T4 is Free to Move About

Free thyroxine (FT4) is the form in the blood that is not bound to proteins and is a better reflection of thyroid status than total T4. Changes in binding proteins such as thyroid binding globulin may falsely shift the levels of total T4 but should not affect levels of the free fraction. 

Assessing FT4 in those with a mildly elevated TSH can help differentiate age-related adaptation to stress in which FT4 increases versus impending hypothyroidism in which FT4 decreases. Interestingly, research suggests that a free T4 at the lower end of the conventional range had better mobility, fitness, and energy levels versus the higher end in subjects considered to have normal thyroid function. 

Low FT4 is associated with hypothyroidism, decreased hypothalamic or pituitary function, iodine insufficiency, renal failure, Cushing syndrome, and certain medications. Elevated FT4 is associated with hyperthyroidism, acute thyroid inflammation, hepatitis, and certain medications.

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