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Dietary Sources of Iodine
§ Ionized salt
§ Seafood
§ Dairy products
§ Meat
§ Vegetables
§ Eggs
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Transport of iodine into thyroid cells
Na+/I- active symporter
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Iodine is oxidized to thyroglobulin
thyroid peroxidase (TPO)
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Iodine + Tyrosine
monoiodotyrosine (MIT)
and
diiodotyrosine (DIT)
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iodine deficiency MIT:DIT ratio
inc. MIT:DIT ratio
inc. T3:T4 ratio
inc. serum TSH
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Proteolysis of thyroglobulin
inc. T3, T4 & iodotyrosines
inhibited by excess iodine and lithium
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Unutilized iodine
Recycled
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Thyroid hormone transporters
§ Thyroxine-binding globulin (TBG)
§ Thyroxine-binding prealbumin (TBPA)
§ Albumin
T3 and T4 >99% bound (esp. T4)
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T4 Parameters
80 µg from thyroid
100% secreted from thyroid
t1/2 7 days
low activity
0.04% unbound
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T3 Parameters
30 µg from thyroid
20% secreted from thyroid
t1/2 1 days
high activity
0.04% unbound
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Thyrotropin-releasing hormone (TRH)
released from hypothalamus
- stims synth and release of TSH & prolactin
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- secretion stim'ed by dec T3 or T4
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- blocked by inc T3 or T4
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Thyrotropin or Thyroid-stimulating hormone (TSH)
Released from the pituitary
Synth controlled by T3 or T4 and TRH level
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Drugs that inhibit TSH
- somatostatin
- dopamine
- dopamine agonists
- steroids
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T4 -> T3 conversion
in peripheral tissues
5’ deiodinase
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TSH testing
o Recommended for initial eval
o Most sensitive for hyper, hypo, and replacement therapy
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TT4 testing
o Total free and bound T4
o Specific and sensitive test if no alterations in TBG
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TT3 testing
o Total free and bound T3
o Detects early hyper and T3 toxicosis
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FT4
o Direct measurement of free thyroxine
- o “Gold standard” is by the equilibrium
- dialysis technique
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FT4I
o Calculated free thyroxine index
- o Compensates for alterations in TBG by
- using T3 resin-uptake
o Not valid in pts w/euthyroid sick syndrome
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RAI-U
o Radioactive Iodine Uptake (I123 or I131)
o no correlation to hormone synth
o Falsely decreased w/ excess iodide intake
o Elevated in hyperthyroidism
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Thyroid Scan
o Trace dose of I123 or I131 prior to scan
o assess gland size, shape, and tissue activity
o Can detect “hot” or “cold” areas in nodular disease
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Hypothyroidism: General
dec circulating thyroid hormone conc
slowing down of metabolic process
Hashimoto’s (autoimmune) most common
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Hashimoto's
goitrous enlargement = mild hypothyroidism
atrophy = more severe hormone deficiency
antibodies v. thyroid peroxidase and thyroglobulin
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Iatrogenic Hypothyroidism
post radiation/surgery
3-12 months after 131I
1 month following surgery
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Alt. Hypothyroid causes
Iodine deficiency/excess
Enzyme defects
Thyroid hypoplasia
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Secondary Hypothyroidism
Much less common
- Pituitary disease
- Hypothalamic disease
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Primary Hypothyroidism
high TSH
low T4
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Secondary Hypothyroidism
normal to low TSH
low T4
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Subclinical Hypothyroidism
high TSH
normal T4
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Hypothyroid Tx Goals
normal thyroid hormone concentrations
symptomatic relief
prevent neurological deficits in newborns
avoid overtreatment
should imp. QoL
decreases atherosclerotic risk (LDL)
decreases risk of complications
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Levothyroxine: General
