Thyroid PCT (exam 6)

ITAL

inhibit thyroid synthesis T4 to T3

-iodide

-tyrosine kinase inhibitors

-amiodarone

-lithium

estrogen

increases binding to TBG, decreases free thyroid hormone

salicylates

displaces T3 and T4 from binding from TBG, increases free thyroid hormone

3A4 inducers

increase metabolism so enhance degradation of thyroid hormones 

warfarin

-increases catabolism of clot factors

-decreased available clot factors

-increase INR

-want to decrease warfarin dose

glucose

can be affected by both hyper and hypothyroidism

amiodarone

-blocks D1 (deiodinase enzyme), induce hypothyroidism 

OR

-can induce hyperthyroidism

type 1 thyrotoxicosis

iodine induced (from amiodarone), occurs in pt with underlying thyroid disease 

type 2 thyrotoxicosis

inflammation causes leakage of thyroid hormone, treat with corticosteroids

induced by amiodarone

methimazole 

-inhibits thyroid peroxidase (and therefore blocks organification)

propylthiouracil

-inhibits thyroid peroxidase (and therefore inhibits organification)

-blocks T4 to T3 conversion in peripheral tissue

which is more potent: methimazole or propylthiouracil

methimazole, also is actively concentrated in thyroid gland

traits of both MMI and PTU

-does not work on circulating thyroid hormone

-readily cross the placenta and are excreted in breast milk

is remission possible in graves disease?

yes, after treatment of 12-24 months (or more) with anti thyroid meds

when is remission in graves more likely to occur?

-pt > 40 yrs

-small goiter

-short duration of graves (<6 months)

-no relapse with anti thyroid meds) 

-duration of PCT > 1-2 yrs 

remission + relapse info?

-follow pt q6-12m after remission

-if relapse occurs, treat with RAI

antithyroid med serious AE

-agranulocytosis (need broad spectrum antibiotics)

-vasculitis

-hepatic damage/failure (PTU)

-acute pancreatitis (MMI)

antithyroid common SE 

-itchy, papular rash

-arthralgia

-GI intolerance 

warfarin dose titration once levels go hyper to euthyroid?

-metabolism and therefore catabolism of clot factors decrease

-more clot factors available

-warfarin as an anticoagulant has a harder time doing its job now

-therefore INR will be decreased

-need to increase warfarin dose

monitoring for antithyroid meds:

-CBCs (can be low in graves) and LFTs (abnormal in thyrotoxicosis)

-free T4, total T3, and TSH q2-4 weeks

-symptom improvement within 3-8 weeks

-reduce dose once hypothyroid levels are received

RAI pregnancy/lactation considerations:

-CI in these populations

-must have a negative pregnancy test within 48 hrs prior to RAI

-delay conception for 6-12 months if possible

(delay in women until euthyroid, delay in med 3-4 months due to sperm turnover rate)

-D/C breastfeeding for 4-6 weeks prior RAI

RAI

-CI in thyroid malignancies who now cannot uptake any iodine

-not recommended in people with already affected sight

-rapid absorption after oral admin

-permanent treatment/cure (can take 1-2 doses, or sometimes >2), wait >/= 6 months before next dose

-may cause hypothyroidism

-is fixed dose or calculated based on thyroid size

-could induce thyroid storm (rare AE), or exacerbation of TED

-no iodide intake at this time (1-2 weeks prior)

-after want to flush RAI out of system with hydration, excess voiding, salivary flow 

CONCOMITANT MEDS:

-BB: symptom control for tachycardia, start prior RAI (but tech. can give at any time of tx)

-antithyroid drugs: stop 3 days prior RAI, start again 4 days post RAI, taper over 4-6 weeks 

who responds best to RAI/increase chance of success:

-high ablative dose

-females

-lower free T4 levels at dx

-no palpable goiter

TED (thyroid eye disease) considerations:

-pre treat with steroids to minimize impact of release of thyroid hormones on eye

-oral prednisone or dexamethasone (corticosteroids) or immunosuppressant (tepezza mab)

-start it AFTER RAI therapy

RAI monitoring

-assess within first 1-2 months

-again at 4-6 week intervals for 6 months (until pt becomes hypothyroid)

what value do you use to dose thyroid replacement?

