The use of levothyroxine absorption tests in clinical practice

Abstract

Although levothyroxine (LT4) is a widely prescribed drug, more than 30% of LT4-treated patients fail to achieve the recommended serum level of thyrotropin with a body weight-based dose of LT4. An LT4 absorption test (LT4AT) is part of the workup for confirming normal LT4 absorption or diagnosing malabsorption. We searched PubMed with the terms levothyrox*, L-T4, LT4, TT4, FT4, FT3, TT3, test, loading, uptake, absorp*, "absorb*, bioavailab*, bioequiv* malabsorb*, and pseudomalabsorb*. A total of 43 full-text publications were analyzed. The published procedures for LT4AT differ markedly in the test dose, formulation, test duration, frequency of blood collection, analyte (total thyroxine [TT4] or free thyroxine [FT4]), metric (absolute or relative peak or increment, or area under the curve) and the threshold for normal absorption. In a standardized LT4AT for routine use, the physician could advise the patient to not consume food, beverages, or medications the morning of the test; administer 1000 µg of LT4 in the patient's usual formulation as the test dose; ensure that the patient is supervised throughout the LT4AT; perform a 4-hour test, with hourly blood samples; assay FT4; and consider that normal LT4 absorption corresponds to an FT4 increment of more than 0.40 ng/dL (5.14 pmol/L) or a TT4 increment of more than 6 μg/dL (77.23 nmol/L) for a test dose of at least 300 µg, or a percentage TT4 absorption of more than 60%. If the test indicates abnormal LT4 absorption, the physician can increase the LT4 dose, change the formulation or administration route, and/or refer the patient to a gastroenterologist.