Triiodothyronine (T3)

Triiodothyronine (T3) (also known as liothyronine) is the active form of the thyroid hormone, thyroxine. Approximately 20% of T3 is secreted into the bloodstream directly by the thyroid gland. The remaining 80% is produced from conversion of thyroxine by organs such as the liver and kidneys. In psychiatry, liothyronine is sometimes used as an augmentation medication for depression in combination with antidepressants.

Liothyronine is the name of the manufactured form of triiodothyronine.

Pharmacokinetics of Triiodothyronine

Absorption 90% absorption, peaks in 1-2 hours (absorption decreases with age)
Distribution 99.8% bound to plasma proteins
Metabolism Mainly metabolized in the liver where it is deiodinated to diiodothyronine and monoiodothyronine
Elimination Mainly renal
Half-life 19 hours

Triiodothyronine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) -
Induces -
Inhibits CYP3A[1]

T3 may increase levels of thyrotropin-releasing hormone, corticotrophin releasing factor, and brain derived neurotrophic factor (BDNF).

  • Thyroxine overdose rarely causes hyperthyroidism and symptoms are usually mild
    • Mild symptoms of toxicity may include fever, sweating, tachycardia, restlessness, agitation, hypertension, headache, nausea, diarrhea, and/or vomitting.
  • Severe toxicity is more likely to occur with chronic overuse or abuse
    • Severe symptoms include angina, myocarditis, cardiac arrhythmias, thyrotoxicosis and thyroid storm.
  • Prior to starting T3, check for TSH, free T3, and free T4.
    • If any of the levels are abnormal, recheck labs to rule out laboratory error or transient stressors as causes. Individuals may also require primary care or specialist involvement if there is concern about an underlying thyroid disorder.

Dosing for Triiodothyronine

Starting Start with 25 mcg daily (12.5mcg in older adults or those with medication sensitivities)[2]
Titration Titrate to 50 mcg daily after at least one week
Maximum In depression adjunct studies, doses exceeding 50 mcg have been noted to cause toxicity symptoms.
Taper Over a period of 4-8 weeks is recommended.
  • Triiodothyronine comes in oral formulation.
  • Once started, recheck thyroid hormones at 3 months, 6 months, then annually.[3]
  • The target TSH level is the lower limit of the normal range (or below) in the absence of hyperthyroid symptoms.
    • Free T3 level can be maintained at the upper limit of the normal range based on the severity of depressive symptoms and overall response to T3.
  • Because of the effects of thyroid hormones and osteoporosis, make sure to monitor bone density with densitometry every 2 years in postmenopausal women.[4]
  • Adrenal cortical insufficiency
  • Untreated thyrotoxicosis
  • Oral anticoagulants (compensatory increases in clotting factor synthesis are impaired)
  • Insulin or oral hypoglycemics (may need to be increased)
  • Cholestyramine binds both T4 and T3 in the intestine, impairing absorption
  • Digitalis (toxic effects of digitalis may be increased)
  • Vasopressors (increased risk for coronary insufficiency)
  • Ketamine (may cause tachycardia or hypertension)
  • Common side effects may include shortness of breath, headaches, tremors, irritability, anxiety, diarrhea, irregular menstrual periods, or weight loss.
  • Prescribers should discuss and document the risk-benefit profile of T3, including the risk for arrhythmia and osteoporosis.[5]