Thyroid Hormone Replacement

Aka: Thyroid Hormone Replacement, Thyroid Replacement, Levothyroxine, Synthroid, Thyroxine Replacement, T4 Replacement, Tirosint, Unithroid

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II. Indications

  1. Hypothyroidism

III. Contraindications

  1. Euthyroid patients
    1. Avoid use for weight loss in Obesity when Thyroid function is normal
    2. See Adverse Effects below, related to Excessive Thyroid Replacement

IV. Mechanism

  1. See Thyroid Physiology

V. Medicatons

  1. See oral and intravenous dosing below
  2. Generic Levothyroxine is of similar quality to brand drugs
    1. However agents from different manufacturers are not bioequivalent
    2. When manufacturer changes, recheck TSH level in 6 to 8 weeks after change
  3. Levothyroxine alone is the only recommended replacement strategy
    1. T4 is converted in peripheral tissues to T3
    2. T3-T4 combination is not recommended
    3. Desiccated Thyroid Hormone is not recommended
    4. Grozinsky-Glasberg (2006) J Clin Endocrinol Metab 91(7): 2592-9 [PubMed]
  4. Available Formulations
    1. Capsules are also available under the trade name Tirosint
    2. Levothyroxine Tablets: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200 and 300 mcg
      1. Tablets may be crushed for use in infants and children

VI. Dosing: Oral

  1. Use lower dosing in Subclinical Hypothyroidism
    1. See Subclinical Hypothyroidism
  2. Dosing precautions
    1. Take Levothyroxine at a consistent time each day
      1. However, any time of day is just as efficacious as another
    2. Doses should be taken 1 hour before a meal or 4 hours after the last meal (e.g. at bedtime) to maximize absorption
      1. Commonly taken before breakfast or at bedtime
      2. However, consistently taking Levothyroxine in the same way every day is more important than an empty Stomach
        1. If patient can only take at mealtime, then consistently take with meals and adjust dosing
    3. Avoid within 4 hours of products that decrease Levothyroxine absorption (e.g. Calcium, iron, Multivitamins)
      1. See Drug Interactions above
  3. Anticipated total dose (50 to 200 mcg/day in adults, maximum 300 mg/day)
    1. Child 0 to 6 months: 8 to 10 mcg/kg/day orally daily
    2. Child 6 to 12 months: 6 to 8 mcg/kg/day orally daily
    3. Child 1 to 5 years: 5 to 6 mcg/kg/day orally daily
    4. Child 6 to 12 years: 4 to 5 mcg/kg/day orally daily
    5. Child >12 years: 2 to 3 mcg/kg/day orally daily
    6. Adults: 1.6 mcg/kg/day (1.5 to 1.8 mcg/kg/day, or roughly 1 mcg/lb)
    7. Elderly: 1 mcg/kg/day
  4. Younger persons (no comorbid conditions)
    1. Usual starting dose: 75 to 100 mcg daily
    2. Options for initiating dosing
      1. Option 1
        1. Start at 75 to 100 mcg daily
      2. Option 2
        1. Start at 0.8 mcg/kg/day (50% of anticipated dose)
        2. Increase to 1.6 mcg/kg/day at 2 weeks
    3. Titrate dose based on Thyroid Stimulating Hormone
      1. Adjust dose by 12.5 to 25 mcg increments every 6 weeks until full replacement dose reached
    4. Typical dose
      1. Range: 100 to 200 mcg/day
      2. Maximum: 300 mcg/day
  5. Age over 50 years or history of heart disease
    1. Start at 25-50 mcg daily
    2. Adjust dose by 12.5 to 25 mcg increments every 6 weeks until full replacement dose reached
    3. Follow Thyroid Stimulating Hormone (TSH) closely
  6. Pregnancy
    1. See Hypothyroidism in Pregnancy
    2. Maintaining euthyroid state in pregnancy is critical

VII. Dosing: Intravenous dosing

  1. Maintenance (patient unable to take oral dose for >7 days)
    1. Parenteral dose is 70-80% of usual oral dose
  2. Myxedema Coma (Hypothyroid Coma)
    1. Load 300 to 500 mcg IV once
    2. Next: 50 to 100 mcg IV daily until patient able to take oral dosing

