Liothyronine

Last updated

Liothyronine sodium
Liothyronine.svg
Liotironina sodica3D.png
Clinical data
Trade names Cytomel, Tertroxin, others
AHFS/Drugs.com Monograph
MedlinePlus a682462
License data
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding 99.7%
Elimination half-life 2.5 days
Identifiers
  • sodium (S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.203 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H11I3NNaO4
Molar mass 672.959 g·mol−1
3D model (JSmol)
  • [Na+].[O-]C(=O)[C@@H](N)Cc2cc(I)c(Oc1cc(I)c(O)cc1)c(I)c2.O
  • 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 Yes check.svgY
  • Key:IRGJMZGKFAPCCR-LTCKWSDVSA-M Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Liothyronine is a manufactured form of the thyroid hormone triiodothyronine (T3). [1] It is most commonly used to treat hypothyroidism and myxedema coma. [1] It can be taken by mouth or by injection into a vein. [1]

Contents

Side effects may occur from excessive doses. [1] This may include weight loss, fever, headache, anxiety, trouble sleeping, arrythmias, and heart failure. [1] Use in pregnancy and breastfeeding is generally safe. [2] [1] Regular blood tests are recommended to verify the appropriateness of the dose being taken. [1]

Liothyronine was approved for medical use in 1956. [1] It is available as a generic medication. [2] In 2020, it was the 218th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [3] [4]

Medical uses

Liothyronine may be used when there is an impaired conversion of T4 to T3 in peripheral tissues. [1] The dose of liothyronine for hypothyroidism is a lower amount than levothyroxine due it being a higher concentrated synthetic medication. [1] About 25 μg of liothyronine is equivalent to 100 μg of levothyroxine. [2]

In thyroid cancer or Graves' disease, ablation therapy with radioactive iodine (131I) can be used to remove trace thyroid tissue that may remain after thyroidectomy (surgical excision of the gland). For 131I therapy to be effective, the trace thyroid tissue must be avid to iodine, which is achieved by elevating the person's TSH levels. [5] For patients taking levothyroxine, TSH may be boosted by discontinuing levothyroxine for 3–6 weeks. [5] This long period of hormone withdrawal is required because of levothyroxine's relatively long biological half-life, and may result in symptoms of hypothyroidism in the patient. The shorter half-life of liothyronine permits a withdrawal period of two weeks, which may minimize hypothyroidism symptoms. One protocol is to discontinue levothyroxine, then prescribe liothyronine while the T4 levels are falling, and finally stop the liothyronine two weeks before the radioactive iodine treatment. [5]

Liothyronine may also be used for myxedema coma because of its quicker onset of action when compared to levothyroxine. [6] Use for the treatment of obesity is not recommended. [1]

Depression

Adding liothyronine to tricyclic antidepressants appears useful, especially in women. [7] An algorithm developed from the STAR*D trial recommends liothyronine as an option when people have failed two antidepressant medications. [8]

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. [10] [11]

Nursing

Breastmilk contains a low amount of thyroid hormone, so it is important to exercise caution when breastfeeding while taking liothyronine. [10]

Elderly

Older people should be started on lower doses of liothyronine. [9] Plasma T3 concentrations in this population are decreased by 25% to 40%. [10] 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. [10]

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. [9]

Side effects

Liothyronine may cause a number of side effects, mostly similar to symptoms of hyperthyroidism, which include: [12]

Boxed warning

The package insert contains the following boxed warning, as do all thyroid hormones: [9]

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.

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. [13] 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.

Pricing

The British Competition and Markets Authority launched an investigation into the alleged "excessive and unfair pricing" of liothyronine tablets in 2017. It alleged that Advanz Pharma overcharged the NHS from before 2007 to July 2017. The price of a pack increased by almost 1,600% from £4.46 before it was debranded in 2007 to £258.19 by July 2017. [14]

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Thyroid gland disease that involves an overproduction of thyroid hormone

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus (pl.: isthmi). The thyroid gland is a butterfly-shaped gland located in the neck below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis and growth and development in children. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

<span class="mw-page-title-main">Graves' disease</span> Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goitre. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

<span class="mw-page-title-main">Iodothyronine deiodinase</span> Class of enzymes

Iodothyronine deiodinases (EC 1.21.99.4 and EC 1.21.99.3) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor, influences the expression of genes in practically every vertebrate cell. Iodothyronine deiodinases are unusual in that these enzymes contain selenium, in the form of an otherwise rare amino acid selenocysteine.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Triiodothyronine</span> Chemical compound

Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.