Synthetic T4 (converted to T3)
DOC
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Levothyroxine PK
t1/2 7 days
F = 40-80%
Highly protein bound
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Levothyroxine CIs
Untreated thyrotoxicosis
Acute MI
Untreated adrenal insufficiency
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Levothyroxine precautions
- Untreated thyrotoxicosis
- Acute MI
- Untreated adrenal insufficiency
NTI
Elderly
CV disease
Mucosal disease
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Levothyroxine drug interactions
- Impaired GI absorption:
- cholestyramine
- calcium carbonate
- sucralfate
- aluminum hydroxide
- ferrous sulfate
- dietary fiber supplements
- Increased non-deiodinative T4 clearance:
- carbamazepine
- phenytoin
T4 -> T3 blockade: amiodarone
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Levothyroxine in Pregnancy & Lactation
Category A
Minimal excretion in human milk
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Levothyroxine ARs
over replacement S/Sx
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Levothyroxine Dosage Forms
PO:IV 1.33:1
200 & 500 mcg IV vials
25 - 300 mcg PO tabs
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Levothyroxine Dosing
Maintenance usu. ~125 mcg/day
Initiate @ 50 mcg/day (25 mcg in elderly)
Increase 25-50 mcg q6-8wks based on TSH
estimate @ 1.6 mcg/kg/day
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Levothyroxine Counseling
empty stomach (seperate from other meds 1hr)
do not sub brands w/o MD approval
S/Sx of overtreatment
Imp. in 2-3wks
Resolution over months
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Liotrix
4:1 ratio of T4:T3 (mimics normal ratio)
expensive
lack of Tx rationale
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Dessicated thyroid
Extracted from hog, beef, or sheep
Use is rare and unwarranted
Unpredictable tablet conc.
Unpredictable pt response
no brand bioequivalence
may be antigenic
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Hypothyroid Monitoring
Treatment is usually lifelong
TSH q6-8 weeks until euthyroid then annually
FT4 can determine adherence or malabsorption
TSH no goodw/ 2o hypo (monitor T4)
TSH treatment goal: 0.5-2.5
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Subclinical Hypothyroidism
symptoms may be absent or non-specific
- controversy over treating
- guidelines recommend only if symptomatic
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Hypothyroidism in Pregnancy
inc rate of still-birth & lower psych scores
necessary for fetal growth
fetus can't make own fro first 2 months
Levothyroxine dose may inc 25-50%
TSH should be monitored
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Hypothyroidism in Elderly
Initiate at lower starting dose (25 mcg/day)
Dosing requirements may decrease with age
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Myxedema Coma
End stage of uncontrolled hypothyroidism
Acute medical emergency (ICU)
Mortality of 60-70%
usu. require intubation and mech. vent.
w/ treatment imp. expected w/in 24 hours
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Clinical Features of Myxedema Coma
hypothermia
adv. stages of hypothyroid symptoms
delirium/coma
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Myxedema Tx
IV T4 300-500 mcg, then 75-100 mcg daily PO
Support: IV steroids, fluids (give with caution)
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Normal TSH
Euthyroid
OR
2o Hypothyroidism
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High TSH
Low FT4
Hypothyroidism
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High TSH
Normal FT4
Subclinical Hypothyroidism
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Low TSH
High FT4
Hyperthyroidism
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Low TSH
Normal FT4
High Serum T3
T3-Thyrotoxicosis
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Low TSH
Normal FT4
Normal Serum T3
Subclinical Hyperthyroidism
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Grave's
- Autoimmune
- Thyroid-stimulating antibodies (TSAb)
- Genetic link likely
- Any age
- Hyperthyroidism
- Diffuse thyroid enlargement,
- Exophtalamos,
- Pretibial myxedema,
- Thyroid acropachy
- Genetic link likely
- Any age
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TSH-secreting pituitary adenomas
Release TSH w/o normal feedback loop
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Toxic adenoma
Autonomous thyroid nodule (independent of pituitary control)
“hot” nodules on radioiodine scan
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Multinodular goiters
- Insidiously onset (years)
- Usu. older pts w/ long-standing goiters
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Painful, subacute thyroid disease
- self-limiting
- locally painful
