Thyroxine

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 13.09.2021

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Synonym(s)

3,3',5,5'-tetraiodo-L-thyronine, 2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid; 55-03-8; CAS No: 51-48-9; DL-Thyroxine; Levothyroxine; L-(-)-Thyroxine; (S)-Thyroxine; T4; Tetraiodothyronine; Thyroxinum

Definition
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Thyroxine (from Greek "thyreoeides" thyroid-like) also called T4, is a hormone that is produced in the thyroid gland of humans (formation also in mammals); it serves as a prohormone for triiodothyronine, also known as T3. T4 is converted peripherally by monoiodination (outer ring deiodination) into the actually biologically active triiodothyronine (T3).

Deiodination of the inner ring results in the inactive reverse T3 (see below inhibition of T4-T3 conversion). The naturally present T4-homone is L-thyroxine (if "thyroxine" is listed without prefix in the scientific literature, L-thyroxine is usually meant).

Thyroxine is secreted pulsatively by the thyroid gland. Between 100-150ug T4 are produced per day. In the blood, lipophilic T4 is bound to binding proteins (transproteins), 75% to TGB (thyroxine-binding globulin, a protein synthesized in the liver), 15% to prealbumin, 10% to albumin. 0.03% of T4 (fT4) and 0.4% of T3(fT3) are present in free form.

General information
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Biochemically, thyroxine is a non-proteinogenic alpha-amino acid with the molecular formula C15H11I4NO4. Like triiodothyronine, thyroxine is essential for energy metabolism and an important partner for many other hormones such as insulin, glucagon, somatotrophic hormone and adrenaline. The superordinate pituitary regulatory hormone is the thyroid-stimulating hormone, TSH also called thyrotropin. The thyroxine molecule contains four 4-iodine atoms (tetraiodothyronine; hence the name T4). The half-life of thyroxine is about 8 days.

Enzyme immunological and radioimmunological methods are available for the detection of thyroxine in serum and for therapy control.

Occurrence
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Reference ranges:

Healthy adults: 77-142 nmol/l

Children have higher, older adults lower reference ranges (so-called skewed normal distribution). Pathologically elevated thyroxine is found in hyperthyroidism; also possible in the early stages of Hashimoto's thyroiditis. Lower values in hypothyroidism (e.g. after strumectomy, radioiodine therapy, thyrostatic therapy).

Incorrectly elevated thyroxine values due to an increase in TGB (estrogens, e.g. in pregnancy, contraceptives, drugs such as amiodarone, fluorouracil, heroin) - Note: fT4 is not elevated!

Incorrectly lowered thyroxine values due to TGB lowering (protein synthesis disorders, e.g. in liver cirrhosis, protein losses in nephrotic syndrome, genetically determined synthesis disorders - rare).

Internal therapy
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Thyroxine is used for the treatment of hypothyroidism. The hormone is among the 5 most frequently prescribed drugs worldwide. Patients with hypothyroidism are usually dependent on lifelong hormone replacement. The dose in humans is usually between 12.5 µg and 200 µg per day. In addition to its use in hypothyroidism, thyroxine is used to supplement an adequate iodine supply to treat goiter. Furthermore, the thyroid hormone is used to prevent recurrences of resected thyroid carcinomas. The administration of thyroxine is generally contraindicated in hyperthyroidism. Thyroid hormones induce insulin resistance when overdosed; the risk of osteoporosis increases in post-menopausal women.

Note(s)
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Fault in T4-T3 conversion:

  • Various severe non thyroid-related diseases (euthyroid sick syndrome, non-thyroid illness, NTI) cause disruption of T4-T3 conversion and direct monodeiodination from biologically active T3 to biologically inactive rT3. T3 is reduced; the typical low-T3 syndrome occurs.
  • Medication: Versch. Drugs may influence this conversion mechanism: Glucocorticosteroids, beta-blockers, thyrostatics, amiodarone (is iodine-substituted).

Preparations:

  • Euthyrox® (A, CH, D), L-Thyrox® (D), L-Thyroxin® (D)
  • Combination preparations with triiodothyronine: Novothyral® (A, CH, D), Prothyrid ®(D), Thyreocomb® (D)
  • Combination preparations with potassium iodide: Iodothyrox® (D, A), L-Thyrox Iodine® (D)

Literature
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  1. Böhm BO (2018) Thyroid hormones. In: Neumeister B et al. (Eds) Clinical guide to laboratory diagnostics. Elsevier GmbH S. 296-297

Tables
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General patient information

  • L-thyroxine is a thyroid hormone and is used, among other things, to treat hypothyroidism.
  • It can take weeks (up to months) to find the right strength for the patient.
  • L-thyroxine is well tolerated when taken at the correct dose. However, it can easily be underdosed or overdosed. The latter manifests itself in the typical symptoms of hyperthyroidism.
  • People with cardiovascular diseases should take the active substance very carefully, especially at the beginning - in close consultation with their doctor.
  • L-thyroxine can interact with numerous active substances, but also with food. Milk, for example, interferes with the absorption of L-thyroxine in the intestine, as do certain calcium tablets, iron supplements and antacids. The latter bind stomach acid and are used, among other things, to treat heartburn. Products containing soy and fatty meals can also reduce the absorption of thyroid hormone in the intestine.
  • Drugs such as glucocorticosteroids ("cortisone"), beta-blockers (blood pressure lowering drugs), contraceptives ("the pill") or hormones used to treat menopausal symptoms can reduce the effect of L-thyroxine.
  • For its part, levothyroxine alters the effect of medicines: for example, it can weaken the blood sugar-lowering effect of metformin, insulin or glibenclamide. Especially at the beginning of a therapy with the thyroid hormone, people with diabetes should therefore regularly check their blood sugar. L-thyroxine can also increase the anticoagulant effect of drugs such as phenprocoumon. Regular checks are therefore recommended here too.

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Last updated on: 13.09.2021