Tests During the Medical Use of Levothyroxine (T4)

The dose of levothyroxine cannot be selected by feel — only by test results. But tests are also easy to “spoil”: by taking them too soon after a dose change, after the tablet, or while on biotin. The editorial team explains what competent laboratory monitoring of thyroid therapy looks like.

Why tests are needed on levothyroxine

Levothyroxine is a drug whose dose cannot be selected “by how you feel”. The symptoms of hypothyroidism and thyrotoxicosis are nonspecific: fatigue, weight changes, sleep disturbances, and anxiety can have dozens of other causes. Therefore the main tool for monitoring therapy is laboratory tests.

The need for the hormone differs between people and depends on body weight, the cause of hypothyroidism, age, preserved gland function, the use of other drugs, and the state of the intestine. Even in one person it changes over time. Tests make it possible to notice these changes in time.

The guidelines of the American Thyroid Association (2014) emphasize two goals: to avoid undertreatment, which leaves symptoms of hypothyroidism, and to prevent overtreatment, which creates risks for the heart and bones.

In this material the editorial team explains which tests are prescribed before and during therapy, when to take them, and how to avoid common mistakes. The article is devoted specifically to levothyroxine; we wrote separately about the specifics of monitoring liothyronine.

Examination before starting treatment

Before prescribing levothyroxine, the doctor must confirm the diagnosis of hypothyroidism. For this, TSH and free T4 are usually used. A single elevation of TSH does not always mean disease: it can be temporary, for example after an acute illness, so the test is often repeated.

Antibodies to thyroid peroxidase (anti-TPO) help establish the autoimmune nature of hypothyroidism. They are determined, as a rule, once for diagnosis; there is no need to repeat this test for dose monitoring, and the antibody level is not a treatment target.

The doctor also assesses the general condition: cardiovascular diseases, age, pregnancy or its planning, and the use of other drugs. For older people and patients with ischemic heart disease, the starting dose is usually chosen more cautiously, which is reflected in the official levothyroxine prescribing information.

Subclinical hypothyroidism — elevated TSH with normal free T4 — does not always require treatment. The decision depends on the TSH level, the presence of antibodies, symptoms, age, and pregnancy plans. The review by Biondi and Cooper examines these nuances in detail.

Dose selection: why TSH is not checked right away

Levothyroxine has a long half-life — about a week. For the hormone concentration in the blood to stabilize at a new level, several weeks are needed, and TSH, which reflects the pituitary's response, changes even more slowly. Therefore a test done a week after a dose change is of little informative value.

The ATA guidelines recommend checking TSH several weeks after starting therapy or changing the dose; in practice doctors most often schedule a follow-up after 6–8 weeks. After the dose stabilizes, the test is usually repeated once every 6–12 months or when the condition changes.

The target TSH level is determined by the doctor. For most adults this is the laboratory's reference range, but for pregnant women, the elderly, and patients after thyroid cancer treatment the targets may be different. Therefore comparing your results with “norms from the internet” is incorrect.

In central hypothyroidism, when pituitary function is impaired, TSH does not reflect hormone sufficiency. In such patients, free T4 is used as a guide, and the tests are interpreted by an endocrinologist.

How to take the test correctly

For the comparability of results, it is important to take tests under the same conditions. A few simple rules help avoid false conclusions.

• Take blood in the morning, preferably at the same laboratory.
• Follow the same order regarding the morning tablet: many doctors advise taking it after the blood draw, since free T4 can temporarily rise for several hours after intake.
• Stop taking supplements with high doses of biotin a few days before the test, unless a doctor or the laboratory advises otherwise.
• Inform the doctor about new drugs, in particular estrogens, iron and calcium preparations, and proton pump inhibitors.
• Do not change the dose on your own before the test in order to “improve” the result.

Biotin deserves a separate mention. Supplements for hair and nails can contain doses many times higher than the daily requirement. Depending on the laboratory's method, they can falsely lower TSH and raise free hormones, creating a picture of thyrotoxicosis.

Acute illnesses, severe stress, and hospitalization also affect thyroid indicators. Scheduled monitoring is better done when a person is healthy.

If the results suddenly change without a dose change, the doctor looks for a cause: a new drug, a change of tablet manufacturer, a violation of the intake regimen, pregnancy, or intestinal disease.

When additional examinations are needed

If an unusually high dose is needed to achieve normal TSH, the doctor may check whether there is a malabsorption problem. The review by Liwanpo and Hershman names among the causes celiac disease, atrophic gastritis, Helicobacter pylori infection, as well as taking drugs that bind the hormone. Sometimes the cause turns out to be irregular tablet intake.

For people receiving doses that suppress TSH — for example after thyroid cancer treatment — monitoring of the bones and heart is important. A study by Flynn and colleagues showed that suppressed TSH on long-term therapy is associated with an increased risk of fractures and cardiovascular events.

In pregnant women, monitoring becomes more frequent: the ATA guidelines (2017) recommend regularly checking TSH in the first half of pregnancy, since the need for the hormone rapidly increases.

Older people and patients with arrhythmias need attention to the heart: ECG, monitoring of pulse and blood pressure. Biondi and Cooper, in their review, showed that even a subclinical excess of the hormone increases the risk of atrial fibrillation.

Editorial conclusions

The basis of monitoring levothyroxine therapy is TSH. It is checked several weeks after each dose change, and after stabilization — once every 6–12 months.

For results to be comparable, it is important to take blood in the morning, under the same conditions, without biotin, and with full information for the doctor about other drugs.

An unusually high need for the hormone is a reason to look for a cause rather than simply increase the dose.

Also on the blog: tests during the use of liothyronine (T3), interactions of levothyroxine with other drugs, and levothyroxine and women.

References

1. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751.
2. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–389.
3. U.S. Food and Drug Administration. Synthroid (levothyroxine sodium) tablets: prescribing information. Silver Spring (MD): FDA.
4. Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781–792.
5. Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010;95(1):186–193.
6. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76–131.
7. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550–1562.