Thyroid Medications —
Synthroid, Armour, Cytomel & More

Generic levothyroxine is the most prescribed drug in the United States, used by tens of millions of patients for hypothyroidism. The active molecule — levothyroxine sodium, the sodium salt of the naturally occurring thyroid hormone thyroxine (T4) — is identical across all FDA-approved formulations. T4 serves as a prohormone: once absorbed, it circulates in the blood and is converted to the biologically active T3 (triiodothyronine) by deiodinase enzymes in tissues including the liver, kidney, and brain.

The 7-day half-life is the defining pharmacokinetic feature of T4. Unlike T3, which peaks and troughs sharply, T4 creates a remarkably stable blood level on once-daily dosing — missing a single dose has minimal clinical consequence, and the body equilibrates over weeks rather than hours. This stability makes TSH monitoring easy: a blood test drawn at any time of day after a few weeks at a steady dose accurately reflects the patient's thyroid status.

Available in a wide range of strengths from 25 mcg to 300 mcg. Generic tablets must be taken on an empty stomach — typically 30–60 minutes before breakfast — with only water. Many substances impair absorption significantly, including calcium, iron, antacids, PPIs, coffee, and soy. See the absorption rules section below for specifics.

Synthroid is the brand-name formulation of levothyroxine manufactured by AbbVie. It contains the identical active ingredient as all other levothyroxine products but uses AbbVie's proprietary inactive ingredient blend — acacia, confectioner's sugar, lactose monohydrate, magnesium stearate, povidone, and talc, with color-coded FD&C dyes at each dose strength for easy visual identification.

The long-standing clinical argument for brand-name Synthroid is not that it is pharmacologically superior, but that it is pharmacologically consistent. Levothyroxine has a narrow therapeutic index — small differences in blood levels translate to measurable TSH changes, which in turn affect how patients feel. Once a patient's TSH is well-controlled on a specific formulation, some endocrinologists recommend staying on that formulation to avoid introducing unnecessary variables, even if the formulation is a more expensive brand.

The FDA requires all generic levothyroxine products to demonstrate bioequivalence to the brand reference listed drug, meaning their absorption must fall within 80–125% of the brand's AUC and Cmax. For most patients this range is clinically acceptable; for those with finely tuned TSH targets (e.g., thyroid cancer patients on suppression therapy, or patients with symptoms at TSH values that differ by only tenths of a unit), the margins matter more. Available in strengths from 25 mcg to 300 mcg.

Levoxyl is Pfizer's branded levothyroxine formulation. Its distinguishing characteristic is a compressed tablet designed to dissolve rapidly after swallowing. Unlike standard levothyroxine tablets, Levoxyl is specifically formulated to disintegrate quickly in the mouth if not swallowed promptly with water — the prescribing information warns against allowing the tablet to sit in the mouth, as it may dissolve and swell, presenting a potential choking risk.

The faster dissolution profile is a design choice intended to begin absorption more promptly than slower-dissolving competitors. Whether this translates to meaningful clinical differences in steady-state T4 levels has not been definitively demonstrated in head-to-head trials against other formulations, but anecdotally some patients report preference for it.

Levoxyl's excipient profile differs from Synthroid — it is made without acacia, and some patients who have difficulty with Synthroid's inactive ingredients (though true excipient intolerance with thyroid tablets is rare) have been switched to Levoxyl with success. Available in strengths from 25 mcg to 200 mcg. Like all tablet-form levothyroxine, it should be taken on an empty stomach.

Tirosint represents the most significant formulation innovation in levothyroxine delivery. Instead of a compressed tablet with fillers and binders, it is a soft gel capsule containing only four components: levothyroxine sodium, gelatin, glycerin, and water. No dyes, no lactose, no acacia, no talc, no magnesium stearate — just the active drug in a liquid medium inside a capsule shell.

This minimal excipient profile matters for several patient populations. Patients with lactose intolerance historically had to manage their levothyroxine tablets (which contain lactose monohydrate as an excipient) carefully. Patients with celiac disease or gluten sensitivity may benefit from a completely filler-free formulation. More clinically important, the gel capsule formulation has been demonstrated in studies to have superior absorption consistency compared to tablet forms in patients with GI conditions that impair T4 absorption — including atrophic gastritis, celiac disease, short bowel syndrome, and patients on proton pump inhibitors (PPIs).

PPIs raise gastric pH, and higher gastric pH reduces levothyroxine tablet dissolution and absorption. Tirosint, being a liquid-in-capsule formulation, bypasses this dissolution step. Studies have shown that Tirosint maintains stable TSH in PPI users where standard tablets may fail. Additionally, research has shown that Tirosint is less affected by coffee consumption taken shortly after dosing than standard tablets — though taking it with water on an empty stomach remains the recommended approach. Available in strengths from 13 mcg to 150 mcg.

