Endocrine: Thyroid

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Author:
jcbarbery
ID:
211522
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Endocrine: Thyroid
Updated:
2013-04-07 18:46:19
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thyroid
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Description:
Pharm Tx and general information regarding endocrine disorders of the thyroid
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  1. Dietary Sources of Iodine
    §  Ionized salt

    §  Seafood

    §  Dairy products

    §  Meat

    §  Vegetables

    §  Eggs
  2. Transport of iodine into thyroid cells
    Na+/I- active symporter
  3. Iodine is oxidized to thyroglobulin
    thyroid peroxidase (TPO)
  4. Iodine + Tyrosine
    monoiodotyrosine (MIT)

    and

    diiodotyrosine (DIT)
  5. T3
    MIT + DIT
  6. T4
    DIT + DIT
  7. iodine deficiency MIT:DIT ratio
    inc. MIT:DIT ratio

    inc. T3:T4 ratio

    inc. serum TSH
  8. Proteolysis of thyroglobulin
    inc. T3, T4 & iodotyrosines

    inhibited by excess iodine and lithium
  9. Unutilized iodine
    Recycled
  10. Thyroid hormone transporters
    §  Thyroxine-binding globulin (TBG)

    §  Thyroxine-binding prealbumin (TBPA)

    §  Albumin


    T3 and T4 >99% bound (esp. T4)
  11. T4 Parameters
    80 µg from thyroid

    100% secreted from thyroid

    t1/2 7 days

    low activity

    0.04% unbound
  12. T3 Parameters
    30 µg from thyroid

    20% secreted from thyroid

    t1/2 1 days

    high activity

    0.04% unbound
  13. Thyrotropin-releasing hormone (TRH)
    released from hypothalamus

    • stims synth and release of TSH & prolactin
    •      
    • secretion stim'ed by dec T3 or T4
    •      
    • blocked by inc T3 or T4
  14. Thyrotropin or Thyroid-stimulating hormone (TSH)
    Released from the pituitary

    Synth controlled by T3 or T4 and TRH level
  15. Drugs that inhibit TSH
    • somatostatin
    • dopamine
    • dopamine agonists
    • steroids
  16. T4 -> T3 conversion
    in peripheral tissues

    5’ deiodinase
  17. TSH testing
    o   Recommended for initial eval

    o   Most sensitive for hyper, hypo, and replacement therapy
  18. TT4 testing
    o   Total free and bound T4

    o   Specific and sensitive test if no alterations in TBG
  19. TT3 testing
    o   Total free and bound T3

    o   Detects early hyper and T3 toxicosis
  20. FT4
    o Direct measurement of free thyroxine

    • o “Gold standard” is by the equilibrium
    • dialysis technique
  21. 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
  22. 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
  23. 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
  24. Hypothyroidism: General
    dec circulating thyroid hormone conc

    slowing down of metabolic process

    Hashimoto’s (autoimmune) most common
  25. Hashimoto's
    goitrous enlargement = mild hypothyroidism

    atrophy = more severe hormone deficiency

    antibodies v. thyroid peroxidase and thyroglobulin
  26. Iatrogenic Hypothyroidism
    post radiation/surgery

    3-12 months after 131

    1 month following surgery
  27. Alt. Hypothyroid causes
    Iodine deficiency/excess

    Enzyme defects

    Thyroid hypoplasia
  28. Secondary Hypothyroidism
    Much less common

    • Pituitary disease
    • Hypothalamic disease
  29. Primary Hypothyroidism
    ­high TSH

    low T4
  30. Secondary Hypothyroidism
    normal to low TSH

    low T4
  31. Subclinical Hypothyroidism
    high TSH

    normal T4
  32. 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
  33. Levothyroxine: General
    Synthetic T4 (converted to T3)

    DOC
  34. Levothyroxine PK
    t1/2 7 days

    F = 40-80%

    Highly protein bound
  35. Levothyroxine CIs
    Untreated thyrotoxicosis

    Acute MI

    Untreated adrenal insufficiency
  36. Levothyroxine precautions




          • Untreated thyrotoxicosis

          • Acute MI

          • Untreated adrenal insufficiency





    NTI

    Elderly

    CV disease

    Mucosal disease
  37. 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
  38. Levothyroxine in Pregnancy & Lactation
    Category A

