Validity of the Rapid Thyroxine Absorption Test for the Differentiation Between Levothyroxine Non-compliance and Malabsorption in Thyroid-Stimulating Hormone Refractory Hypothyroidism.

Introduction Thyroid-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. Methods A 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. Results In 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. Conclusion The 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.

Alhassan AA ，Alidrisi HA ，Mansour AA 《Cureus》

The Use of Levothyroxine Absorption Tests in Clinical Practice.

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.

Caron P ，Declèves X 《-》

The clinical utility of free thyroxine in oral levothyroxine absorption testing.

Sun GE ，Pantalone KM ，Faiman C ，Gupta M ，Olansky L ，Hatipoglu B ... -  《Endocrine Practice》

The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic.

Gonzales KM ，Stan MN ，Morris JC 3rd ，Bernet V ，Castro MR ... -  《-》

Levothyroxine liquid oral substitution as an alternative treatment for refractory hypothyroidism due to gastrointestinal malabsorption: A case report.

Tablets of levothyroxine (LT4) are the most used form for the treatment of hypothyroidism. Some patients may present with refractory hypothyroidism despite a high daily LT4 dose. We report the case of a 49-year-old woman who was admitted to our department for refractory hypothyroidism. She was treated with 300 μg oral LT4 tablets daily (3.9 μg/kg/day). Despite good compliance and regular intake of high doses of LT4, she had persistent symptoms of hypothyroidism and a thyroid-stimulating hormone level of 92.4 mIU/L. LT4 absorption test was consistent with the diagnosis of malabsorption. Etiological investigations revealed Helicobacter pylori gastritis. Helicobacter infection was adequately treated, but symptoms of hypothyroidism and elevated thyroid-stimulating hormone persisted. Increased LT4 doses (400 μg) failed to normalize thyroid-stimulating hormone levels. Thus, she was put on LT4 liquid form at a dose of 80 drops/day per day (400 µg). Two weeks later, she presented with clinical and biological improvement with a normal free thyroxine level of 1.14 ng/dL. Patients with gastrointestinal disorders may present with refractory hypothyroidism despite increasing doses of LT4. Switching to liquid formulation may resolve this problem.

Cherchir F ，Oueslati I ，Mouelhi Y ，Talbi E ，Feki M ，Yazidi M ，Chihaoui M ... -  《SAGE Open Medical Case Reports》