Liothyronine is synthetic T3 — the biologically active thyroid hormone that directly binds to thyroid hormone receptors in cell nuclei. While T4 (levothyroxine) functions as a prohormone that is converted to T3 peripherally by deiodinase enzymes, liothyronine bypasses this conversion step entirely, delivering the active form of the hormone directly.

The pharmacokinetic profile of T3 is fundamentally different from T4. With a half-life of approximately one day (vs T4's seven days), blood levels of T3 rise rapidly after oral dosing — peaking within 2–4 hours — and fall sharply thereafter. This means that on once-daily liothyronine dosing, patients experience pronounced peaks and troughs in circulating T3. Some protocols use twice-daily dosing to blunt this variation, and a sustained-release liothyronine formulation has been studied (though is not commercially available in the US as of 2025) specifically to address this limitation.

The clinical rationale for adding liothyronine to levothyroxine centers on patients with genetic polymorphisms in type 2 deiodinase (DIO2), the enzyme responsible for converting T4 to T3 in key tissues including the brain and pituitary. A common DIO2 variant (Thr92Ala) affects an estimated 12–36% of the population and has been associated in some studies with reduced T4-to-T3 conversion efficiency — meaning these patients may maintain "normal" TSH while having suboptimal T3 in key tissues. Some research supports that patients with this variant report better psychological well-being on T4+T3 combination therapy than on T4 alone.

However, mainstream endocrinology guidelines (ATA, ETA) do not recommend routine addition of T3 to hypothyroid treatment, citing: the difficulty of managing T3 fluctuations safely, cardiovascular risks from elevated T3 peaks (particularly in older patients and those with cardiac disease), lack of large randomized trial evidence, and normal TSH maintenance that fails to capture T3 variability adequately. Liothyronine is available in strengths from 5 mcg to 50 mcg.

Armour Thyroid is the most widely used desiccated thyroid extract (DTE) in the United States. It is derived from the dried (desiccated) thyroid glands of pigs and contains all four thyroid hormones the gland naturally produces: T4, T3, T2 (diiodothyronine), and T1 (monoiodothyronine), as well as calcitonin and thyroglobulin. Its clinical appeal is that it provides T3 directly — no conversion required — along with the other thyroid hormones that synthetic levothyroxine monotherapy does not supply.

The porcine thyroid has a T4:T3 ratio of approximately 4:1 by weight. Human thyroid glands naturally produce hormones in a ratio closer to 14:1 (T4:T3). This discrepancy means that Armour Thyroid delivers significantly more T3 per microgram of T4 equivalent than the human gland would. When dosed to a TSH within normal range, patients on Armour tend to have higher circulating free T3 and lower free T4 compared to patients on levothyroxine alone — which is either an advantage (providing T3 directly) or a concern (supraphysiologic T3 peaks with each dose) depending on perspective.

The patient experience data on Armour is striking despite limited randomized trial evidence: surveys of hypothyroid patients consistently find that those who have tried both DTE and levothyroxine report preferring DTE at rates of 2:1 or more, with particular differences in energy, mood, and cognitive clarity. A well-cited 2013 study by Hoang et al. found that patients on Armour Thyroid lost more weight and reported greater satisfaction than patients randomized to levothyroxine over one year — though this study was small and has not been replicated in larger trials. Armour Thyroid is standardized by USP to contain specified levels of total iodine, not by direct hormone assay, which introduces some batch-to-batch variability in T4 and T3 content.

Armour Thyroid is available in grain-based strengths (1/4 grain = 15 mg, 1/2 grain = 30 mg, 1 grain = 60 mg, etc.) reflecting its historical pharmaceutical origins.

NP Thyroid is Acella Pharmaceuticals' desiccated thyroid extract product, functionally similar to Armour Thyroid in composition — porcine-derived, containing T4, T3, T2, and T1 in the same approximate porcine ratios, standardized by iodine content. It is available in similar grain-based strengths as Armour Thyroid.

The clinical differences between NP Thyroid and Armour Thyroid are modest and primarily relate to tablet formulation and excipients rather than active ingredient content. Some patients who switch between the two report experiencing differences, particularly because the excipient profiles differ — NP Thyroid contains different binders and fillers. Whether these differences produce meaningful pharmacokinetic variation has not been rigorously studied in head-to-head trials.

NP Thyroid has experienced significant supply shortages, including a notable FDA-mandated voluntary recall in 2020 related to superpotency (higher-than-labeled hormone content in some lots). Patients who depend on NP Thyroid should be aware of this supply history and should have a contingency plan — typically transitioning to Armour Thyroid or to synthetic levothyroxine with or without liothyronine — if shortages recur.

