Thyroid Replacement Medications

The thyroid gland produces hormones called thyroxine (T4) and triiodothyronine (T3), which play important roles in processes such as metabolism, tissue growth, development, and in other regulatory pathways. When an individual’s thyroid does not produce enough hormones to maintain these processes, they are given synthetic or nonsynthetic forms of T3 and T4. These medications include levothyroxine, liothyronine, and desiccated thyroid extract. Correct dosing and intake of these hormones is important. Overdosing can cause symptoms of hyperthyroidism, and underdosing may not fully resolve the symptoms of hypothyroidism. It is important to be aware of various drug and food interactions that can either decrease or increase the effect of these medications.

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Pathophysiology of hypothyroidism

  • Medical condition defined by deficiency of thyroid hormones: 
    • Thyroxine (T4)
    • Triiodothyronine (T3
  • These hormones play an integral role in various functions:
    • Metabolism
    • Growth and development 
    • Catecholamine function
    • Pituitary hormone synthesis regulation (feedback loop)
  • Clinically, a deficiency in these hormones can lead to abnormal changes in:
    • Energy levels
    • Weight
    • Thermoregulation
    • HR
    • Bowel movements
    • Mood

Thyroid replacement medications

The 3 drugs used for treatment of hypothyroidism are:

  • Levothyroxine (L-T4)
  • Liothyronine (L-T3)
  • Desiccated thyroid extract



  • Levothyroxine is a synthetic levo-isomer of T4
  • The prohormone T4 is converted to T3 (active) or reverse T3 (inactive) in the liver and other peripheral tissues via deiodination. 
  • ↑ T4 and T3 levels lead to:
    • Normalization of hormone effects on metabolic, growth, and development functions 
    • ↓ Pituitary overproduction of thyroid-stimulating hormone (TSH)


  • Absorption: 
    • 40%‒80% absorbed from GI tract; can be erratic 
    • Food can ↓ absorption 
  • Distribution: Approximately 99% of T4 and T3 binds to plasma proteins (thyroxine-binding globulin (TBG)). 
  • Metabolism:
    • Deiodination in the liver and other peripheral tissues (including kidneys) to the active form, T3
    • Renal and hepatic impairment can ↓ conversion to T3.
  • Excretion:
    • Urine (primarily)
    • Feces


  • Hypothyroidism (primary, secondary, and tertiary)
    • Levothyroxine is the drug of choice.
    • Goal is to mimic normal endogenous T4 production
    • Has a longer half-life than L-T3
    • Less chance of hypermetabolic side effects
  • Myxedema coma (in combination with L-T3)
  • TSH suppression in thyrotropin-dependent thyroid cancers (papillary and follicular)

Adverse effects

  • Hypermetabolic state:
    • Can occur with:
      • Overtreatment 
      • Elderly individuals
      • Initiation of therapy
    • Signs and symptoms:
      • Palpitations
      • Tachycardia (including atrial fibrillation)
      • Widened pulse pressure
      • Sweating
      • Weight loss
      • Diarrhea 
      • Agitation and restlessness
  • Allergy to the dye or filler:
    • Swelling
    • Dyspnea
  • Untreated adrenal insufficiency: Levothyroxine can precipitate acute adrenal crisis.


  • Pregnancy: 
    • Associated with ↑ metabolic needs.
    • Normal physiologic ↑ in TBG and TSH → ↑ thyroid hormones
    • Pregnancy: Mothers require ↑ in L-T4 dosage.
    • Remember to change back to prepregnancy dose postpartum.
  • Elderly individuals or those with cardiovascular disease:
    • Thyroid hormone therapy has inotropic and chronotropic effects on the heart, which can result in angina.
    • Older individuals (> 60 years) and those with cardiovascular disease should be started on a lower dose.
    • This low dose can be slowly titrated upward (“start low, go slow”)
  • Individuals with diabetes mellitus may need to have the dosage of their antidiabetes medication adjusted with administration of L-T4.

Drug and food interactions

  • Foods that interfere with absorption (medication should be taken on empty stomach):
    • High-fiber foods
    • Calcium-containing foods
    • Grapefruit
    • Coffee
  • Drugs that interfere with absorption:
    • Calcium carbonate
    • Iron supplements
    • Bile acid sequestrants 
    • Aluminum-containing antacids
  • Severe drug interactions:
    • Ketamine: hypertension and tachycardia
    • Tricyclic antidepressants (TCAs): ↑ arrhythmogenic effect

Drugs that may alter levothyroxine efficacy

Table: Drugs that may alter levothyroxine efficacy
MechanismDrugsLevothyroxine adjustment
Drugs that ↑ hepatic conversion of T4 to T3
  • Phenobarbital
  • Phenytoin
  • Carbamazepine
  • Rifampin
  • Sertraline
  • Imatinib
↑ Dosage may be necessary
Drugs that ↑ serum TBG concentration
  • Estrogen
  • Tamoxifen
  • Raloxifene
  • Clofibrate
  • Opioids
  • Fluorouracil
  • Capecitabine
↑ Dosage may be necessary
Drugs that ↓ serum TBG concentration
  • Glucocorticoids
  • Androgens
↓ Dosage may be necessary



  • Liothyronine is the synthetic form of active T3
  • Effects are stronger and faster than those of L-T4.


  • Absorption: 
    • Rapid 
    • Well absorbed (approximately 95%)
  • Distribution: approximately 99% bound to proteins, such as TBG
  • Excretion:
    • Urine (primarily)
    • Feces


  • Hypothyroidism
    • Not typically used alone owing to short half-life
    • Used in individuals who continue to have symptoms despite L-T4 therapy
  • Myxedema coma (in conjunction with L-T4)
  • Nontoxic goiter

Adverse effects, precautions, and drug interactions

Adverse effects, precautions, and drug interactions are similar to those for L-T4.

Desiccated Thyroid


  • Nonsynthetic thyroid hormone extracted from the thyroid of domesticated animals (e.g., pigs, sheep, cows) 
  • Contains both T3 and T4 in a ratio that does not naturally occur in human beings


  • Absorption: 40%–80% 
  • Distribution: protein-bound (similar to L-T3 and L-T4)
  • Metabolism: T4 component is converted to T3
  • Excretion:
    • Urine (primarily)
    • Feces


Desiccated thyroid is a rarely used treatment for hypothyroidism.

  • May be considered for individuals who want a natural treatment
  • Not FDA-approved

Adverse effects

  • Side effects are similar to those for the synthetic thyroid medications
  • Manufacturing and quality control issues are common because of variable hormone concentrations.


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  2. Synthroid, Levoxyl (levothyroxine) dosing, indications, interactions, adverse effects, and more. (2021). MedScape. Retrieved August 3, 2021, from
  3. DrugBank Online. (2021). Levothyroxine: uses, interactions, mechanism of action.
  4. American Thyroid Association. (2020). Thyroid hormone treatment.
  5. Ross, D.S. (2021). Treatment of primary hypothyroidism in adults. UpToDate. Retrieved July 31, 2021, from
  6. Dong, B.J., Greenspan, F.S. (2012). Thyroid & antithyroid drugs. In: Katzung, B.G., Masters, S.B., Trevor, A.J. (Eds.), Basic & Clinical Pharmacology, 12th ed. McGraw-Hill Lange, pp. 681–696.

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