (Consider concurrent beta-blockade (eg, propranolol) in the
immediate preoperative period to reduce the risk of thyroid storm) - Thyrotoxic crisis (An hour after Anti-thyroid drugs are administered) After a
radioactive iodine exposure, potassium iodide can be used to block uptake
of radioiodine by the thyroid, reducing the risk of thyroid cancer. - Endemic goitre Endemic goitre occurs in iodine-deficient areas. Goitre is
an adaptive process: iodine is essential for the production of thyroid
hormones; iodine deficiency impairs thyroid hormone synthesis; to
compensate, the thyroid gland increases in volume. Thyroid function usually
remains normal. Iodide is used as overcome the iodine deficiency
adr of iodide
- allergic reactions: angioedema, laryngeal edema > suffocation and rashes
- chronic intoxication with iodide (iodism): metallic taste, gi intolerance, soreness of the teeth and gums, increased salivation, irritation of the eyes, along with lacrimation and rhinorrhea, severe headache - disappear spontaneously within a few days after stopping adm of iodide
can radioactive iodine be used in pregnancy and lactation?
no, c/i!
- concentration of isotope in the fetal thyroid
- exposure of fetal tissues to radiation
- only can be used 6 wk after breast-feeding has stopped
adr of radioactive iodine
- high incidence of delayed hypothyroidism
- small but significant incr in certain types of cancer (incl stomach, kidney and breast) - these tissues express the sodium iodide transporter
- a/w worsening graves’ opthalmopathy
^ adr may set in 1-2 months after treatment
when is thyroidectomy best performed during pregnancy?
second trimester
PTU dose
initial: 300mg in 3 divided doses
usual maintenance: 100-150mg in 3 equally divided doses
treatment of thyrotoxic storm
antithyroid drugs (PTU 250mg Q4H after a loading dose of 500-100mg, or thiamazole 20mg Q6H), block thyroid hormone synthesis > inorganic iodine (saturated solution of KI 250mg Q6H or 1g IB Q12H), decr release of preformed T3 and T4, given 1 hr later
reduction of circulating thyroid hormones: cholestyramine up to 4g Q6H, enhance hormone fecal excretion
peripheral effects of thyroid hormones: BB
resolution of systemic manifestation:
- glucocorticoids (hydrocortisone, dexamethasone)l reduce T4 conversion to T3 and treat potential risk of adrenal insufficiency due to severe thyrotoxicosis (destructs effect on cortisol)
- paracetamol for fever
goals of therapy
- Preserve bone mass – stable or increasing BMD is considered a good response to treatment)
- Correct calcium deficiency
- Prevent future falls and fractures
- Pain relief
- Strengthen muscles and restore mobility and improve quality of life through physiotherapy
risk factors for osteoporosis
female
ca deficiency
low body mass
elderly
drugs: PPI
conditions: RA
smoking
excessive alcohol
physical inactivity
poor nutrition
Calcium absorption plateaus after
ingestion of more than 500mg-600mg elemental calcium in a single setting
calcium carbonate vs calcium citrate: absorption
calcium citrate not affected by gastric pH for absorption
calcium carbonate soluble in acid, take after food
Atypical femoral fracture: Look out for development of
dull aching pain in the hip, groin or thigh. Also look out for the development of severe bone, joint or muscle pain. Consult the doctor if any of those symptoms appears.
Osteonecrosis of the jaw: After starting the medication, monitor for any
oral symptoms (e.g. tooth ache, loose teeth, non-healing of sores or discharge) and practice good oral hygiene. Brush your teeth twice a day, floss regularly and visit the dentist at least twice a year. Let your dentist know that you are taking this medication before any dental procedure.
cellulitis, look out for
skin redness and swelling
signs or symptoms of low calcium
numbness of the lips, tingling in your hands or feet, muscle cramps, muscle weakness or seizures
Acute phase reaction:
For the first infusion, some patients may experience flu-like symptoms (headache, fever, muscle ache, joint pain) after the infusion, which may last for 1-7 days. This is most common after the first infusion, and less common for subsequent infusions. Take paracetamol 1g 30 minutes prior to infusion, and every 6 hours thereafter as needed for the next 2-3 days if symptoms develop. Your temperature, heart rate and blood pressure will be measured before, during and after the infusion. You will be observed for 45 minutes after the infusion to monitor for side effects.
