endo: thyroid

Question 1

thyroid hormones are impt for

Answer 1

normal growth, development and for controlling energy metabolism

Question 2

production of thyroid hormones are dependent on

Answer 2

TSH
- secreted by the pituitary gland, in response to stimulation from hypothalamus in the brain

Question 3

our thyroid gland secretes 3 main hormones:

Answer 3

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

Question 4

T4 converted to T3 by the body

Answer 4

where it is transferred by blood to tissues of the body, where it acts

Question 5

regulation of thyroid hormone secretion

Answer 5

1. myrial neural inputs influence hypothalamic secretion of thyrotropin-releasing hormone (TRH)
2. TRH stimulates release of thyrotropin (TSH, thyroid-stimulating hormone) from the anterior pituitary
3. TSH stimulates the synthesis and release of the thyroid hormones (T3 and T4)
4. T3 and T4 feedback to inhibit synthesis and release of TRH and TSH
5. Low levels of I- are required for T4 synthesis, but high levels inhibit T4 synthesis and release

Question 6

wolff-chaikoff effect

Answer 6

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

Question 7

s/sx of hypothyroidism

Answer 7

• fatigue and lethargy
• mental slowness
• dry skin
• weight gain
• irregular menses
• hair loss

Question 8

when is liothyronine preferred over levothyroxine?

Answer 8

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)

Question 9

overdosing of levothyroxine or liothyronine can cause

Answer 9

cardiac arrest, hypertension, palpitations, tachycardia, anxiety, heat intolerance, hyperactivity, insomnia, irritability, weight loss
- in children: insomnia, restlessness, accelerated growth and bone maturation

Question 10

long term use of high dose levothyroxine has been associated with

Answer 10

incr bone resorption and reduced bone mineral density, esp in post-menopausal women

Question 11

onset of action - levothyroxine vs liothyronine

Answer 11

3-5 days (oral), within 6-8hrs (iv)

VS 3hrs (oral or iv)

Question 12

persistently elevated TSH levels despite treatment with levothyroxine may happen due to

Answer 12

inadequate dosing, poor compliance, malabsorption, drug or food interaction

Question 13

levothyroxine should be taken (time of the day)?

Answer 13

30-45mins before breakfast, on an empty stomach

Question 14

with estrogen hormone replacement treamtent, incr/decr in levotyroxine dose required?

Answer 14

incr, due to incr thyroxine-binding globulin levels > binds levothyroxine and reduces the amt avail for action

Question 15

drugs and supplements that reduces absorption of levothyroxine

Answer 15

iron, calcium carbonate, cholestyramine, soya, fiber, caffeine, antacids

Question 16

drugs and supplements that increases clearance of levothyroxine

Answer 16

phenytoin, carbamazepine, phenobarbital, rifampicin

Question 17

drugs and supplements that increases binding of levothyroxine

Answer 17

estrogen hormone replacement therapy

Question 18

levothyroxine enhance effects of (drugs)

Answer 18

warfarin, amitriptyline

Question 19

levothyroxine decr effects of (drugs)

Answer 19

propranolol

Question 20

when should we treat subclinical hypothyroidism? and w what?

Answer 20

TSH>10mIU/L, levothyroxine shown to reduce cv events and mortality

Question 21

levothyroxine dose requirement gradually incr or decr w age? and why?

Answer 21

decr, due to age-related decr in thyroxine degradation and in lean body mass

Question 22

levothyroxine replacement may precipitate ___ in an elderly person with asymptomatic IHD

Answer 22

severe angina or myocardial infarction

Question 23

in people >65yo, levothyroxine should be

Answer 23

started at a small dose and dose titration should be carried out slowly

Question 24

over-replacement of levothyroxine in the elderly population have been associated with

Answer 24

reduced bone mineral density and incr risk of fractures

Question 25

thyroid hormone insufficiency in pregnancy can result in

Answer 25

impaired neuropsychological development of the offspring (who only starts developing thyroid hormone after 12 weeks)

Question 26

maternal hypothyroidism is associated with

Answer 26

miscarriage, premature death, and low birth weight - can be prevented with optimum thyroid hormone replacement

Question 27

most women with known hypothyroidism need a _____ incr/decr dose of levothyroxine during pregnancy

Answer 27

30-50% incr, as early as first 4-6 weeks of gestation - patients will need a reduction of their levothyroxine dose after pregnancy

Question 28

general consensus that subclinical hypothyroidism in pregnant women should or should not be treated?

