skeleton with thyroid gland in the background, and bottles of thyroid medications in the foreground with text bubble saying confusing thyroid blood work with thyroxin medications

Thyroid medications (such as Eltroxin and Synthroid) are some of the most prescribed medications in the world. Patients taking these medicationss often undergo routine blood work to track the progress of their hypothyroidism. Often times, patients taking thse thyroxin based medications have blood work that doesn’t make sense based on their symptoms. This article will discuss the reasons why.

Normal Thyroid Function

Normal thyroid function is based on various glands and hormones working properly together. The image below depicts normal thyroid function. Click here to learn more about basic thyroid physiology.

a full schematic of thyroid physiology, including hypothalamus, anterior pituitary gland, thyroid gland and the hormones TSH, T3 and T4

Various tests are conducted to asses thyroid function, including blood work for TSH, T3, T4 and reverse T3. Click here to review the basics of lab testing.

Most times lab values relate perfectly with the patient's signs and symptoms; however, we regularly find the lab work doesn’t make sense [5], [6]. The topic of confusing thyroid blood work can be accessed here.

What is Levothyroxine?

Levothyroxine (L-T4) is a synthetic form of T4; it is given to people with hypothyroidism. Levothyroxine is the generic name; brand names you may recognize are Synthroid and Eltroxin [7].

schematic showing how synthroid and eltroxin affect thyroid physiology in hypothyroidism

How is L-T4 Monitored?

Doctors aim to ‘normalize’ T3 and T4. Doctors will typically run blood work every few months to monitor until the proper dosage is obtained. In most cases TSH is measured (not T4 or T3). Keep in mind, there are many pitfalls in testing TSH alone, so if you have abnormal blood work, request more comprehensive testing.  Testing T3 and T4 may be helpful. Most patients feel better once T4 is in the upper half of normal range (110-165 nmol/L) [7].

Anomalous Blood Work with Levothyroxine Therapy

Normal Expectations of Levothyroxine Therapy

We generally expect TSH to drop, and T4 and T3 to normalize. Symptoms should subside.

It should be noted that it is also normal for someone on thyroxine replacement to normalize TSH and Free T3 levels but have mildly elevated free T4 [4].

TSH: normal     FT4: mildly ↑ or normal

Cause:

  • Normal physiological variant: To abolish symptoms and normalise TSH concentrations, some individuals exhibit mildly elevated FT4. This could reflect less efficient conversion of T4 to T3). Free T3 is typically normal [5], [6]

Common Causes of Confusing Thyroid Blood Work for Someone on Levothyroxine (L-T4)

TSH: ↑     FT4:↓ (or low end of normal)

Causes:

  • Maladministration: L-T4 should be taken on an empty stomach[3], [5], [6]; certain foods (e.g. fibre, coffee) and some medications (e.g. iron, calcium, PPIs, sucralfate, aluminium hydroxide, cholestyramine) may impair L-T4 absorption
  • Malabsorption syndromes: L-T4 malabsorption occurs with various gastrointestinal conditions, such as Celiac Disease, achlorhydria, or lactose intolerance (lactose is a constituent of some L-T4 preparations) [3], [5],[6]
  • Increased thyroid hormone (T3 and T4) metabolism or excretion: Many factors increase L-T4 requirements by enhancing the liver metabolism of thyroid hormone [3], [5], [6].
  • Increased thyroid hormone binding capacity: Oral estrogen therapy or gonadotrophin-induced rise in estrogen concentrations (e.g. IVF treatment) results in a marked increase in thyroid binding globulins and hence thyroid hormone binding capacity, necessitating an increase in L-T4 therapy; similar effects are seen with SERMs and mitotane [3], [5],[6]. For more information about factors which affect thyroid carrier proteins, click here.

Unexpected change in L-T4 dosage requirements

This describes a case where L-T4 dose was adjusted and things were fine. Suddenly something changes and the dose needs to be adjusted.

Cause:

  • Change in LT4 preparation: There are various L-T4 preparations. They differ in potency and bioavailability. Changes in preparation are generally best avoided but, if necessary, should prompt more frequent blood test monitoring [3], [5],[6]

TSH: ↑     FT4: Normal

Cause:

  • TSH assay interference: Heterophilic antibody interference in the TSH assay may yield falsely elevated results; FT3 is normal [3] [5], [6]. Click here to learn more.

Persistent ↑TSH, with ↓, ↑ or normal FT4, despite treatment with high L-T4 dosages

Cause:

  • Poor compliance: Owing to their differing half-lives, intermittent thyroxine ingestion may result in normal or even elevated thyroid hormone concentrations, but fails to normalize TSH [3] [5], [6]

Supraphysiologic L-T4 required to normalize TSH, but with resultant ↑FT4 (and ↑FT3)

Cause:

  • Resistance to thyroid hormone: Typically seen following inappropriate thyroid ablation or concomitant primary hypothyroidism in a patient with a genetic mutation in the human thyroid hormone receptor β (THRB) gene [3] [5], [6]. Click here to learn more about resistance.

Summary

As you can see, there are many factors that go into L-T4 metabolism, excretion and utilization. This information is not intended to provide a template for dosing adjustments; it is merely to inform patients and doctors alike that these factors all play a role and potentially complicate blood testing associated with thyroid health. If you fall under one of these categories, please book with your Endocrinologist or Naturopath to discuss more.

References

Interested in learning more?

Read on in our series of articles on Thyroid Health!

About the Author - Dr. Johann de Chickera

Dr. Johann de Chickera is a naturopath at Absolute Health and Wellness in Paris Ontario

Dr. Johann is a licensed naturopathic doctor and co-owner of Absolute Health and Wellness. He completed his 4-year degree at the Canadian College of Naturopathic Medicine (CCNM). His clinical focus lies in chronic disease, such as those related to the Gastrointestinal, Endocrine, and Immune Systems.

His approach to medicine relies on working with the patient to come up with a feasible, multi-factorial approach that addresses all complaints at once. He employs a strong background in diagnostic medicine and human physiology and pathology to diagnose and treat. His treatment involve a combination of nutritional counselling, botanical medicine, eastern medicine (acupuncture), nutraceutical supplementation and hands on physical medicine.

To book in please call us at (519) 442-2206 or click here.

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