    Minimal excretion in human milk
  39. Levothyroxine ARs
    over replacement S/Sx
  40. Levothyroxine Dosage Forms
    PO:IV 1.33:1

    200 & 500 mcg IV vials

    25 - 300 mcg PO tabs
  41. 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
  42. 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
  43. Liotrix
    4:1 ratio of T4:T3 (mimics normal ratio)

    expensive

    lack of Tx rationale
  44. 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
  45. 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
  46. Subclinical Hypothyroidism
    symptoms may be absent or non-specific

    • controversy over treating
    •       guidelines recommend only if symptomatic
  47. 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
  48. Hypothyroidism in Elderly
    Initiate at lower starting dose (25 mcg/day)

    Dosing requirements may decrease with age
  49. 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
  50. Clinical Features of Myxedema Coma
    hypothermia

    adv. stages of hypothyroid symptoms

    delirium/coma
  51. Myxedema Tx
    IV T4 300-500 mcg, then 75-100 mcg daily PO

    Support: IV steroids, fluids (give with caution)
  52. Normal TSH
    Euthyroid

    OR

    2o Hypothyroidism
  53. High TSH
    Low FT4
    Hypothyroidism
  54. High TSH
    Normal FT4
    Subclinical Hypothyroidism
  55. Low TSH
    High FT4
    Hyperthyroidism
  56. Low TSH
    Normal FT4
    High Serum T3
    T3-Thyrotoxicosis
  57. Low TSH
    Normal FT4
    Normal Serum T3
    Subclinical Hyperthyroidism
  58. Grave's
    • Autoimmune
    • Thyroid-stimulating antibodies (TSAb)
    • Genetic link likely
    • Any age
  59. Hyperthyroidism
    • Diffuse thyroid enlargement,
    • Exophtalamos,
    • Pretibial myxedema,
    • Thyroid acropachy
    • Genetic link likely
    • Any age
  60. TSH-secreting pituitary adenomas
    Release TSH w/o normal feedback loop
  61. Toxic adenoma
    Autonomous thyroid nodule (independent of pituitary control)

    “hot” nodules on radioiodine scan
  62. Multinodular goiters
    • Insidiously onset (years)
    • Usu. older pts w/ long-standing goiters
  63. Painful, subacute thyroid disease
    • self-limiting
    • locally painful
    • viral invasion of parenchyma
    • unlikely to recur
  64. Hyperthyroidism Tx Goals
    • Reverse S/Sx and lab values
    • Return TSH to normal range
    • Avoid overcorrection (hypothyroidism)
  65. 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
  66. 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
  67. 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
  68. Antithyroid Drug Interactions
    Warfarin - clotting factors will have dec. metabolism --> dec. warfarin response
  69. Antithyroid Drug ARs
    Minor: fever, rash, arthralgias, transient leucopenia

    Major: agranulocytosis, hepatitis, vasculitis, lupus-like syndrome

    Assume major reactions are cross-sensitive
  70. Antithyroid Drug Monitoring
    • Baseline – leukocyte count (controversial)
    • Labs – TSH, FT4, TT4 (once symptoms resolve monitor yearly)

    ARs – weakness, fatigue, easy bruising/bleeding, urinary symptoms
  71. 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
  72. 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)
  73. 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
  74. Beta-blockers
    propranolol

    Inhibit adrenergic effect

    No significant antithyroid action
  75. CCBs
    Calcium channel blocker

    verapamil or diltiazem

    alt if beta-blocker cannot be used
  76. 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
  77. 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)
  78. 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
  79. Iatrogenic hyperthyroidism
    Pts w/ too much thyroid hormone supplementation

    Decrease levothyroxine dose
  80. Thyroid storm
    Uncommon, life-threatening; Mortality of 20%

    Precipitated by an ystressful illness
  81. Thyroid storm S/Sx
    • high fever
    • tachycardia
    • tachypnea
    • dehydration
    • delirium
    • CHF
    • rapid aFib
  82. 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
  83. 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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