In patients who have had their entire thyroid removed due to thyroid cancer, the amount of type 2 deiodinase enzyme present in remaining thyroid tissue is lower when thyroid-stimulating hormone (TSH) levels are high (above 4.2 mU/L) than when TSH levels are low (below 2.0 mU/L), even when thyroid hormone levels in the blood are normal.

In patients who have had their thyroid removed and are taking levothyroxine, those with high TSH levels despite high FT4 levels show reduced activity of an enzyme that converts T4 to T3, lower T3 relative to T4, and increased sensitivity to thyroid hormones in the brain, suggesting a biological mechanism may limit the effectiveness of hormone replacement therapy.

People taking synthetic thyroid hormone (levothyroxine) for thyroid conditions show lower levels of a specific enzyme activity that converts T4 to T3 in the body, compared to people whose thyroid glands overproduce hormones due to Graves' disease or a toxic nodule.

In patients who have had their thyroid removed and are taking levothyroxine, those whose TSH levels remain above 2.0 mU/L show higher indicators of reduced pituitary sensitivity to thyroid hormones in the blood.