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

Summary

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.