Combination T4+T3 therapy involves prescribing synthetic levothyroxine and liothyronine together — typically at a reduced levothyroxine dose with a small amount of liothyronine added. This approach attempts to replicate the therapeutic rationale of DTE (providing T3 directly) without the use of a porcine-derived product. It is appealing to patients who object to animal-derived medications but still believe they need direct T3 supplementation, and to clinicians who are more comfortable titrating two separate drugs than prescribing DTE.

The challenge of combination therapy lies in managing liothyronine's pharmacokinetics. Most protocols prescribe liothyronine in small doses (typically 5 mcg) taken once or twice daily alongside levothyroxine. Even at small doses, T3 peaks in the blood within hours of each dose and declines to trough levels before the next dose — a pattern that can cause some patients to notice cyclic symptoms (energy and warmth peaking in the morning, fatigue returning by evening). Twice-daily T3 dosing blunts this somewhat.

Research comparing combination therapy to levothyroxine monotherapy has produced mixed results. Some trials show no difference in quality of life; others show improvements in specific patient subgroups, particularly those with DIO2 polymorphisms. The 2019 study by Idrees et al. and others suggest that patient subgroup matters more than the treatment alone — a finding that supports targeted use rather than broad adoption.

Methimazole is the first-line antithyroid drug for Graves' disease and most other causes of hyperthyroidism. It belongs to the thioamide class and works by competitively inhibiting thyroid peroxidase (TPO) — the enzyme responsible for organifying iodine and coupling iodothyrosines to form thyroid hormones T4 and T3. By blocking TPO, methimazole effectively stops the thyroid from producing new hormone. Existing stores of preformed thyroid hormone continue to be released for several weeks after starting treatment, which is why thyroid hormone levels normalize gradually over 4–8 weeks, not immediately.

Methimazole has a relatively long half-life (~6 hours) and can often be given once daily at lower doses, improving adherence compared to the more frequent dosing required by PTU. It is generally considered to have a more favorable safety profile than PTU — specifically, it lacks PTU's risk of severe hepatotoxicity — making it the preferred choice for most non-pregnant adults with Graves' disease.

The most feared adverse effect of methimazole is agranulocytosis — a sudden, severe drop in white blood cells (specifically neutrophils) that leaves patients vulnerable to life-threatening infections. Agranulocytosis occurs in approximately 0.1–0.5% of patients, typically within the first 90 days of treatment. Patients should be counseled to immediately stop the medication and seek emergency care if they develop fever, sore throat, or signs of infection, as these symptoms may indicate agranulocytosis. Routine monitoring of complete blood count is standard practice when starting therapy.

Methimazole is teratogenic and should not be used in the first trimester of pregnancy. It has been associated with specific fetal malformations (aplasia cutis, choanal atresia) when used early in pregnancy. PTU is preferred in the first trimester, and patients are often switched back to methimazole in the second trimester when PTU's hepatotoxicity risk becomes the larger concern. Available in 5 mg and 10 mg tablets.

Propylthiouracil (PTU) is the older of the two antithyroid thioamides and carries an important distinction in its mechanism: in addition to blocking thyroid peroxidase and halting new hormone synthesis (the same mechanism as methimazole), PTU also inhibits the peripheral conversion of T4 to T3 by blocking the type 1 deiodinase enzyme (DIO1). This dual mechanism means PTU can lower circulating T3 more rapidly than methimazole — an advantage in thyroid storm, where the immediate reduction of active T3 is clinically urgent.

The more significant clinical distinction, however, is PTU's teratogenic profile relative to methimazole. Both drugs cross the placenta and can affect the fetal thyroid, but their teratogenic risks appear different in nature. Methimazole has been associated with specific fetal malformations (particularly choanal atresia and aplasia cutis). PTU's teratogenic risk, while real, appears to manifest as a different and generally less specific pattern of effects. Current guidelines recommend PTU as the preferred antithyroid agent during the first trimester of pregnancy, when organogenesis is occurring and the teratogenic risks of methimazole are greatest. After the first trimester, many patients are switched back to methimazole to avoid PTU's hepatotoxicity risk during the remainder of pregnancy.

PTU carries an FDA black box warning for severe hepatotoxicity — including fatal and life-threatening liver injury, requiring liver transplant in some cases. This risk is the primary reason PTU is no longer a first-line antithyroid agent in non-pregnant patients. The hepatotoxicity is idiosyncratic (not dose-related) and unpredictable. Patients on PTU should be monitored for signs of liver injury — nausea, fatigue, right upper quadrant discomfort, jaundice, dark urine — and the medication should be discontinued promptly if these develop.

PTU's short half-life (~1–2 hours) requires 3-times-daily dosing in most patients, which is a practical disadvantage compared to methimazole's once-daily or twice-daily dosing. Available in 50 mg tablets.