Endocrine Abstracts

Introduction: Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant condition that was first reported in 1979. It is caused by a mutant albumin molecule with an increased affinity for serum thyroxine (T4), despite the serum albumin level being normal. FDH causes increase in total T4 and T3 level with normal TSH level. As FDH patients are clinically euthyroid and asymptomatic, they do not require treatment.

Case report: 68-year-old female, with no past medical history first seen in 2015 in the clinic following referral from the general practitioner with abnormal Thyroid function test (Normal TSH (3.9mU/l) with elevated T4 (24.9 pmol/l) and T3 (6.5 pmol/l)). There were not any symptoms to suggest hyperthyroidism at that point apart from change in bowel habit and occasional palpitations. There was no headaches or visual disturbances, no family history of thyroid illness and bed side examination was normal. Initial works up was design to exclude or confirm TSH secreting pituitary adenoma (TSHoma) and thyroid hormone resistant. Hence, she underwent whole pituitary profile hormone check (Prolactin 151mU/l, LH 21.5U/l, FSH 32.5U/l, Testosterone 1.0nmol/l, IGF-1 11nmol/l), TRH test, alpha subunit (0.51 IU/l) and thyroxine binding protein which all came back withing normal range. Different lab has been used to check for assay interference which had the similar result. Then suspicion of FDH has been raised for which bloods sent to Addenbrooke’s hospital, Cambridge to check TFT via different method which confirms the diagnosis of FDH. Furthermore, genetic test was conducted using fluorescent sequencing analysis of exon 7 of the albumin (ALB) gene using Mutation Surveyor with the result showed ‘This patient is heterozygous for the common c.725G>A p.(Arg242His) pathogenic variant in the ALB gene, which is known to cause elevated serum thyroxine levels associated with autosomal dominant FDH’ with the recommendation of no further TFT or genetic testing needed as finding explain the abnormal TFT.

Discussion: FDH is cause of discordant TFT due to interference in FT4 assays and can be diagnosed by assessing gene variants in the albumin (ALB) gene. R218H, R218P, R222I, and R218S variants have been described. Diagnosis of FDH prevent unnecessary investigation and treatment. Consider discussing referral of family member for genetic testing as 50% risk of inheritance to children.