Thyroid Hormone Replacement

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

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II. Indications

  1. Hypothyroidism

III. Preparations

  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. T3-T4 combination is not recommended
    2. Desiccated Thyroid Hormone is not recommended
    3. Grozinsky-Glasberg (2006) J Clin Endocrinol Metab 91(7): 2592-9 [PubMed]

IV. 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

V. Dosing

  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)
    1. Children: up to 4 mcg/kg/day (full replacement)
    2. Adults: 1.6 mcg/kg/day (1.5 to 1.8 mcg/kg/day, or roughly 1 mcg/lb)
    3. 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
  5. Age over 50 years or history of heart disease
    1. Start at 25-50 mcg daily
    2. Increase by 25 mcg increments every 4 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

VI. Management: Intravenous dosing

  1. Parenteral dose is 70-80% of usual oral dose
  2. Indications
    1. Unable to take oral dose for >7 days
    2. Myxedema Coma (Hypothyroid Coma)

VII. 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

VIII. 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

IX. 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
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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