Levothyroxine sodium

Thyroid hormones

ATC code: H03AA01 (Levothyroxine sodium)

Brand names

Synthroid, Levoxyl, Tirosint, Unithroid

Mechanism of action

Synthetic analogue of endogenous thyroxine (T4). Deiodinated in tissues to the biologically active triiodothyronine (T3), which binds nuclear thyroid hormone receptors and regulates genes controlling basal metabolism, growth, and development. Affects carbohydrate, lipid, and protein metabolism, the cardiovascular system, CNS, and skeleton.

Indications

Post-thyroidectomy state

First line

Lifelong replacement is required after total thyroidectomy. In thyroid cancer, TSH suppression to below 0.1 mU/L is the target in high-risk patients (per AJCC and ATA staging) and 0.1–0.5 mU/L in intermediate risk. After subtotal resection for benign disease, the goal is euthyroidism with the same TSH target as for hypothyroidism.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Primary hypothyroidism

First line

Replacement therapy in primary hypothyroidism — first-line and sole therapy per ATA 2014 and NICE. Starting dose in young adults is 1.6 mcg/kg/day. In elderly and patients with ischemic heart disease, start at 12.5–25 mcg and titrate slowly. TSH target is 0.4–4.0 mU/L, with an upper limit up to 6 mU/L acceptable in the elderly. T4+T3 combinations are not routinely recommended.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Subclinical hypothyroidism

Individual decision

Subclinical hypothyroidism (TSH 4.5–10 mU/L, normal T4) may be treated selectively. ATA recommends therapy when TSH exceeds 10 mU/L, in patients with TPO antibodies and hypothyroid symptoms, and in women who are pregnant or planning pregnancy. Asymptomatic elderly patients are generally not treated because of iatrogenic thyrotoxicosis risk.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Weight loss in euthyroid patients (marketed indication)

Not recommended

Using levothyroxine for weight loss in euthyroid patients is not supported by international guidelines and is potentially harmful. Iatrogenic thyrotoxicosis increases the risk of atrial fibrillation, osteoporosis, and cardiomyopathy without producing sustained weight loss.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Practical notes

Timing and administration

Take in the morning on an empty stomach, 30–60 minutes before breakfast, with water only. During this window avoid coffee, tea, juice, milk, soy, and soy products. Alternative: bedtime dosing at least 3 hours after the last meal. Within 4 hours after the dose avoid: iron, calcium, magnesium, omega-3, proton pump inhibitors (pantoprazole, omeprazole), antacids, cholestyramine, and sevelamer — all impair absorption.

Monitoring

Check TSH 6–8 weeks after initiation or dose change. On stable therapy, recheck every 6–12 months. In pregnancy, check TSH every 4 weeks until mid-gestation, then every 6–8 weeks. When switching between brand-name and generic formulations, recheck TSH in 6–8 weeks (bioavailability may differ).

Pregnancy

Levothyroxine requirement increases 25–50 % from early pregnancy. In women with known hypothyroidism, the dose is increased immediately after pregnancy confirmation (2 additional tablets per week or 25–30 % daily dose increase). TSH target: below 2.5 mU/L in the first trimester, below 3 mU/L in the second and third trimesters.

Common myths

Myth: 'hormone medication is dangerous, better use herbs'. Fact: levothyroxine is bioidentical to endogenous thyroxine. Herbal products contain no active hormone and cannot compensate for hypothyroidism. Myth: 'I can take a break from therapy'. Fact: replacement for primary hypothyroidism is lifelong. Discontinuation leads to symptom return within weeks and risks myxedema coma with prolonged decompensation. Myth: 'levothyroxine helps with weight loss'. Fact: in euthyroid patients it does not produce sustained weight loss and is harmful (see the 'weight loss in euthyroid patients' indication).

Safety

Contraindications

Untreated thyrotoxicosis
Acute myocarditis
Acute myocardial infarction
Untreated adrenal insufficiency
Hypersensitivity

Serious adverse effects

Iatrogenic thyrotoxicosis from chronic overdosing
Atrial fibrillation (on overdose, especially in elderly)
Decreased bone mineral density (on chronic suppressive doses)

Common adverse effects

Symptoms of overdose at excessive doses: tachycardia, tremor, weight loss, sweating, nervousness
Headache

PregnancyFDA A

FDA category A. Safe and required in pregnancy for hypothyroid women. Inadequate replacement is associated with miscarriage, preterm birth, and impaired cognitive development of the child.

Breastfeeding

Compatible with breastfeeding. The amount transferred to milk is physiologically insignificant.