Confused doctor looking at vials of bloodwork with text bubble saying confusing blood work: thyroid binding proteins

Thyroid lab tests are commonly run. Oftentimes, the lab results make sense and treatment is straightforward. However, there are a lot of cases where the lab results don’t correlate with your symptoms, or the lab results contradict each other.

Click here to learn more about how thyroid test results can be confusing.

This article focuses one possible cause: altered thyroid binding proteins.

Thyroid Binding Proteins

If you review basic thyroid physiology and anatomy, you’ll see that the thyroid gland produces T4 and T3, as depicted in the image below. The thyroid gland produces significantly more T4 than T3.

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

Upon deeper analysis, most thyroid hormones are bound to carrier proteins. We refer to these carrier proteins as Thyroid Binding Globulins (TBGs), and they include Thyroxine binding globulin, albumin and transthyretin [2].

thyroid gland physiology showing the effects of bound hormones as it relates to the results of basic thyroid lab testing

Free vs Bound Hormone and TSH

Free thyroid hormone is the unbound hormone, floating free around the blood. Bound thyroid hormone it is attached to the carrier proteins. Total hormone is the sum of the two.

Free thyroid hormone affects TSH most accurately. So if Free thyroid hormone increases, it will decrease TSH.

schematic showing thyroid anatomy and the effects of free thyroid hormone and TSH when interpreting results of thyroid lab testing

Altered TBG Binding

Since much of the thyroid hormone (T3 and T4) is bound to carrier proteins, anything that displaces the hormone from the protein carrier would raise free Thyroid hormone (FT3 and FT4). These would transiently elevate FT4 and FT3 concentrations and depress TSH.

Factors that displace T3 and T4 from Binding Proteins [1]

  • furosemide (especially with doses >80 mg/day and when given intravenously) [1],[3], [4]
  • aspirin [1],[3], [4]
  • nonsteroidal anti-inflammatory agents [1],[3], [4]
  • phenytoin and heparin[1], [3], [4]
  • Genetic variants of albumin (familial dysalbuminaemic hyperthyroxemia (FDH)) can cause higher albumin, thus causing over estimations of T4 (and less frequently T3) [1],[3], [4]

Altered TBG Synthesis

Naturally, increases and decreases in concentrations of TBGs are possible. Increased binding molecules would lead to increased Total T4 and Total T3; whereas lowered TBG would lower Total T4 and Total T3. Most blood tests monitoring thyroid hormones would measure free T3 and free T4 rather than total T3 and total T4, so these issues can be easily monitored with blood testing. The following may be causes for abnormal results pertaining to total T3 and T4. Transient alterations in FT4 and FT3 have occasionally been observed [1], but quickly normalize.

Factors that raise TBG: (these will raise total thyroid hormone, but won't affect free hormone) [1], [2]

  • Pregnancy
  • Estrogens (oral contraceptives, hormone replacement, tamoxifen)
  • Liver disorders
  • Rarely hereditary disease
  • Drugs: raloxifene, mitotane, fluorouracil, methadone and heroin

Factors that lower TBG: (these lower total thyroid hormone, not free hormone) [1], [2]

  • Androgens
  • Chronic glucocorticoid therapy and nicotinic acid


In most cases, thyroid blood work is straightforward and helps guide treatment. If you’ve got thyroid results back, and they don’t make sense, make sure your doctor is considering any factors which may affect your thyroid binding proteins.


Interested in learning more?

Read on in our series of articles on Thyroid Health!

About the Author - Dr. Johann de Chickera

man facing camera

Dr. Johann is a fully licensed Naturopathic Doctor. His approach emphasizes the importance of living a healthy lifestyle and improving one’s health naturally. Dr. Johann obtained a Doctor of Naturopathy at the Canadian College of Naturopathic Medicine (CCNM). Education at CCNM is a vigorous four years, with a curriculum involving biomedical sciences, physical diagnosis, clinical nutrition, traditional Chinese medicine and acupuncture, botanical (herbal) medicine, physical medicine, homeopathy and lifestyle management.

While Dr. Johann has a general practice, he focuses on fertility, hormonal imbalances, gut health, and autoimmune disease.

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

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