Liothyronine

This article is about liothyronine as a pharmaceutical drug. For its role as a hormone, see Triiodothyronine.

Liothyronine sodium

Systematic (IUPAC) name
sodium (S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate
Clinical data
Trade names	Cytomel
AHFS/Drugs.com	monograph
MedlinePlus	a682462
Pregnancy category	US: A (No risk in human studies)
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	99.7%
Biological half-life	2.5 days
Identifiers
CAS Number	6893-02-3 Y
ATC code	H03AA02 (WHO)
PubChem	CID: 16218759
IUPHAR/BPS	2634
DrugBank	DB00279 Y
ChemSpider	17346129 Y
UNII	06LU7C9H1V Y
ChEBI	CHEBI:6484 N
ChEMBL	CHEMBL1201119 N
PDB ligand ID	T3 (PDBe, RCSB PDB)
Chemical data
Formula	C15H11I3NNaO4
Molecular mass	672.96 g/mol
SMILES [Na+].[O-]C(=O)[C@@H](N)Cc2cc(I)c(Oc1cc(I)c(O)cc1)c(I)c2.O
InChI InChI=1S/C15H12I3NO4.Na.H2O/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22;;/h1-4,6,12,20H,5,19H2,(H,21,22);;1H2/q;+1;/p-1/t12-;;/m0../s1 Y Key:IRGJMZGKFAPCCR-LTCKWSDVSA-M Y
NY (what is this?)  (verify)

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. It is marketed as the sodium salt under the brand name Cytomel (or Tertroxin in Australia).

Uses

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 Liothyronine instead can be taken and withdrawn from for two weeks to starve the thyroid tissue.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.

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. According to a 2001 meta-analysis that analyzed the effectiveness of adding Liothyronine to tricyclic antidepressants, women in particular may benefit from Liothyronine. The average effective dose for depression was 45 mcg of Liothyronine daily, which is lower than the doses used for treating hypothyroidism. About 9% of patients stopped taking liothyronine due to side effects. The difference in gender response may be due to differences in metabolism of thyroid precursors.

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

Advantages in thyroid hormone replacement

Liothyronine is an option for routine thyroid hormone replacement. See Hypothyroidism for an in-depth explanation of hormone replacement. It has a half-life of 24 hours. (although the stated biological half-life is 2.5 days). This compares to a half life of 7 days with levothyroxine. The shorter half life allows patients to find their ideal dose in much less time, 3-7 days compared to 3-7 weeks. Additionally, the shorter half life allows for adjustments which can take place over the same time interval, again with an advantage to liothyronine. It is recommended that labs be drawn weekly and the dose increased until the patients hypothyroid symptoms resolve. Uptodate recommends weekly dosage increases up to a total daily dose of 100 mcg daily in treating hypothyroidism. Starting dose may start at 5-25 mcg daily and increase by 12.5-25 mcg every week.

Contraindications

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.

Side effects

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

• 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:

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. 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.

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

Elderly Elderly patients should be started on lower doses of liothyronine. Plasma (T₃) concentrations in this population are decreased by 25% to 40%. 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.

Pharmacology

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 central nervous system. 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

• Levothyroxine
• Major depressive disorder
• Hypothyroidism