IntroductionThyroid-stimulating hormone refractory hypothyroidism is a common problem. This is due to either non-compliance or malabsorption with levothyroxine (LT4). The study aimed to assess the validity of the rapid LT4 absorption test in the differentiation between LT4 malabsorption and non-compliance.MethodsA cross-sectional study was done from January to October 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, Southern Iraq. Twenty-two patients with thyroid-stimulating hormone (TSH) refractory hypothyroidism were evaluated by rapid LT4 absorption test with measurements of TSH before 1000 μg LT4 intake, and free thyroxine (pmol/l) and total thyroxine before (nmol/l) (baseline TT4 and baseline FT4) and two hours after (2-HR TT4 and 2-HR FT4). The findings were compared with the following four-week-long supervised LT4 absorption test results.ResultsIn the rapid LT4 absorption test, patients with (2-HR FT4 minus baseline FT4 ≤1.28 pmol/l (0.1 ng/dl) or 2-HR FT4 minus baseline FT4 1.28-6.43 pmol/l (0.1-0.5 ng/dl) plus 2-HR TT4 minus baseline TT4<72.08 nmol/l (5.6 µg/dl)), eight out of 10 patients were correctly diagnosed with malabsorption. And in those with (2-HR FT4 minus baseline FT4 ≥6.43 (0.5 ng/dl) or 2-HR FT4 minus baseline FT4 1.28-6.43 (0.1-0.5 ng/dl) plus 2-HR TT4 minus baseline TT4≥72.08 (5.6 µg/dl)), 11 out of 12 patients were correctly diagnosed as non-compliant. This criterion showed 88.8% sensitivity, 15.4% specificity, 80% positive predictive value, and 91.6% negative predictive value for diagnosing LT4 malabsorption.ConclusionThe rapid LT4 absorption test showed good diagnostic accuracy in differentiating non-compliance from malabsorption when (2-HR FT4 minus baseline FT4) and (2-HR TT4 minus baseline TT4) were used as criteria.