How can I select the right thyroid hormone formulation for my patient with hypothyroidism?

T4 considerations

When switching a patient’s thyroid medication (eg, patients with fluctuating absorption or who need tight control of thyroid-stimulating hormone such as those with thyroid cancer), clinicians must keep in mind that variations in dose and bioavailability in T4 formulations may cause fluctuations in thyroid-stimulating hormone levels; however, studies of this effect have shown conflicting results.^6–8 The American Thyroid Association guidelines⁹ recommend reevaluating serum thyroid-stimulating hormone levels if switching levothyroxine formulations, but cite this as a weak recommendation with low-quality evidence.

It is recommended that T4 medications be stored away from direct moisture and heat at a temperature between 68°F and 77°F (20°C–25°C).⁹ This recommendation may be difficult to follow for individuals who travel frequently. Euthyrox (levothyroxine) is blister packed and may have longer preserved potency compared with bottle-packed or amber vials.¹⁰

T3 considerations

T3 is the active form of thyroid hormone. Prohormone T4 is converted to T3 regardless of whether the patient has thyroid disease or the thyroid gland is present. Because a patient’s T3 level increases rapidly after intake and then declines, those taking T3 medications may need multiple doses (up to 3 times a day). This dosing schedule may be difficult for patients to follow, and once-daily dosing might not provide physiologic replacement.¹¹ T4, however, has a half-life of 1 week, so it is dosed daily and reaches a steady state after a month.

Desiccated thyroid extract and combination T4 and T3

Desiccated thyroid extract, thyroid hormone extracted from porcine thyroid gland, contains both T4 and T3; the T4:T3 ratio differs from that in humans, with desiccated thyroid extract having a significantly higher T3 component. For patients who avoid pork-derived products, formulations that contain thyroid hormone extracted from bovine thyroid glands can be purchased online. Neither bovine nor porcine formulations are approved by the US Food and Drug Administration. Also, bovine thyroid extract is not standardized, its dosing may not be consistent, and it is not available in retail pharmacies. Porcine thyroid extract may be inconsistent between batches but is more standardized than bovine extract and is available in retail pharmacies.

If a patient’s hypothyroid symptoms persist with T4 monotherapy despite achieving an optimal thyroid-stimulating hormone level, combination therapy with levothyroxine and liothyronine (T3) or switching to desiccated thyroid extract can be considered.^11–15 Patients receiving T4 who have a presumed genetic polymorphism that leads to inadequate deiodinase function will need the addition of T3 or treatment with desiccated thyroid extract.¹⁶

Research data are sparse and controversial and professional society guidelines are ambiguous and open to wide interpretation, but we advise caution when considering T3 or desiccated thyroid extract for patients older than 65; those with religious preferences that conflict with formulations that have porcine or bovine extracts; and those with unstable cardiovascular disease, active malignancy, or uncontrolled psychiatric disease.^17,18

T3 does not cross the placenta and should not be used during pregnancy.¹⁷ Pregnant patients taking T3 or desiccated thyroid extract should be switched to T4, and the T4 dose should be increased by 30%, which can be achieved by taking 2 extra tablets per week.

Patients with dietary requirements and preferences

Formulations that contain gelatin, which is made from animal collagen, may have limited use in vegetarians, vegans, or individuals with religious preferences. Some formulations also contain lactose, gluten, or dye (Table 1). These formulations should be avoided in those with certain medical conditions, allergies, intolerances, or sensitivities.

Patients with absorption problems

Patients who have absorption challenges, such as those who have undergone gastrointestinal surgeries or have gastrointestinal diseases, may need higher T4 doses. If absorption difficulty continues, other options include taking the T4 crushed, switching to liquid Tirosint (levothyroxine), adding T3, or switching to desiccated thyroid extract.² If these changes have no effect on absorption problems, then weekly or biweekly intramuscular levothyroxine injections can be considered.¹⁹