Thyroid Hormone Replacement

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

1. Indications
   1. Hypothyroidism
2. Preparations
   1. Generic Levothyroxine are of similar quality to brand drugs
      1. However agents from different manufacturers are not bioequivalent
      2. When manufacturer changes, recheck TSH level in 6 weeks after change
   2. See oral and intravenous dosing below
3. Drug Interactions (Take 4 hours apart)
   1. Grapefruit should be avoided regardless of time taken
   2. Interfere with GI absorption (lower levels)
      1. Cholestyramine
      2. Colestipol
      3. Ferrous Sulfate
      4. Orlistat
      5. Sucralfate
      6. Aluminum hydroxide antacids
      7. Calcium Supplementation
      8. Soy products
   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 (lower levels)
      1. Lithium
      2. Amiodarone
      3. Medications containing iodine
   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
4. Dosing (lower dosing in Subclinical Hypothyroidism)
   1. See Subclinical Hypothyroidism
   2. Dosing precautions
      1. Take Levothyroxine at a consistent time each day
      2. Doses should be taken 60 minutes before meals
         1. Commonly taken before breakfast or at bedtime
      3. Avoid within 4 hours of products that decrease Levothyroxine absorption
         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
      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 qd
         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
5. Dosing: Pregnancy
   1. Endocrinology consult
   2. Increase Levothyroxine dose at earliest knowledge of pregnancy
      1. Pregnancy requires an increased Levothyroxine dose
         1. Increased dose by 30-47% over baseline required in most pregnant patients
         2. Increased dose required for remainder of pregnancy (with frequent monitoring of TSH)
      2. Add 2 additional doses per week (9 total doses)
      3. Example
         1. Patient on 100 mcg daily before pregnancy
         2. When pregnancy diagnosed, start taking an extra dose (total 200 mcg) on Tuesday and Saturday
      4. Recheck Thyroid Stimulating Hormone (TSH) at 5 weeks after dose change
      5. Decrease dose to baseline immediately after delivery, and recheck TSH in 6-8 weeks
   3. TSH Monitoring
      1. TSH at earliest pregnancy diagnosis (Levothyroxine increased at this time)
      2. TSH 5 weeks after initial Levothyroxine increase and every 4-5 weeks after dose change
      3. TSH a minimum of every trimester
      4. TSH at 6-8 weeks after delivery (levoothyroxine dose decreased to baseline at delivery)
6. Management: Intravenous dosing
   1. Indicated if unable to take oral dose for >7 days
   2. Parenteral dose is 70-80% of usual oral dose
7. 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
8. 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
      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
9. References
   1. Svec (2001) CMEA Medicine Lecture, San Diego
   2. Dong (1997) JAMA, 277:1205-13
   3. Hueston (2001) Am Fam Physician 64:1717-24
   4. Mercuro (2000) J Clin Endocrinol Metab 85:159
   5. Singer (1995) JAMA 273:808-12
   6. Surks (1995) N Engl J Med 333:1688-94