<span class="mw-page-title-main">Myxedema</span> Medical condition

Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hypothyroidism and (rare) paradoxical cases of hyperthyroidism. In this latter sense, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. One manifestation of myxedema occurring in the lower limb is pretibial myxedema, a hallmark of Graves disease, an autoimmune form of hyperthyroidism. Myxedema can also occur in Hashimoto thyroiditis and other long-standing forms of hypothyroidism.

<span class="mw-page-title-main">Hashimoto's thyroiditis</span> Autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. A slightly broader term is autoimmune thyroiditis, identical other than that it is also used to describe a similar condition without a goitre.

<span class="mw-page-title-main">Levothyroxine</span> Thyroid hormone

Levothyroxine, also known as L-thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken orally (by mouth) or given by intravenous injection. Levothyroxine has a half-life of 7.5 days when taken daily, so about six weeks is required for it to reach a steady level in the blood.

<span class="mw-page-title-main">Propylthiouracil</span> Medication used to treat hyperthyroidism

Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is typically only used when methimazole, surgery, and radioactive iodine is not possible. It is taken by mouth.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid. TFTs may be requested if a patient is thought to suffer from hyperthyroidism or hypothyroidism, or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.

Desiccated thyroid, also known as thyroid extract, is thyroid gland that has been dried and powdered for medical use. It is used to treat hypothyroidism. It is less preferred than levothyroxine. It is taken by mouth. Maximal effects may take up to three weeks to occur.

<span class="mw-page-title-main">Hypothalamic–pituitary–thyroid axis</span> Part of the neuroendocrine system

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

An antithyroid agent is a hormone inhibitor acting upon thyroid hormones.

Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.

Myxedema coma is an extreme or decompensated form of hypothyroidism and while uncommon, is potentially lethal. A person may have laboratory values identical to a "normal" hypothyroid state, but a stressful event precipitates the myxedema coma state, usually in the elderly. Primary symptoms of myxedema coma are altered mental status and low body temperature. Low blood sugar, low blood pressure, hyponatremia, hypercapnia, hypoxia, slowed heart rate, and hypoventilation may also occur. Myxedema, although included in the name, is not necessarily seen in myxedema coma. Coma is also not necessarily seen in myxedema coma, as patients may be obtunded without being comatose.

<span class="mw-page-title-main">Thyroid hormones</span> Hormones produced by the thyroid gland

Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, derived from food. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Liothyronine Sodium Monograph for Professionals". Drugs.com. Retrieved 27 February 2019.
  2. 1 2 3 British National Formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 757. ISBN   9780857113382.
  3. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  4. ↑ "Liothyronine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  5. 1 2 3 "Thyroid Cancer (Papillary and Follicular)". American Thyroid Association. Retrieved 25 December 2016.
  6. ↑ Klubo-Gwiezdzinska J, Wartofsky L (March 2012). "Thyroid emergencies". The Medical Clinics of North America. 96 (2): 385–403. doi:10.1016/j.mcna.2012.01.015. PMID   22443982.
  7. ↑ Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP, et al. (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. doi:10.1176/appi.ajp.158.10.1617. PMID   11578993.
  8. ↑ Gaynes BN, Rush AJ, Trivedi MH, Wisniewski SR, Spencer D, Fava M (January 2008). "The STAR*D study: treating depression in the real world". Cleveland Clinic Journal of Medicine. 75 (1): 57–66. doi:10.3949/ccjm.75.1.57. PMID   18236731.
  9. 1 2 3 4 Cytomel (Liothyronine Sodium) Drug Information: Warnings and Precautions - Prescribing Information at RxList, retrieved on 29-October-2014
  10. 1 2 3 4 "Liothyronine (Lexi-Drugs)". LexiComp. Retrieved 29 October 2014.
  11. ↑ Montalvo JM, Wahner HW, Mayberry WE, Lum RK (August 1973). "Serum triiodothyronine, total thyroxine, and thyroxine to triiodothyronine ratios in paired maternal-cord sera and at one week and one month of age". Pediatric Research. 7 (8): 706–11. doi: 10.1203/00006450-197308000-00006 . PMID   4200034.
  12. ↑ MedlinePlus. "Liothyronine." Last accessed 14 July 2007.
  13. ↑ Rosenthal LJ, Goldner WS, O'Reardon JP (October 2011). "T3 augmentation in major depressive disorder: safety considerations". The American Journal of Psychiatry. 168 (10): 1035–40. doi:10.1176/appi.ajp.2011.10030402. PMID   21969047.
  14. ↑ "CMA investigates 1,600% price increase of liothyronine over eight-year period". Pharmaceutical Journal. 31 January 2019. Archived from the original on 30 December 2019. Retrieved 17 March 2019.
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