Not many organs in the body are easily replaced with a pill,
but we are lucky the thyroid is one of them.
Hypothyroidism, regardless of cause, is treated with thyroid hormone
replacement. As straightforward as this
sounds, once treatment is recommended, the questions begin: Synthetic or biologic? Levothyroxine (LT4)
only, or in combination with liothyronine(LT3)?
Synthetic thyroid hormones (Synthroid, Levothroid, Tirosint,
to name a few) have the same molecular structure as the levothyroxine (LT4) our
native thyroids produce. They have been
available since the 1950s, but in 1997, documentation of stability, consistency,
safety and efficacy, was required as part of a New Drug Application by the year
2000. However, all formulations were allowed to
remain on the market during that interval due to necessity of the
medicine. Synthetic forms are now
approved (most recently Tirosint in 2006) and regulated by the FDA. This is important, as cooperation with the
FDA can lead to appropriate (perhaps over-cautious) precautions for
patients. Recently Levoxyl was recalled
for an uncharacteristic odor. The
factories are off-line, and Levoxyl is not expected to be available until 2014. Generic forms are typically lower in cost,
but ensuring the source is always the same factory is difficult. Even within the same factory, there can be
about a 6% variability from lot to lot, which is additive when more than one
factory is involved. For some patients,
minimizing error is crucial to maintaining euthyroidism, and it is difficult to
achieve when mixing multiple sources in this very-low-dose medication.
Animal (pig) extracts of thyroid (e.g. Armour, Nature-Throid),
have been available since 1862. They
received the same invitation to submit a New Drug Application to the FDA the
synthetic forms did, but have not done so.
They remain available on the market as they have been “grandfathered” in,
having come into production before 1938.
There was a shortage of extracts in 2009 for unclear reasons, but their
production was specifically not disrupted by the FDA, as had been rumored. These medications do contain both LT4 and
LT3, and remain a favorite amongst certain patients and providers for this
reason. The ratio of LT4 and LT3 is
different in pigs than in humans (pigs have more T3). This is important to keep in mind when
reviewing labs of patients on this form of thyroid hormone replacement, as the Total
or Free T4 will frequently be low in the setting of a normal (or suppressed)
TSH and normal (or elevated) Total or Free T3.
Compounded forms of LT4 and LT3 allow customization of dose,
format, and flavor. They are not
regulated by the FDA, though there is some regulation of compounding pharmacies
on the state level. The same concerns
remain regarding safety and efficacy.
Also, the stability of the medications is not verified, and no
assurances are made the products are free of impurities. A slow-release T3 is marketed, though there
are no FDA-approved forms available at this time.
Should LT4 be dosed alone, or in combination with LT3
(Cytomel or liothyronine)? When
patients’ symptoms persist despite a normal TSH or T4, consideration may be
given to adding the more potent form of thyroid hormone, LT3. Most patients have the enzyme deiodinase D2,
which converts LT4 to LT3, in organs other than the thyroid. In fact, 75-80% of circulating LT3 has been peripherally
converted from LT4, rather than produced in the thyroid. Of 16 randomized, controlled studies
investigating the advantages of adding LT3, only one demonstrated objective
benefit. Four demonstrated subjective
benefit, and 4 studies indicated a patient preference for the combination. This option should be tailored individually,
with a goal of keeping the Total T3 and TSH in the normal range.
When there are this many treatment options available, it is
clearly because no one treatment fits all patients. However, knowledge of the risks and benefits
of the different options is the key to optimizing each patient’s condition.
