Familial dysalbuminaemic hyperthyroxinaemia: a rapid and novel mass spectrometry approach to diagnosis.

BackgroundFamilial dysalbuminaemic hyperthyroxinaemia is an important cause of discordant thyroid function test results (due to an inherited albumin variant); however, the diagnosis can be challenging. A 51-year-old man had persistently elevated free thyroxine (T4), with discordant normal thyroid-stimulating hormone and normal free triiodothyronine. He was clinically euthyroid and had a daughter with similar thyroid function test results. We aimed to apply a whole protein mass spectrometry method to investigate this case of suspected familial dysalbuminaemic hyperthyroxinaemia.MethodsIntact serum albumin was assessed directly using electrospray time-of-flight mass spectrometry. Results were confirmed using tryptic peptide m/z mapping and targeted DNA sequencing (exons 3 and 7 of the albumin gene). We also used this sequencing to screen 14 archived DNA samples that were negative for thyroid hormone receptor mutations (in suspected thyroid hormone resistance).ResultsMass spectrometry analysis demonstrated h...