VIII. Adverse Effects: Excessive Thyroid Replacement

  1. Osteoporosis
  2. Atrial Fibrillation
  3. Cardiac hypertrophy
    1. Increased Intraventricular septum thickness
    2. Increased Left Ventricular posterior wall thickness
    3. Increased End Diastolic Dimension
    4. Increased Left Ventricular Mass Index
  4. Decreased Exercise Tolerance
    1. Decreased VO2 Max
    2. Decreased Anaerobic threshold

IX. Safety

  1. Considered safe in Lactation
  2. Considered safe in pregnancy
    1. See Hypothyroidism in Pregnancy
    2. Maintaining euthyroid state in pregnancy is critical

X. Monitoring

  1. Protocols for monitoring
    1. Monitoring every 6 to 8 weeks
      1. TSH not yet stabilized after initiation
      2. Recent change in Thyroid Replacement dosing
      3. Recent change in manufacturer
    2. Consider monitoring less frequently than annually (usually done annually in this group)
      1. Requires dose stable
      2. Age under 50 years with weight stable
      3. No comorbid condition
      4. Levothyroxine dose 125 mcg or less
      5. Pecina (2014) Am J Med 127(3): 240-5 [PubMed]
    3. Monitoring at least annually (when on stable dose)
      1. Age over 50 years
      2. Weight change
  2. Specific Testing
    1. Thyroid Stimulating Hormone
      1. Lags Levothyroxine dose change by 6 weeks
      2. Target adjusting TSH to the normal mid-range (<3 mg/dl)
    2. Thyroxine (T4)
      1. Lags Levothyroxine dose change by 1-2 weeks

XI. Drug Interactions (Take 4 hours apart)

  1. Foods that interfere with Levothyroxine absorption (lower levels)
    1. Regular use of these foods may require increased dose
    2. Grapefruit should be avoided regardless of time taken
    3. Walnuts
    4. Dietary Fiber
    5. Soy products including soybean flour
  2. Interfere with GI absorption (lower levels)
    1. Bile Acid Sequestrants (e.g. Cholestyramine, Colestipol)
    2. Ferrous Sulfate
    3. Orlistat
    4. Sucralfate
    5. Aluminum hydroxide or Magnesium HydroxideAntacids
    6. Calcium Supplementation (e.g. Calcium Carbonate)
    7. Proton Pump Inhibitors
    8. Cation-Exchange Resin (e.g. Sodium Polystyrene Sulfonate)
  3. Increase metabolism of Thyroxine (lowers levels)
    1. Phenytoin (Dilantin)
    2. Carbamazepine (Tegretol)
    3. Rifampin
    4. Phenobarbital
    5. Warfarin (Coumadin)
    6. Oral Hypoglycemic agents
    7. Selective Serotonin Reuptake Inhibitors or Tricyclic Antidepressants
      1. Most common with Sertraline (Zoloft)
  4. Medications interfere with T4 production and T3 conversion (lower levels)
    1. Lithium
    2. Amiodarone
    3. Medications containing Iodine
    4. Beta Adrenergic Agonists
    5. Glucocorticoids
  5. Medications increasing Protein binding (lowers levels)
    1. Pregnancy (high Estrogenic state)
    2. Oral Contraceptive
    3. Estrogen Replacement
  6. Medications decreasing Protein binding (raises levels)
    1. Furosemide (Lasix)
    2. Mefenamic Acid (Ponstel)
    3. Salicylates
    4. Androgens
    5. Decreased Serum Proteins with aging
    6. Nephrotic Syndrome
    7. Cirrhosis
    8. Protein-losing Enteropathy

XII. Resources

  1. Levothyroxine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e95720f2-91c9-a6d0-f7d5-8bcb94d07bbc

XIII. References

  1. (2023) Presc Lett 30(7): 39-40
  2. Svec (2001) CMEA Medicine Lecture, San Diego
  3. Dong (1997) JAMA, 277:1205-13 [PubMed]
  4. Hueston (2001) Am Fam Physician 64:1717-24 [PubMed]
  5. Jonklaas (2014) Thyroid 24(12):1670-751 +PMID:25266247 [PubMed]
  6. Mercuro (2000) J Clin Endocrinol Metab 85:159 [PubMed]
  7. Singer (1995) JAMA 273:808-12 [PubMed]
  8. Surks (1995) N Engl J Med 333:1688-94 [PubMed]