Answer 28

should be treated, with levothyroxine

Question 29

prolonged untreated hypothyroidism can lead to

Answer 29

persistent bradycardia, an adverse atherogenic lipid profile, and deterioration in myocardial function

Question 30

newly diagnosed hypothyroid patients with IHD should be started on

Answer 30

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

Question 31

s/sx of hyperthyroidism

Answer 31

- increased motor activity, metabolism - incr heat production (flushed, warm moist skin) - incr appetite, and weight loss w insufficient intake - incr hr, anxiety

Question 32

causes of hyperthyroidism

Answer 32

- 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

Question 33

what is grave's disease precipitated by?

Answer 33

environmental factors like stress, smoking, infection, iodine exposure, pregnancy

Question 34

moa of thioamides

Answer 34

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

Question 35

PTU additional MOA

Answer 35

inhibits deiodination of T4 to T3

Question 36

carbimazole is converted to active metabolite

Answer 36

thiamazole, after absorption - anti-thyroid effects are due to thiamazole

Question 37

PTU vs carbimazole: dosing frequency

Answer 37

1-4 times daily, once or twice daily

Question 38

PTU vs carbimazole: plasma half life

Answer 38

75mins vs 4-6hrs (thiamazole: 5-13hrs)

Question 39

PTU vs carbimazole: which is preferred for treatment of thyroid storm?

Answer 39

PTU, has a small but additional effect of blocking the peripheral conversion of T4 to T3

Question 40

when can we expect improvement of grave's disease following thioamide treatment?

Answer 40

3-6 weeks

Question 41

therapeutic uses of thioamides

Answer 41

- grave's disease - thyroid storm - overactive thyroid gland - to attain a euthyroid state rapidly in preparation for radioiodine therapy or thyroidectomy

Question 42

most serious reaction seen to develop from PTU or thiamazole

Answer 42

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

Question 43

most common reaction from thioamides

Answer 43

mild, occasionally purpuric, urticarial papular rash - often subsides spontaneously without interrupting treatment

Question 44

black box warning for PTU

Answer 44

liver failure

Question 45

hyperthyroidism in pregnancy

Answer 45

thyroid dysfunction diminishes as pregnancy proceeds - hence, reduction of dosage of thioamides may be possible

Question 46

PTU use during pregnancy

Answer 46

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

Question 47

thiamazole use in pergnancy

Answer 47

may be associated with rare development of fetal abnormalities such as aplasia cutis and choanal atresia, only used in 2nd and 3rd trimester

Question 48

effect of iodide once discontinued

Answer 48

effect may not be maintained - may produce severe exacerbations of thyrotoxicosis when the gland 'escapes' from iodide block, following withdrawal of the iodides

Question 49

iodide moa

Answer 49

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)

Question 50

can iodide be used in pregnancy and lactation?

Answer 50

no, crosses the placenta and may cause fetal goiter

Question 51

therapeutic uses of iodide

Answer 51

1. 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) 2. 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. 3. 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

Question 52

adr of iodide

Answer 52

- 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

Question 53

can radioactive iodine be used in pregnancy and lactation?

Answer 53

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

Question 54

adr of radioactive iodine

Answer 54

- 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

Question 55

when is thyroidectomy best performed during pregnancy?

Answer 55

second trimester

Question 56

PTU dose

Answer 56

initial: 300mg in 3 divided doses usual maintenance: 100-150mg in 3 equally divided doses

Question 57

treatment of thyrotoxic storm

Answer 57

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

Question 58

goals of therapy

Answer 58

- 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

Question 59

risk factors for osteoporosis

Answer 59

female ca deficiency low body mass elderly drugs: PPI conditions: RA smoking excessive alcohol physical inactivity poor nutrition

Question 60

Calcium absorption plateaus after

Answer 60

ingestion of more than 500mg-600mg elemental calcium in a single setting

Question 61

calcium carbonate vs calcium citrate: absorption

Answer 61

calcium citrate not affected by gastric pH for absorption calcium carbonate soluble in acid, take after food

Question 62

Atypical femoral fracture: Look out for development of

Answer 62

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.

Question 63

Osteonecrosis of the jaw: After starting the medication, monitor for any

Answer 63

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.

Question 64

cellulitis, look out for

Answer 64

skin redness and swelling

Question 65

signs or symptoms of low calcium

Answer 65

numbness of the lips, tingling in your hands or feet, muscle cramps, muscle weakness or seizures

Question 66

Acute phase reaction:

Answer 66

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.