What is T4 (Levothyroxine)?
Levothyroxine (T4) is a synthetic thyroid hormone that replaces the body's own thyroxine production. It is the principal form of thyroid hormone secreted by the thyroid gland, bound to thyreoglobulin. After absorption, a portion of T4 is converted to T3 (triiodothyronine) in tissues, which is biologically more active.
Levothyroxine is the standard hormone for treating hypothyroidism and is also used to suppress TSH in thyroid cancer. This information is for research and educational purposes only. No medical advice.
Comparison
T4 and T3 in the lexicon
Both hormones occupy the same receptors. T4 is partly converted into T3 in the tissues. Tap a card to open its entry.
According to ChEMBL: levothyroxine and liothyronine are both agonists at the thyroid hormone receptor (TRα and TRβ). 7
How it works
Levothyroxine acts as a replacement for the natural thyroid hormone thyroxine. Its biological effects occur through:
- Binding to thyroid hormone receptors in nucleus and cytoplasm
- Increased metabolism and heat production
- Enhanced heart rate and cardiac output
- Improved mental function and cognitive ability
- Regulation of the nervous system through central and peripheral effects
- Partial conversion to T3 in peripheral tissues
Where it acts
Where levothyroxine acted in studies
Tap a point or a card. Grey = observed in studies.
Targets in the ChEMBL database7
Compound CHEMBL2103741: two recorded mechanisms, all Agonist.
- Gene
- THRA
- UniProt
- P10827
- ChEMBL
- CHEMBL1860
- Action
- Agonist
- Gene
- THRB
- UniProt
- P10828
- ChEMBL
- CHEMBL1947
- Action
- Agonist
Administration and dosing
Dosing
Dosing, titration and syringe
Loading the dosing information …
- Getting started and stepping up, drawn as a staircase
- Units on the U-100 syringe for every step
- How long one vial lasts
What the research shows
Clinical trials indicate that levothyroxine:
- Remains the standard treatment for hypothyroidism with worldwide acceptance
- Shows different dosing requirements in thyroid cancer patients (2.11 mcg/kg) versus primary hypothyroidism patients (1.63 mcg/kg)
- When combined with T3, lowers TSH levels and increases FT3
- Is effective in many patients at dosages of 75-150 mcg daily
- Has a 7-day half-life enabling once-daily dosing
- Is affected by genetic and individual differences in absorption and metabolism
Study results
What the trials measured
Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.
TSH after 1 year4
Mean in mIU/l, 737 people aged 65 or older with subclinical hypothyroidism
Values from the abstract. The dose was adjusted to the TSH value, on placebo only as a sham.
Change in symptoms after 1 year4
Points on a 0 to 100 scale, more means more symptoms
Values from the abstract. 9 points counted as clinically important. The secondary outcomes showed no benefit either.
Children's IQ at age 55
Median, two trials with 677 and 526 pregnant women
Values from the abstract, neither difference significant. Treatment from week 8 to 20 of pregnancy.
Need per kg body weight for a normal TSH1
Ratio, benign hypothyroidism = 1.0; 44 patients after cancer, 113 with hypothyroidism
Calculated from the per-kg-per-day values in the abstract. The authors explain the difference with residual thyroid tissue that still makes hormone in benign hypothyroidism.
Research status
Where the research stands
Levothyroxine has been approved for decades. On ClinicalTrials.gov 338 trials list levothyroxine among their interventions. Shown are the trials behind TRUST and the pregnancy study plus ongoing trials on the combination with T3. As of 26 Oct 2026. 6
- Preclinical Basis: agonist at the thyroid hormone receptor
- Phase 1 no registered trial
- Phase 2 no registered trial
- Phase 3 5 trials, 2 completed
- Approval since 1982 according to ChEMBL
Show all 6 phase 3 and 4 trials on a timelineHide timeline
NCT00388297 · 1,203 participants, started Oct 2006, primary endpoint reached Aug 2015.
Registry entry ↗ · Results: Casey et al., New England Journal of Medicine, 2017
LEVOLIO · NCT03053115 · 160 participants, started Mar 2017, primary endpoint reached Sept 2021. Tests several agents.
Registry entry ↗ · Results not yet in PubMed
T3-4-Hypo · NCT05682482 · 600 participants (planned), started Oct 2022, primary endpoint planned Jan 2028. Tests several agents.
NCT06345339 · 2,701 participants, started Apr 2024, primary endpoint planned Sept 2027. Tests several agents.
NCT07332273 · 286 participants (planned), started Nov 2025, primary endpoint planned Nov 2026.
TRUST · NCT01660126 · 737 participants, started May 2014, primary endpoint reached Nov 2016.
Registry entry ↗ · Results: Stott et al., New England Journal of Medicine, 2017
Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.
Side effects
With overtreatment, may occur:
- Tremor and nervousness
- Palpitations and arrhythmias
- Sleep disturbances
- Weight loss
- Heat intolerance
- Bone density loss with prolonged over-suppression
With under-dosing:
- Fatigue and lethargy
- Weight gain
- Cold intolerance
- Depression and cognitive impairment
- Bradycardia
Storage
Levothyroxine tablets should be stored in a dry, cool place, protected from light. Storage temperature should be between 15-25 degrees Celsius. Original containers protect against moisture and should remain tightly sealed. Do not refrigerate. Levothyroxine is stable at room temperature when protected from moisture.
