Familial dysalbuminaemic hyperthyroxinaemia: a novel mass spectrometry approach to diagnosis

Background and aims Familial dysalbuminaemic hyperthyroxinaemia (FDH) is an important cause of discordant thyroid function tests (TFT). Free thyroxine (T4) levels are falsely elevated on some assays and current diagnostic tests for FDH are laborious. We aimed to investigate a novel, mass spectrometry approach to diagnosis of FDH in a 51-year-old man with persistently elevated free T4 levels, discordant normal TSH and normal free triiodothyronine. He was clinically euthyroid and had a daughter with similar TFT profile. Methods Serum albumin was assessed using electrospray time-of-flight (TOF) liquid chromatography/mass spectrometry (LC/MS). Targeted sequencing of exons 3 and 7 of the albumin gene was used to confirm mutations and to screen 15 archived DNA samples that were negative for thyroid hormone receptor mutations. Results LC/MS demonstrated heterozygosity for an albumin variant with a 19 Da decrease in mass, indicative of an Arg→His substitution. This was confirmed by DNA sequencing which showed a guanine to adenine transition at codon 218 of exon 7, a mutation known to increase T4 binding. Discussion TOF LC/MS is a novel procedure for diagnosing FDH. The test is rapid (taking