T4

surgery pretreatment

-MMI, prior to iodide, start 6-8 weeks prior surgery to achieve euthyroid

-propranolol to maintain HR < 90, several weeks prior and 7-10 days after

-iodides to decrease vascularity, 10-14 days prior

surgery pretreatment in pt who cant take anti thyroid meds

-propranolol for rate control 

-dexamethasone to decrease T4 to T3 conversion

-cholestyramine (bind thyroid hormones and promote their excretion)

-SSKI (or lugol’s solution): iodide to decrease vascularity 

adjunct therapy for thyrotoxicosis

BB (antagonize the adrenergic effects)- good in older pt, HR> 90, CVD

iodide salts/iodine (pre-op for thyroidectomy or treat thyroid storm), only use after anti thyroid med

• cons: increases intracellular iodine stores

• thyroid escapes iodine block in 2-8 weeks

• withdrawal can exacerbate thyrotoxicosis

• can cross placenta and cause fetal goiter if chronic use

• not for chronic use in general

Tepezza (teprotumumab) 

-immunosuppressant that treats TED 

main cause of thyroid storm?

-withdrawal from anti thyroid meds

how to treat thyroid storm?

-BB (propranolol = DOC), anti thyroid med (PTU is preferred), inorganic iodide, corticosteroid

-avoid NSAIDs

levothyroxine

-protein binding is > 99% 

-half life = 7 days so onset of effect/in your body for 1 month 

levothyroxine dosing

-older pt and those with CVD: 12.5-25 mcg/day

-healthy, young middle age pt:

• calculated daily T4 = 1.6 mcg/kg/day, not to exceed 200 mcg/day, typically reserved for pt in thyroid surgery

• typically 25-50 mcg/day

-start low and go slow

-adjustments guided by TSH

-monitor TSH and T4 q4-6m

-can switch to 1x/week or 2x/week in pt with compliance issues

-take first thing in the AM on empty stomach or at least 30-60 min prior food (because there are so many binding drugs- ex: PPI, cipro, soy, coffee, calcium so milk)

-can also take >/= 3 hrs after evening meal

-separate interacting meds by 4 hours

-tirosint = gel capsule, can be given 15 min prior to breakfast, no interaction with PPIs, increased bioavailability

-wait 4-6 weeks to assess levothyroxine therapy because it takes this long to work

levothyroxine AE?

-excess replacement (HF, angina, MI)

-allergic/idiosyncratic reactions, synthroid 50 mcg tab = no dyes

-osteoporosis if chronic use

liothyronine

-is T3, only use as adjunct therapy with T4 

-use in pt with persistent symptoms despite RAI or surgery or pt symptomatic on T4 alone 

-avoid liothyronine in pregnancy and cardiac disease

only thyroid replacement for pregnant populations?

levothyroxine

desiccated thyroid hromone

-T4:T3 content is 4:1 (higher content vs physiologically produced) 

-leads to supraphysiologic levels of T3 

-FDA said we must be D/C, no evidence to support use

subclinical hypothyroidism treatment levels

-1 mcg/kg/day

or

-25-75 mcg/day

hypothyroidism and pregnancy

-adverse outcomes such as miscarriage, preterm delivery, preeclampsia

-basically is very dangerous 

-increase dose of levothyroxine as soon as possible with pregnancy

-monitor TSH and total T4 q4weeks

myxedema coma 

-rare, aggressive treatment is needed (levothyroxine ± liothyronine, hydrocortisone, supportive therapy, and glycemic control)

-manifests as hypothermia, advanced hypothyroid symptoms, altered sensorium, hypoglycemia, hypoventilation