Liothyronine sodium
Systematic (IUPAC) name
sodium (S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate
Clinical data
Trade names Cytomel
Pregnancy cat.
Legal status
Pharmacokinetic data
Protein binding 99.7%
Half-life 2.5 days
CAS number  YesY
ATC code H03
IUPHAR ligand
ChemSpider  YesY
PDB ligand ID T3 (, )
Chemical data
Formula C15H11I3NNaO4 
Mol. mass 672.96 g/mol

Liothyronine is a synthetic form of thyroid hormone (T3) used to treat hypothyroidism and myxedema coma. It is also used as an augmentation strategy in treating Major Depressive Disorder when used in combination with antidepressants.[1] It is marketed as the sodium salt under the brand name Cytomel (or Tertroxin in Australia).


  • Uses 1
  • Disadvantages in thyroid hormone replacement 2
  • Contraindications 3
  • Side effects 4
  • Boxed warning 5
  • Safety considerations 6
  • Pharmacology 7
  • See also 8
  • References 9
  • External links 10


Physicians can use this instead of or in addition to levothyroxine (T4) for patients undergoing thyroid withdrawal. When a patient has thyroid cancer or Graves' disease, ablation therapy with radioactive iodine (131I) can be used to remove any trace thyroid tissue. For 131I therapy to be effective, the trace thyroid tissue must be avid to iodine. The best method is to starve the tissue of iodine but this can lead to hypothyroid symptoms for the patient. Withdrawal from levothyroxine can be done but it takes six weeks of withdrawal for the remaining thyroid tissue to be completely starved. Six weeks is needed owing to levothyroxine's long half life. Six weeks can be inconvenient for the patient and delay treatment. Liothyronine instead can be taken and withdrawn from for two weeks to starve the thyroid tissue. This is much safer and more convenient than levothyroxine. Also, due to its quicker onset of action when compared to levothyroxine, it sometimes is a better option in patients with myxedema coma or in patients preparing for 133I therapy for thyroid cancer.[2]

Low-dose liothyronine has been shown to improve depression symptoms in patients with normal thyroid function who do not have adequate relief from their depression after trying several different antidepressants. When added to existing medications, liothyronine helped achieve remission in 24% of patients participating in a subset of the large STAR*D depression trial.[3] According to a 2001 meta-analysis that analyzed the effectiveness of adding Liothyronine to tricyclic antidepressants, women in particular may benefit from Liothyronine.[4] The average effective dose for depression was 45 mcg of Liothyronine daily, which is lower than the doses used for treating hypothyroidism.[3] About 9% of patients stopped taking liothyronine due to side effects.[3] The difference in gender response may be due to differences in metabolism of thyroid precursors.[5]

An algorithm developed from the STAR*D trial recommends liothyronine as an option when patients have failed two antidepressant medications.[6][7]

Disadvantages in thyroid hormone replacement

Liothyronine is not recommended for routine thyroid hormone replacement. See Hypothyroidism for an in-depth explanation of hormone replacement. It also has a short half-life of 1.5 hours requiring frequent dosing throughout the day.[8] Due to its rapid absorption, there is a risk of elevated plasma T3 levels after oral intake which may lead to mild thyroid toxicities in patients.[8] There is also the possibility of misinterpreting low FT4 levels during T3 administration.[8] This could lead to over-administration of hormone. Therefore, (T3) levels must be carefully and regularly monitored.


Any person with a hypersensitivity to liothyronine sodium or any active ingredient of the formulation should not be on this medication. If there is uncorrected adrenal insufficiency or thyrotoxicosis, a different approach to therapy must be considered.[9]

Side effects

Liothyronine may cause a number of side effects, mostly similar to symptoms of hyperthyroidism, which include:[10]

  • weight loss
  • tremor
  • headache
  • upset stomach
  • vomiting
  • diarrhea
  • stomach cramps
  • nervousness
  • irritability
  • insomnia
  • excessive sweating
  • increased appetite
  • fever
  • changes in menstrual cycle
  • sensitivity to heat