- viral invasion of parenchyma
- unlikely to recur
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Hyperthyroidism Tx Goals
- Reverse S/Sx and lab values
- Return TSH to normal range
- Avoid overcorrection (hypothyroidism)
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Methimazole (MMI)
- Init @ 30-60 mg/day in 3 div. doses
- Maintain @ 5-30 mg/day (taper @ 4-8wks)
- Tx is 12-24 months
- Max 120 mg/day
- Inhibits thyroid peroxidase
- (T4/T3 synthesis – coupling of MIT and DIT)
CI w/pregnancy or lactation
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Propylthiouracil (PTU)
- Init @ 300-600 mg / day in 3-4 div. doses
- Maintain @ 50-300 mg in 2-3 div. doses (taper @ 4-8wks)
- Tx is 12-24 months
- Max 1200 mg/day
- Inhibits thyroid peroxidase
- (T4/T3 synthesis)
- Inhibits 5’ deiodinase
- (peripheral conversion of T4 to T3)
CI w/pregnancy
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Antithyroid Drug PK
- Rapidly and completely absorbed from GI Actively concentrated in the thyroid
- Half-life: PTU 1 hour; MMI 5 hours
- Duration of action: PTU 6-10 hrs; MMI 24 hrs Clearance dec. in renal and hepatic disease
MMI 10-12 times more potent than PTU
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Antithyroid Drug Interactions
Warfarin - clotting factors will have dec. metabolism --> dec. warfarin response
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Antithyroid Drug ARs
Minor: fever, rash, arthralgias, transient leucopenia
Major: agranulocytosis, hepatitis, vasculitis, lupus-like syndrome
Assume major reactions are cross-sensitive
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Antithyroid Drug Monitoring
- Baseline – leukocyte count (controversial)
- Labs – TSH, FT4, TT4 (once symptoms resolve monitor yearly)
ARs – weakness, fatigue, easy bruising/bleeding, urinary symptoms
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131I
- -> follicular necrosis
- pref. in Grave's pts
- 20% req.retreat in 6-12 months
- Avoid pregnancy for 6-12months (CI)
- Usu. hypothyroid in 4-12 months
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131I Special Considerations
d/t transient thyroid elevations pretreat elderly and cardiac pts w/MMI/PTU (controversial)
- exacerbates thyroid eye disease (exopthalmos)
- -inc. risk in smoker's
- -initiate glucocorticoids 4-7d post 131I dose and taper 2-3 months
- -Prednisone 0.4-0.5 mg/kg/day (or equivalent)
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Indications for thyroid surgery
Pediatric pt w/ toxic rxn to antithyroid meds
Pregnant pt needing high dose PTU or w/ toxic rxn to PTU
Pt must be euthyroid before procedure
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Beta-blockers
propranolol
Inhibit adrenergic effect
No significant antithyroid action
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CCBs
Calcium channel blocker
verapamil or diltiazem
alt if beta-blocker cannot be used
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Hyperthyroidism during pregnancy
PTU preferred agent (highlt protein bound)
Use lowest possible dose
Inadequate Tx --> fetal tachycardia, severe growth restriction, premature birth, and 9-fold increased incidence of low birth weight
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Type 1 Amiodarone-induced thyroiditis
occurs d/t drug metabolism (iodine-induced)
treat w/ thioamides
- add lithium in severe cases
- (200-400 mg/day titrating to 0.6-1.2 mEq/L)
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Type 2 Amiodarone-induced thyroiditis
occurs d/t direct toxic effects (inflammation)
Prednisone 0.5-1.25 mg/kg/day; taper over 2-3 months
Usu. 40-60 mg/day
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Iatrogenic hyperthyroidism
Pts w/ too much thyroid hormone supplementation
Decrease levothyroxine dose
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Thyroid storm
Uncommon, life-threatening; Mortality of 20%
Precipitated by an ystressful illness
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Thyroid storm S/Sx
- high fever
- tachycardia
- tachypnea
- dehydration
- delirium
- CHF
- rapid aFib
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Thyroid storm Tx
- § PTU 600mg x1 dose, then 200-300mg q6h
- § Propranolol 40-80 mg q4-6h
- § Iodide – SSKI 1-5 gtts PO TID
- OR
- Lugol’s soln 5-10 gtts PO TID in H2O/juice
- § Must wait 1 hour post PTU load
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Thyroid Storm Supportive Care
§ PTU 600 mg x1 dose, then 200-300 mg q6 hours
§ Propranolol 40-80 mg q4-6 hours
§ Iodide – SSKI 1-5 gtts PO TID OR Lugol’s solution 5-10 gtts PO TID in water or juice
§ Must wait 1 hour post PTU load
Fluids and electrolytes
Antibiotics if infectious etiology
Antipyretic – APAP only
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