Levothyroxine

What it is

Levothyroxine is the standard first-line treatment for hypothyroidism, a condition affecting up to 5% of people worldwide, with women diagnosed roughly 5–10 times more often than men. Also known by its Canadian brand names Synthroid and Eltroxin, levothyroxine is a synthetic form of thyroxine (T4), the primary hormone produced by the thyroid gland. It is one of the most commonly prescribed medications in Canada, dispensed to millions of patients annually through provincial drug benefit programs including Ontario's ODB and BC PharmaCare.

Hypothyroidism (underactive thyroid) occurs when the thyroid gland fails to produce sufficient T4, slowing metabolism, impairing cognition, and disrupting cardiovascular and reproductive function. Levothyroxine replaces the missing hormone molecule-for-molecule, restoring normal thyroid hormone levels when dosed correctly.

Causes and mechanism

The thyroid gland normally secretes T4 into the bloodstream, where most of it is converted in peripheral tissues to triiodothyronine (T3), the biologically active form. When the gland is damaged — most often by Hashimoto's thyroiditis (an autoimmune condition), thyroid surgery, or radioiodine treatment — T4 output falls and thyroid-stimulating hormone (TSH) from the pituitary rises in compensation.

Levothyroxine works by supplying exogenous T4 that undergoes the same peripheral conversion to T3. Once absorbed, it binds nuclear thyroid hormone receptors and regulates gene expression governing metabolism, heart rate, body temperature, and neurological function. Because T4 has a half-life of approximately 7 days, once-daily dosing maintains stable blood levels.

Approved indications for levothyroxine:

Indication	Notes
Primary hypothyroidism	Most common use; includes Hashimoto's and post-thyroidectomy
Secondary hypothyroidism	Pituitary failure causing low TSH
Tertiary hypothyroidism	Rare; hypothalamic TRH deficiency
Thyroid cancer (adjunct)	TSH suppression after surgery + radioiodine
Myxedema coma	IV formulation used in hospital
Goitre reduction	Off-label in some cases

Symptoms and diagnosis

Undertreated or untreated hypothyroidism produces fatigue, weight gain, cold intolerance, constipation, dry skin, hair thinning, depression, and slowed heart rate. In Canada, diagnosis is confirmed by a serum TSH test, available through LifeLabs and Dynacare across most provinces. A TSH above the laboratory reference range (typically above 4.0–5.0 mIU/L, depending on the lab) combined with a low free T4 confirms overt hypothyroidism and warrants treatment.

Levothyroxine dosing is highly individualized. Starting doses for otherwise healthy adults are typically 1.6 mcg/kg/day, with lower starting doses (12.5–25 mcg/day) used in older patients or those with cardiac disease. TSH is rechecked 6–8 weeks after any dose change; the therapeutic target for most adults is a TSH of 0.5–2.5 mIU/L, though targets shift in pregnancy and thyroid cancer management.

Treatment options

Levothyroxine tablets (generic and brand-name Synthroid or Eltroxin) are the standard form dispensed in Canada. Liquid-filled capsules and oral solutions exist for patients with absorption problems, though these are less widely stocked in Canadian pharmacies.

Key administration points:

• Take on an empty stomach, 30–60 minutes before food or other medications
• Separate from calcium, iron supplements, antacids, and certain cholesterol drugs (e.g., cholestyramine) by at least 4 hours, as these reduce absorption
• Consistent timing each day matters more than the specific time chosen
• Do not switch between brand and generic without informing your prescriber — small bioavailability differences between formulations can shift TSH

For patients who remain symptomatic on levothyroxine alone despite normal TSH, some clinicians consider combination therapy with liothyronine (T3), though this remains off-guideline for routine use. The Endocrine Society notes insufficient evidence to recommend combination therapy broadly.

When to see a clinician in Canada

Canadians can access levothyroxine prescriptions through family physicians, endocrinologists, or nurse practitioners. Virtual care platforms — including Maple, Felix, Cleo, and others — can initiate or renew thyroid prescriptions in most provinces, though initial diagnosis typically requires in-person bloodwork. Levothyroxine is listed on most provincial formularies and is covered under ODB (Ontario), BC PharmaCare, Alberta Blue Cross (for eligible recipients), and equivalent programs in other provinces; patients should confirm their specific plan's criteria.

Seek prompt medical attention if you develop chest pain, rapid or irregular heartbeat, uncontrollable tremor, or severe anxiety while taking levothyroxine — these may indicate over-replacement (iatrogenic hyperthyroidism). Pregnant patients require particularly close monitoring: TSH targets tighten to 0.1–2.5 mIU/L in the first trimester, and dose requirements often increase by 25–50% during pregnancy.

Limitations and open questions

Research is still emerging on the optimal TSH target range for older adults, with some evidence suggesting that mildly elevated TSH (up to 6–7 mIU/L) may be physiologically normal in patients over 70 and does not always warrant treatment. Health Canada has not issued specific guidance distinguishing age-adjusted TSH thresholds from standard adult ranges.

The question of whether combination T4/T3 therapy benefits a subset of patients — particularly those with persistent fatigue and cognitive symptoms despite normal TSH — remains unresolved. Several randomized trials have shown no consistent benefit over levothyroxine monotherapy, but patient-reported outcomes vary, and genetic variation in deiodinase enzymes (which convert T4 to T3) may explain why some individuals respond differently. Ongoing research into personalized dosing strategies has not yet produced actionable clinical guidelines in Canada.

Brand-to-generic substitution is a practical concern: Canadian pharmacies may dispense different manufacturers' tablets on refill. While Health Canada requires bioequivalence testing, some patients and clinicians report TSH fluctuations with switches. Patients with narrow therapeutic windows (e.g., thyroid cancer on suppressive therapy) are generally advised to stay on a consistent formulation.