Dextrothyroxine (D-T4)
Dextrothyroxine is the D-isomer of thyroxine, formerly marketed as Choloxin for hypercholesterolaemia. It lowers LDL via thyroid-hormone-like hepatic effects but was withdrawn after a trial showed increased cardiac mortality, illustrating the risk of non-selective thyromimetics.
01 Overview
Dextrothyroxine was developed to exploit thyroid hormone's cholesterol-lowering action while minimising metabolic potency, on the theory that the D-isomer had less thyromimetic activity than natural L-thyroxine. It did lower LDL, but purity issues meant it retained meaningful thyroid activity.
The Coronary Drug Project found excess cardiac events and mortality in patients with heart disease taking dextrothyroxine, leading to its withdrawal. It stands as a cautionary example of why non-selective thyroid analogues fell out of favour for lipid or fat-loss use.
02 Mechanism
As a thyroxine isomer it binds thyroid hormone receptors, upregulating hepatic LDL-receptor expression and cholesterol clearance; residual systemic thyromimetic activity raises cardiac workload.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Hypercholesterolaemia (historical) | 4–8 mg/day | Oral | Withdrawn indication; historical dosing |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| LDL cholesterol reductionReduced LDL and total cholesterol via hepatic thyroid effects. | Meaningful LDL lowering | Clinical | |
| Increased metabolic rateResidual thyromimetic activity raises basal metabolic rate and thermogenesis. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Thyrotoxic symptomsPalpitations, tremor and heat intolerance from thyroid activity. | Moderate | Dose-dependent | Clinical | |
| Increased cardiac mortalityExcess arrhythmia and cardiac death in patients with heart disease. | Life-threatening | In cardiac patients | Clinical |