Thyroid hormone is one of the most commonly prescribed medications in the US, with most of these prescriptions for levothyroxine. Pharmacy filling of prescriptions of thyroid hormone have increased from 8.9 million in 2007 to 11.6 million in 2016, with 97% being for levothyroxine. The main clinical indication for the use of levothyroxine is overt hypothyroidism, a condition where the TSH level is increased and the FT4 levels is low. On the other hand, subclinical hypothyroidism, where the FT4 is normal with an increased TSH, is more common and treatment with levothyroxine is more controversial. Indeed, the treatment of subclinical hypothyroidism contributes significantly to the number of prescriptions.
In this study, the authors were interested in understanding the use of levothyroxine in the United States over time.
THE FULL ARTICLE TITLE
Brito JP et al 2021 Levothyroxine Use in the United States, 2008-2018. JAMA Intern Med. Epub 2021 Jun 21. PMID: 34152370.
SUMMARY OF THE STUDY
The authors were able to access a large data base called OptumLabs Data Warehouse which includes both commercially insured and Medicare Advantage enrollees in the US. Information on prescriptions and labs are available without specific patient identification. They identified adult patients who were newly started on levothyroxine and had a TSH measured within 3 months prior to starting the medication. They excluded patients with a history of thyroid surgery, thyroid cancer, central hypothyroidism and current pregnancy. A total of 110,842 patients were identified between 2008 and 2018. The average age was 46.1 and ~75% of patients were women. The average TSH was 5.3-5.8 mIU/L depending on the year.
There were 58,706 patients who also had thyroxine levels and were further classified according to their hormone status into overt hypothyroidism (elevated TSH with low thyroxine), mild subclinical hypothyroidism (TSH 4.5 to <10 mIU/L, normal thyroxine), moderate subclinical hypothyroidism (TSH 10–19.9 mIU/L, normal thyroxine), severe subclinical hypothyroidism (TSH >19.9 mIU/L, normal thyroxine) and normal thyroid function (normal TSH, normal thyroxine). Only 8.4% of the patients had overt hypothyroidism and 30.5% of patients had normal thyroid function. The remaining 61% were classified as subclinical hypothyroidism. There was a small increase over time in the proportion of patients with overt hypothyroidism (7.6% in 2008 to 8/4% in 2018) and a small decrease in those with severe subclinical hypothyroidism (2.5% in 2008 to 1.3% in 2018). The other classifications did not change significantly.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Only 10% of patients in this study had overt hypothyroidism prior to beginning thyroid hormone treatment. Of more concern, ~30% of prescriptions seemed to be for patients with normal thyroid function. There is no evidence that patients with normal thyroid function will benefit from thyroid hormone therapy. With regards to patients with subclinical hypothyroidism (as defined by an elevated TSH, normal thyroxine level), treatment is debatable.
The study is limited since it is retrospective and we cannot know how many patients were diagnosed with hypothyroidism and were on levothyroxine prior to entry into this database. In addition, we do not know how many patients with biochemical subclinical hypothyroidism had symptoms and do not know whether any of these patients had underlying autoimmune thyroiditis. However, it suggests that there are many patients on thyroid hormone who may not benefit from the medication. In particular, we know that TSH increases with age and the treatment of subclinical hypothyroidism has questionable benefit in patients 65 and older. In addition, in non-pregnant adults, treatment does not uniformly improve quality of life or thyroid related symptoms.
Thus, it is important for patients to discuss their expectations of treatment in detail with their physicians and particularly to repeat thyroid function tests prior to starting medication. It is also important to recognize that thyroid related symptoms can have other causes that need to be addressed to avoid the potential risks of thyroid hormone replacement and unnecessary costs.
—Marjorie Safran, MD
ABBREVIATIONS & DEFINITIONS
TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.
Thyroxine (T4): the major hormone produced by the thyroid gland. T4 gets converted to the active hormone T3 in various tissues in the body.
Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tirosint™ and generic preparations.
Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.
Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not.
Overt Hypothyroidism: clear hypothyroidism an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with thyroid hormone pills.