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A dose of paracetamol for the levothyroxine absorption test We report the levothyroxine/paracetamol absorption test for the diagnosis of levothyroxine pseudomalabsorption. Paracetamol was coadministered with levothyroxine to differentiate between levothyroxine malabsorption and pseudomalabsorption. Levothyroxine dose requirements vary between individuals. In most cases, an appropriate dose can be established by dose titra- tion to biochemical targets, primarily TSH. However, therapeutic failure occurs in a small proportion of patients. Pseudomalab- sorption, nonadherence to levothyroxine therapy, is the most common cause of levothyroxine therapy failure. 1 After clinical evaluation and investigation has ruled out other likely causes of refractory hypothyroidism, the levothyroxine absorption test can be used to distinguish between pseudo- and actual levothyroxine malabsorption. Other causes of apparently refractory hypothyroidism include: decreased bioavailability from gastrointestinal disease; heavy pro- teinuria (with urinary thyroxine loss); increased thyroxine clear- ance, such as in pregnancy; and concurrent medication that reduces absorption or alters (increases or decreases) the metabo- lism of thyroxine. 2 The oral bioavailability of levothyroxine is 60–90%, and it is absorbed in the jejunum and ileum with a with a T max of 2–4 h. 3 An appropriate increase in free T4 following supervised ingestion of levothyroxine 1000 lg excludes an intrinsic absorp- tion defect. The levothyroxine absorption test assumes the levo- thyroxine reaches the small intestine and the test should be closely supervised by trained staff. A 27-year-old woman with primary hypothyroidism and per- sistently high TSH and low free T4 concentrations was reviewed in the endocrine clinic. She had a history of obesity and depres- sion. She was diagnosed with hypothyroidism 8 years earlier and over that period had been prescribed doses of levothyroxine up to 750 lg/day. She had been persistently clinically and biochem- ically hypothyroid except during a pregnancy 3 years previously. During the pregnancy, she was prescribed 400 lg a day and had “normal” thyroid function test results. There were no features to suggest malabsorption of other substances. She was on no medi- cation known to reduce thyroxine absorption (e.g. iron, calcium or a proton-pump inhibitor). On examination, she appeared hypothyroid, her face was puffy, her skin was thickened, and she had slow reflexes. Her weight was 140 kg, height was 168 cm (body mass index 49 mg/kg 2 ), and there was no goitre. Laboratory results confirmed hypothy- roidism with TSH 30 mIU/l (0Á5–4Á5) and free T4 9 pM (10–20). Coeliac antibodies and H. pylori serology were negative. Poor adherence with treatment was considered the most likely cause and subsequent treatment progressed to attendance at the endocrine clinic for directly observed treatment with 1000 lg of levothyroxine twice weekly. Her thyroid function test results did not change. A levothyroxine absorption test, with the adminis- tration of 1000 lg of thyroxine after an overnight fast, was undertaken in the endocrine test centre under the direct supervi- sion of an experienced endocrine nurse (Table 1, Test 1). The test result suggested levothyroxine malabsorption, but pseudo- malabsorption was still suspected. After discussing the result with the patient, she agreed to undergo a repeat thyroxine absorption test concurrently with a paracetamol absorption test (Table 1, Test 2). After an overnight fast, 1000 lg of thyroxine and 1000 mg of paracetamol were given and blood samples collected at baseline and hourly for 4 h © 2012 John Wiley & Sons Ltd Clinical Endocrinology (2013), 78, 966–969 968 Letters to the Editor