Boxed warning

The package insert for Cytomel contains the following boxed warning, as do all thyroid hormones:[11]

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Safety considerations

Pregnancy Per the U.S. FDA, liothyronine is categorized as Pregnancy Category A.[9] Thyroid hormone is minimally transferred to the fetus or placenta, however as of October 2014, studies have not shown any adverse effects to the fetus. Hypothyroid mothers should continue to take thyroid hormone replacement therapy throughout pregnancy to avoid adverse events.[12][13]

Nursing Breastmilk contains a low amount of thyroid hormone, so it is important to exercise caution when breastfeeding while taking liothyronine.[12]

Elderly Elderly patients should be started on lower doses of liothyronine.[9] Plasma (T3) concentrations in this population are decreased by 25% to 40%.[12] TSH must be routinely monitored since there is a risk of coronary artery disease, hyperthyroidism and excessive bone loss from inadequate or abnormal thyroid replacement.[12]


Liothyronine is the most potent form of thyroid hormone. As a salt of triiodothyronine (T3), it is chemically similar and pharmacologically equivalent to T3. As such, it acts on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. As monotherapy or in combination therapy with SSRIs, liothyronine may also enhance generation of new neurons in the CNS.[1] The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds.

In comparison to levothyroxine (T4), liothyronine has a faster onset of action as well as a shorter biological half-life, which may be due to less plasma protein binding to thyroxine-binding globulin and transthyretin.

See also


  1. ^ a b "The American Journal of Psychiatry". Retrieved 29 Oct 2014. 
  2. ^
  3. ^ a b c Nierenberg, AA; Fava, M; Trivedi, MH; Wisniewski, SR; Thase, ME; McGrath, PJ; Alpert, JE; Warden, D; Luther, JF; Niederehe, G; Lebowitz, B; Shores-Wilson, K; Rush, AJ (September 2006). >. "A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report.". The American journal of psychiatry 163 (9): 1519–30; quiz 1665.  
  4. ^ Altshuler, LL; Bauer, M; Frye, MA; Gitlin, MJ; Mintz, J; Szuba, MP; Leight, KL; Whybrow, PC (October 2001). "Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature.". The American journal of psychiatry 158 (10): 1617–22.  
  5. ^ Berent, Dominika; Zboralski, Krzysztof; Orzechowska, Agata; Gałecki, Piotr (18 January 2014). "Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder". Molecular Biology Reports 41 (4): 2419–2425.  
  6. ^ Cooper-Kazaz, R; Cohen, R; Karagichev, L; Muhammed-Moussa, S; Grupper, D; Drori, T; Newman, ME; Sackeim, HA; Glaser, B; Lerer, B (2007). "Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial.". Arch Gen Psychiatry 64: 679–688.  
  7. ^ G, Bradley; Rush, J; Trivedi, M; Wisniewski, S; Spencer, D; Fava, M (2008). "The STAR*D Study: Treating Depression in the Real World.". Cleveland Clinic Journal of Medicine 75.1: 57–66.  
  8. ^ a b c Koda-Kimble, MA; Alldredge, BK (2012). Applied therapeutics: the clinical use of drugs (10th ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins.  
  9. ^ a b c Cytomel (Liothyronine Sodium) Drug Information: Warnings and Precautions - Prescribing Information at RxList, retrieved on 29-October-2014
  10. ^ MedlinePlus. "Liothyronine." Last accessed July 14, 2007.
  11. ^ Cytomel (Liothyronine Sodium) Drug Information: Warnings and Precautions - Prescribing Information at RxList, retrieved on 14-April-2014
  12. ^ a b c d "Liothyronine (Lexi-Drugs)". LexiComp. Retrieved 29 October 2014.
  13. ^ Montalvo, JM; Wahner, HW; Mayberry, WE; Lum, RK (Aug 1973). "Serum triiodothyronine, total thyroxine, and thyroxine to triiodothyronine ratios in paired maternal-cord sera and at one week and one month of age.". Pediatr Res 7: 706–711.  

External links