Wisdom Wednesday: Levothyroxine

Up to 7% of the general population has hypothyroidism, which is corrected with thyroid hormone treatment. The general goals of thyroid hormone replacement are to provide resolution of patient symptoms and hypothyroid signs, including biological and physiologic markers of hypothyroidism; achieve normalization of serum thyroid-stimulating hormone (TSH) concentrations with improvement in circulating thyroid hormone concentrations; and avoid overtreatment (eg, iatrogenic thyrotoxicosis), especially in elderly persons.

Levothyroxine, a synthetically made thyroxine (T4), is the predominant form of thyroid hormone replacement used on patients with hypothyroidism. In healthy and iodine-sufficient individuals, the majority of thyroid hormone produced is T4, synthesized exclusively by the thyroid gland, with a smaller amount of T3, which is produced by the thyroid and in peripheral tissues via diodination of the circulating T4.

In the setting of fluctuating T4 levels, deiodinase activity is tightly regulated to maintain normal T3 levels at the various target tissues. In hypothyroidism, the 5’ deiodinase is activated to allow greater conversion of T4 to the bioactive form of thyroid hormone, T3.
Given the high prevalence of hypothyroidism in the general population, levothyroxine has consistently been the most frequently prescribed medication in the United States over the past several years. In 2016, approximately 123 million prescriptions for levothyroxine were dispensed.



Since 2007, the US Food and Drug Administration (FDA) has required that the synthetic T4 content in pills be within 5% of the stated dose, such that brand-name prescriptions can now be therapeutically interchanged with generic levothyroxine unless explicitly stated against by the prescriber.

However, some patients and clinicians have an interest in replacing T3 along with T4. Reasons include the persistence of hypothyroid symptoms despite achieving biochemically normal serum TSH concentrations with levothyroxine therapy, the desire to have more options for therapy, or concern about possibly have type II deiodinase polymorphism.

Although there is some evidence that patients prefer the use of regimens containing T3, outcomes evaluating quality of life or psychological endpoints have been inconsistent. Some might have a preference for animal-derived, non-synthetic, natural forms of treatment, such as desiccated thyroid extract (DTE) from bovine and porcine sources, which contain both T3 and T4 at an approximate physiologic ratio of 1:4.
DTE has been in use since at least 1891 before the FDA in 1938 was required to begin regulating the efficacy and safety of new medications in the United States. Thus, DTE formulations are considered “grandfathered” drugs, which technically remain FDA-unapproved for thyroid hormone replacement to this day.

My Take:
Dr. Angela Leung does a very good job of describing hypothyroidism, testing and treatment. Of course, the incidence of hypothyroidism is much higher than 7%, but only 7% are receiving medical treatment.

Go back to the second paragraph and reread “in healthy and iodine sufficient individuals.” The first step in treating hypothyroidism is to make sure they are iodine sufficient. Often they are not.

She also fails to make any mention of Hashimoto’s Thyroiditis. This autoimmune disease is thought to be responsible for at least a third of all cases of hypothyroidism. Personally, I think it’s much higher, closer to half of all hypothyroid patients. If your immune system is attacking your thyroid it must be modulated to resolve symptoms of hypothyroidism.

Bottom Line:
Prior to considering whether to take levothyroxine or DTE, check your iodine status and run laboratory testing for Hashimoto’s Thyroiditis (thyroid autoantibodies and a thyroid peroxidase (TPO)). Insist on a free T3 and T4, not just the TSH. Regardless of therapy, monitor the TSH using the optimal level of 1-2 uIU/mL, rather than the medical norm of 0.4 to 4.5 uIU/mL. When combined with the current status of hypothyroid symptoms, the narrow range of TSH is the best indicator of thyroid health.

Source: October 25, 2018 NIH