A Novel Approach to the Levothyroxine Absorption Test Using Only Two Free T4 Measurements

Background and aims: Levothyroxine (LT4) pseudomalabsorption is a factitious disorder. The LT4 absorption test is a non-invasive method for distinguishing true LT4 malabsorption from LT4 pseudomalabsorption in people with hypothyroidism. This study aimed to evaluate a simplified method by estimating the optimal cutoff point for free T4 (FT4) increment at four hours to predict levothyroxine absorption. Methods: Data was retrieved from the medical records of patients with hypothyroidism and persistent elevated thyroid stimulant hormone (TSH) who underwent levothyroxine absorption. Next, we estimated the two and four-hour FT4 increment. Finally, we calculated an optimal threshold value for the four-hour FT4 delta that maximizes the absolute sensitivity and specificity values. Results: Data from 76 patients was analyzed; 90% were women. The median age at the time of the test was 39 (IQR 16.5) years. The median FT4 increment at two hours was 0.8 ng/dL (95%CI 0.75 to 0.95); after four hours, it was 1.0 ng/dL (95%CI 0.92 to 1.07). To predict a qualitative absorption greater than 60% using the FT4 four-hour increment, we found an optimal cutoff point of 0.62 ng/dL with 94% sensitivity, 100% specificity, and a 0.98 area under the curve (AUC). Conclusions: Using 60% qualitative absorption of FT4 as the threshold, a 0.62 ng/dL increase after four hours of initial LT4 dose could be used to differentiate pseudomalabsorption from true malabsorption. This simple approach simplifies the levothyroxine absorption test.