Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test

BACKGROUND: Levothyroxine (LT(4)) pseudomalabsorption due to medication non-adherence results in significant costs for Health Service. High dose LT(4) or LT(4)/paracetamol absorption test is used in such cases. Hence, establishment of an optimal test protocol and timing of sample collection is of utmost importance. CASE PRESENTATION: A 34-year old woman was admitted to our Department because of severe hypothyroidism [on admission thyrotropin (TSH) > 100 μIU/ml, free thyroxine (FT(4)) 0.13 ng/dl (ref. range 0.93–1.7)] despite apparently taking 1000 μg of LT(4) a day. Autoimmune hypothyroidism had been diagnosed 4 years before during post-partum thyroiditis. Subsequently, it was not possible to control her hypothyroidism despite several admissions to two University Hospitals and despite vehement denial of compliance problems. There was no evidence of coeliac disease or other malabsorption problems, though gluten-free and lactose-free diet was empirically instigated without success. A combined paracetamol (1000 mg)/LT(4) (1000 μg) absorption test was performed in one of these Hospitals. This showed good paracetamol absorption (from < 2 μg/ml to 14.11 μg/ml at 120 min), with inadequate LT(4) absorption (FT(4) increase from 5.95 pmol/l to 9.92 pmol/l at 0 and 120 min respectively). About 2 years prior to admission to our Department the patient was treated with escalating doses of levothyroxine [up to 3000 μg of T(4) and 40 μg of triiodothyronine (T(3)) daily] without significant impact on TSH (still > 75 μIU/ml, and FT(4) still below reference range). After admission to our Department we performed a 2500 μg LT(4) absorption test with controlled ingestion of crushed tablets, strict patient monitoring and sampling at 30 min intervals. We observed a quick and striking increase in FT(4) from 0.13 to 0.46, 1.78, 3.05 and 3.81 ng/dl, at 0, 30, 60, 90 and 120 min, respectively. Her TSH concentration decreased to 13.77 μIU/ml within 4 days. When informed, that we had managed to “overcome” her absorption problems, she discharged herself against medical advice and declined psychiatric consultation. CONCLUSIONS: Adequate patient supervision and frequent sampling (e.g. every 30 min for 210 min) is the key for successful implementation of LT(4) absorption test. Paracetamol coadministration appears superfluous in such cases.