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Related Studies

Cost: Medications

levothyroxine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LEVOTHYROXINE 100 MCG CAPSULE Generic $3.83 each
LEVOTHYROXINE 100 MCG TABLET Generic $0.11 each
LEVOTHYROXINE 112 MCG TABLET Generic $0.15 each
LEVOTHYROXINE 125 MCG CAPSULE Generic $3.99 each
LEVOTHYROXINE 125 MCG TABLET Generic $0.14 each
LEVOTHYROXINE 137 MCG CAPSULE Generic $3.53 each
LEVOTHYROXINE 137 MCG TABLET Generic $0.14 each
LEVOTHYROXINE 150 MCG TABLET Generic $0.14 each
LEVOTHYROXINE 175 MCG TABLET Generic $0.18 each
LEVOTHYROXINE 200 MCG TABLET Generic $0.14 each
LEVOTHYROXINE 25 MCG CAPSULE Generic $3.97 each
LEVOTHYROXINE 25 MCG TABLET Generic $0.09 each
LEVOTHYROXINE 300 MCG TABLET Generic $0.16 each
LEVOTHYROXINE 50 MCG CAPSULE Generic $3.97 each
LEVOTHYROXINE 50 MCG TABLET Generic $0.10 each
LEVOTHYROXINE 75 MCG CAPSULE Generic $4.01 each
LEVOTHYROXINE 75 MCG TABLET Generic $0.12 each
LEVOTHYROXINE 88 MCG CAPSULE Generic $3.62 each
LEVOTHYROXINE 88 MCG TABLET Generic $0.12 each
synthroid (on 1/14/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
SYNTHROID 100 MCG TABLET Generic $0.11 each
SYNTHROID 112 MCG TABLET Generic $0.15 each
SYNTHROID 125 MCG TABLET Generic $0.14 each
SYNTHROID 137 MCG TABLET Generic $0.14 each
SYNTHROID 150 MCG TABLET Generic $0.14 each
SYNTHROID 175 MCG TABLET Generic $0.18 each
SYNTHROID 200 MCG TABLET Generic $0.14 each
SYNTHROID 25 MCG TABLET Generic $0.09 each
SYNTHROID 300 MCG TABLET Generic $0.16 each
SYNTHROID 50 MCG TABLET Generic $0.10 each
SYNTHROID 75 MCG TABLET Generic $0.12 each
SYNTHROID 88 MCG TABLET Generic $0.12 each
tirosint (on 7/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
TIROSINT 100 MCG CAPSULE Generic $3.83 each
TIROSINT 112 MCG CAPSULE $4.24 each
TIROSINT 125 MCG CAPSULE $4.27 each
TIROSINT 13 MCG CAPSULE $4.24 each
TIROSINT 137 MCG CAPSULE $4.24 each
TIROSINT 150 MCG CAPSULE $4.26 each
TIROSINT 175 MCG CAPSULE $4.28 each
TIROSINT 200 MCG CAPSULE $4.29 each
TIROSINT 25 MCG CAPSULE Generic $3.97 each
TIROSINT 50 MCG CAPSULE Generic $3.97 each
TIROSINT 75 MCG CAPSULE $4.25 each
TIROSINT 88 MCG CAPSULE $4.24 each
TIROSINT-SOL 200 MCG/ML SOLN $4.23 per ml
TIROSINT-SOL 50 MCG/ML SOLN $4.27 per ml
unithroid (on 6/22/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
UNITHROID 100 MCG TABLET Generic $0.11 each
UNITHROID 112 MCG TABLET Generic $0.15 each
UNITHROID 125 MCG TABLET Generic $0.14 each
UNITHROID 137 MCG TABLET Generic $0.09 each
UNITHROID 150 MCG TABLET Generic $0.14 each
UNITHROID 175 MCG TABLET Generic $0.19 each
UNITHROID 50 MCG TABLET Generic $0.10 each
UNITHROID 75 MCG TABLET Generic $0.12 each
UNITHROID 88 MCG TABLET Generic $0.12 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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